Sample records for mg tnb dose

  1. Flunarizine in migraine prophylaxis: efficacy and tolerability of 5 mg and 10 mg dose levels.

    Centonze, V; Magrone, D; Vino, M; Caporaletti, P; Attolini, E; Campanale, G; Albano, O


    The use of flunarizine, a drug which has proven its efficacy in migraine, is often associated with important side effects. The aim of this paper has been to check their incidence at different dose levels (5 mg vs 10 mg). Our data confirm the occurrence of important side effects (in particular weight gain); on the other hand, they emphasize the dose-dependency of the side effects.

  2. Atazanavir increases the plasma concentrations of 1200 mg raltegravir dose.

    Krishna, Rajesh; East, Lilly; Larson, Patrick; Valiathan, Chandni; Deschamps, Kathleen; Luk, Julie Ann; Bethel-Brown, Crystal; Manthos, Helen; Brejda, John; Gartner, Michael


    Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice-daily (b.i.d.). Raltegravir 1200 mg once-daily (q.d.) (investigational q.d. formulation of 2 × 600 mg tablets; q.d. RAL) was found to be generally well tolerated and non-inferior to the marketed 400 mg b.i.d. dose at 48 weeks in a phase 3 trial. Since raltegravir is eliminated mainly by metabolism via a uridine diphosphate glucuronosyltransferase (UGT) 1A1-mediated glucuronidation pathway, co-administration of UGT1A1 inhibitors may increase the plasma levels of q.d. RAL. To assess this potential, the drug interaction of 1200 mg raltegravir using atazanavir, a known UGT1A1 inhibitor, was studied. An open-label, randomized, 2-period, fixed-sequence phase 1 study was performed in adult healthy male and female (non-childbearing potential) subjects ≥ 19 and ≤ 55 years of age, with a body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m(2) . Subjects (n = 14) received a single oral dose of 1200 mg raltegravir in period 1. After a washout period of at least 7 days, the subjects received oral doses of 400 mg atazanavir q.d. for 9 consecutive days, with a single oral dose of 1200 mg raltegravir co-administered on day 7 of period 2. Serial blood samples were collected for 72 h following raltegravir dosing and analysed using a validated bioanalytical method to quantify raltegravir plasma concentrations. Co-administration with atazanavir yielded GMRs (90% CIs) for raltegravir AUC0-∞ , Cmax and C24 of 1.67 (1.34, 2.10), 1.16 (1.01, 1.33) and 1.26 (1.08, 1.46), respectively. There was no effect of raltegravir on serum total bilirubin. In contrast, atazanavir increased the mean bilirubin by up to 200%, an effect that was preserved in the atazanavir/raltegravir treatment group. Administration of single q.d. RAL alone and co-administered with multiple oral doses of atazanavir were generally well tolerated in healthy subjects. The results show that

  3. Low dose Mifepristone (100 mg for medical termination of pregnancy

    Shikha Seth


    Full Text Available Background: Abortion is the most common entity in the practice of obstetrics and gynaecology. Different methods and modes have been opted for until now to find an effective regimen with the least complications. We have tried the minimal dose (100 mg of Mifepristone (PO instead of the presently recommended 200 mg for medical abortion in early first trimester cases. Objectives: The objective of the study was to determine the efficacy of low dose (100 mg Mifepristone for medical termination of early pregnancy with oral Misoprostol 800 μg, 24 hours later.Design: A prospective analytical study was conducted on a population of 82 early-pregnant patients who have requested medical abortions.Method: Pregnant women of less than 56 days gestation age from their last menstrual period, requesting medical abortion were selected over a period of 14 months from January 2007 to March 2008. They were given 100 mg Mifepristone orally on Day-1, followed by 800 μg Misoprostol orally 24 hours later on Day-2, keeping the patient in the ward for at least 6 hours. Abortion interval, success rate, post-abortion bleeding and side-effects were noted. Success was defined as complete uterine evacuation without the need for surgical intervention.Results: The total success rate of this minimal dose Mifepristone regimen was 96.25%. Pain and nausea were the predominant side-effects noted. In total 72 (90% women had completely aborted within 5 hours of taking Misoprostol. Three (3.75% women only required suction aspiration, hence termed as failed medical abortion. The abortion interval increased with the gestation age. All three failures were of the more-than-42-day gestational age group. The overall mean abortion interval was 4.68 ± 5.32 hours.Conclusion: Mifepristone 100 mg, followed 24 hours later by Misoprostol 800 μg orally, is a safe and effective regimen for medical abortion.

  4. Comparison of initial loading doses of 5 mg and 10 mg for warfarin therapy

    Sidnei Lastória


    Full Text Available CONTEXT: The question of what is the best loading dosage of warfarin when starting anticoagulant treatment has been under discussion for ten years. We were unable to find any comparative studies of these characteristics conducted here in Brazil. OBJECTIVE: To compare the safety and efficacy of two initial warfarin dosage regimens for anticoagulant treatment. METHODS: One-hundred and ten consecutive patients of both sexes, with indications for anticoagulation because of venous or arterial thromboembolism, were analyzed prospectively. During the first 3 days of treatment, these patients were given adequate heparin to keep aPTT (activated partial thromboplastin time between 1.5 and 2.5, plus 5 mg of warfarin. From the fourth day onwards, their warfarin doses were adjusted using International Normalized Ratios (INR; target range: 2 to 3. This prospective cohort was compared with a historical series of 110 patients had been given 10 mg of warfarin on the first 2 days and 5 mg on the third day with adjustments based on INR thereafter. Outcomes analyzed were as follows: recurrence of thromboembolism, bleeding events and time taken to enter the therapeutic range. RESULTS: Efficacy, safety and length of hospital stay were similar in both samples. The sample that were given 10 mg entered the therapeutic range earlier (means: 4.5 days vs. 5.8 days, were on lower doses at discharge and had better therapeutic indicators at the first return appointment. CONCLUSIONS: The 10 mg dosage regimen took less time to attain the therapeutic range and was associated with lower warfarin doses at discharge and better INR at first out-patients follow-up visit.


    Sikander A . K


    Full Text Available Macular edema is a frequent manifestation of diabetic retinopathy and animportant cause of visual disturbance in diabetic patients. AIM: To compare the efficacy and safety of 1mg and 4mg intravitreal triamcinolone acetonide (IVTA in the management of diabetic macular edema. SETTING: Sarojini Devi Eye Hospital, Hyderabad. MATERIAL AND METHODS: 42 eyes of 42 patients with diabetic macular edema were randomly assigned torecei ve either 1 - mg or 4 - mg dose of Intravitreal triamcinolone acetonide (IVTA. Each patient underwent a complete comprehensive eye examination at baseline andat each visit.Fundus fluorescein angiography and optical coherence angiographywas done at baseline an d at 1, 3 and 6 months.BCVA, lens status, IOP wererecorded at each follow up visit. Each patient’s BCVA was measured in snellen’s lines and converted into logarithm of minimum angle of resolution (log MAR scale for analysis. STATISTICAL ANALYSIS USED : The data were statistically evaluated using the Wilcoxon signedrank test, Mann - Whitney test and t tests wherever applicable. A p value of lessthan . 05 was considered significant. RESULTS: There was no statistically significant difference in the mean foveal thickness measurement at baseline (p=.723 or at 3 rd month (p=.878 between the sub - groups. BCVA significantly improved from baseline to subsequent visits in both the groups, but there was no statistically significant difference observed in the mean baseli ne BCVA between the two sub - groups (p=.754. There was no statistically significant difference observed in IOP between the two sub - groups at any follow up visit. CONCLUSIONS: The results of our study suggest that 1 - mg dose of IVTA is as effective as 4 - mgdo se of IVTA in improving the functional and anatomical outcome in macularedema associated with diabetic retinopathy.

  6. Warfarin Dosing Algorithms Underpredict Dose Requirements in Patients Requiring ≥7 mg Daily: A Systematic Review and Meta-analysis.

    Saffian, S M; Duffull, S B; Wright, Dfb


    There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3-94.1, I(2) = 24%). © 2017 American Society for Clinical Pharmacology and Therapeutics.

  7. Single-dose rasburicase 6 mg in the management of tumor lysis syndrome in adults.

    McDonnell, Anne M; Lenz, Kristi L; Frei-Lahr, Debra A; Hayslip, John; Hall, Philip D


    Rasburicase is currently approved at a dosage of 0.15-0.2 mg/kg once/day for 5 days in pediatric patients with cancer to lower plasma uric acid concentrations and manage tumor lysis syndrome (TLS). Information on rasburicase dosing in adults is limited, with some data on using rasburicase as a single dose instead of multiple daily doses. Therefore, we evaluated the efficacy of a single dose of rasburicase for preventing or managing TLS in adults. We collected retrospective data for 11 adults with hematologic malignancies who received a single 6-mg dose of rasburicase. All patients received intravenous hydration with urinary alkalinization and allopurinol; however, due to adverse reactions, two patients received short courses of allopurinol. Only patients at high risk for TLS (e.g., large tumor burden, increasing uric acid concentration) or those with TLS received rasburicase. The single dose of rasburicase 6 mg resulted in a median 0.0773-mg/kg dose (range 0.0232-0.1361 mg/kg). The single 6-mg dose rapidly lowered uric acid concentrations in 10 of the 11 patients. The median uric acid concentration of 11.7 mg/dl (range 7.4-17.4 mg/dl) declined to 2.0 mg/dl (range 0.5-15.4 mg/dl) within a day after rasburicase administration (p=0.022). In these 10 patients, uric acid concentrations remained low despite subsequent chemotherapy, and none required additional rasburicase doses. The only patient who did not respond to the single 6-mg rasburicase dose was a morbidly obese man (259 kg, body mass index 87 kg/m2) who subsequently responded to an additional dose of rasburicase 12 mg. These results warrant further investigation of a single 6-mg dose of rasburicase in adults with TLS or at high-risk for developing TLS.

  8. Conceptual framework of Tenaga Nasional Berhad (TNB) cost of service (COS) model

    Zainudin, WNRA; Ishak, WWM; Sulaiman, NA


    One of Malaysia Electricity Supply Industry (MESI) objectives is to ensure Tenaga Nasional Berhad (TNB) economic viability based on a fair economic electricity pricing. In meeting such objective, a framework that investigates the effect of cost of service (COS) on revenue is in great need. This paper attempts to present a conceptual framework that illustrate the distribution of the COS among TNB’s various cost centres which are subsequently redistributed in varying quantities among all of its customer categories. A deep understanding on the concepts will ensure optimal allocation of COS elements between different sub activities of energy production processes can be achieved. However, this optimal allocation needs to be achieved with respect to the imposed TNB revenue constraint. Therefore, the methodology used for this conceptual approach is being modelled into four steps. Firstly, TNB revenue requirement is being examined to ensure the conceptual framework addressed the requirement properly. Secondly, the revenue requirement is unbundled between three major cost centres or business units consist of generation, transmission and distribution and the cost is classified based on demand, energy and customers related charges. Finally, the classified costs are being allocated to different customer categories i.e. Household, Commercial, and Industrial. In summary, this paper proposed a conceptual framework on the cost of specific services that TNB currently charging its customers and served as potential input into the process of developing revised electricity tariff rates. On that purpose, the finding of this COS study finds cost to serve customer varies with the voltage level that customer connected to, the timing and the magnitude of customer demand on the system. This COS conceptual framework could potentially be integrated into a particular tariff structure and serve as a useful tool for TNB.

  9. On LiF:Mg,Cu,P and LiF:Mg,Ti phosphors high & ultra-high dose features

    Obryk, Barbara; de Barros, Vinicius S; Guzzo, Pedro L; Bilski, Paweł


    LiF:Mg,Ti and LiF:Mg,Cu,P are well known thermoluminescence (TL) dosimetry materials since many years. A few years ago their properties seemed well known and it was widely believed that they are not suitable for the measurement of doses above the saturation level of the TL signal, which for both materials occur at about 1 kGy. The high-dose high-temperature TL emission of LiF:Mg,Cu,P observed at the IFJ in 2006, which above 30 kGy takes the form of the so-called TL peak B, opened the way to use this material for measuring the dose in the high and ultra-high range, in particular for the monitoring of ionizing radiation around the essential electronic elements of high-energy accelerators, also fission and fusion facilities, as well as for emergency dosimetry. This discovery initiated studies of high and ultra-high dose characteristics of both of these phosphors, which turned out to be significantly different in many aspects. These studies not only strive to refine the method for measuring high doses based on th...

  10. TNB Experience in Developing Solar Hybrid Station at RPS Kemar, Gerik, Perak Darul Ridzuan

    Aziz, K. A.; Shamsudin, K. N.


    This paper will discuss on TNB experience in developing Solar Hybrid Station at RPS Kemar, Gerik, Perak. TNB has been approached by KKLW to submit proposal to provide electricity in the rural area namely RPS Kemar. Looking at area and source available, Solar Hybrid System was the best method in order to provide electricity at this area. This area is far from national grid sources. Solar Hybrid System is the best method to produce electrical power using the renewable energy from Solar PV, Battery and Diesel Generator Set. Nowadays, price of petroleum is slightly high due to higher demand from industry. Solar energy is good alternative in this country to practice in order to reduce cost for produce of electrical energy. Generally, Solar will produce energy during daytime and when become cloudy and dark, automatically battery and diesel generator set will recover the system through the hybrid controller system.

  11. Frequency and severity of reactions to a 325-mg aspirin dose during desensitization.

    Schuler, Charles F; Baldwin, James L; Baptist, Alan P


    The frequency with which patients with aspirin-exacerbated respiratory disease (AERD) react to 325 mg of aspirin during aspirin desensitization, or fail to react at all, is not fully known. To determine the rate and type of reaction at 325 mg of aspirin during desensitization. A retrospective study of 104 patients who underwent aspirin desensitization from 2010 to 2016 was performed. A standard desensitization protocol (starting at 20-40 mg, progressing through 325 mg, and extinguishing reactions by dose repetition) was used. Reactions were defined by upper respiratory tract symptoms, lower respiratory tract symptoms, and/or forced expiratory volume in 1 second decrease of 15% or greater. Patients who did and did not react were compared by logistic regression. Eighty-four patients reacted (81%) and 20 did not (19%). Seventy-seven patients who had a provoking reaction at 162 mg of aspirin or less subsequently extinguished their reactions before they reached a dose of 325 mg and had no problems at that dose; one subsequent 325-mg reaction occurred during a protocol violation. One initial provoking reaction to 325 mg occurred. Both 325-mg reactions were mild, and neither met the forced expiratory volume in 1 second criterion for a clinically meaningful change. The remaining 5 patients could not complete the protocol because of persistent reactions or social reasons. Reactors were more likely to have had asthma for more than 10 years than nonreactors (odds ratio, 3.2; 95% confidence interval, 1.0-10.3; P = .05). During aspirin desensitization for AERD, provoking reactions at the 325-mg dose are rare (1%) and mild. Patients who react at 162 mg or less and extinguish their reactions may be able to administer the 325-mg dose at home. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  12. Investigation of TNB/NNAP cocrystal synthesis, molecular interaction and formation process

    Chen, Peng-Yuan; Zhang, Lin; Zhu, Shun-Guan; Cheng, Guang-Bin; Li, Ning-Rui


    A novel cocrystal of 1,3,5-trinitrobenzene (TNB) and 1-nitronaphthalene (NNAP) was synthesized by solution and mechanochemical method, respectively. The crystal structure was characterized by single crystal X-ray diffraction (SXRD). Then the intermolecular interaction was illustrated quantitatively by Hirshfeld surface analysis accordingly. Two other isostructural cocrystals, TNT (2,4,6-trinitrotoluene)/NNAP and TNP (2,4,6-trinitrophenol)/NNAP were also calculated for comparison. Among the three cocrystals, TNB/NNAP cocrystal has the largest proportion of π-π stacking interaction (12.7%). While TNP/NNAP cocrystal has a greater percentage of hydrogen bonding than the other two cocrystals, which is 43.2% of the total interactions. These results indicate electronic effect has an influence on the intermolecular interaction in the cocrystal. The IR spectra of the intermediate products provide more information about the formation process of hydrogen bonding and π-π stacking. We can tell from the differential scanning calorimetry (DSC) thermograms that a eutectic mixture was generated first after TNB and NNAP were physically mixed without grinding, and then turned into the cocrystal and finally transformed completely.

  13. Low-dose mifepristone 200 mg and vaginal misoprostol for abortion

    Schaff, EA; Eisinger, SH; Stadalius, LS; Franks, P; Gore, BZ; Poppema, S


    The objectives of this study were to determine the effectiveness, side effects, and acceptability of one-third the standard 600 mg dose of mifepristone (200 mg) to induce abortion. A prospective trial at seven sites enrolled women greater than or equal to 18 years, up to 8 weeks pregnant, and wantin

  14. Low-dose mifepristone 200 mg and vaginal misoprostol for abortion

    Schaff, EA; Eisinger, SH; Stadalius, LS; Franks, P; Gore, BZ; Poppema, S


    The objectives of this study were to determine the effectiveness, side effects, and acceptability of one-third the standard 600 mg dose of mifepristone (200 mg) to induce abortion. A prospective trial at seven sites enrolled women greater than or equal to 18 years, up to 8 weeks pregnant, and wantin

  15. Flexible dosing with fesoterodine 4 and 8 mg: a systematic review of data from clinical trials.

    Wyndaele, J J; Schneider, T; MacDiarmid, S; Scholfield, D; Arumi, D


    To systematically review dose-escalation data from flexible-dose studies of fesoterodine and summarise factors associated with dose-escalation decisions. A PubMed search was conducted using the terms (fesoterodine AND flexible dose), with no limits. Articles were included if they contained fesoterodine dose-escalation data for efficacy or safety outcomes or factors associated with dose-escalation decisions. Of 13 articles identified by the search, 10 articles (six clinical studies) met inclusion criteria. In flexible-dose trials of fesoterodine, 51-63% of subjects initially receiving fesoterodine 4 mg opted for dose escalation to fesoterodine 8 mg. Escalators generally reported significantly more severe overactive bladder (OAB) symptoms, greater OAB symptom bother and worse health-related quality of life at baseline than non-escalators. Escalators demonstrated less treatment benefit with fesoterodine 4 mg than non-escalators. Non-escalators generally had a higher rate of dry mouth and constipation with fesoterodine 4 mg than escalators. The decision to escalate appeared to be determined by the efficacy/tolerability responses; fesoterodine escalators demonstrated a lower sensitivity (less efficacy and fewer adverse events) before their decision to escalate. By study end (8-11 weeks after escalation decision), the efficacy and tolerability profiles were similar in escalators and non-escalators. Data from flexible-dose studies provide strong evidence that fesoterodine provides treatment benefit to individual subjects with OAB because of its true dose-response effect. In clinical practice, it can be worthwhile to escalate to fesoterodine 8 mg in individual subjects who require additional efficacy benefit. © 2014 John Wiley & Sons Ltd.

  16. Efavirenz does not meaningfully affect the single dose pharmacokinetics of 1200 mg raltegravir.

    Krishna, Rajesh; East, Lilly; Larson, Patrick; Siringhaus, Tara; Herpok, Lisa; Bethel-Brown, Crystal; Manthos, Helen; Brejda, John; Gartner, Michael


    Raltegravir is a human immunodeficiency virus (HIV)-1 integrase strand transfer inhibitor currently marketed at a dose of 400 mg twice daily (BID). Raltegravir for once daily regimen (QD) at a dose of 1200 mg (2 x 600 mg) is under development and offers a new treatment option for HIV-1 infected treatment-naive subjects. Since raltegravir is eliminated mainly by metabolism via an UDP-glucuronosyltransferase (UGT) 1 A1-mediated glucuronidation pathway, co-administration of UGT1A1 inducers may alter plasma levels of raltegravir. Efavirenz, an UGT1A1 inducer, was used to assess the impact of altered UGT activity on a 1200 mg QD dose of raltegravir. An open label, randomized, 2-period fixed-sequence Phase 1 study was performed in adult healthy male and female subjects (non-childbearing potential) ≥ 19 and ≤55 years of age, with a body mass index (BMI) ≥ 18.5 and ≤32.0 kg/m(2) . Subjects (n = 21) received a single oral dose of 1200 mg raltegravir at bedtime on an empty stomach on Day 1 in Period 1. After a washout period of at least 7 days, subjects received oral doses of 600 mg efavirenz QD at bedtime for 14 consecutive days in Period 2. Subjects received a single oral dose of 1200 mg raltegravir co-administered with 600 mg efavirenz on Day 12 of Period 2. Pharmacokinetic (PK) samples were collected for 72 hours following raltegravir dosing and analyzed using a validated bioanalytical method to quantify raltegravir plasma concentrations. PK parameters were estimated using non-compartmental analysis. Administration of single 1200 mg oral doses of raltegravir alone and co-administered with multiple oral doses of efavirenz were generally well tolerated in healthy subjects. Co-administration with efavirenz yielded geometric mean ratios (GMRs) and their associated 90% confidence intervals (90% CIs) for raltegravir AUC0-∞, Cmax , and C24 of 0.86 (0.73, 1.01), 0.91 (0.70, 1.17), and 0.94 (0.76, 1.17), respectively. The results show that efavirenz

  17. Measuring public understanding on Tenaga Nasional Berhad (TNB) electricity bills using ordered probit model

    Zainudin, WNRA; Ramli, NA


    In 2016, Tenaga Nasional Berhad (TNB) had introduced an upgrade in its Billing and Customer Relationship Management (BCRM) as part of its long-term initiative to provide its customers with greater access to billing information. This includes information on real and suggested power consumption by the customers and further details in their billing charges. This information is useful to help TNB customers to gain better understanding on their electricity usage patterns and items involved in their billing charges. Up to date, there are not many studies done to measure public understanding on current electricity bills and whether this understanding could contribute towards positive impacts. The purpose of this paper is to measure public understanding on current TNB electricity bills and whether their satisfaction towards energy-related services, electricity utility services, and their awareness on the amount of electricity consumed by various appliances and equipment in their home could improve this understanding on the electricity bills. Both qualitative and quantitative research methods are used to achieve these objectives. A total of 160 respondents from local universities in Malaysia participated in a survey used to collect relevant information. Using Ordered Probit model, this paper finds respondents that are highly satisfied with the electricity utility services tend to understand their electricity bills better. The electric utility services include management of electricity bills and the information obtained from utility or non-utility supplier to help consumers manage their energy usage or bills. Based on the results, this paper concludes that the probability to understand the components in the monthly electricity bill increases as respondents are more satisfied with their electric utility services and are more capable to value the energy-related services.

  18. Low-dose (2.5 mg/day) finasteride treatment in hirsutism.

    Bayram, F; Müderris, I; Güven, M; Ozçelik, B; Keleştimur, F


    This study was performed to confirm the therapeutic effects of low-dose, (2.5 mg/day) finasteride in hirsute women. Our study was a non-randomized prospective clinical trial. Twenty-nine patients with hirustism were included in the study. The patients received 2.5 mg finasteride once a day over a period of 12 months. Follicle stimulating hormone, luteinizing hormone, sex hormone binding globulin, 17 alpha-hydroxyprogesterone, estradiol, androstenedione, total and free testosterone, dehydroepiandrosterone sulfate levels and hirsutism scores were determined in all patients before treatment and at every 6 months during the therapy. The hirsutism score decreased from a mean of 18.4 +/- 4.6 to 8.4 +/- 4.2 during the study. The per cent reduction in hirsutism score (mean +/- SD) at 6 and 12 months was 29.2 +/- 14.5 and 55.7 +/- 14.9%, respectively. There were no significant differences in any of the hormone levels and no serious side-effects were observed during the treatment. In conclusion, low-dose finasteride (2.5 mg/day) is a cost-effective, well-tolerated therapeutic agent without significant abnormal biochemical findings and can be used in place of high-dose (5 mg/day) finasteride in the treatment of hirsutism.

  19. Dose Dependence of Mechanoluminescence Properties in MgAl2O4: Dy Phosphor

    Kabita K. Satapathy


    Full Text Available A reliable dosimetry is fundamental for quality assurance of the processes and irradiation products. All dosimetric systems for high doses have some limitation with regard to their use. Dosimetric system should be easy to use, fast to measure, and of low cost. Good phosphor which shows high luminescence properties may fulfil the above criteria in some way. MgAl2O4: Dy phosphor has been prepared by solution combustion technique and confirmed with the help of XRD. ML has been excited impulsively by dropping a load of mass 0.7 kg onto the phosphors from various heights; two distinct ML peaks are observed for all the samples. It is observed that MgAl2O4: Dy phosphor shows linear response to gamma-ray dose and low fading which can be used for dosimetric purpose.

  20. The pharmacokinetic profile of fesoterodine 8 mg with daytime or nighttime dosing.

    Malhotra, Bimal K; Crownover, Penelope H; LaBadie, Robert; Glue, Paul; MacDiarmid, Scott A


    Diurnal variation can affect drug pharmacokinetics. Fesoterodine is a new antimuscarinic drug for the treatment of overactive bladder (OAB). We estimated the relative bioavailability of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine, following nighttime and daytime administration. In this randomized, open-label, two-period, two-treatment crossover, single-dose study, healthy subjects received daytime and nighttime oral dosing of fesoterodine 8-mg sustained-release tablets, separated by a minimum 60-h washout period. Blood samples for 5-HMT PK determination were collected before dosing and at specified intervals up to 48 h postdose. Safety was assessed by adverse event (AE) reports. Fourteen subjects completed the study. Plasma concentration versus time profiles (AUC) of 5-HMT were similar for daytime and nighttime dosing. Mean AUC(infinity) 5-HMT values were 47.9 and 51.4 ng h/mL for nighttime and daytime dosing, respectively; the mean time to reach maximum concentration (C(max)) values were 3.9 and 5.0 ng/mL, respectively. Nighttime versus daytime AUC(infinity) and C(max) ratios of 5-HMT were 93 and 79%, respectively; 90% confidence intervals (CIs) indicated equivalence for AUC(infinity) but not for C(max). The median time to reach maximum concentration (T(max)) was 5.0 h for both dosing regimens, and the mean terminal elimination half-life (T((1/2))) was 5.9 and 5.7 h for nighttime and daytime dosing, respectively. Seven treatment-related AEs, most commonly headache, occurred in five subjects. The AUC values for daytime and nighttime administration of fesoterodine were equivalent. The 21% reduction in the C(max) for nighttime dosing is unlikely to be clinically relevant. No safety issues were apparent. These results support both daytime and nighttime administration of fesoterodine for OAB treatment.

  1. Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate

    Ströberg, P; Kaminetsky, J C; Park, N C; Goldfischer, E R; Creanga, D L; Stecher, V J


    The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate. PMID:20596083

  2. Pharmacokinetics and buccal mucosal concentrations of a 15 milligram per kilogram of body weight total dose of liposomal amphotericin B administered as a single dose (15 mg/kg), weekly dose (7.5 mg/kg), or daily dose (1 mg/kg) in peripheral stem cell transplant patients.

    Gubbins, Paul O; Amsden, Jarrett R; McConnell, Scott A; Anaissie, Elias J


    The pharmacokinetics and safety of extended-interval dosing of prophylactic liposomal amphotericin B (L-AMB) in peripheral stem cell transplant recipients were evaluated. The patients received L-AMB daily at 1 mg/kg of body weight or weekly at 7.5 mg/kg or received L-AMB as a single dose (15 mg/kg). The buccal mucosal tissue concentrations of L-AMB were measured. Of the 24 patients enrolled, 5 withdrew after the initial dose due to an infusion-related reaction (n = 2) or significant increases in the serum creatinine (Scr) levels (n = 3). Weekly L-AMB dosing (7.5 mg/kg) produced mean plasma concentrations of >0.300 microg/ml for the first 7 days and >0.220 microg/ml for 7 days after the second dose. A single L-AMB dose (15 mg/kg) produced mean plasma concentrations of >0.491 microg/ml for at least 7 seven days. These concentrations are within the range of the MICs reported in the literature for susceptible strains of Candida and are at the lower limits of the MICs for Aspergillus spp. Extended-interval dosing produced buccal mucosal tissue concentrations well in excess of the MICs reported in the literature for susceptible strains of Candida and Aspergillus spp. Infusion-related reactions occurred in 24% of the patients. Baseline and end-of-study Scr, electrolyte (K+, Mg2+, PO4), and serum transaminase levels were similar across the dosage groups. Five (31%) patients met the nephrotoxicity definition prior to completion of the study. Patients in the weekly or single-dose groups experienced nephrotoxicity significantly faster than the patients in the daily dosing cohort. A weekly L-AMB dose (7.5 mg/kg) or a single L-AMB dose (15 mg/kg) produced sufficient concentrations in plasma and highly vascular tissue to warrant further studies of the safety, efficacy, and practicality of the weekly prophylactic administration of L-AMB.


    Hema Divakar


    Full Text Available BACKGROUND The aim of the study is to determine the non-inferiority of a single dose of 500 mg Ferric Carboxymaltose (FCM (Group 1 to a single dose of 1000 mg (Group 2 in treating women with postpartum anaemia. MATERIALS AND METHODS Women were recruited within 24 hours of delivery and randomised to one of the two study groups excluded were mothers with non-iron deficiency anaemia, iron intolerance and haematological disease. Haematological markers were measured at baseline and at 6 weeks after treatment. Main Outcome Measures- The primary outcome was an Hb increase ≥20 g/L. Secondary outcomes included the proportion of patients attaining Hb ≥120 g/L and the mean Hb change. Design- Open label, randomised, non-blinded, prospective study. Setting- Maternity units of four hospitals in Southern India. Population- Women ≥18 years old with haemoglobin of >60 - 20 g/L between Groups 1 and 2 (91.4% versus 96.7%. Similar proportions of women in both groups became non-anaemic achieving an Hb of >120 g/L (57% versus 45.7%. The mean Hb change was comparable between the groups and both doses were well tolerated. CONCLUSION A single dose of 500 mg FCM (cost INR 2000.00 is non-inferior to a 1000 mg dose (cost INR 5000.00 in the treatment of postpartum anaemia. This has major implications for the scaling up of the eradication of iron-deficiency anaemia in India, since double the number of women who would otherwise have been treated with the 1000 mg dose can be treated with half the dose at less than half the cost with similar outcomes. Tweetable Abstract- A single dose of 500 mg FCM is a safe, efficacious and cost-effective treatment for PPA in India.

  4. Platelet response to increased aspirin dose in patients with persistent platelet aggregation while treated with aspirin 81 mg.

    Gengo, Fran; Westphal, Erica S; Rainka, Michelle M; Janda, Maria; Robson, Matthew J; Hourihane, J Maurice; Bates, Vernice


    This study demonstrates that patients who are taking 81 mg of aspirin and are nonresponsive benefit from a dose of 162 mg or greater vs a different antiplatelet therapy. We identified 100 patients who were nonresponsive to aspirin 81 mg via whole blood aggregometry and observed how many patients became responsive at a dose of 162 mg or greater. Platelet nonresponsiveness was defined as >10 Ω of resistance to collagen 1 µg/mL and/or an ohms ratio of collagen 1 µg/mL to collagen 5 µg/mL >0.5 and/or >6 Ω to arachidonate. Borderline response was defined as an improvement in 1 but not both of the above criteria. Of the initial 100 patients who were nonresponsive to an aspirin dose of 81 mg, 79% became responsive at a dose of 162 mg or >162 mg. Only 6% did not respond to any increase in dose. We believe that patients treated with low-dose aspirin who have significant risk for secondary vascular events should be individually assessed to determine their antiplatelet response. Those found to have persistent platelet aggregation despite treatment with 81 mg of aspirin have a higher likelihood of obtaining an adequate antiplatelet response at a higher aspirin dose.

  5. A single-blind, randomized comparison of olanzapine at a starting dose of 5 mg versus 20 mg in acute schizophrenia.

    Mauri, Massimo Carlo; Colasanti, Alessandro; Rossattini, Matteo; Moliterno, Donatella; Baldi, Marialuisa L; Papa, Pietro


    Acute psychotic episodes represent critical situations during the course of schizophrenia. Olanzapine (OLZ), a second-generation antipsychotic, is efficacious in acute settings at dosages of 5 to 20 mg/d, and it can be considered a first-line treatment for patients with an acute episode of schizophrenia. The aim of this study was to evaluate the efficacy and tolerability of OLZ at a starting dose of 5 mg versus 20 mg in acute schizophrenic patients and to compare titration versus nontitration.Fifty-one schizophrenic inpatients were randomly assigned to receive OLZ at 5 mg/d (26 patients, group 1) or 20 mg/d (25 patients, group 2) as a starting dosage during an exacerbation phase. In group 1, the OLZ dosage was increased to a mean dosage of 10.55 (+/- 4.00) mg/d. Group 2 received OLZ at a fixed dose of 20 mg throughout the hospitalization period. Olanzapine was significantly and clinically effective on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale, PANSS positive symptoms, and Hamilton Rating Scale for Depression in both groups. There were no significant differences between groups 1 and 2 in the percent improvement in BPRS, Positive and Negative Syndrome Scale, PANSS positive symptoms, PANSS negative symptoms, or Hamilton Rating Scale for Depression; but group 2 was significantly superior in the mean percent improvement in the BPRS items of anxiety (P < 0.001) and suspiciousness (P < 0.05). In conclusion, the higher doses evidence more efficacy on anxiety and suspiciousness, so it seems to be useful to begin therapy with a full dose of the drug to obtain the maximum effect without any significant side effects.

  6. Single dose bioequivalence study of two brands of olanzapine 10 mg tablets in Iranian healthy volunteers.

    Zakeri-Milani, P; Islambulchilar, Z; Ghanbarzadeh, S; Valizadeh, H


    This single dose, randomized, open label, 2-period and crossover study in healthy Iranian adult volunteers was conducted to compare the bioavailability of 2 branded formulations of olanzapine 10 mg tablets. 24 volunteers received one tablet of each olanzapine 10 mg formulation. Drugs were administered after a 12 h overnight fast in each of 2 treatment days which separated by a 2-week washout period. Serial blood samples were collected over a period of 72 h. Plasma was analyzed using a validated high performance liquid chromatography method with ultraviolet detection in the range of 2-24 ng/mL with a lower limit of quantitation of 1.25 ng/mL. A non-compartmental method was employed to determine the pharmacokinetic properties (Cmax, Tmax, AUC0-t, AUC0-∞ and T1/2) to test to bioequivalence. Cmax, AUC0-t and AUC0-∞ were used to test the bioequivalence after log-transformation of plasma data. The mean (SD) Cmax, AUC0-t and AUC0-∞ for the test formulation were 15.82 (3.15) ng/mL, 447.19 (100.64) ng.h/L and 570.75 (130.55) ng.h/L respectively. Corresponding values for the test formulation were 15.72 (4.25) ng/mL, 440.37 (98.75) ng.h/mL and 558.66 (129.57) ng.h/mL. For test formulation vs. the reference formulation, the 90% CIs of the least squares mean test/reference ratios of Cmax, AUC0-t and AUC0-∞ were 97.6-110.0%, 96.4-109.4% and 97.3-109.2%. In these volunteers, based on the FDA regulatory definition, results from the pharmacokinetic analysis suggested that the test and reference formulations of olanzapine 10 mg tablets were bioequivalent.

  7. Safety, tolerability, and efficacy of a fixed-dose combination of olmesartan 40 mg and hydrochlorothiazide 12.5/25 mg in daily practice

    Bramlage, Peter; Zemmrich, Claudia; Ketelhut, Reinhard; Wolf, Wolf-Peter; Fronk, Eva-Maria; Schmieder, Roland E


    Background The safety and efficacy of olmesartan 40 mg and hydrochlorothiazide (HCTZ) as a fixed-dose combination has been investigated in clinical trials leading to its approval. The aims of the present study were to confirm these data in an unselected patient population in daily practice and to determine the impact of physical activity on blood pressure control. Methods In a multicenter, noninterventional study, 3,333 patients with either insufficient blood pressure control on olmesartan 40 mg alone or on a fixed/free combination of olmesartan 40 mg and HCTZ 12.5/25 mg were primarily assessed for safety and tolerability of the fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg at 24 ± 2 weeks. Secondary objectives were blood pressure reduction, treatment compliance, and impact of physical activity as measured by the sum of weekly energy costs. Results The mean patient age was 63.2 ± 11.46 years, mean baseline blood pressure was 159.6 ± 15.28/93.5 ± 9.52 mmHg, and 70.9% had at least one additional cardiovascular risk factor. Adverse drug reactions were rare (n = 19), and no serious adverse drug reactions occurred. Compliance with drug therapy was at least sufficient in more than 99% of patients at the end of the study. Blood pressure at the last available visit was reduced by 26.1 ± 15.5/13.0 ± 10.1 mmHg versus baseline (P olmesartan 40 mg and HCTZ 12.5/25 mg in a large, unselected patient population, independent of physical activity level. PMID:24039432

  8. Should the dose of tenofovir be reduced to 200–250 mg/day, when combined with protease inhibitors?

    Andrew Hill


    Full Text Available Introduction: The approved dose of tenofovir disproxil fumarate, 300 mg once daily, was established in clinical trials in combination with efavirenz, which does not significantly affect tenofovir concentrations. Combining tenofovir with lopinavir/r, darunavir/r or atazanavir/r increases tenofovir concentrations, which could raise the risk of renal adverse events. Newly approved tenofovir tablets are available at lower strength (200 or 250 mg for use in paediatrics. Methods: A literature search was used to assess the effects of lopinavir/r, darunavir/r and atazanavir/r on tenofovir plasma Cmax, AUC and Cmin (Geometric Mean Ratio and 90% confidence intervals. Assuming linear dose-proportional pharmacokinetics (as observed in dose-ranging studies, the 250 mg tablet was predicted to achieve plasma concentrations 17% lower than the 300 mg dose, and the 200 mg tablet to achieve plasma levels 33% lower. Effects on tenofovir plasma Cmax, AUC and Cmin concentrations were assessed for combined dosing of each protease inhibitor with 250 or 200 mg daily doses of tenofovir, versus standard dose tenofovir (300 mg daily without protease inhibitors. Results: In drug-drug interaction studies, lopinavir/ritonavir significantly increased tenofovir Cmax, AUC and Cmin. Effects of each PI on tenofovir Cmin were greater than effects on Cmax or AUC. Using a 250 mg paediatric dose of tenofovir with lopinavir/ritonavir, tenofovir Cmin was predicted to remain higher than tenofovir 300 mg used with efavirenz (GMR=1.26, 95% CI 1.14–1.38. Similar results were observed for use of tenofovir 250 mg with atazanavir/ritonavir (GMR=1.07, 95% CI 1.01–1.13 and with darunavir/ritonavir (GMR=1.14, 95% CI 0.99–1.31. Predicted tenofovir AUC levels for the 250 mg dose with protease inhibitors were all within the bioequivalence range, relative to use with efavirenz. Using a 200 mg paediatric dose of tenofovir with lopinavir/ritonavir, the tenofovir Cmin was predicted to be

  9. [Lormetazepam in preoperative sleeplessness. Dose dependance of the effect and comparison with 100 mg pentobarbital (author's transl)].

    Ott, H; Doenicke, A; Abress, C; Fischl, R; Hemmerling, K G; Fichte, K


    Lormetazepam (0.5, 1, 2, 4, 8 mg)--a new benzodiazepine--was tested versus Pentobarbital (100 mg) under double blind conditions on 240 preoperative inpatients for night-time sedative and side effects after acute oral intake. Results are based on p less than 0.05. Additionally p less than 0.125 in binomial-two-sample-tests was accepted. Lormetazepam shows dose dependent increase in hypnotic effects (e.g. reduction in sleep latency and number of awakenings, increase of total sleep duration), and side effects (e.g. dopiness, dizziness), but no relevant change in vital signs. About 0.5 mg of Lormetazepam are equivalent to 100 mg of Pentobarbital. 2 mg of Lormetazepam seem to be the optimum dose regarding the relation between hypnotic and side effects. In the view of anaesthesists Lormetazepam is preferable to Pentobarbital because of more favorable safety aspects.




    Full Text Available ABSTRACT: AIMS : This study aimed to find out the efficacy of single oral dose 150mg of fluconazole in treatment of acute vulvovaginal candidiasis, to e valuate its safety assessment and the clinical and mycological efficacy assessment. MATERIALS AND METHODS: T his study is carried out in department of obstetrics and gynaecology Gandhi medical college sultania hospital Bhopal and with the help of microbiolo gy department Gandhi medical college Bhopal over a period of one year. It is a hospital based clinical prospective study. RESULTS : Maximum age incidence was found between 21 - 30years. Mostly patients belonged to low socioeconomic status and were uneducated. Maximum patients were married (98% and multiparous (92%, nulliparous formed the smallest group (8%. In factors predisposing to candidiasis, contraceptive methods were found to be important in which maximum incidence was found in patients using oral con traception about 32% and 12% of IUCD users were affected. Other factors were antibiotic treatment (5% and diabetes (2%. Vaginal discharge and pruritis were the two commonest symptoms found. Among the signs vaginal discharge and white plaques was the comm onest sign. On follow up visits 88 cases had complete clinical cure and only 6 cases showed failure and 9 recurrence s . In mycological assessment maximum 135 cases showed complete cure, 6 were failure and 9 recurrence. In overall results, excellent results were found in 88cases, good in 38 cases, fair in 9 cases and recurrence in 9 cases. Recurrences were mainly due to rectal carriers. CONCLUSION: In co n clusion fluconazole was found effective as a systemic single oral dose therapy for acute vulvovaginal cand idiasis. It is proved safe in terms of tolerance and preferred by patients. So in view of its favourable patients acceptability and compliance profile, it is considered as a first line therapeutic choice for treatment of women with vaginal candidiasis.

  11. Measurements of low photon doses using LiF:Mg,Cu,P and CaF{sub 2}:Cu dosimeters

    Prokert, K. [Dresden Univ. of Technology (Germany). Inst. of Radiation Protection Physics; Mann, G. [Dresden Univ. of Technology (Germany). Inst. of Radiation Protection Physics


    The new thermoluminophors LiF:Mg, Cu, P and CaF{sub 2}:Cu in form of pellets exhibit a significantly higher TL-response than the well-known dosimeters of the types TLD-100 (LiF:Mg, Ti), TLD-400 (CaF{sub 2}:Mn), TLD-900 (CaSO{sub 4}:Dy), etc. Furthermore, the thermoluminophor LiF:Mg, Cu, P shows besides its high sensitivity a good tissue equivalence and therefore, only a small variation of the dose response with the photon energy. The lower limits of detection of these new materials are about 5 {mu}Gy and 0.2 {mu}Gy resp. Therefore, short term measurements of absorbed dose can be realised in radiation fields at very low dose rates (environmental radiation, scattering radiation at medical equipment`s etc.) with an accuracy of {+-}10%. In the field of environmental monitoring the period of exposure can be limited to about 10 days. Using CaF{sub 2}:Cu detectors an exposure of 24 hours is sufficient for dose measurements with lower accuracy. The reusability of CaF{sub 2}:Cu pellets is guaranteed without loss of sensitivity independently of the application of different reading and annealing procedures. In the case of LiF:Mg, Cu, P detectors special procedures are needed in order to keep constant TL-properties. The results of dose measurements at low dose levels in different radiation fields demonstrate the advantages of these detector types. (orig.)


    Scheen, A J


    Liraglutide is an analogue of Glucagon-Like Peptide-1 (GLP-1) already indicated under the trade name of Victoza for the treatment of type 2 diabetes, at usual doses of 1.2 or 1.8 mg as once daily subcutaneous injection. It is henceforth indicated at a dose of 3.0 mg, also as once daily subcutaneous injection, for the treatment of obesity or overweight with comorbidities under the trade name of Saxenda, in combination with diet and exercise. Besides a specific action on the endocrine pancreas, mainly responsible for the antihyperglycaemic effect, liraglutide helps controlling appetite at the hypothamalic level. A specific programme of controlled trials (especially SCALE studies) demonstrated both efficacy and safety of the 3.0 mg dose of liraglutide in obese or overweight patients with various comorbidities.


    Pratibha Rai


    Full Text Available BACKGROUND Mifepristone is Selective Progesterone Receptor Modulators (SPRMS and is emerging as a best medical treatment increasing the quality of life as well as saving the patient from surgery. This drug has shown great effectiveness, e.g.: 2.5 mg, 5 mg and 10 mg, but with less reduction in uterine volume as well as reduction in fibroids size. Ref. 1 Yang Y et al. AIM The aim of this study was to evaluate the safety and improvement of life pattern using 10 mg and 25 mg daily doses of Mifepristone for six months with a nine month follow-up period for the regress of fibroids as well as uterine volume to improve quality of life without any surgery in premenopausal women with complaint of menorrhagia, dysmenorrhoea, abdominal discomfort, dyspareunia, rectal pain, urinary problem and weakness due to anaemia. DESIGN The research was a randomized double blind clinical study undertaken at Patliputra Medical College Hospital, Dhanbad (Jharkhand. SEARCH METHOD I had searched a number of international journals, reference lists, databases and ongoing trails and the internet. Also searched the specialised register of Cochrane menstrual disorders and subfertility (Cochrane menstrual disorder and subfertility. The Cochrane central register of control trails (Central. The Cochrane library 2011, Issue 4. METHODOLOGY The trial was done on 100 patients. Patients were divided into two equal groups (All were with symptomatic uterine fibroids to evaluate safety as well as quality of life. Dose decided was 10 mg (A and 25 mg (B of Mifepristone. Subjects were taken from Gynaecological outdoor of Patliputra Medical College Hospital, Dhanbad, (Jharkhand, after taking their consent. All women were between the age group of 35 to 48 years with symptomatic multiple fibroids of various sizes and site. At enrolment patients of both groups underwent clinical assessment, Per Abdomen (P/A and Per Vaginal (P/V examination, USG for uterine volume and size of fibroid. Endometrial

  14. Comparator pH study to evaluate the single-dose pharmacodynamics of dual delayed-release dexlansoprazole 60 mg and delayed-release esomeprazole 40 mg

    Kukulka M


    Full Text Available Michael Kukulka1, Corey Eisenberg2, Sai Nudurupati31Clinical Pharmacology, 2Clinical Science, 3Statistics, Takeda Global Research & Development Center Inc, Deerfield, IL, USABackground: This paper describes a Phase 1, single-center, randomized, open-label, two-period crossover study which compared the pharmacodynamic effects of single doses of dexlansoprazole modified-release 60 mg and esomeprazole 40 mg on 24-hour intragastric pH in healthy adult subjects.Methods: Forty-four subjects aged 20–54 years were randomized in a 1:1 ratio to two sequence groups defining the order in which they received dexlansoprazole and esomeprazole in periods 1 and 2. Primary pharmacodynamic end points over 24 hours postdose were percentage of time with intragastric pH > 4 and mean pH, and secondary pharmacodynamic end points were percentage of time intragastric pH > 4, and mean pH at 0–12 hours, and at >12–24 hours postdose. Each drug was given after an overnight fast and one hour before breakfast. Continuous pH recording began immediately before dosing through to 24 hours postdose.Results: At 0–24 hours postdose, the mean percentage of time with pH > 4 for dexlansoprazole and esomeprazole was 58% and 48%, respectively; the difference was statistically significant (P = 0.003. The average of mean pH values at 0–24 hours postdose for dexlansoprazole and esomeprazole were 4.3 and 3.7, respectively; the difference was statistically significant (P < 0.001. At >12–24 hours postdose, mean percentage of time with pH > 4 and average of mean pH were greater for dexlansoprazole (60% and 4.5, respectively compared with esomeprazole (42% and 3.5, respectively; the difference was statistically significant (P < 0.001 for both intervals. At 0–12 hours postdose, the difference in dexlansoprazole and esomeprazole values for the pharmacodynamic end points was not statistically significant.Conclusion: For the entire 24-hour postdose period, predominantly resulting from

  15. Ototoxicity of 12 mg/kg cisplatin in the Fischer 344/NHsd rat using multiple dosing strategies.

    Harrison, Ryan T; Seiler, Brittany M; Bielefeld, Eric C


    Ototoxicity continues to be a major dose-limiting side effect of cis-diamminedichloroplatinum(II) (cisplatin). With an ongoing need to develop pharmaceutical protection strategies for cisplatin's ototoxicity, there is also a need to develop stable in-vivo mammalian models of cisplatin ototoxicity. The current study examined the difference in ototoxicity of a cumulative 12 mg/kg dose of cisplatin in the Fischer 344/NHsd rat when administered over four different dosing protocols. Hearing sensitivity was measured using free-field auditory brainstem response thresholds under anesthesia. Rats were divided into four groups. The first group was administered 12 mg/kg of cisplatin in a single bolus infusion. The second group was administered two 6 mg/kg infusions separated by 7 days. The third group was administered 3 mg/kg injections once per day for 4 consecutive days. The fourth group was administered 3 mg/kg injections in four injections separated by 3 days each. Hearing thresholds and body weights were measured at 3 and 7 days after the final cisplatin exposure. Postmortem sensory cell counts were used to confirm injury to the auditory system. The 4 consecutive days of 3 mg/kg induced a greater mortality rate and greater hearing loss at day 3 than the other experimental protocols. The 3 mg/kg administered every 3 days induced less sensory cell loss than the other conditions. The findings indicate that 4 consecutive days of 3 mg/kg cisplatin is not a viable ototoxicity model in the Fischer 344/NHsd rat, but that the other models are all effective in inducing comparable cochlear injuries.

  16. Safety, tolerability, and efficacy of a fixed-dose combination of olmesartan 40 mg and hydrochlorothiazide 12.5/25 mg in daily practice

    Bramlage P


    Full Text Available Peter Bramlage,1 Claudia Zemmrich,1 Reinhard Ketelhut,2 Wolf-Peter Wolf,3 Eva-Maria Fronk,4 Roland E Schmieder5 1Institut für Pharmakologie und Präventive Medizin, Mahlow, Germany; 2Institut für Sportmedizin, Universitätsklinikum Charité, Humboldt Universität zu Berlin, Berlin, Germany; 3Daiichi Sankyo Deutschland GmbH, Munich, Germany; 4Daiichi Sankyo Europe GmbH, Munich, Germany; 5Universitätsklinikum Erlangen, Klinik für Nephrologie und Hypertensiologie, Erlangen, Germany Background: The safety and efficacy of olmesartan 40 mg and hydrochlorothiazide (HCTZ as a fixed-dose combination has been investigated in clinical trials leading to its approval. The aims of the present study were to confirm these data in an unselected patient population in daily practice and to determine the impact of physical activity on blood pressure control. Methods: In a multicenter, noninterventional study, 3,333 patients with either insufficient blood pressure control on olmesartan 40 mg alone or on a fixed/free combination of olmesartan 40 mg and HCTZ 12.5/25 mg were primarily assessed for safety and tolerability of the fixed-dose combination of olmesartan 40 mg and HCTZ 12.5/25 mg at 24 ± 2 weeks. Secondary objectives were blood pressure reduction, treatment compliance, and impact of physical activity as measured by the sum of weekly energy costs. Results: The mean patient age was 63.2 ± 11.46 years, mean baseline blood pressure was 159.6 ± 15.28/93.5 ± 9.52 mmHg, and 70.9% had at least one additional cardiovascular risk factor. Adverse drug reactions were rare (n = 19, and no serious adverse drug reactions occurred. Compliance with drug therapy was at least sufficient in more than 99% of patients at the end of the study. Blood pressure at the last available visit was reduced by 26.1 ± 15.5/13.0 ± 10.1 mmHg versus baseline (P < 0.0001, but had reduced effectiveness in patients ≥75 years with diabetes or impaired renal function. In 69% of patients

  17. Whole-body dose and energy measurements in radiotherapy by a combination of LiF:Mg,Cu,P and LiF:Mg,Ti.

    Hauri, Pascal; Schneider, Uwe


    Long-term survivors of cancer who were treated with radiotherapy are at risk of a radiation-induced tumor. Hence, it is important to model the out-of-field dose resulting from a cancer treatment. These models have to be verified with measurements, due to the small size, the high sensitivity to ionizing radiation and the tissue-equivalent composition, LiF thermoluminescence dosimeters (TLD) are well-suited for out-of-field dose measurements. However, the photon energy variation of the stray dose leads to systematic dose errors caused by the variation in response with radiation energy of the TLDs. We present a dosimeter which automatically corrects for the energy variation of the measured photons by combining LiF:Mg,Ti (TLD100) and LiF:Mg,Cu,P (TLD100H) chips. The response with radiation energy of TLD100 and TLD100H compared to (60)Co was taken from the literature. For the measurement, a TLD100H was placed on top of a TLD100 chip. The dose ratio between the TLD100 and TLD100H, combined with the ratio of the response curves was used to determine the mean energy. With the energy, the individual correction factors for TLD100 and TLD100H could be found. The accuracy in determining the in- and out-of-field dose for a nominal beam energy of 6MV using the double-TLD unit was evaluated by an end-to-end measurement. Furthermore, published Monte Carlo (M.C.) simulations of the mean photon energy for brachytherapy sources, stray radiation of a treatment machine and cone beam CT (CBCT) were compared to the measured mean energies. Finally, the photon energy distribution in an Alderson phantom was measured for different treatment techniques applied with a linear accelerator. Additionally, a treatment plan was measured with a cobalt machine combined with an MRI. For external radiotherapy, the presented double-TLD unit showed a relative type A uncertainty in doses of -1%±2% at the two standard deviation level compared to an ionization chamber. The type A uncertainty in dose was in

  18. Detection of sub micro Gray dose levels using OSL phosphor LiMgPO{sub 4}:Tb,B

    Rawat, N.S., E-mail: [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India); Dhabekar, Bhushan [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India); Muthe, K.P. [Technical Physics Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India); Koul, D.K.; Datta, D. [Radiological Physics and Advisory Division, Bhabha Atomic Research Centre, Trombay, Mumbai (India)


    Highlights: • LiMgPO4:Tb,B has been studied and shown to possesses minimum measurable dose (MMD) in sub micro Gray region. • MMD as low as 0.49 µGy in readout time of less than 1 s at stimulation intensity of 32 mW/cm{sup 2} has been achieved. • The OSL measurements for low doses has strengthened and validated this claim. • OSL spectrum shows several emission peaks and the prominent peak around 380 nm. - Abstract: Detection of sub micro Gray doses finds application in personnel and environmental monitoring, and nuclear forensics. Recently developed LiMgPO{sub 4}:Tb,B (LMP) is highly sensitive Optically Stimulated Luminescence (OSL) phosphor with excellent dosimetric properties. The OSL emission spectrum of LMP consists of several peaks attributed to characteristic Tb{sup 3+} emission. The OSL emission peak at 380 nm is favorable for bi-alkali PMT used in RISO reader system. It is demonstrated that significant improvement in dose detection threshold can be realized for LMP by optimization of continuous wave (CW–) OSL parameters like stimulation intensity and readout time. The minimum measurable dose (MMD) as low as 0.49 µGy in readout time of less than 1 s at stimulation intensity of 32 mW/cm{sup 2} has been achieved using this phosphor. The recommendations for choice of parameters for personnel and environmental monitoring are also discussed.

  19. Toxicity associated with stavudine dose reduction from 40 to 30 mg in first-line antiretroviral therapy.

    Mar Pujades-Rodríguez

    Full Text Available BACKGROUND: To compare the incidence and timing of toxicity associated with the use of a reduced dose of stavudine from 40 to 30 mg in first-line antiretroviral therapy (ART for HIV treatment and to investigate associated risk factors. METHODS: Multicohort study including 23 HIV programs in resource-limited countries. Adults enrolled between January 2005 and December 2009. Four-year rates of all-cause and stavudine-specific toxicity were estimated. Multilevel mixed-effect Poisson and accelerated failure models were used to investigate factors associated with toxicity and timing of diagnosis. FINDINGS: A total of 48,785 patients contributed 62,505 person-years of follow-up. Rate of all-cause toxicity was 7.80 (95%CI 7.59-8.03 per 100 person-years, but varied greatly across sites (range 0.41-21.76. Patients treated with stavudine 40 mg had higher rates of toxicity (adjusted rate ratio [aRR] 1.18, 95%CI 1.06-1.30 during the first year of ART; and 1.51, 95%CI 1.32-1.71 during the second year. Women, older age, initial advanced clinical stage, and low CD4 count were associated with increased toxicity rate ratios. Timing of lipodystrophy and peripheral neuropathy diagnosis were 12% and 13% shorter, respectively, in patients treated with stavudine 40 mg than in those receiving 30 mg stavudine dose (P = 0.03 and 0.07, respectively. INSTERPRETATION: Higher rates of drug-related toxicity were reported in patients receiving stavudine 40 mg compared with 30 mg, and the time to toxicity diagnosis was shorter in patients treated with the higher dose. Higher rates of toxicity were observed during the first two years of ART.

  20. Safety and efficacy of a fixed-dose cyclosporin microemulsion (100 mg) for the treatment of psoriasis.

    Shintani, Yoichi; Kaneko, Natumi; Furuhashi, Takuya; Saito, Chiyo; Morita, Akimichi


    Cyclosporin is a second-line modality for the treatment of psoriasis. The long-term efficacy of cyclosporin and potential adverse side-effects, however, are a concern to patients. Therefore, a cyclosporin microemulsion (Neoral), which is steadily absorbed at an ultra-low dosage (1-2 mg/kg per day) or low dosage (2-3 mg/kg per day), is currently recommended. The dose must be calculated based on patient bodyweight and the blood concentration monitored regularly, which is time-consuming. Furthermore, the concentration is related to the safety profile, but not to efficacy. We examined whether a fixed-dose cyclosporin microemulsion (100 mg/day) is effective for treating psoriasis. Enrolled patients (n = 40) were given either 100 mg cyclosporin emulsion once daily (group A) or 50 mg twice daily (group B), regardless of patient weight and condition, before meals in a randomized controlled study. Patient bodyweight ranged 50-80 kg. We assessed the serum cyclosporin concentration 1 h after administrating the medicine (C1 score), Psoriasis Area and Severity Index (PASI) score, quality of life, and the results of regular blood examinations. The improvement rate was 69.4 ± 4.8% in group A and 73.4 ± 4.3% in group B. PASI-50 was achieved by 82% in group A and 84% in group B. At 6 weeks, the number of patients with PASI-50 was significantly higher in group A than in group B. PASI-75 and -90 were also achieved in both groups with no significant difference between groups. Administration of a fixed-dose cyclosporin microemulsion (100 mg/day) is practical for second-line psoriasis treatment. © 2011 Japanese Dermatological Association.

  1. Lanreotide Autogel 120 mg at extended dosing intervals in patients with acromegaly biochemically controlled with octreotide LAR: the LEAD study.

    Neggers, Sebastian J C M M; Pronin, Vyacheslav; Balcere, Inga; Lee, Moon-Kyu; Rozhinskaya, Liudmila; Bronstein, Marcello D; Gadelha, Mônica R; Maisonobe, Pascal; Sert, Caroline; van der Lely, Aart Jan


    To evaluate extended dosing intervals (EDIs) with lanreotide Autogel 120 mg in patients with acromegaly previously biochemically controlled with octreotide LAR 10 or 20 mg. Patients with acromegaly had received octreotide LAR 10 or 20 mg/4 weeks for ≥ 6 months and had normal IGF1 levels. Lanreotide Autogel 120 mg was administered every 6 weeks for 24 weeks (phase 1); depending on week-24 IGF1 levels, treatment was then administered every 4, 6 or 8 weeks for a further 24 weeks (phase 2). Hormone levels, patient-reported outcomes and adverse events were assessed. proportion of patients on 6- or 8-week EDIs with normal IGF1 levels at week 48 (study end). 107/124 patients completed the study (15 withdrew from phase 1 and two from phase 2). Of 124 patients enrolled, 77.4% were allocated to 6- or 8-week EDIs in phase 2 and 75.8% (95% CI: 68.3-83.3) had normal IGF1 levels at week 48 with the EDI (primary analysis). A total of 88.7% (83.1-94.3) had normal IGF1 levels after 24 weeks with 6-weekly dosing. GH levels were ≤ 2.5 μg/l in > 90% of patients after 24 and 48 weeks. Patient preferences for lanreotide Autogel 120 mg every 4, 6 or 8 weeks over octreotide LAR every 4 weeks were high. Patients with acromegaly achieving biochemical control with octreotide LAR 10 or 20 mg/4 weeks are possible candidates for lanreotide Autogel 120 mg EDIs. EDIs are effective and well received among such patients. © 2015 European Society of Endocrinology.

  2. A pharmacokinetic comparison of single doses of once-daily cyclobenzaprine extended-release 15 mg and 30 mg: a randomized, double-blind, two-period crossover study in healthy volunteers.

    Darwish, Mona; Chang, Steven; Hellriegel, Edward T


    The purpose of this study was to compare the pharmacokinetics and tolerability of single oral doses of cyclobenzaprine extended-release (CER) 15- and 30-mg capsules. This was a randomized, double-blind, 2-period crossover study in healthy adults aged 18 to 40 years. Subjects were assigned to receive a single dose of either CER 15 mg or 30 mg on days 1 and 15, separated by a 14-day washout. Study comparisons included the plasma cyclobenzaprine AUC to 168 hours after dosing (AUC(0-168)), AUC(0-infinity), and C(max). Plasma cyclobenzaprine T(max), terminal elimination t(1/2), and adverse events (AEs) were also assessed. Sixteen subjects (9 women, 7 men) were randomized to receive cyclobenzaprine 15 mg or 30 mg; 13 (81.3%) were white and 3 (18.8%) were black. Mean age and weight were 30.2 years and 70.7 kg, respectively. The shapes of the pharmacokinetic profiles for CER 15 and 30 mg were parallel. Mean observed values for dose-dependent pharmacokinetic parameters of CER 15 and 30 mg were as follows: AUC(0-168), 318.3 and 736.6 ng . h/mL, respectively; AUC(0-infinity)), 354.1 and 779.9 ng . h/mL; and C(max), 8.3 and 19.9 ng/mL. Dose-independent parameters were comparable across doses. Median observed Tmax was 6.0 hours for both CER doses; mean t(1/2) was 33.4 hours for CER 15 mg and 32.0 hours for CER 30 mg. The bioavailability of the 2 doses, as indicated by the least squares mean AUC(0-infinity), was 330.3 ng . h/mL for CER 15 mg and 755.1 ng . h/mL for CER 30 mg. During the CER 15-mg treatment sequence, 5 subjects experienced 5 AEs (headache, dizziness, musculoskeletal pain, dermatitis, and glossodynia); during the CER 30-mg treatment sequence, 2 subjects experienced 2 AEs (somnolence and dysmenorrhea). All AEs were mild in intensity. No serious AEs occurred during the study. Once-daily CER 15 and 30 mg exhibited similarly shaped pharmacokinetic profiles. AUC(0-168), AUC(0-infinity)), and C(max) values for the 30-mg dose were approximately double those for the 15-mg

  3. Nanocrystalline MgB{sub 4}O{sub 7}:Dy for high dose measurement of gamma radiation

    Lochab, S.P. [Inter-University Accelerator Centre, Aruna Asaf Ali Marg, New Delhi-110067 (India); Pandey, A. [Department of Physics, Sri Venkateswara College, University of Delhi, Benito Juarez Road, Dhaula Kuan, New Delhi-110021 (India); Sahare, P.D.; Ranjan, Ranju [Department of Physics and Astrophysics, University of Delhi, Delhi-110007 (India); Chauhan, R.S. [Department of Physics, RBS College, B. R. Ambedkar University, Agra-282002 (India); Salah, Numan [Department of Physics, Faculty of Applied Sciences, Thamar University, Thamar (Yemen)


    Magnesium borate activated by dysprosium (MgB{sub 4}O{sub 7}:Dy) is a low-Z{sub eff}, tissue-equivalent material that is commonly used for medical dosimetry of ionizing radiations such as gamma and X-rays using the thermoluminescence (TL) technique. Nanocrystals of the same material are produced and their TL characteristics are studied. It is found that the nanocrystalline MgB{sub 4}O{sub 7}:Dy with a dopant concentration of 1000 ppm is the most sensitive amongst varying dopant concentrations, with its sensitivity equal to 0.025 times that of the standard phosphor CaSO{sub 4}:Dy. The glow curve has two peaks at 154 C and 221 C. The nanophosphor has very poor sensitivity for low doses up to 10 Gy but beyond this dose the phosphor exhibits a linear response up to 5000 Gy. On increasing the dose further the response first becomes supralinear and then sublinear, finally resulting into saturation. Considering also its low fading particularly under post-irradiation annealing and excellent reusability features, this nanophosphor may be used for high dose (10-5000 Gy) measurements of ionizing radiations. (copyright 2007 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  4. Thermoluminescent characteristics of LiF:Mg,Cu,P and CaSO$_4$:Dy for low dose measurement

    Fernández, S Del Sol; Mendoza, J Guzmán; Sánchez-Guzmán, D; Rodríguez, G Ramírez; Gaona, E; Montalvo, T Rivera


    Thermoluminescence (TL) characteristics for LiF:Mg,Cu,P, and CaSO$_4$:Dy under the homogeneous field of X-ray beams of diagnostic irradiation and its verification using thermoluminescence dosimetry is presented. The irradiation were performed utilizing a conventional X-ray equipment installed at the Hospital Ju\\'arez Norte of M\\'exico. Different thermoluminescence characteristics of two material were studied, such as batch homogeneity, glow curve, linearity, detection threshold, reproducibility, relative sensitivity and fading. Materials were calibrated in terms of absorbed dose to the standard calibration distance and they were positioned in a generic phantom. The dose analysis, verification and comparison with the measurements obtained by the TLD-100 were performed. Results indicate that the dosimetric peak appears at 202$^o$C and 277.5$^o$C for LiF:Mg,Cu,P and CaSO$_4$:Dy, respectively. TL response as a function of X-ray dose showed a linearity behavior in the very low dose range for all materials. However...

  5. Single-dose bioequivalence of 105-mg fenofibric acid tablets versus 145-mg fenofibrate tablets under fasting and fed conditions: a report of two phase I, open-label, single-dose, randomized, crossover clinical trials.

    Godfrey, Anthony R; Digiacinto, Jennifer; Davis, Matthew W


    Fenofibrate is used to treat primary hypercholesterolemia, mixed lipidemia, and hypertriglyceridemia in adults who do not respond to nonpharmacologic measures. Fenofibrate is a prodrug that is rapidly and completely hydrolyzed to fenofibric acid, the active moiety. A new orally administered agent, fenofibric acid, was developed as an alternative to fenofibrate. Two separate studies were conducted to evaluate the bioequivalence of fenofibric acid relative to fenofibrate under fasted and fed (standard breakfast) conditions, characterize the pharmacokinetic profile, and assess the safety and tolerability of fenofibric acid. In study 1 (fasted), during each study period, volunteers received a single 105-mg dose of fenofibric acid or single 145-mg dose of fenofibrate (depending on their randomization scheme) after an overnight fast (a minimum fast of 10 hours). A 7-day washout period followed the first treatment period, after which the volunteers received the alternate treatment. Study 2 followed a similar dosing scheme and differed only in that volunteers received their single dose after being fed a standard meal (575 calories, of which 36% were contributed by fat). Serial blood samples in both studies were collected up to 72 hours after drug administration. The pharmacokinetic parameters of interest for assessing bioequivalence were AUC(0-t), AUC(0-∞), C(max), and T(max). The criterion for a lack of difference between products was a 90% CI between 0.80 and 1.25 for the fenofibric acid:fenofibrate ratios for AUC(0-t), AUC(0-∞), and C(max.) Tolerability was assessed by adverse events (AEs), laboratory parameters, vital signs, and physical examinations. Volunteers in study 1 (fasted; n = 54) were aged 18 to 43 years; 19 (35%) were men and 35 (65%) were women; mean weight was 155.2 pounds (range, 103.0-267.0 pounds); and 48 (89%) were white, 1 (2%) was black, and 5 (9%) were white/American Indian/Alaskan native/Asian. Volunteers in study 2 (fed; n = 54) were aged 18

  6. Efficacy, safety and tolerability of escitalopram in doses up to 50 mg in Major Depressive Disorder (MDD: an open-label, pilot study

    Crawford Gordon M


    Full Text Available Abstract Background Escitalopram is licensed for use at doses up to 20 mg but is used clinically at higher doses. There is limited published data at higher doses and none in the treatment of Major Depressive Disorder (MDD. Methods This open-label, pilot study was designed to investigate the efficacy, safety and tolerability of escitalopram in doses up to 50 mg in MDD. It was conducted in 60 primary care patients with MDD who had not responded to adequate treatment with citalopram. Patients were treated with escalating doses of escitalopram up to 50 mg for up to 32 weeks until they achieved remission (Montgomery-Asberg Depression Rating Scale [MADRS] ≤8 or failed to tolerate the dose. Results Forty-two patients (70% completed the study. Twenty-one patients (35% achieved remission with 8 of the 21 patients (38% needing the 50 mg dose to achieve remission. Median time to remission was 24 weeks and median dose in remission was 30 mg. No significant safety issues were identified although tolerability appeared to decline above a dose of 40 mg with 26% of patients unable to tolerate 50 mg. Twelve (20% patients had adverse events leading to discontinuation. The most common adverse events were headache (35%, nausea, diarrhoea and nasopharyngitis (all 25%. Minor mean weight gain was found during the study, which did not appear to be dose-related. Half of the patients who completed the study chose to continue treatment with escitalopram rather than taper down the dose at 32 weeks. Conclusions Dose escalation with escitalopram above 20 mg may have a useful role in the management of patients with MDD, although further studies are needed to confirm this finding. Trial Registration NCT00785434

  7. Patch test concentrations (doses in mg/cm(2) ) for the 12 non-mix fragrance substances regulated by European legislation

    Bruze, Magnus; Svedman, Cecilia; Andersen, Klaus Ejner;


    Background. According to EU legislation, 26 fragrance substance allergens must be labelled on cosmetic products. For 12 of them, the optimal patch test concentration/dose has not been evaluated. Objectives. To establish the optimal patch test doses in mg/cm(2) for the 12 fragrance substances......, it is recommended that half of the maximum patch test dose (mg/cm(2) ) be used for aimed and screening patch testing....

  8. Safety and pharmacokinetics of a single 1500-mg dose of famciclovir in adolescents with recurrent herpes labialis.

    Block, Stan L; Yogev, Ram; Waldmeier, Felix; Hamed, Kamal


    An open-label study evaluated the safety (n = 53) and pharmacokinetics (n = 8) of single-dose therapy with 1500 mg famciclovir (prodrug of penciclovir) for recurrent herpes labialis in adolescents. Mean Cmax, mean AUC0-∞, and clearance for penciclovir were 9.37 μg/mL, 31.8 μg · h/mL, and 38.2 L/h, respectively, and within the range extrapolated from data in adults. Adverse events were generally mild and transient.

  9. Gabapentin enacarbil for the treatment of moderate to severe primary restless legs syndrome (Willis-Ekbom disease: 600 or 1,200 mg dose?

    Kume A


    Full Text Available Akito Kume1,21KUME Clinic, 2Nagoya Clinical Neuropharmacology Laboratory, Nagoya, JapanAbstract: Gabapentin enacarbil is a prodrug of the anticonvulsant gabapentin. The efficacy and safety of gabapentin enacarbil for the treatment of moderate to severe primary restless legs syndrome (RLS has been evaluated in several clinical trials in the United States and Japan. Although most clinical trials assessed gabapentin enacarbil at doses greater than 600 mg/day and demonstrated the overall safety and efficacy (defined as improvements in the coprimary endpoints of the international RLS rating scale [IRLS] total score and Clinical Global Impression-Improvement response, the US Food and Drug Administration approved the 600 mg once-daily dosage because doses higher than 600 mg/day were considered to provide no additional benefits and were associated with higher rates of adverse events, such as somnolence and dizziness. Nonetheless, the results of clinical trials and post hoc meta-analyses have indicated that the 1,200 mg once-daily dosage was the most validated gabapentin enacarbil treatment for not only subjective RLS symptoms but also severe sleep disturbance associated with RLS. A Japanese dose-finding study showed that 900 mg/day, the intermediate dose between 600 and 1,200 mg, failed to show a significant improvement in IRLS total score, probably because many of the patients who discontinued treatment did so early, suggesting that a half-landing dose may cause more adverse effects than favorable ones in some RLS patients early in the treatment. Gabapentin enacarbil may have two distinct therapeutic doses for the treatment of RLS: 600 mg/day or lower doses for the treatment of subjective RLS symptoms and 1,200 mg/day or higher doses for the treatment of both subjective RLS symptoms and associated problems such as severe sleep disturbances.Keywords: gabapentin enacarbil, restless legs syndrome, meta-analysis, dose-finding

  10. Thermomechanical Fatigue Behavior of the Intermetallic γ-TiAl Alloy TNB-V5 with Different Microstructures

    Roth, Marcel; Biermann, Horst


    The cyclic deformation and fatigue behavior of the γ-TiAl alloy TNB-V5 is evaluated under thermomechanical load for three different microstructures. For this purpose, strain-controlled thermomechanical fatigue (TMF) tests were carried out with different temperature-strain cycles, different temperature ranges from 400 °C to 800 °C (673 K to 1073 K), and with two different strain ranges to set a fatigue-life relation. Cyclic deformation curves, stress-strain hysteresis loops, and fatigue lives of the tests are presented. The microstructures near-gamma (NG) and duplex (DP) show comparable fatigue lives under all test parameters. The microstructure fully-lamellar (FL) offers longer fatigue lives at the same loading conditions. For a general life prediction, the damage parameter of Smith, Watson, and Topper, P SWT vs fatigue life, is well suitable, if the testing and the application temperature ranges, respectively, include temperatures above the ductile-brittle transition (approximately 750 °C). In the completely brittle material behavior regime the quality of the lifetime prediction is unacceptable. The damage parameter P HL by Haibach and Lehrke shows a comparable correlation to the fatigue life as P SWT. The results are discussed with microstructural investigations.

  11. Tramadol hydrochloride 75 mg/dexketoprofen 25 mg oral fixed-dose combination in moderate-to-severe acute pain: sustained analgesic effect over a 56-h period in the postoperative setting.

    Montero Matamala, A; Bertolotti, M; Contini, M P; Guerrero Bayón, C; Nizzardo, A; Paredes Lario, I; Pizà Vallespir, B; Scartoni, S; Tonini, G; Capriati, A; Pellacani, A


    Multimodal analgesia constitutes a common strategy in pain management. A tramadol hydrochloride 75 mg/dexketoprofen 25 mg oral fixed combination (TRAM/DKP 75 mg/25 mg) has been recently registered and released in Europe for the treatment of moderate-to-severe acute pain. This paper provides additional analyses on the results of two phase III clinical trials (DEX-TRA-04 and DEX-TRA-05) on postoperative pain to document its sustained effect. The analysis was applied to a modified intention-to-treat population (mITT, n = 933) of patients undergoing active treatment from the first dose, to assess the sustained effect of TRAM/DKP 75 mg/25 mg on pain intensity (PI-VAS 0-100) over 56 h from first drug intake. The superior analgesic effect of TRAM/DKP 75 mg/25 mg over 56 h in terms of difference in PI-VAS (mean [SE]) was shown for DEX-TRA-04 (-11.0 [0.55] over dexketoprofen 25 mg and -9.1 [0.55] over tramadol 100 mg, P ≤ 0.0001) and for DEX-TRA-05 (-10.4 [0.51] over dexketoprofen 25 mg and -8.3 [0.51] over tramadol 100 mg, P ≤ 0.0001). The statistical analysis performed on data coming from both studies confirms the superior sustained analgesia of TRAM/DKP 75 mg/25 mg over tramadol 100 mg and dexketoprofen 25 mg. These results are consistent with the previously published data obtained on the ITT population and strongly support the role of this oral fixed-dose combination in the treatment of moderate-to-severe acute pain. Copyright 2017 Clarivate Analytics.

  12. Gabapentin enacarbil for the treatment of moderate to severe primary restless legs syndrome (Willis-Ekbom disease): 600 or 1,200 mg dose?

    Kume, Akito


    Gabapentin enacarbil is a prodrug of the anticonvulsant gabapentin. The efficacy and safety of gabapentin enacarbil for the treatment of moderate to severe primary restless legs syndrome (RLS) has been evaluated in several clinical trials in the United States and Japan. Although most clinical trials assessed gabapentin enacarbil at doses greater than 600 mg/day and demonstrated the overall safety and efficacy (defined as improvements in the coprimary endpoints of the international RLS rating scale [IRLS] total score and Clinical Global Impression-Improvement response), the US Food and Drug Administration approved the 600 mg once-daily dosage because doses higher than 600 mg/day were considered to provide no additional benefits and were associated with higher rates of adverse events, such as somnolence and dizziness. Nonetheless, the results of clinical trials and post hoc meta-analyses have indicated that the 1,200 mg once-daily dosage was the most validated gabapentin enacarbil treatment for not only subjective RLS symptoms but also severe sleep disturbance associated with RLS. A Japanese dose-finding study showed that 900 mg/day, the intermediate dose between 600 and 1,200 mg, failed to show a significant improvement in IRLS total score, probably because many of the patients who discontinued treatment did so early, suggesting that a half-landing dose may cause more adverse effects than favorable ones in some RLS patients early in the treatment. Gabapentin enacarbil may have two distinct therapeutic doses for the treatment of RLS: 600 mg/day or lower doses for the treatment of subjective RLS symptoms and 1,200 mg/day or higher doses for the treatment of both subjective RLS symptoms and associated problems such as severe sleep disturbances.

  13. Efficacy and safety of deferasirox doses of >30 mg/kg per d in patients with transfusion-dependent anaemia and iron overload

    Taher, Ali; Cappellini, Maria D; Vichinsky, Elliott; Galanello, Renzo; Piga, Antonio; Lawniczek, Tomasz; Clark, Joan; Habr, Dany; Porter, John B


    The highest approved dose of deferasirox is currently 30 mg/kg per d in many countries; however, some patients require escalation above 30 mg/kg per d to achieve their therapeutic goals. This retrospective analysis investigated the efficacy (based on change in serum ferritin levels) and safety of deferasirox >30 mg/kg per d in adult and paediatric patients with transfusion-dependent anaemias, including β-thalassaemia, sickle cell disease and the myelodysplastic syndromes. In total, 264 patients pooled from four clinical trials received doses of >30 mg/kg per d; median exposure to deferasirox >30 mg/kg per d was 36 weeks. In the overall population there was a statistically significant median decrease in serum ferritin of 440 μg/l (P30 mg/kg per d was consistent with previously published data. There was no worsening of renal or liver function following dose escalation. Deferasirox >30 mg/kg per d effectively reduced iron burden to levels lower than those achieved prior to dose escalation in patients with transfusion-dependent anaemias. This has important implications for patients who are heavily transfused and may require higher doses to reduce body iron burden. PMID:19764988

  14. Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers.

    Aarnoutse, R.E.; Kleinnijenhuis, J.; Koopmans, P.P.; Touw, D.J.; Wieling, J.; Hekster, Y.A.; Burger, D.M.


    OBJECTIVE: In the treatment of human immunodeficiency virus infection, the protease inhibitor ritonavir is used in a low dose (100 mg twice daily) to inhibit cytochrome P450 (CYP) 3A4 and thereby increase plasma concentrations of coadministered protease inhibitors. When applied in a therapeutic dose

  15. Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers

    Aarnoutse, Rob E; Kleinnijenhuis, Johanneke; Koopmans, Peter P; Touw, Daan J; Wieling, Jaap; Hekster, Yechiel A; Burger, David M


    OBJECTIVE: In the treatment of human immunodeficiency virus infection, the protease inhibitor ritonavir is used in a low dose (100 mg twice daily) to inhibit cytochrome P450 (CYP) 3A4 and thereby increase plasma concentrations of coadministered protease inhibitors. When applied in a therapeutic dose

  16. Long-term cardiac follow-up of children treated with anthracycline doses of 300 mg/m2 or less for acute lymphoblastic leukemia

    Rathe, Mathias; Carlsen, Niels Lauritz Torp; Oxhøj, Henrik;


    The cardiotoxic effect of anthracyclines has been well described for moderate to high cumulative doses (>350 mg/m(2)). However, the question of whether sub-clinical signs of cardiomyopathy may develop and progress over time in children receiving doses of...

  17. A multicentre randomized controlled trial of the efficacy and safety of single-dose praziquantel at 40 mg/kg vs. 60 mg/kg for treating intestinal schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil.

    Piero L Olliaro


    Full Text Available BACKGROUND: Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally. METHODOLOGY/PRINCIPAL FINDINGS: Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n  =  428 or 60 mg/kg (n  =  428. While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania, no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%-98% at individual sites with 40 mg/kg and 92.8% (88%-97% with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR, change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR  =  0.78, 95% CI  = [0.63;0.96]. Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78% reported 1327 adverse events (AE 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p<0.001. At 24 h post-dosing, 456 patients (54% had 918 AEs with no difference between arms. The most frequent AE was abdominal pain at both 4 h and 24 h (40% and 24%. CONCLUSION: A higher dose of 60 mg/kg of praziquantel offers no significant efficacy advantage over standard 40 mg/kg for treating intestinal schistosomiasis caused by either S. mansoni or S

  18. A multicentre randomized controlled trial of the efficacy and safety of single-dose praziquantel at 40 mg/kg vs. 60 mg/kg for treating intestinal schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil.

    Olliaro, Piero L; Vaillant, Michel T; Belizario, Vincente J; Lwambo, Nicholas J S; Ouldabdallahi, Mohamed; Pieri, Otavio S; Amarillo, Maria L; Kaatano, Godfrey M; Diaw, Mamadou; Domingues, Analucia C; Favre, Tereza C; Lapujade, Olivier; Alves, Fabiana; Chitsulo, Lester


    Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally. Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n  =  428) or 60 mg/kg (n  =  428). While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania), no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%-98% at individual sites) with 40 mg/kg and 92.8% (88%-97%) with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR), change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR  =  0.78, 95% CI  = [0.63;0.96]). Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78%) reported 1327 adverse events (AE) 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p<0.001). At 24 h post-dosing, 456 patients (54%) had 918 AEs with no difference between arms. The most frequent AE was abdominal pain at both 4 h and 24 h (40% and 24%). A higher dose of 60 mg/kg of praziquantel offers no significant efficacy advantage over standard 40 mg/kg for treating intestinal schistosomiasis caused by either S. mansoni or S. japonicum. The results of this study support WHO recommendation and

  19. A Multicentre Randomized Controlled Trial of the Efficacy and Safety of Single-Dose Praziquantel at 40 mg/kg vs. 60 mg/kg for Treating Intestinal Schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil

    Olliaro, Piero L.; Vaillant, Michel T.; Belizario, Vincente J.; Ouldabdallahi, Mohamed; Pieri, Otavio S.; Amarillo, Maria L.; Kaatano, Godfrey M.; Diaw, Mamadou; Domingues, AnaLucia C.; Favre, Tereza C.; Lapujade, Olivier; Alves, Fabiana; Chitsulo, Lester


    Background Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally. Methodology/Principal Findings Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n = 428) or 60 mg/kg (n = 428). While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania), no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%–98% at individual sites) with 40 mg/kg and 92.8% (88%–97%) with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR), change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR = 0.78, 95%CI = [0.63;0.96]). Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78%) reported 1327 adverse events (AE) 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p<0.001). At 24 h post-dosing, 456 patients (54%) had 918 AEs with no difference between arms. The most frequent AE was abdominal pain at both 4 h and 24 h (40% and 24%). Conclusion A higher dose of 60 mg/kg of praziquantel offers no significant efficacy advantage over standard 40 mg/kg for treating intestinal schistosomiasis caused by either S. mansoni or S. japonicum. The results

  20. [Comparison of the efficacy and safety of praziquantel administered in single dose of 40 versus 60 mg/kg for treating urinary schistosomiasis in Mauritania].

    Ouldabdallahi, M; Ousmane, B; Ouldbezeid, M; Mamadou, D; Konaté, L; Chitsulo, L


    During the last twenty years, praziquantel (PZQ) was the drug of choice for the treatment of schistosomiasis in the majority of national programs. However, a lower rate of cure had been significantly noted on the left bank of the Senegal River. To explain this unusual rate of cure, the assumption of a possible resistance to the drug as well as under-dosing was considered. With an aim of testing this hypothesis of underdosing, we compared the amount of a single dose of 60 mg/kg of PZQ versus the standardized dose of 40 mg/kg used in curing urinary schistosomiasis in Mauritania. One hundred and fifty-one children aged from 10 to 19 years, including 77 in the group of 60 mg/kg and 74 in the group of 40 mg/ kg, were included in the study. The rates of cure were respectively 64.8% for 60 mg/kg and 67.5% for 40 mg/kg three weeks after the administration of the treatment without statistically significant difference. For the majority of the patients, the drug was well tolerated and no serious adverse events were noted; however, clinical signs in the form of abdominal pain associated or not with diarrhea and vomiting were noted. Praziquantel remains an effective and well-tolerated drug: the amount of 40 mg/kg of body weight can still be maintained for the treatment of schistosomiasis in Mauritania.




    1 The effects of a new antihistamine, ebastine (10, 20 and 30 mg), on several parameters of driving performance in actual traffic were studied in 15 healthy male volunteers. Subjects were treated for 5 days, and their driving performance tested on day 1 and day 5. The study was double-blind, placebo

  2. Single-dose pharmacokinetics of once-daily cyclobenzaprine extended release 30 mg versus cyclobenzaprine immediate release 10 mg three times daily in healthy young adults : a randomized, open-label, two-period crossover, single-centre study.

    Darwish, Mona; Hellriegel, Edward T; Xie, Fang


    Cyclobenzaprine immediate release (CIR) has shown efficacy in the treatment of muscle spasm associated with acute, painful musculoskeletal conditions. An extended-release formulation of cyclobenzaprine (CER) has been developed to provide effective muscle spasm relief with once-daily dosing. The objective of this study was to compare the pharmacokinetics of CER and CIR. This was a single-centre study of 18 healthy young adults (aged 18-45 years). Healthy volunteers were assigned to receive either a single dose of CER 30 mg or three doses of CIR 10 mg on days 1 and 15 (separated by a 14-day washout) in an open-label, two-period crossover study. Pharmacokinetic parameters were monitored through 168 hours after the last dose in each dose period; adverse events (AEs) were monitored during the study through 3 weeks after the last dose of study drug. Cyclobenzaprine was administered as a single oral 30 mg dose of CER or three 10 mg oral doses of CIR given every 8 hours over 24 hours. Statistical tests were conducted against a two-sided alternative hypothesis at a 0.05 level of significance with equivalence limits of 80% and 125%. Measures included area under the plasma cyclobenzaprine concentration versus time curve (AUC) to 168 hours and infinity, maximum plasma cyclobenzaprine concentration (C(max)), and time to observed C(max) (t(max)). Eighteen subjects were randomized and 17 completed both periods of the study. CER exhibited a consistent concentration-time profile with a single peak, in contrast to the pharmacokinetic profile for CIR, which displayed multiple peaks and troughs over the 24-hour period. The pharmacokinetic profile of CER 30 mg was characterized by an absorption phase with a median t(max) of approximately 6 hours, compared with the initial peak of CIR (following the first dose) of about 4 hours. Mean plasma concentrations at 4 hours were comparable (12.1 ng/mL for CER; 12.4 ng/mL for CIR). Systemic cyclobenzaprine exposure (AUC and C(max)) was similar

  3. Evaluation of sedative effects of single and repeated doses of 50 mg and 150 mg tolperisone hydrochloride. Results of a prospective, randomized, double-blind, placebo-controlled trial.

    Dulin, J; Kovács, L; Ramm, S; Horvath, F; Ebeling, L; Kohnen, R


    Sedative effects of single and repeated doses of 50 mg and 150 mg tolperisone hydrochloride (Mydocalm), a centrally active muscle-relaxing agent, were evaluated in a placebo-controlled double-blind clinical trial. A total of 72 healthy young adults balanced by sex were randomized to receive 50 mg or 150 mg tolperisone hydrochloride or placebo t.i.d. for a period of 8 days. Control examinations were performed in the mornings of days 1 and 8 before intake of the morning dose and at 1.5, 4 and 6 hours postdose. The psychomotoric test battery used in this trial revealed no sedative effects of tolperisone hydrochloride in the given doses at any control examination. Subjective mood ratings quantified by the Welzel Colored Scales were not impaired either. The lack of differences in sedative potentials of tolperisone hydrochloride and placebo was confirmed by tests on differences and by tests on equivalence using 95% CI. The present study substantiates clinical experience and previous clinical trials demonstrating that tolperisone hydrochloride, though being a centrally active muscle relaxant, does not cause any sedation and does not impair reaction times.


    PENG Mian; YU Xue-tao; CHEN Shu; CAI Xiao-hua; PENG Yi-chao; PENG Xiao-rong


    Objective To investigate the direct effect of leptin on osteoblast-like cell line MG63. Methods Human osteoblast-like cell line MG63 was incubated with leptin of different doses for 24, 48 and 72 h, respectively.The proliferation of MG63 was determined by methylene blue assay. Alpha1 (Ⅰ) collagen gene expression in MG63was determined by real time flourescence quantitive PCR (FQ-PCR), both with 17β-E2 as positive control.Results Leptin accelerated the proliferation and differentiation of MG63 in dose and time-dependent manners,with the best effect at 10-7 mol/L at 72 h. Compared with 17β-E2 , leptin showed a weaker promoting effect at all of the three time point: 24, 48 and 72 h. While the effects of the two hormones have an approaching trend the time prolonged. Conclusion Leptin has the effects of accelerating the proliferation and differentiation of MG63 cells in vitro, which is more enduring and later than that of 17β-E2.

  5. Prevalence of gastroduodenal ulcers/erosions in patients taking low-dose aspirin with either 15 mg/day of lansoprazole or 40 mg/day of famotidine: the OITA-GF study 2.

    Tamura, Akira; Murakami, Kazunari; Kadota, Junichi


    The preventive effects of histamine 2 receptor antagonists vs. proton pump inhibitors on low-dose aspirin (LDA)-related gastroduodenal mucosal injury have not been fully investigated. We conducted a cross-sectional study to compare the prevalence of gastroduodenal ulcers or erosions in patients taking LDA with either 40 mg/day of famotidine or 15 mg/day of lansoprazole for at least three months. Of 84 eligible patients, two taking 40 mg/day of famotidine and four taking 15 mg/day of lansoprazole refused to undergo upper gastrointestinal endoscopy. Ultimately, we performed upper gastrointestinal endoscopy in 78 patients taking either 40 mg/day of famotidine (group F, n = 31) or 15 mg/day of lansoprazole (group L, n = 47). The prevalence of gastroduodenal ulcers or erosions and the magnitude of gastric mucosal injury evaluated using modified Lanza scores were compared between the two groups. No patients in either group had gastroduodenal ulcers. Gastroduodenal erosions were more prevalent in group F than in group L (48.4% vs. 17.0%, p = 0.005). The modified Lanza scores (mean ± SD) were significantly higher in group F than in group L (0.9 ± 1.3 vs. 0.3 ± 0.7, p = 0.007). A multivariate logistic regression analysis showed that the use of lansoprazole was negatively associated with gastroduodenal erosions. This study suggests that 15 mg/day of lansoprazole may be more effective in preventing the development of LDA-related gastroduodenal erosions than 40 mg/day of famotidine. The preventive effects of these two regimens on the development of LDA-related gastroduodenal ulcers require further investigation.

  6. Pharmacokinetic profile of rizatriptan 10-mg tablet and 10-mg orally disintegrating tablet administered with or without water in healthy subjects: an open-label, randomized, single-dose, 3-period crossover study.

    Swan, Suzanne K; Alcorn, Harry; Rodgers, Anthony; Hustad, Carolyn M; Ramsey, Karen E; Woll, Susan; Skobieranda, Franck


    This open-label, 3-period crossover study compared the plasma concentration profiles of rizatriptan tablet, orally disintegrating tablet with water (ODTc), and ODT without water (ODTs) in 24 healthy volunteers aged 18 to 45 years. At each period, subjects received a single dose of either 10-mg rizatriptan tablet, 10-mg rizatriptan ODTs, or 10-mg rizatriptan ODTc. The authors hypothesized that ODTc has a greater geometric mean AUC(0-2h) than ODTs and that ODTc has a greater geometric mean AUC(0-1h) than tablet. A secondary end point was to compare the time of occurrence of the maximum rizatriptan plasma concentration (t(max)) of each dosing method. ODTc had a statistically significantly greater geometric mean AUC(0-2h) compared with ODTs (33.84 h x ng/mL vs 18.83 h x ng/mL; P rizatriptan tablet (17.07 h x ng/mL vs 13.32 h x ng/mL). The median t(max) was 0.67 hours for ODTc and tablet and 1.33 hours for ODTs. ODTc showed a slightly, but not significantly, faster rate of absorption compared with tablet. ODTs with water had a faster rate of absorption than ODTc. Future studies are needed to determine whether this pharmacokinetic difference produces differential efficacy in a clinical setting.

  7. Arterial occlusion sites on magnetic resonance angiography influence the efficacy of intravenous low-dose (0.6 mg/kg) alteplase therapy for ischaemic stroke.

    Nakashima, T; Toyoda, K; Koga, M; Matsuoka, H; Nagatsuka, K; Takada, T; Naritomi, H; Minematsu, K


    To determine the predictors of efficacy, including magnetic resonance imaging information, for low-dose intravenous alteplase therapy for stroke patients. Seventy-eight patients were prospectively enrolled in a single Stroke Unit (SU) receiving alteplase at a dose of 0.6 mg/kg during the initial 27 months after its approval in Japan. Ischaemic changes and vascular lesions were identified using computed tomography, diffusion-weighted magnetic resonance imaging, and magnetic resonance angiography. Early ischaemic signs were assessed using the Alberta Stroke Program Early CT Score. The median baseline National Institutes of Health Stroke Scale score of 78 patients was 12. In 19 patients (24%), the National Institutes of Health Stroke Scale score improved by >or=8 points at 24 h. After multivariate adjustment, occlusion at the internal carotid artery (odds ratio 11.82, 95% confidence interval 1.73-142.74), Alberta Stroke Program Early CT Score on diffusion-weighted imaging Stroke Scale score (1.24, 1.08-1.47, per 1-point decrease) were inversely correlated with early improvement. Four patients (5%) had symptomatic intracranial haemorrhage. At 3 months, 76 patients (98%) survived, and 36 of 78 patients (46%) overall, but only two of 19 patients (11%) with internal carotid artery occlusion, had a favourable functional outcome, corresponding to a modified Rankin scale score Stroke Program Early CT Score on diffusion-weighted imaging dose of 0.6 mg/kg resulted in a relatively good overall outcome when compared with outcomes reported by western studies using an alteplase dose of 0.9 mg/kg. However, patients with occlusion at the internal carotid artery did not respond to this low-dose alteplase therapy.

  8. Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination.

    Schneider, M; Paulin, A; Dron, F; Woehrlé, F


    The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl(®) ). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4-16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively.

  9. Pharmacokinetic Dose Proportionality Between Two Strengths (12.5 mg and 25 mg) of Doxylamine Hydrogen Succinate Film-Coated Tablets in Fasting State: A Single-Dose, Randomized, Two-Period Crossover Study in Healthy Volunteers

    Videla, Sebastián; Cebrecos, Jesús; Lahjou, Mounia; Wagner, France; Guibord, Pascal; Xu, Zhengguo; Cabot, Anna; Encabo, Mercedes; Encina, Gregorio; Sicard, Eric; Sans, Artur


    Background Doxylamine succinate, an ethanolamine-based antihistamine, is used in the short-term management of insomnia because of its sedative effects. No data on the dose proportionality of the pharmacokinetics of doxylamine are available, although this drug has been marketed in European countries for more than 50 years. Objective The objective of this study was to evaluate and compare the dose proportionality between two marketed strengths (12.5 mg and 25 mg) of doxylamine hydrogen succinat...

  10. The influence of dose on the kinetic parameters and dosimetric features of the main thermoluminescence glow peak in α-Al2O3:C,Mg

    Kalita, J. M.; Chithambo, M. L.


    The influence of dose (0.1-100 Gy) on the kinetic parameters and the dosimetric features of the main glow peak of α-Al2O3:C,Mg have been investigated. Thermoluminescence (TL) measured at 1 °C/s shows a very high intensity glow peak at 161 °C and six secondary peaks at 42, 72, 193, 279, 330, 370 °C respectively. Analysis shows that the main peak follows first order kinetics irrespective of the irradiation dose. The activation energy is found to be consistent at 1.37 eV and the frequency factor is of the order of 1014 s-1 for any dose between 0.1 and 100 Gy. Further, the analysis for thermal quenching of the main peak of 0.1 Gy irradiated sample shows that the activation energy for thermal quenching is (0.94 ± 0.04) eV. Regarding the dosimetric features of α-Al2O3:C,Mg, the dose response of the main peak is superlinear within 0.1 to 30 Gy of beta dose and then it becomes sublinear up to 100 Gy. Fading analysis shows that the intensity of the main peak drops to ∼22% of its initial value within 2400 s after irradiation and thereafter to ∼14% within 64,800 s. Analysis of the reproducibility shows that the coefficient of variation in the results for 10 identical TL measurements show that reproducibility improves with increase in dose.

  11. Single shot spinal anesthesia with very low hyperbaric bupivacaine dose (3.75 mg) for hip fracture repair surgery in the elderly. A randomized, double blinded study.

    Errando, C L; Peiró, C M; Gimeno, A; Soriano, J L


    Single shot spinal anesthesia is used worldwide for hip fracture repair surgery in the elderly. Arterial hypotension is a frequent adverse effect. We hypothesized that lowering local anesthetics dose could decrease the incidence of arterial hypotension, while maintaining quality of surgical anesthesia. In a randomized double blinded study, 66 patients over the age of 65 years, with hip fracture needing surgical repair, were assigned to B0.5 group 7.5mg hyperbaric bupivacaine 5mg/ml (control group), and B0.25 group 3.75mg hyperbaric bupivacaine 2.5mg/ml (study group). Sensory and motor block level, and hemodynamic parameters including blood presure, heart rate and vasopressor dose administration were registered, along with rescue anesthesia needs, the feasibility of surgery, its duration, and regression time of sensory anesthesia to T12. After exclusions, 61 patients were included in the final analysis. Arterial hypotension incidence was lower in the B0.25 group (at the 5, 10, and 15min determinations), and a lower amount of vasopressor drugs was needed (mean accumulated ephedrine dose 1.6mg vs. 8.7mg in the B0.5 group, p<0.002). Sensory block regression time to T12 was shorter in the B0.25 group, mean 78.6±23.6 (95% CI 51.7-110.2)min vs. 125.5±37.9 (95% CI 101.7-169.4)min in the B0.5 group, p=0.033. All but one patient in the B0.25 group were operated on under the anesthetic procedure first intended. No rescue anesthesia was needed. Lowering bupivacaine dose for single shot spinal anesthesia for hip fracture repair surgery in elderly patients was effective in decreasing the occurrence of arterial hypotension and vasopressor use, while intraoperative quality remained. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Pharmacokinetic comparison study of a combination containing 500 mg of Naproxen and 20 mg of Esomeprazole: a randomized, single-dose, 2-way crossover, open-label study in healthy Korean men.

    Choi, Hyun-Gyu; Jeon, Ji-Young; Kwak, Seong-Shin; Kim, Hyunil; Jin, Changyun; Im, Yong-Jin; Kim, Eun-Young; Wang, Hye Min; Kim, Yunjeong; Lee, Sun Young; Kim, Min-Gul


    Nonsteroidal anti-inflammatory drugs have been used for analgesic, anti-inflammatory, and antithrombotic effects, but they carry a risk of major gastrointestinal damage. This risk can be greatly reduced by the coadministration of inhibitors of gastric acid secretion, such as proton pump inhibitors. This study was performed for the subsequent marketing of a combination drug that contained 500 mg of naproxen and 20 mg of esomeprazole in Korea. We evaluated the comparative bioavailability and tolerability of the test and reference formulations in healthy men. A total of 60 healthy men were enrolled in this single-dose, randomized, open-label, 2-period, 2-sequence, crossover study. During each period, men received a combination of 500 mg of naproxen and 20 mg of esomeprazole for test or reference, and between each period, there was a 1-week washout period. Blood samples were obtained 21 times throughout each period before dosing and 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 48, and 72 hours after oral administration. Plasma concentrations were determined using LC-MS/MS. The pharmacokinetic parameters, including Cmax, AUC0-t, AUC0-∞, and Tmax, were measured, and all treatment-emergent adverse events and their associations with the study medications were recorded throughout the entire study. A total of 59 men completed the study. No significant differences were found in the prevalence of AEs between the 2 formulations. In addition, there were no serious or unexpected AEs during the study. Both formulations had very similar Cmax, AUC, and t½ values, but the Tmax of naproxen appeared earlier in the test formulation than in the reference formulation and that of esomeprazole appeared later in the test formulation than in the reference formulation. This study suggests that the test and reference formulations of a combination of 500 mg of naproxen and 20 mg of esomeprazole are bioequivalent in the extent of absorption and peak concentration

  13. Radial distribution of dose within heavy charged particle tracks. Models and experimental verification using LiF:Mg,Cu,P TL detectors

    Gieszczyk, W; Olko, P; Obryk, B


    A new method of experimental verification of radial dose distribution models using solid state thermoluminescent (TL) detectors LiF:Mg,Cu,P has been recently proposed. In this work the method was applied to verify the spatial distribution of energy deposition within a single 131Xe ion track. Detectors were irradiated at the Department of Physics of the University of Jyv\\"askyl\\"a, Finland. The obtained results have been compared with theoretical data, calculated according to the Zhang et al., Cucinotta et al. and Geiss et al. radial dose distribution (RDD) models. At the lowest dose range the Zhang et al. RDD model exhibited the best agreement as compared to experimental data. In the intermediate dose range, up to 104 Gy, the best agreement was found for the RDD model of Cucinotta et al. The probability of occurrence of doses higher than 104 Gy within a single 131Xe ion track was found to be lower than predicted by all the studied RDD models. This may be a result of diffusion of the charge, which is then capt...

  14. Chemoprophylaxis of leprosy with a single dose of 25 mg per kg rifampin in the southern Marquesas; results after four years.

    Cartel, J L; Chanteau, S; Moulia-Pelat, J P; Plichart, R; Glaziou, P; Boutin, J P; Roux, J F; Grosset, J H


    In January-February 1988, a program of chemoprophylaxis for leprosy, using a single 25 mg/kg dose of rifampin, was conducted among 2786 (98.7%) inhabitants of the Southern Marquesas and 3144 South Marquesan "emigrants" and their families. Among the treated population, during the 4 years which followed the implementation of the program, two leprosy patients were detected, one of whom can be considered as a failure of chemoprophylaxis because she was not known by the leprosy control unit. During the same period (1988-1991), a decrease in detection rates for leprosy in the entire French Polynesian population has been observed, an event which makes the interpretation of these findings very difficult. Nevertheless, according to presently available data, the effectiveness of chemoprophylaxis with a single dose of 25 mg/kg rifampin is estimated to be about 40% to 50%. When considering not only the results of the present study but also the financial and logistic constraints raised by such a program, one is led to the conclusion that chemoprophylaxis, even with a single dose of rifampin, is not likely to become an effective component of leprosy control programs.

  15. Using LiF:Mg,Cu,P TLDs to estimate the absorbed dose to water in liquid water around an {sup 192}Ir brachytherapy source

    Lucas, P. Avilés, E-mail:; Aubineau-Lanièce, I.; Lourenço, V.; Vermesse, D.; Cutarella, D. [CEA, LIST, Laboratoire National Henri Becquerel, 91191 Gif-sur-Yvette (France)


    Purpose: The absorbed dose to water is the fundamental reference quantity for brachytherapy treatment planning systems and thermoluminescence dosimeters (TLDs) have been recognized as the most validated detectors for measurement of such a dosimetric descriptor. The detector response in a wide energy spectrum as that of an{sup 192}Ir brachytherapy source as well as the specific measurement medium which surrounds the TLD need to be accounted for when estimating the absorbed dose. This paper develops a methodology based on highly sensitive LiF:Mg,Cu,P TLDs to directly estimate the absorbed dose to water in liquid water around a high dose rate {sup 192}Ir brachytherapy source. Methods: Different experimental designs in liquid water and air were constructed to study the response of LiF:Mg,Cu,P TLDs when irradiated in several standard photon beams of the LNE-LNHB (French national metrology laboratory for ionizing radiation). Measurement strategies and Monte Carlo techniques were developed to calibrate the LiF:Mg,Cu,P detectors in the energy interval characteristic of that found when TLDs are immersed in water around an{sup 192}Ir source. Finally, an experimental system was designed to irradiate TLDs at different angles between 1 and 11 cm away from an {sup 192}Ir source in liquid water. Monte Carlo simulations were performed to correct measured results to provide estimates of the absorbed dose to water in water around the {sup 192}Ir source. Results: The dose response dependence of LiF:Mg,Cu,P TLDs with the linear energy transfer of secondary electrons followed the same variations as those of published results. The calibration strategy which used TLDs in air exposed to a standard N-250 ISO x-ray beam and TLDs in water irradiated with a standard{sup 137}Cs beam provided an estimated mean uncertainty of 2.8% (k = 1) in the TLD calibration coefficient for irradiations by the {sup 192}Ir source in water. The 3D TLD measurements performed in liquid water were obtained with a

  16. Evaluation of the Entrance Skin Dose in Animals Undergoing Diagnostic Radiology Using LiF, Mg, Ti Thermoluminescence Dosimetry (TLD-100

    Sedigheh Sina


    Full Text Available Introduction According to the International Commission on Radiological Protection publication numbers 60 and 21, the environmental control standards should ensure human and other species protection to a desirable degree. Since application of radiographic procedures in Veterinary Medicine has increased significantly, in this study, we aimed to evaluate the entrance skin dose to the animals (e.g., dogs, cats, horses, and birds undergoing diagnostic radiology. Materials and Methods The entrance skin dose to the animals in different radiology procedures were estimated through a indirect estimation using the output of X-ray tubes and b direct measurement using LiF:Mg, Ti  (TLD-100  thermoluminescence dosimeter. Regression analysis was performed for comparison of the two methods. The animals included in this study were cats, dogs, small birds, horses, parrots, and chough. Results The dose received by the animals varied from 20 mGy to 1189.2 mGy, depending on the animal thickness, focal spot to surface distance, imaging technique, and animal type. Conclusion Optimized procedures are suggested for obtaining high-quality images, with a reasonably low dose imposed to the animals.

  17. Pharmacokinetic profiles of artesunate following multiple intravenous doses of 2, 4, and 8 mg/kg in healthy volunteers: Phase 1b study

    Miller Robert


    Full Text Available Abstract Background Severe malaria results in over a million deaths every year, most of them in children aged less than five years and living in sub-Saharan Africa. Injectable artesunate (AS was recommended as initial treatment for severe malaria by WHO in 2006. The Walter Reed Army Institute of Research (WRAIR has been developing a novel good manufacturing practice (GMP injection of AS, which was approved by the US FDA for investigational drug use and distribution by the CDC. Methods Tolerability and pharmacokinetics of current GMP intravenous AS, as an anti-malarial agent, were evaluated after ascending multiple doses of 2, 4, and 8 mg/kg daily for three days with 2-minute infusion in 24 healthy subjects (divided into three groups in the Phase 1 clinical trial study. Results Results showed that there were no dose-dependent increases in any adverse events. Drug concentrations showed no accumulation and no decline of the drug during the three days of treatment. After intravenous injection, parent drug rapidly declined and was converted to dihydroartemisinin (DHA with overall mean elimination half-lives ranging 0.15-0.23 hr for AS and 1.23-1.63 hr for DHA, but the peak concentration (Cmax of AS was much higher than that of DHA with a range of 3.08-3.78-folds. In addition, the AUC and Cmax values of AS and DHA were increased proportionally to the AS climbing multiple doses. Discussion The safety of injectable AS, even at the highest dose of 8 mg/kg increases the probability of therapeutic success of the drug even in patients with large variability of parasitaemia.

  18. Pharmacokinetics of colistin and colistimethate sodium after a single 80-mg intravenous dose of CMS in young healthy volunteers.

    Couet, W; Grégoire, N; Gobin, P; Saulnier, P J; Frasca, D; Marchand, S; Mimoz, O


    Colistin pharmacokinetics (PK) was investigated in young healthy volunteers after a 1-h infusion of 80 mg (1 million international units (MIU)) of the prodrug colistin methanesulfonate (CMS). Concentration levels of CMS and colistin were determined in plasma and urine using a new chromatographic assay and analyzed simultaneously with a population approach after correcting the urine-related data for postexcretion hydrolysis of CMS into colistin. CMS and colistin have low volumes of distribution (14.0 and 12.4 liters, respectively), consistent with distribution being restricted to extracellular fluid. CMS is mainly excreted unchanged in urine (70% on average), with a typical renal clearance estimated at 103 ml/min-close to the glomerular filtration rate. Colistin elimination is essentially extrarenal, given that its renal clearance is 1.9 ml/min, consistent with extensive reabsorption. Colistin elimination is not limited by the formation rate because its half-life (3 h) is longer than that of CMS. The values of these pharmacokinetic parameters will serve as reference points for future comparisons with patients' data.

  19. Rate of relapse in multibacillary patients after cessation of long-course dapsone monotherapy supplemented by a final supervised single dose of 1500 mg of rifampin.

    Cartel, J L; Naudin, J C


    When multidrug therapy was implemented in Senegal, 406 multibacillary (MB) patients who had been treated for more than 10 years by dapsone alone, and who had become clinically inactive and skin-smear negative, were released from treatment. Of these 406 patients, 298 were given a supervised single dose of 1500 mg of rifampin. Subsequently, 302 of them (229 who had been given rifampin and 73 who had not) were followed up by means of annual clinical and bacteriological examinations. Of the former 229 followed up for a mean period of 4.9 years, 34 patients relapsed (22 males and 12 females), giving a crude relapse rate of 15% and an overall risk of relapse of 3.1 per 100 patient-years. Of the latter 73 followed up for a mean period of 2.4 years, 5 relapsed (4 males and 1 female), giving a crude relapse rate of 6.8% and an overall risk of relapse of 2.9 per 100 patient-years. Such results, which are in agreement with those of a similar study conducted recently in Mali, indicate that the intake of a single dose of 1500 mg of rifampin by MB patients when they are released from long-course dapsone monotherapy does not result in a decrease of the relapse rate. Therefore, MB patients who have been treated with dapsone alone, even for long periods, should be put under multidrug therapy prior to their release from control.

  20. Effects of low-dose paroxetine 7.5 mg on weight and sexual function during treatment of vasomotor symptoms associated with menopause.

    Portman, David J; Kaunitz, Andrew M; Kazempour, Kazem; Mekonnen, Hana; Bhaskar, Sailaja; Lippman, Joel


    Two phase 3, randomized, placebo-controlled trials demonstrated that low-dose paroxetine 7.5 mg reduced the frequency and severity of vasomotor symptoms (VMS) associated with menopause and had a favorable tolerability profile. The impact of paroxetine 7.5 mg on body weight and sexual function was evaluated in a pooled analysis. Postmenopausal women aged 40 years or older who had moderate to severe VMS were randomly assigned to receive paroxetine 7.5 mg or placebo once daily for 12 or 24 weeks. Assessments included changes in body mass index (BMI) and weight, Arizona Sexual Experiences Scale score, Hot Flash-Related Daily Interference Scale sexuality subscore, and adverse events related to weight or sexual dysfunction. Pooled efficacy and safety populations comprised 1,174 and 1,175 participants, respectively. Baseline values were similar for median weight (∼75 kg), median BMI (∼28 kg/m), and the proportion of women with sexual dysfunction (∼58%). No clinically meaningful or statistically significant changes from baseline in weight or sexual function assessments occurred in the paroxetine 7.5 mg group. Small but statistically significant increases in weight and BMI were observed in the placebo group only on week 4. No significant difference between treatment groups was observed in the proportion of participants who had 7% or higher gain in body weight on week 4, 12, or 24. Rates of adverse events suggestive of sexual dysfunction were low and similar in both treatment groups. Paroxetine 7.5 mg does not cause weight gain or negative changes in libido when used to treat menopause-associated VMS in postmenopausal women.

  1. Influence of CYP2D6 activity on the pharmacokinetics and pharmacodynamics of a single 20 mg dose of ibogaine in healthy volunteers.

    Glue, Paul; Winter, Helen; Garbe, Kira; Jakobi, Hannah; Lyudin, Alexander; Lenagh-Glue, Zoe; Hung, C Tak


    Conversion of ibogaine to its active metabolite noribogaine appears to be mediated primarily by CYP2D6. We compared 168 hours pharmacokinetic profiles of both analytes after a single oral 20 mg dose of ibogaine in 21 healthy subjects who had been pretreated for 6 days with placebo or the CYP2D6 inhibitor paroxetine. In placebo-pretreated subjects, ibogaine was rapidly converted to noribogaine. Median peak noribogaine concentrations occurred at 4 hours. Compared with placebo-pretreated subjects, paroxetine-pretreated subjects had rapid (Tmax  = 1.5 hours) and substantial absorption of ibogaine, with detectable levels out to 72 hours, and an elimination half-life of 10.2 hours. In this group, ibogaine was also rapidly converted to noribogaine with a median Tmax of 3 hours. Extent of noribogaine exposure was similar in both groups. CYP2D6 phenotype was robustly correlated with ibogaine AUC0-t (r = 0.82) and Cmax (r = 0.77). Active moiety (ibogaine plus noribogaine) exposure was ∼2-fold higher in paroxetine-pretreated subjects. Single 20 mg ibogaine doses were safe and well tolerated in all subjects. The doubling of exposure to active moiety in subjects with reduced CYP2D6 activity suggests it may be prudent to genotype patients awaiting ibogaine treatment, and to at least halve the intended dose of ibogaine in CYP2D6 poor metabolizers.

  2. Therapeutic Doses of Nonsteroidal Anti-Inflammatory Drugs Inhibit Osteosarcoma MG-63 Osteoblast-Like Cells Maturation, Viability, and Biomineralization Potential

    E. De Luna-Bertos


    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are frequently used to reduce pain and inflammation. However, their effect on bone metabolisms is not well known, and results in the literature are contradictory. The present study focusses on the effect of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid, at therapeutic doses, on different biochemical and phenotypic pathways in human osteoblast-like cells. Osteoblasts (MG-63 cell line were incubated in culture medium with 1–10 μM of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid. Flow cytometry was used to study antigenic profile and phagocytic activity. The osteoblastic differentiation was evaluated by mineralization and synthesis of collagen fibers by microscopy and alkaline phosphatase activity (ALP by spectrophotometric assay. Short-term treatment with therapeutic doses of NSAIDs modulated differentiation, antigenic profile, and phagocyte activity of osteoblast-like cells. The treatment reduced ALP synthesis and matrix mineralization. However, nonsignificant differences were observed on collagen syntheses after treatments. The percentage of CD54 expression was increased with all treatments. CD80, CD86, and HLA-DR showed a decreased expression, which depended on NSAID and the dose applied. The treatments also decreased phagocyte activity in this cellular population. The results of this paper provide evidences that NSAIDs inhibit the osteoblast differentiation process thus reducing their ability to produce new bone mineralized extracellular matrix.

  3. Dependence of the thermoluminescent high-temperature ratio (HTR) of LiF:Mg,Ti detectors on proton energy and dose

    Bilski, P; Swakon, J; Weber, A


    The high-temperature ratio (HTR) is a parameter quantifying changes of the shape of the high-temperature part of the LiF:Mg,Ti glow-curve after exposure to densely ionizing radiation. It was introduced in order to estimate the effective LET of an unknown radiation field and to correct the decreased relative TL efficiency for high Linear Energy Transfer (LET) radiation. In the present work the dependence of HTR on proton energy (14.5 to 58 MeV) and dose (0.5 to 30 Gy) was investigated. All measured HTR values were at the level of 1.2 or higher, therefore significantly different from the respective value for gamma rays (HTR is equal to 1), but HTR was found to be insensitive to changes of proton energy above 20 MeV. As a result the relationship between HTR and relative TL efficiency is not unequivocal. The HTR was found to be dependent on absorbed dose even for the lowest studied doses.

  4. Nutrição de mudas de angico-vermelho (Anadenanthera macrocarpa (Benth. Brenan submetidas a doses de N, P, K, Ca E Mg

    Elzimar de Oliveira Gonçalves


    Full Text Available Neste trabalho, objetivou-se verificar o teor e conteúdo de N, P, K, Ca e Mg, bem como determinar o nível crítico desses nutrientes no solo e na planta. As mudas foram cultivadas, no período de dezembro de 2004 a maio de 2005, em vasos com capacidade para 2,1 dm-3 contendo amostras de solo de três classes (Argissolo Vermelho-Amarelo AVA, Latossolo Vermelho-Amarelo Álico LVA e Latossolo Vermelho-Amarelo Distrófico - LVD. Os tratamentos foram delimitados segundo uma matriz baconiana, onde se variaram os macronutrientes, em três doses, e dois tratamentos adicionais (zero e referência, com quatro repetições. Verificou-se que, em geral, as mudas da espécie absorveram maior quantidade de N, P, K, Ca e Mg, à medida que a disponibilidade destes aumentava no solo. Tal fato refletiu em maior concentração dos nutrientes aplicados em todas as partes da planta. Entretanto, em alguns casos não houve resposta em crescimento correspondente a esse aumento. Os nutrientes que mais proporcionaram efeitos foram o P, o N e o S; poucas respostas foram observadas nos demais nutrientes (Ca, Mg e K. A espécie tem baixo requerimento nutricional, sendo o nível crítico dos nutrientes, no solo e na planta, menores do que os observados em outras espécies florestais. Para o K e o Ca, sugerem-se estudos com doses dentro das faixas de valores encontrados, para melhor definição dos níveis críticos.

  5. Assessment of the mean glandular dose using LiF:Mg,Ti, LiF:Mg,Cu,P, Li2B4O7:Mn and Li2B4O7:Cu TL detectors in mammography radiation fields

    Fartaria, M. J.; Reis, C.; Pereira, J.; Pereira, M. F.; Cardoso, J. V.; Santos, L. M.; Oliveira, C.; Holovey, V.; Pascoal, A.; Alves, J. G.


    The aim of this paper is the characterization of four thermoluminescence detectors (TLD), namely, LiF:Mg,Ti, LiF:Mg,Cu,P, Li2B4O7:Mn and Li2B4O7:Cu for the measurement of the entrance surface air kerma (ESAK) and estimation of the mean glandular dose (MGD) in digital mammography examinations at hospitals and clinics. Low-energy x-ray beams in the typical energy ranges of mammography, produced with a tungsten target and additional 60 µm molybdenum filtration were implemented and characterized at the Laboratory of Metrology of Ionizing Radiation at Instituto Superior Técnico. These beams were used for the characterization of the TLDs in terms of sensitivity, linearity, reproducibility, energy dependence and fading at 40 °C. The energy dependence test was further extended using clinical beams produced by mammography units at hospitals and clinics. The method proposed by the International Atomic Energy Agency was used for the measurement of ESAK and assessment of MGD. The combined standard uncertainty for the measurement of ESAK (and MGD) was determined in accordance to the Guide to the expression of uncertainty in measurement. The x-ray beams generated in the 23-40 kVp range presented HVL values from 0.36 to 0.46 mm Al. The beam produced at 28 kVp (HVL 0.39 mm Al) was considered as reference. The radiation field defined a circle with 84 mm diameter with a maximum variation of the beam intensity of less than 1% at the top flat (plateau) within 4 cm of the central axis. The estimated total uncertainty for the measurement of air kerma was 0.42%. All the TL detectors tested showed good performance except the commercial Li2B4O7:Mn (or TLD-800) which was excluded due to its poor sensitivity in our experimental set up. Both lithium fluorides showed better linearity and reproducibility as well as lower energy dependence and fading when compared to lithium borates. The stable behaviour of LiF:Mg,Ti and LiF:Mg,Cu,P detectors is reflected in the low combined standard

  6. Comparative pharmacokinetics and tolerability of branded etanercept (25 mg) and its biosimilar (25 mg): a randomized, open-label, single-dose, two-sequence, crossover study in healthy Korean male volunteers.

    Gu, Namyi; Yi, Sojeong; Kim, Tae-Eun; Kim, Jaewoo; Shin, Sang-Goo; Jang, In-Jin; Yu, Kyung-Sang


    The biosimilar is a recombinant dimeric tumor necrosis factor receptor (TNFR) under development for the treatment of rheumatoid arthritis. The aim of this study was to compare the pharmacokinetics and/or tolerability of branded etanercept and its biosimilar in healthy Korean men before investigating the clinical efficacy of the biosimilar in subjects. Etanercept (reference, 25 mg) or its biosimilar (test, 25 mg) was subcutaneously injected to the periumbilical area of healthy volunteers in a randomized, open-label, single-dose, active-controlled, two-sequence, crossover study. Plasma concentrations of TNFR in serial blood samples for 480 hours after dosing were measured by ELISA. The primary outcome, pharmacokinetic characteristics, was assessed via geometric mean ratios (GMRs) of the log-transformed pharmacokinetic parameters. The second outcome, tolerability, was evaluated using physical examinations, electrocardiograms, clinical laboratory tests, vital sign measurements, and adverse events (AEs) by unmasked investigators. Twenty-three men of mean age (%CV) 25.8 years (17.1%) and weight 70.5 kg (12.8%) were administered study medication. Four subjects dropped out after the first period; their data were included in the analysis. Both test and reference drugs were absorbed with a median T(max) of 72 (range, 36-144) hours and eliminated with mean (%CV) t(½) of 92.7 (20.9%) and 87.4 (16.6%) hours, respectively. The GMRs (90% CIs) of the test to reference drug for C(max), AUC(0-t), and AUC(0-∞) were 0.99 (0.83-1.17), 0.95 (0.79-1.13), and 0.95 (0.80-1.13), respectively. Eleven of 21 (52.4%) and 8 of 21 (38.1%) subjects administered the test and reference drugs reported 22 and 21 AEs, respectively. Common AEs were headache (14.3%), throat irritation (8.5%), and epistaxis (9.5%). Three serious AEs related to a traffic accident (back, neck, and musculoskeletal pain) were reported in a test drug-treated subject. In this select group of Korean healthy male volunteers

  7. Effect of food on the pharmacokinetics of canagliflozin/metformin (150/1,000 mg) immediate-release fixed-dose combination tablet in healthy participants.

    Murphy, Joseph; Wang, Shean-Sheng; Stieltjes, Hans; Wajs, Ewa; Devineni, Damayanthi


    To assess the effect of food on the pharmacokinetics (PK) of canagliflozin and metformin following administration of a canagliflozin/metformin (150/1,000 mg) immediate-release (IR) fixed-dose combination (FDC) tablet. A randomized, open-label, singlecenter, single-dose, 2-period, 2-sequence crossover study was conducted in healthy participants. Participants were randomized to 2 sequences of fasted and fed (or vice versa) administration of one 150/1,000 mg canagliflozin/metformin IR FDC, with 10-14 day washout between treatments PK parameters (AUC, Cmax, tmax, t1/2) were assessed for canagliflozin and metformin. Safety was evaluated. When comparing the IR FDC tablet administered with and without food, PK parameters of canagliflozin were bioequivalent as the 90% confidence intervals (CIs) for log-transformed AUClast, AUC∞, and Cmax were within the bioequivalence limits of 80-125%. For metformin, overall exposure was similar under fed and fasted conditions as geometric mean ratios for AUC and associated 90% CI were contained within the bioequivalence limits, but geometric mean Cmax decreased by 16% in the fed compared to fasted state. Both treatments were well tolerated with similar adverse events and most common were gastrointestinal events, generally attributed to metformin. Food did not affect canagliflozin bioavailability parameters (Cmax and AUCs) or AUCs of metformin. The Cmax of metformin was decreased by 16%, which is not considered clinically meaningful. The canagliflozin/metformin FDC tablet is recommended to be taken with meals to reduce the symptoms of gastrointestinal intolerability associated with metformin.

  8. Influence of Food on the Bioavailability of an Enteric-Coated Tablet Formulation of Omeprazole 20 mg Under Repeated Dose Conditions

    ABR Thomson


    Full Text Available The objective of this study was to investigate the influence of food on the bioavailability of omeprazole (20 mg given as an enteric-coated tablet under repeated dose conditions. This open randomized crossover study consisted of three seven-day treatment periods, each separated by a drug-free period. During each treatment period an enteric-coated tablet of omeprazole was taken once daily either under fasting conditions, or immediately before or after a standardized breakfast. On the last day of each treatment period, blood samples for the determination of plasma omeprazole concentrations were collected at baseline and at predetermined intervals over the 24 h period following drug administration. Fifty-seven male and female subjects, aged 18 to 52 years, completed the study according to the protocol. No statistically significant differences were found when comparing either the before breakfast or after breakfast treatment regimens with the fasting regimen for the estimated mean area under the plasma concentration-time curve (AUC. The maximum plasma concentration was not found to differ significantly among any of the treatment regimens. However, the lower limit of the CI for the comparison of fasting/before breakfast was not contained within the limits of bioequivalence. The time to reach maximum plasma concentration was significantly different when fasting and after breakfast regimens were compared. Thus, under repeated dose conditions, food has no influence on the bioavailability (expressed as AUC of omeprazole given as the enteric-coated tablet formulation.

  9. Earliest use of initial prophylactic dose of magnesium sulphate (MgSO4 in severe pre-eclampsia to improve maternal and perinatal outcome, in a rural medical college, WB, India

    Suresh Chandra Mondal


    Conclusions: Initial dose prophylactic magnesium sulphate (MgSO4 the earliest, can prevent both maternal perinatal maternal mortality. So, prophylactic magnesium sulphate (MgSO4 must be started at the first point of contact by trained health providers. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 653-655

  10. Average bioequivalence of single 500 mg doses of two oral formulations of levofloxacin: a randomized, open-label, two-period crossover study in healthy adult Brazilian volunteers

    Eunice Kazue Kano


    Full Text Available Average bioequivalence of two 500 mg levofloxacin formulations available in Brazil, Tavanic(c (Sanofi-Aventis Farmacêutica Ltda, Brazil, reference product and Levaquin(c (Janssen-Cilag Farmacêutica Ltda, Brazil, test product was evaluated by means of a randomized, open-label, 2-way crossover study performed in 26 healthy Brazilian volunteers under fasting conditions. A single dose of 500 mg levofloxacin tablets was orally administered, and blood samples were collected over a period of 48 hours. Levofloxacin plasmatic concentrations were determined using a validated HPLC method. Pharmacokinetic parameters Cmax, Tmax, Kel, T1/2el, AUC0-t and AUC0-inf were calculated using noncompartmental analysis. Bioequivalence was determined by calculating 90% confidence intervals (90% CI for the ratio of Cmax, AUC0-t and AUC0-inf values for test and reference products, using logarithmic transformed data. Tolerability was assessed by monitoring vital signs and laboratory analysis results, by subject interviews and by spontaneous report of adverse events. 90% CIs for Cmax, AUC0-t and AUC0-inf were 92.1% - 108.2%, 90.7% - 98.0%, and 94.8% - 100.0%, respectively. Observed adverse events were nausea and headache. It was concluded that Tavanic(c and Levaquin(c are bioequivalent, since 90% CIs are within the 80% - 125% interval proposed by regulatory agencies.

  11. [Evaluation of the antihypertensive effect and tolerability of a new delayed-action calcium channel blocker: nitrendipine, prescribed as a single daily dose of 20 mg].

    Herpin, D; Amiel, A; Boutaud, P; Ciber, M A; Demange, J


    The authors have studied the effects of Nitrendipine, orally given in a dose of 20 mg, once a day for 30 days, in patients with mild to moderate hypertension. Twelve patients initially entered the study but four of them discontinued the treatment during the first week, because of unwanted side-effects: headaches, palpitation, sensations of burning skin. The remaining eight patients underwent a comparative evaluation at the end of a placebo period (DO) and at the end of the active treatment (D30), including successively: an automatic blood pressure recording with a Bard-Sentron device for 3 hours, then a determination of plasma renin activity, aldosterone and catecholamines, and finally a measurement of the blood pressure with a mercury manometer, at rest and during a standardized exercise on an ergometric bicycle. At D30, the Nitrendipine tablet was given one hour after the beginning of the automatic recording. The blood pressure measured with the mercury manometer (i.e. approximately 2 hours after the dose of Nitrendipine) significantly decreased from D0 to D30, at rest and during exercise, respectively from 161.5/104.6 to 132.8/82.5 mmHg and from 210.0/116.8 to 190.0/95.6 mmHg. The automatic recording provided, at D0, a mean blood pressure value of 152.4/90.6 mmHg; at D30, this mean value was as high as 142.6/90.7 mmHg during the hour preceding the dose of Nitrendipine (NS) and as high as 129.2/78.6 mmHg during the 2nd hour following the intake of the tablet (p less than 0.01). Plasma aldosterone and plasma renin activity significantly (p less than 0.05) increased from D0 to D30, whereas catecholamines did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Quality control for thermoluminescent dosemeters TLD-100 de Li F: Mg, Ti for high dose rate treatments using Ir-192 sources in breast, esophagus and bronchus; Control de calidad con dosimetros thermoluminiscentes TLD-100 de Li F: Mg, Ti para tratamientos de alta tasa de dosis com fuentes de Ir-192 en canceres de seno, esofago y bronchio

    Torres, F. [Universidad Nacional de Colombia, Bogota (Colombia)]. E-mail:; Plazas, M.C. [Instituto Nacional de Cancerologia, Bogota (Colombia); Cavadia, W. [Universidad de Cordoba (Colombia)


    Rods - shaped, TLD - 100, LiF: Mg,Ti thermoluminescence dosimeters are used to check duality control during breast, esophagus and bronchus cancer treatments with high rate dose and Ir -192 source. We conclude that the specificity dose in prescription points is in agreement with parameters given in international protocols. (author)

  13. Verapamil COER-24 180/240mg na hipertensão arterial leve a moderada em dose única diária avaliado pela monitorização ambulatorial da pressão arterial Single daily dose of verapamil (COER-24 180/240mg in mild and moderate hypertension evaluated by ambulatory blood pressure monitoring

    Katia Coelho Ortega


    Full Text Available OBJETIVO: Avaliar a eficácia terapêutica do verapamil COER-24 180/240 mg, em dose única, ao deitar, como monoterapia para a hipertensão arterial leve a moderada. MÉTODOS: Estudo multicêntrico, aberto, não comparativo com 81 pacientes de ambos os sexos, com idade >20 anos e hipertensão arterial essencial leve e moderada. Medimos a pressão arterial no consultório e com a monitorização ambulatorial (MAPA durante 24h antes e ao final de 8 semanas do uso da medicação. RESULTADOS: Verificou-se diminuição (pOBJECTIVE: To evaluate the anti-hypertensive effecft of verapamil COER-24 180/240 mg in a single dose at bedtime as single therapy in mild to moderate hypertensives. METHODS: A multicentric, open, placebo controlled study of 81 hypertensive patients older than 20 years-old followed to 8 weeks. Blood pressure was measured in doctor's office and by 24h ambulatory monitoring (ABPM. RESULTS: We observed a decreased in systolic and diastolic blood pressure in doctor's office at 4th and 8th weeks. ABPM showed that both systolic, diastolic and mean blood pressure, heart rate and the mean 24-hour blood pressure load decreased after the 8-week treatment. In addition, there was a reduction of the double-product, especially in the morning and 68% of the patients didn't have any adverse events. CONCLUSION: The theraphy verapamil COER-24 180/240mg in a single dose is useful for mild and moderate hypertensive patients, with significant pressure decrease in both office blood pressure measurements and in the ABPM/24 hours, as well as showing good tolerability.

  14. Evaluation of radioprotection conditions and patient dose in thorax exams carried out in a public children's hospital in Belo Horizonte, MG, Brazil; Avaliacao das condicoes de radioprotecao e dose paciente em exames de torax realizados em um hospital publico infantil de Belo Horizonte, MG

    Lacerda, Marco A.S.; Silva, Teogenes A. da; Guedes, Elton C. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Khoury, Helen J. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Azevedo, Ana C.P. [Fundacao Oswaldo Cruz (ENSP-CESTEH), Rio de Janeiro, RJ (Brazil)


    We conducted a survey of the conditions of radiation protection, radiographic techniques, dose and risk for pediatric patients undergoing chest X-rays exams in a children's hospital in Belo Horizonte-MG, Brazil. From a total of 125 chest exams (projections AP and PA) were noted the patient data (gender, weight, and age) and parameters of radiographic technique (kV, mAs and distance focus-skin). I was also evaluated the working procedures and the conditions of radiation protection. The values of input air kerma (K{sub a,e}) and effective dose (E) were determined using the DoseCal software developed by Radiological Protection Center of Saint Georges's Hospital in London. With respect to the procedures and conditions for radiation protection, many aspects of Portaria 453 are not considered. The use of radiographic techniques with high values of mAs and low voltage values are not according with the quality criteria adopted by the European Community (EC). The values of Ka for patients aged 1 to 5 years varied between 51 {mu}Gy and 64 {mu}Gy, below the reference levels proposed by the EC. For patients over 5 years old, the values of Ka were substantially higher than those for other patients. The results allow to conclude that there is a need for optimization of the procedures adopted in order to reduce the dose and the risk to patients.

  15. Repeat spinal anesthesia in cesarean section: A comparison between 10 mg and 12 mg doses of intrathecal hyperbaric (0.05%) bupivacaine repeated after failed spinal anesthesia: A prospective, parallel group study.

    Bhar, Debasish; RoyBasunia, Sandip; Das, Anjan; Chhaule, Subinay; Mondal, Sudipta Kumar; Bisai, Subrata; Chattopadhyay, Surajit; Mandal, Subrata Kumar


    Spinal anesthesia for cesarean section is not a 100% successful technique. At times, despite straightforward insertion and drug administration, intrathecal anesthesia for cesarean section fails to obtain any sensory or motor block. Very few studies and literature are available regarding repeat administration of spinal anesthesia and its drug dosage, especially after first spinal failure in cesarean section lower segment cesarean section (LSCS) due to fear of the excessive spread of drug. The aim of our study is to compare the outcome between two different doses of 0.5% hyperbaric bupivacaine repeated intrathecally after failed spinal. After taking informed consent and Ethical Committee approval this prospective, randomized single-blinded study was conducted in 100 parturients of American Society of Anesthesiologists I-II who were posted for elective LSCS and had Bromage score 0 and no sensory block even at L4 dermatome after 10 min of first spinal anesthesia; were included in the study. Group A (n = 50) patients received 2.4 ml and Group B (n = 50) patients received 2 ml of 0.5% hyperbaric bupivacaine respectively for administering repeat spinal anesthesia. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), oxygen saturation, respiratory rate and electrocardiogram were monitored both intra- and post-operatively and complications were recorded. Incidence of high spinal, bradycardia, hypotension, respiratory complications, and nausea vomiting are significantly higher in Group A compared to Group B (P cesarean section with 10 mg of 0.5% hyperbaric bupivacaine provided after first spinal anesthesia, the level of sensory block is below L4 and motor power in Bromage scale is 0.

  16. Effect of a single 1200 Mg dose of Mucinex® on mucociliary and cough clearance during an acute respiratory tract infection.

    Bennett, W D; Kala, A; Duckworth, H; Zeman, K L; Wu, J; Henderson, A; Yopp, M; Rubin, B K


    Observational studies suggest that orally administered guaifenesin (GGE) may thin lower respiratory tract secretions but none have examined its effects on mucociliary and cough clearance (MCC/CC) during a respiratory tract infection (RTI). The current study was a randomized, parallel-group, double-blind, placebo-controlled study in non-smoking adults who suffered from an acute upper RTI. We assessed the effects of a single dose of Mucinex(®) 1200 mg (2 × 600 mg extended release tablets) (ER GGE) on 1) MCC/CC by assessing the rate of removal from the lung of inhaled radioactive tracer particles (Tc99m-sulfur colloid), 2) sputum dynamic rheology by stress/strain creep transformation over the linear part of the curve, 3) sessile drop interfacial tension by the deNouy ring technique, and 4) subjective symptom measures. MCC was measured during the morning (period 1) and compared to that in the afternoon 4 h later (period 2) immediately following either drug (n = 19) or placebo (n = 19). For both period 1 and 2 subjects performed 60 voluntary coughs from 60 to 90 min after inhalation of radio-labeled aerosol for a measure of CC. Sputum properties were measured from subjects who expectorated sputum during the cough period post treatment (n = 8-12 for each cohort). We found no effect of ER GGE on MCC or CC compared to placebo. MCC through 60 min for period 1 vs. 2 = 8.3 vs. 11.8% (placebo) and = 9.7 vs. 11.1% (drug) (NS) and CC for period 1 vs. 2 was 9.9 vs. 9.1% (placebo) and 10.8 vs. 5.6% (drug) (NS). There was no significant difference in sputum biophysical properties after administration of drug or placebo. There was no significant effect of a single dose of ER GGE on MCC/CC or on sputum biophysical properties compared to placebo in this population of adult patients with an acute RTI. Identifier: NCT01114581. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Variable Absorption of Clavulanic Acid After an Oral Dose of 25 mg/kg of Clavubactin® and Synulox® in Healthy Cats

    Tom B. Vree


    Full Text Available The aims of this investigation were to calculate the pharmacokinetic parameters and to identify parameters, based on individual plasma concentration-time curves of amoxicillin and clavulanic acid in cats, that may govern the observed differences in absorption of both drugs. The evaluation was based on the data from plasma concentration-time curves obtained following a single-dose, open, randomised, two-way crossover phase-I study, each involving 24 female cats treated with two Amoxi-Clav formulations (formulation A was Clavubactin® and formulation was B Synulox® ; 80/20 mg, 24 animals, 48 drug administrations. Plasma amoxicillin and clavulanic acid concentrations were determined using validated bioassay methods. The half-life of elimination of amoxicillin is 1.2 h (t1/2 = 1.24 ± 0.28 h, Cmax = 12.8 ± 2.12 μg/ml, and that of clavulanic acid 0.6 h (t1/2 = 0.63 ± 0.16 h, Cmax = 4.60 ± 1.68 μg/ml. There is a ninefold variation in the AUCt of clavulanic acid for both formulations, while the AUCt of amoxicillin varies by a factor of two. The highest clavulanic acid AUCt values indicate the best absorption; all other data indicate less absorption. Taking into account that the amoxicillin–to–clavulanic acid dose ratio in the two products tested was 4:1, the blood concentration ratios may actually vary much more, apparently without compromising the products’ high efficacy against susceptible microorganisms.

  18. A randomised controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day in patients with gout

    Reinders, M. K.; Haagsma, C.; Jansen, T. L. Th A.; van Roon, E. N.; Delsing, J.; de Laar, M. A. F. J. van; Brouwers, J. R. B. J.

    Objectives: To compare the efficacy and tolerability of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day used to attain a target serum urate concentration (sUr) (0.30 mmol/l (5 mg/dl). Methods: A randomised, controlled, open-label, multi-centre trial in gout patients with renal

  19. A randomised controlled trial on the efficacy and tolerability with dose escalation of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day in patients with gout

    Reinders, M. K.; Haagsma, C.; Jansen, T. L. Th A.; van Roon, E. N.; Delsing, J.; de Laar, M. A. F. J. van; Brouwers, J. R. B. J.


    Objectives: To compare the efficacy and tolerability of allopurinol 300-600 mg/day versus benzbromarone 100-200 mg/day used to attain a target serum urate concentration (sUr) (0.30 mmol/l (5 mg/dl). Methods: A randomised, controlled, open-label, multi-centre trial in gout patients with renal functio

  20. Study of the damage processes induced by thermal fatigue in stainless steels F17TNb and R20-12 for automobile application; Etude de l'endommagement en fatigue thermique des aciers inoxydables F17TNb et R20-12 pour application automobile

    Bucher, L.


    Thermal cycling is the main cause of fatigue failure in automobile exhaust manifolds for which the use of stainless steel now rivals that of cast iron which has been traditionally used. An original fatigue test has been developed by Ugine and ALZ, a stainless steel producer, so as to be able to compare different grades of stainless steel alloys. This test is representative of the thermal conditions encountered in the critical zones of exhaust manifolds. However, it has revealed significant differences in damage processes in the ferritic and austenitic grades tested. The subject of this thesis is the damage processes induced by thermal fatigue in stainless steels used for automotive exhaust manifolds. Two stainless steels were studied: a ferritic grade, F17TNb (17%Cr and stabilized with Ti and Nb), and an austenitic grade, R20-12, containing 20% Cr and 12% Ni. The first objective was to understand the different damage processes induced by thermal fatigue in the ferritic and austenitic grades. The second was to develop a numerical design tool of the thermally tested structures. (author)

  1. Iron prophylaxis during pregnancy -- how much iron is needed? A randomized dose- response study of 20-80 mg ferrous iron daily in pregnant women

    Milman, Nils; Bergholt, Thomas; Eriksen, Lisbeth


    To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy.......To determine the lowest dose of iron preventative of iron deficiency and iron deficiency anemia in pregnancy....

  2. The use of enriched 6Li and 7Li Lif:Mg,Cu,P glass-rod thermoluminescent dosemeters for linear accelerator out-of-field radiation dose measurements.

    Takam, R; Bezak, E; Liu, G; Marcu, L


    (6)LiF:Mg,Cu,P and (7)LiF:Mg,Cu,P glass-rod thermoluminescent dosemeters (TLDs) were used for measurements of out-of-field photon and neutron doses produced by Varian iX linear accelerator. Both TLDs were calibrated using 18-MV X-ray beam to investigate their dose-response sensitivity and linearity. CR-39 etch-track detectors (Luxel+, Landauer) were employed to provide neutron dose data to calibrate (6)LiF:Mg,Cu,P TLDs at various distances from the isocentre. With cadmium filters employed, slow neutrons (neutrons. The average in-air photon dose equivalents per monitor unit (MU) ranged from 1.5±0.4 to 215.5±94.6 μSv at 100 and 15 cm from the isocentre, respectively. Based on the cross-calibration factors obtained with CR-39 etch-track detectors, the average in-air fast neutron dose equivalents per MU range from 10.6±3.8 to 59.1±49.9 μSv at 100 and 15 cm from the isocentre, respectively. Contribution of thermal neutrons to total neutron dose equivalent was small: 3.1±7.2 μSv per MU at 15 cm from the isocentre.

  3. A randomized, double-blind, multicentre study comparing daily 2 and 5 mg of tropisetron for the control of nausea and vomiting induced by low-dose cisplatin- or non-cisplatin-containing chemotherapy

    Wymenga, ANM; vanderGraaf, WTA; Wils, JA; vanHeukelom, LS; vanderLinden, GHM; DullemondWestland, AC; Nooy, M; vanderHeul, C; deBruijn, KM; deVries, EGE


    Background: This study compares efficacy safety and tolerability of 2 and 5 mg tropisetron in prevention of nausea and vomiting induced by low-dose cisplatin- or non-cisplatin-containing chemotherapy. Patients and methods: 152 chemotherapy-naive cancer patients were randomized in a double-blind mann

  4. Fontes e doses de fósforo no desenvolvimento e produção do cafeeiro, em um solo originalmente sob vegetação de cerrado de Patrocínio - MG Sources and doses of phosphorus on coffee development and production on soil originally under savannah vegetation of Patrocínio - MG

    Benjamim de Melo


    Full Text Available Conduziu-se este trabalho com o objetivo de avaliar o efeito de diferentes fontes e doses de fósforo no desenvolvimento e na produção do cafeeiro, cultivar Acaiá Cerrado, linhagem MG-1474, em um Latossolo Vermelho distroférrico, da Fazenda Experimental de Patrocínio, da Empresa de Pesquisa Agropecuária de Minas Gerais (EPAMIG. O experimento foi instalado no espaçamento de 3,50 x 0,70 m, segundo o delineamento experimental de blocos casualizados, em esquema fatorial 4 x 5, com quatro repetições. Utilizaram-se como fontes de fósforo, o fosfato de Araxá, o termofosfato magnesiano, o fosfato de Arad e o superfosfato triplo, aplicados em cinco doses, correspondentes a: 0 (zero, 125, 250, 500 e 1.000 g de P2O5 total por metro de sulco. Cada parcela experimental foi constituída por uma linha com oito plantas, sendo adotadas como plantas úteis as quatro centrais. Aos trinta e aos quarenta e um meses após o plantio foram avaliadas as seguintes características: altura de planta (m, diâmetros de caule (mm e de copa (m, e produtividade (sc/ha. As fontes de fósforo testadas comportaram-se de forma semelhante quanto às características de desenvolvimento do cafeeiro, aos 30 e aos 41 meses após o plantio; aos 30 meses, as maiores produtividades foram obtidas quando se utilizou o superfosfato triplo e o termofosfato magnesiano; aos 41 meses, as maiores produtividades foram observadas quando se utilizou os fosfatos de Araxá, de Arad e o termofosfato magnesiano; as doses de P2O5 influenciaram o desenvolvimento vegetativo do cafeeiro, sendo os melhores resultados observados na faixa compreendida pelas doses 618,8 a 674,4 g de P2O5 por metro de sulco; as melhores produtividades, foram obtidas nas doses compreendidas entre 539,7 a 855,0 g de P2O5 por metro de sulco, de acordo com o fertilizante utilizado, à exceção do superfosfato triplo, aos 41 meses após o plantio, em que a dose máxima de P2O5 testada foi insuficiente para se obter um m

  5. Importance of optimal dosing ≥30 mg/kg/d during deferasirox treatment: 2.7-yr follow-up from the ESCALATOR study in patients with β-thalassaemia

    Taher, Ali; Elalfy, Mohsen S; Al Zir, Kusai; Daar, Shahina; Al Jefri, Abdullah; Habr, Dany; Kriemler-Krahn, Ulrike; El-Ali, Ali; Roubert, Bernard; El-Beshlawy, Amal


    Following 1-yr deferasirox therapy in the ESCALATOR study, 57% of previously chelated patients with β-thalassaemia achieved treatment success (maintenance of or reduction in liver iron concentration (LIC) vs. baseline LIC). Seventy-eight per cent had dose increases at median of 26 wk, suggesting that 1-yr results may not have reflected full deferasirox efficacy. Extension data are presented here. Deferasirox starting dose was 20 mg/kg/d (increases to 30/40 mg/kg/d permitted in the core/extension, respectively). Efficacy was primarily assessed by absolute change in LIC and serum ferritin. Overall, 231 patients received deferasirox in the extension; 67.4% (P < 0.0001) achieved treatment success. By the end of the extension, 66.2% of patients were receiving doses ≥30 mg/kg/d. By the end of the 1-yr extension, mean LIC had decreased by 6.6 ± 9.4 mg Fe/g dw (baseline 19.6 ± 9.2; P < 0.001) and median serum ferritin by 929 ng/mL (baseline 3356; P < 0.0001). There was a concomitant improvement in liver function markers (P < 0.0001). Fewer drug-related adverse events were reported in extension than core study (23.8% vs. 44.3%). Doses ≥30 mg/kg/d were generally required because of high transfusional iron intake and high baseline serum ferritin levels, highlighting the importance of administering an adequate dose to achieve net negative iron balance. PMID:21668502

  6. [b][/b]Impact of copper (Cu at the dose of 50 mg on haematological and biochemical blood parameters in turkeys, and level of Cu accumulation in the selected tissues as a source of information on product safety for consumers

    Bogusław Makarski


    Full Text Available Introduction. The current state-of the art points to a positive impact of copper (Cu supplements on the general health status in poultry. Copper induces beneficial changes in the haematological and biochemical blood parameters. It also displays immunostimulating properties and helps maintain a proper microbiological balance in the digestive tract. [b]Objective[/b]. The objective of this study was to investigate the impact of Cu at the dose of 50 mg/kg BW, administered in organic and inorganic form, on the haematological and biochemical blood parameters and level of Cu bioaccumulation in the liver and pectoral muscle. [b]Materials and method[/b]. The study was carried out on 45 BUT-9 turkeys which had been were reared for 16 weeks. They were divided into 3 experimental groups: I – the control group; II – fed with CuSO[sub]4[/sub] at the dose of 50 mg Cu•dm [sup]-3 [/sup]H[sub]2[/sub]O; III – received a Cu chelate with lysine at the same dose. [b]Results[/b]. The administration of Cu at the dose exceeding the nutritional recommendations did not induce beneficial changes in the examined birds. This indicates that it is not necessary to administer Cu doses higher than the recommended levels. The extent of Cu accumulation in the pectoral muscle increased by 40% compared to the control group, whereas in the liver it was higher by 30–35% than in the birds without Cu administration. The level of Cu in tissues does not pose a risk to consumers. [b]Conclusions[/b]. The supplementation of Cu at the dose of 50 mg has a negative impact on the level of the analyzed parameters. The results of the presented study indicate that the administered Cu dose exceeds birds’ demand for this element.

  7. Tl and OSL dose response of LiF:Mg, Ti and Al{sub 2}O{sub 3}:C dosimeters using a PMMA phantom for IMRT technique quality assurance

    Matsushima, L. C.; Veneziani, G. R.; Campos, L. L. [Instituto de Pesquisas Energeticas e Nucleares, Gerencia de Metrologia das Radiacoes / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil); Sakuraba, R. K.; Cruz, J. C., E-mail: [Sociedade Beneficente Israelita Brasileira - Hospital Albert Einstein, Av. Albert Einstein 627/701, Morumbi, 05652-000 Sao Paulo (Brazil)


    The principle of IMRT is to treat a patient from a number of different directions (or continuous arcs) with beams of nonuniform fluences, which have been optimized to deliver a high dose to the target volume and an acceptably low dose to the surrounding normal structures (Khan, 2010). This study intends to provide information to the physicist regarding the application of different dosimeters type, phantoms and analysis technique for Intensity Modulated Radiation Therapy (IMRT) dose distributions evaluation. The measures were performed using dosimeters of LiF:Mg,Ti and Al{sub 2}O{sub 3}:C evaluated by techniques of thermoluminescent (Tl) and Optically Stimulated Luminescence (OSL). A polymethylmethacrylate (PMMA) phantom with five cavities, two principal target volumes considered like tumours to be treated and other three cavities to measure the scattered radiation dose was developed to carried out the measures. (Author)

  8. Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind, Randomized, Placebo-Controlled Trial.

    Kamgno, Joseph; Nguipdop-Djomo, Patrick; Gounoue, Raceline; Téjiokem, Mathurin; Kuesel, Annette C


    Loiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely. Sixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤ 30000, 30001-50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment. None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM treatment arms, respectively. The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas.

  9. Fixed-Dose Combination Gel of Adapalene and Benzoyl Peroxide plus Doxycycline 100 mg versus Oral Isotretinoin for the Treatment of Severe Acne: Efficacy and Cost Analysis.

    Penna, Pete; Meckfessel, Matthew H; Preston, Norman


    Acne vulgaris is a chronic skin disease with a high prevalence. Left untreated or inadequately treated, acne vulgaris can lead to psychological and physical scarring, as well as to unnecessary medical expenses. Oral isotretinoin is an effective treatment for severe resistant nodular and conglobate acne vulgaris. A regimen consisting of a fixed-dose combination of adapalene and benzoyl peroxide gel, 0.1%/2.5% (A-BPO) with oral doxycycline 100 mg (A-BPO/D) has been demonstrated to be efficacious and well tolerated in patients with severe acne and may be an alternative to oral isotretinoin for some patients with severe acne. The objective of this analysis was to compare the relative efficacy and associated costs of A-BPO/D versus oral isotretinoin. In this analysis, comparisons of relative efficacy were made using previously published studies involving similar patient populations with severe acne that warrant the use of oral isotretinoin. The pricing for oral doxycycline and oral isotretinoin was estimated based on the maximum allowable cost from 9 states, and the pricing for A-BPO was calculated as the range between the average wholesale price and the wholesale acquisition cost. For this analysis, 2 treatment models were generated to compare costs: (1) a basic treatment model that examined the costs of an initial regimen of either A-BPO/D or oral isotretinoin without considering probable outcomes, and (2) a long-term model that factored in likely treatment outcomes and subsequent treatments into associated costs. The basic treatment model assumed that patients would be prescribed a single regimen of A-BPO/D for 12 weeks or oral isotretinoin for 20 weeks. The long-term model considered the probability of each treatment successfully managing patients' acne, as well as likely additional regimens of A-BPO monotherapy or an additional regimen of oral isotretinoin. As a result of different treatment durations, the costs for each treatment were normalized to weekly cost of

  10. [Intensive blood pressure reduction in patients with increased cardiovascular risk with high-dose combination therapy of 160 mg valsartan plus 25 mg hydrochlorothiazide. Results of the MACHT II observational study].

    Schühlen, Helmut; Abts, Markus; Kastrati, Dorejd


    Hypertension is one of the most common cardiovascular risk factors. Thus, achievement and maintenance of a sufficient reduction of blood pressure markedly contribute to successful risk prevention. Therefore, the primary objective of this observational postmarketing study MACHT II was to examine the efficacy and the tolerability of the combined therapy with 160 mg valsartan plus 25 mg hydrochlorothiazide (HCT) in a large population of patients with a well-defined individual risk profile and treatment status at baseline. This multicenter, open singlearm trial involved 17,591 patients, either without or with insufficient prior antihypertensive medication. The mean absolute blood pressure improvement obtained for the total population was -26.8 mmHg systolic and -13.5 mmHg diastolic. The maximum absolute improvement in blood pressure was observed in patients with severe hypertension: on average, the systolic blood pressure decreased by 41.7 mmHg and the diastolic blood pressure by 20.5 mmHg compared to baseline. The results demonstrated an effective blood pressure reduction in every subgroup analyzed: mean values of systolic and diastolic blood pressure decreased to high normal values. More than two thirds of the patients achieved normalization of the diastolic blood pressure. Normalization of diastolic blood pressure was observed in 65.2% of the patients with previous antihypertensive medication and in 74.3% of those without previous antihypertensive medication. The overall incidence of adverse drug reactions was 0.6%. The combined antihypertensive therapy with 160 mg valsartan plus 25 mg HCT shows a high degree of efficacy and a very favorable safety profile.

  11. The influence of dose on the kinetic parameters and dosimetric features of the main thermoluminescence glow peak in α-Al{sub 2}O{sub 3}:C,Mg

    Kalita, J.M.; Chithambo, M.L., E-mail:


    Highlights: • Influence of dose on thermoluminescence features of α-Al{sub 2}O{sub 3}:C,Mg have been studied. • Kinetic parameters of the main peak are independent of dose (0.1–100 Gy). • Dose response of the main peak: 0.1–30 Gy, superlinear; 30–100 Gy, sublinear. • Fading of the main peak: ∼22% within 2400 s. • Reproducibility: coefficient of variation in the results of 10 re-cycles: >0.071%. - Abstract: The influence of dose (0.1–100 Gy) on the kinetic parameters and the dosimetric features of the main glow peak of α-Al{sub 2}O{sub 3}:C,Mg have been investigated. Thermoluminescence (TL) measured at 1 °C/s shows a very high intensity glow peak at 161 °C and six secondary peaks at 42, 72, 193, 279, 330, 370 °C respectively. Analysis shows that the main peak follows first order kinetics irrespective of the irradiation dose. The activation energy is found to be consistent at 1.37 eV and the frequency factor is of the order of 10{sup 14} s{sup −1} for any dose between 0.1 and 100 Gy. Further, the analysis for thermal quenching of the main peak of 0.1 Gy irradiated sample shows that the activation energy for thermal quenching is (0.94 ± 0.04) eV. Regarding the dosimetric features of α-Al{sub 2}O{sub 3}:C,Mg, the dose response of the main peak is superlinear within 0.1 to 30 Gy of beta dose and then it becomes sublinear up to 100 Gy. Fading analysis shows that the intensity of the main peak drops to ∼22% of its initial value within 2400 s after irradiation and thereafter to ∼14% within 64,800 s. Analysis of the reproducibility shows that the coefficient of variation in the results for 10 identical TL measurements show that reproducibility improves with increase in dose.

  12. Optimal Dose of Vitamin D3 400 I.U. for Average Adults has A Significant Anti-Cancer Effect, While Widely Used 2000 I.U. or Higher Promotes Cancer: Marked Reduction of Taurine & 1α, 25(OH)2D3 Was Found In Various Cancer Tissues and Oral Intake of Optimal Dose of Taurine 175mg for Average Adults, Rather Than 500mg, Was Found to Be A New Potentially Safe and More Effective Method of Cancer Treatment.

    Omura, Yoshiaki; Lu, Dominic; Jones, Marilyn K; Nihrane, Abdallah; Duvvi, Harsha; Yapor, Dario; Shimotsuura, Yasuhiro; Ohki, Motomu


    During the past 10 years, the author had found that the optimal dose of Vitamin D3 400 I.U. has safe & effective anticancer effects, while commonly used 2000-5000 I.U. of Vit. D3 often creates a 2-3 time increase in cancer markers. We examined the concentration of Taurine in normal internal organs and in cancer using Bi-Digital O-Ring Test. We found that Taurine levels in normal tissue are 4-6ng. But, the amount of Taurine of average normal value of 5.0-5.25ng was strikingly reduced to 0.0025-0.0028ng in this study of several examples in adenocarcinomas of the esophagus, stomach, pancreas, colon, prostate, and lung, as well as breast cancer. The lowest Taurine levels of 0.0002-0.0005ng were found in so called Zika virus infected babies from Brazil with microcephaly. While Vitamin D3 receptor stimulant 1α, 25 (OH)2D3 in normal tissues was 0.45-0.53ng, they were reduced to 0.025-0.006ng in cancers (1/100th-1/200th of normal value), particularly in various adenocarcinomas. All of these adenocarcinomas had about 1500ng HPV-16 viral infection. In 500 breast cancers, about 97% had HPV-16. The optimal dose of Taurine for average adult has been found to be about 175mg, rather than the widely used 500mg. In addition, since Taurine is markedly reduced to close to 1/1000th-1/2000th of its normal value in these cancer tissues, we examined the effect of the optimal dose of Taurine on cancer patients. Optimal dose of Taurine produced a very significant decrease in cancer-associated parameters, such as Oncogene C-fosAb2 & Integrin α5β1 being reduced to less than 1/1,000th, and 8-OH-dG (which increases in the presence of DNA mutation) reduced to less than 1/10th. The optimal dose of Taurine 175mg for average adult various cancer patient 3 times a day alone provide beneficial effects with very significant anti-cancer effects with strikingly increased urinary excretion of bacteria, viruses, & funguses, asbestos, toxic metals & other toxic substances. However, optimal doses of

  13. Impact of cytochrome P450 3A4-metabolized statins on the antiplatelet effect of a 600-mg loading dose clopidogrel and on clinical outcome in patients undergoing elective coronary stent placement.

    Trenk, Dietmar; Hochholzer, Willibald; Frundi, Devine; Stratz, Christian; Valina, Christian M; Bestehorn, Hans-Peter; Büttner, Heinz Joachim; Neumann, Franz-Josef


    Early studies suggested interactions between statins and clopidogrel. Based on the outcome and platelet data, there is now huge evidence of no interactions between statins and 75 to 300 mg clopidogrel; however, data with 600-mg loading are lacking. In a pre-specified analysis of the EXCELSIOR cohort, we investigated the interaction between statins, especially cytochrome P4503A4-metabolized atorvastatin and simvastatin, and the antiplatelet effects of a 600-mg loading dose of clopidogrel. We analyzed 1,395 patients scheduled for coronary angiography (CA). Patients received clopidogrel 600 mg at least two hours before CA and 75 mg daily thereafter in case of percutaneous coronary intervention (PCI). Statin medication on admission was continued unaltered until discharge. Platelet function was assessed by optical aggregometry and flow cytometry of adenosine diphosphate (ADP)-stimulated surface expression of CD62P, CD63 and PAC-1 before clopidogrel and immediately before CA. Residual platelet aggregation (RPA) after addition of ADP 5 muM was similar irrespective of statin treatment at baseline (p = 0.968). RPA at CA was 46.2 +/- 16.8% in patients without statin (n = 682), 45.5 +/- 17.0% in patients with atorvastatin (n = 255), 45.8 +/- 16.3% with simvastatin (n = 335), 47.3 +/- 14.9% with fluvastatin (n = 42) and 45.9 +/- 16.2% with pravastatin (n = 81; p = 0.962). Consistent results were obtained by flow cytometry. In patients with PCI (n = 553), the one-year incidence of death, myocardial infarction and target lesion reintervention did not differ between cohorts stratified according to statin co-medication (p = 0.645). Thus, peri-interventional atorvastatin and simvastatin had no effect on the antiplatelet activity of a loading dose of clopidogrel 600 mg and did not affect clinical outcome after PCI.


    I.Sarath chandiran


    Full Text Available This bioequivalence study was designed to determine the pharmacokinetic, bioavailability and bioequivalence of Venlafaxine HCl 150 mg Extended Release Capsules in comparison with Effexor®-XR 150mg Extended Release Capsules after single dose administration under fed conditions in 20 healthy adult male subjects. Therefore the design of an open label, balanced, randomized, two-sequence, single dose, two way crossover study with a washout period of at least 7 days was used.Each volunteer received a 150 mg capsule of the reference or test drug respectively. On the day of dosing, blood samples were collected before dosing and at various time points up to 72 hours after dosing. Analysis of venlafaxine and its metabolite O-Desmethylvenlafaxine concentrations was performed using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS method. The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2 and Kel were analyzed using the non-compartmental model. Drug safety and tolerability were assessed.The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2 and Kel were analyzed using the non-compartmental model. Drug safety and tolerability were assessed. The primary pharmacokinetic parameters (Cmax, AUC0-t and AUC0-inf 90%CI were within the 80 to 125% interval required for bioequivalence as stipulated in the current regulations of the USFDA acceptance criteria. The geometric mean ratios (Test/Reference between the two products of extended-release venlafaxine capsule under fed condition were 104.91% (92.86%-118.53% and 114.41% (103.43%-124.55% for Cmax ratios, 102.24% (95.95%-108.94% and 105.27% (96.76%-114.53% for AUC0-t ratios and 101.66% (95.73%-107.97% and 104.71% (96.13%-114.05% for AUC0-inf ratios of Venlafaxine and its metabolite O-Desmethylvenlafaxine (ODV respectively. 20 volunteers had completed both treatment periods. There was no significant difference of the Tmax parameter between the two

  15. Experimental determination of the photon-energy dependent dose-to-water response of TLD600 and TLD700 (LiF:Mg,Ti) thermoluminescence detectors

    Schwahofer, Andrea [Vivantes Clinic Neukoelln, Berlin (Germany). Dept. of Radiation Therapy; German Cancer Research Center, Heidelberg (Germany). Medical Physics in Radiation Therapy; Feist, Harald [Munich Univ. (Germany). Dept. of Radiation Therapy; Georg, Holger [PTW Freiburg (Germany). Calibration Lab.; Haering, Peter; Schlegel, Wolfgang [German Cancer Research Center, Heidelberg (Germany). Medical Physics in Radiation Therapy


    The aim of this study has been the experimental determination of the energy dependent dose-to-water response of TLD600 and TLD700 thermoluminescent detectors (Harshaw) in X-ray beams with mean photon energies from about 20 to 200 keV in comparison with {sup 60}Co gamma rays and 6 MV X-rays. Experiments were carried out in collaboration with the German secondary standard laboratory PTW Freiburg. The energy dependent relative responses of TLD600 and TLD700 thermoluminescence detectors were determined at radiation qualities between 30 kV{sub p} and 280 kV{sub p}. The overall uncertainty of the measured values was characterized by standard deviations varying from 1.2 to 3%. The present results agree with previous studies on the energy dependent dose-to-water response of TLD100. As an application example, the results were used to measure doses associated with X-ray imaging in image-guided radiotherapy.

  16. Time to onset of analgesia and analgesic efficacy of effervescent acetaminophen 1000 mg compared to tablet acetaminophen 1000 mg in postoperative dental pain: a single-dose, double-blind, randomized, placebo-controlled study.

    Møller, P L; Nørholt, S E; Ganry, H E; Insuasty, J H; Vincent, F G; Skoglund, L A; Sindet-Pedersen, S


    This randomized, double-blind, placebo-controlled study compared the time to onset of analgesia and the analgesic efficacy of two formulations of acetaminophen 1000 mg--an effervescent solution and tablet--in 242 patients with moderate or severe pain following dental surgery. Onset of analgesia was determined using a two-stopwatch procedure. Analgesia was assessed over a 4-hour period. Treatments were compared using standard indexes of pain intensity and pain relief and summary measures. Both acetaminophen formulations were significantly more effective than their corresponding placebo for all efficacy assessments. The median time to onset of analgesia was significantly shorter with effervescent acetaminophen (20 minutes) compared to tablet acetaminophen (45 minutes). During the first 45 minutes after administration, effervescent acetaminophen was significantly more effective at each scheduled assessment time than tablet acetaminophen. The median time to meaningful pain relief was significantly shorter with effervescent acetaminophen (45 minutes) compared to tablet acetaminophen (60 minutes). At 4 hours after administration, the pain relief was significantly better with tablet acetaminophen than with effervescent acetaminophen. No other significant differences were observed between the active treatments. In conclusion, effervescent acetaminophen produces a significantly faster onset of analgesia than tablet acetaminophen.

  17. Sustained biochemical control in patients with acromegaly treated with lanreotide depot 120 mg administered every 4 weeks, or an extended dosing interval of 6 or 8 weeks: a pharmacokinetic approach

    Gomez-Panzani E


    Full Text Available Edda Gomez-Panzani,1 Stephen Chang,1 Joaquim Ramis,2 Michelle M Landolfi,1 Bert Bakker11Ipsen Biopharmaceuticals, Inc, Basking Ridge, New Jersey, USA; 2Ipsen Innovation SAS, Pharmacokinetic and Drug Metabolism, Les Ulis, FranceObjective: Lanreotide depot is a long-acting somatostatin receptor ligand injected deep subcutaneously every 4 weeks for the treatment of acromegaly. The aim of the presented studies was to establish whether lanreotide depot, administered to patients with acromegaly at an extended dosing interval of 6 or 8 weeks, is effective in maintaining appropriate serum growth hormone (GH and insulin-like growth factor-1 (IGF-1 levels, with acceptable tolerability.Methods: Two studies were conducted. Study B1 compared lanreotide depot 120 mg (every 4, 6, or 8 weeks with lanreotide microparticle formulation 30 mg (every 7, 10, or 14 days in 98 patients who had a GH level of ≤2.5 ng/mL and normalized IGF-1. Study B2 evaluated lanreotide depot 120 mg administered to 64 patients every 8 weeks, after which the dosing interval was adjusted based on GH levels.Results: Mean lanreotide trough serum concentrations at steady state for all dosing intervals were >1.13 ng/mL, shown to achieve a GH level of ≤2.5 ng/mL. In Study B1, following treatment with lanreotide depot given every 6 or 8 weeks, 87.5% and 93.9% of patients, respectively, had normalized GH, whereas 83.3% and 88.5% of patients, respectively, had both normalized GH and IGF-1. In Study B2, 88.9% had normalized GH and 42.9% of patients had normalized GH and IGF-1 following lanreotide depot every 8 weeks. Gastrointestinal disorders, generally mild/moderate in severity, were the most common adverse events.Conclusion: In the studies presented, lanreotide depot 120 mg every 4, 6, or 8 weeks provided effective hormonal control with acceptable safety. An extended dosing interval is a feasible approach for patients adequately controlled with lanreotide depot 60 or 90 mg every 4 weeks

  18. In vitro combined effect of co-amoxiclav concentrations achievable in serum after a 2000/125 mg oral dose, and polymorphonuclear neutrophils against strains of Streptococcus pneumoniae exhibiting decreased susceptibility to amoxicillin.

    Amores, Raquel; Alou, Luis; Giménez, María José; Sevillano, David; Gómez-Lus, María Luisa; Aguilar, Lorenzo; Prieto, José


    The in vitro effect that the presence of components of non-specific immunity (serum plus polymorphonuclear neutrophils) has on the bactericidal activity of co-amoxiclav was explored against Streptococcus pneumoniae strains exhibiting an amoxicillin MIC > or =4 mg/L. Eight penicillin-resistant clinical isolates non-susceptible to co-amoxiclav with MICs of 4 (two strains), 8 (four strains) and 16 mg/L (two strains) were used. Values of MBC were identical to MIC values in all cases. Time-kill curves were performed with co-amoxiclav concentrations achievable in serum after a single oral dose administration of the new 2000/125 mg sustained-release formulation. Results were expressed as percentage of reduction of initial inocula after 3 h incubation. Control curves showed growth with no reduction of initial inocula. Against strains with MIC of 4 and 8 mg/L, the results obtained with the antibiotic alone or with the presence of factors of non-specific immunity were similar, with a weak combined effect due to the intrinsic activity of co-amoxiclav (reductions of initial inocula ranging from 70 to 99.16%). Against strains with MIC of 16 mg/L, the addition of PMN in the presence of serum increased the reduction of bacterial load provided by the aminopenicillin, even at sub-inhibitory concentrations (25.8% versus 51.1% at 0.5 x MIC concentration--8/0.5 mg/L). This combined activity against strains with an amoxicillin MIC of 16 mg/L which decreased the bacterial load may be important in preventing bacterial proliferation within the host and the transmission of resistant clones to others.

  19. A 0.18 micrometer CMOS Thermopile Readout ASIC Immune to 50 MRAD Total Ionizing Dose (SI) and Single Event Latchup to 174MeV-cm(exp 2)/mg

    Quilligan, Gerard T.; Aslam, Shahid; Lakew, Brook; DuMonthier, Jeffery J.; Katz, Richard B.; Kleyner, Igor


    Radiation hardened by design (RHBD) techniques allow commercial CMOS circuits to operate in high total ionizing dose and particle fluence environments. Our radiation hard multi-channel digitizer (MCD) ASIC (Figure 1) is a versatile analog system on a chip (SoC) fabricated in 180nm CMOS. It provides 18 chopper stabilized amplifier channels, a 16- bit sigma-delta analog-digital converter (SDADC) and an on-chip controller. The MCD was evaluated at Goddard Space Flight Center and Texas A&M University's radiation effects facilities and found to be immune to single event latchup (SEL) and total ionizing dose (TID) at 174 MeV-cm(exp 2)/mg and 50 Mrad (Si) respectively.

  20. Risk of bladder cancer among patients with diabetes treated with a 15 mg pioglitazone dose in Korea: a multi-center retrospective cohort study.

    Jin, Sang-Man; Song, Sun Ok; Jung, Chang Hee; Chang, Jin-Sun; Suh, Sunghwan; Kang, Seung Min; Jung, Inkyung; Park, Cheol-Young; Kim, Jae Hyeon; Cho, Jae Hyoung; Lee, Byung-Wan


    It has not yet been determined whether chronic exposure to relatively low doses of pioglitazone increases risk of bladder cancer. We aimed to assess the risk of bladder cancer associated with pioglitazone in Korean patients. This was a retrospective cohort study of diabetic patients who had ≥ 2 clinic visits between November 2005 and June 2011 at one of four tertiary referral hospitals in Korea. A prevalent case-control analysis nested within the cohort was conducted to further adjust confounders. A total of 101,953 control patients and 11,240 pioglitazone-treated patients were included, in which there were 237 and 30 cases of incidental bladder cancer (64.9 and 54.9 per 100,000 person-years; age, sex-adjusted HR 1.135, 95% confidence interval [CI] 0.769-1.677), respectively. In the prevalent case-control analysis nested within the cohort, use of pioglitazone for a duration of > 6 months, but not ever use of pioglitazone, was associated with an increased rate of bladder cancer as compared to never use of pioglitazone. In conclusion, we failed to exclude the possible association between use of pioglitazone for a duration of > 6 months and bladder cancer.

  1. Estudio teorico de las interacciones de dos modelos de ácidos húmicos con los cationes Al3+, Ca2+, Mg2+, Zn2+, K+ y NH4+ a un nivel de calculo DFT y un modelo de solvatación PCM

    Eduardo Espinosa-Fuentes

    Full Text Available In this paper, two models of humic acids, the Temple-Northeastern-Birmingham (TNB and Kolla models, were studied. Also, the complexation reaction of the structures formed by the interaction of the TNB and Kolla models with Al3+, Ca2+, Mg2+, Zn2+, K+ and NH4+ cations, common in agricultural soils, was studied. These calculations were made for the complexes, at PM6 and DFT / LANL2DZ level of theory, both in vacuum and in aqueous medium. We found a strong affinity between Kolla and TNB models, and Al3+, Ca2+, Mg2+, Zn2+, K+ and NH4+ cations, influenced by the solvent that affected the interaction sites; the solvent increased the rate of reactivity and affinity for the cations in nucleophilic regions and decreased it in electrophilic regions of the structures. Calculations of molecular electronic potential, MEP and atomic charges, the local smoothness, Fukui functions and the HSAB principle adequately described the HA/cations interactions which were affected by the number of hydrogen bonds. The most reactive sites were the hydroxyl, phenolic, carbonyls oxygens and nitrogens at both vacuum and aqueous medium, especially carbonyl oxygens. These results are consistent with the properties of HA that make them attractive as components of agricultural soils.

  2. Clinical trial: a novel high-dose 1 g mesalamine suppository (Salofalk) once daily is as efficacious as a 500-mg suppository thrice daily in active ulcerative proctitis.

    Andus, Tilo; Kocjan, Andreas; Müser, Moritz; Baranovsky, Andrey; Mikhailova, Tatyana L; Zvyagintseva, Tatyana D; Dorofeyev, Andrey E; Lozynskyy, Yurii S; Cascorbi, Ingolf; Stolte, Manfred; Vieth, Michael; Dilger, Karin; Mohrbacher, Ralf; Greinwald, Roland


    Mesalamine suppositories are first-line therapy in active ulcerative proctitis; the standard regime still recommends multiple doses per day. The primary objective of this study was to show the noninferiority of once-daily administration of a novel 1 g mesalamine suppository versus thrice-daily administration of the 0.5 g mesalamine suppository. This was a single-blind (investigator-blinded), randomized, multicenter, comparative, Phase III clinical trial. Patients with mild to moderately active ulcerative proctitis inserted either one mesalamine 1 g suppository at bedtime or one mesalamine 0.5 g suppository thrice daily over a 6-week period. The primary endpoint was rate of remission (Disease Activity Index below 4). In all, 354 patients were evaluable for safety and per-protocol analysis. The new regimen demonstrated noninferiority: The percentage of patients with remission was 87.9% for the once-daily 1 g mesalamine suppository and 90.7% for the thrice-daily 0.5 g mesalamine suppository. Each regimen resulted in prompt cessation of clinical symptoms (e.g., median time to ≤3 stools per day (all without blood): 5 days in the 1 g mesalamine once-daily and 7 days in the 0.5 g mesalamine thrice-daily group). Patients preferred applying suppositories once a day. In active ulcerative proctitis the once-daily administration of a 1 g mesalamine suppository is as effective and safe, yet considerably more convenient, than the standard thrice-daily administration of a 0.5 g mesalamine suppository.

  3. Relative bioavailability of two formulations of nevirapine 200-mg tablets in healthy Chinese male volunteers: a single-dose, randomized-sequence, open-label, two-way crossover study.

    Zhu, Yubing; Zhang, Qian; Yu, Cuixia; Zou, Jianjun; Yang, Xiaohong; Hu, Yunfang


    Nevirapine was the first member of the nonnucleoside reverse transcriptase inhibitor class to be approved for the treatment of HIV infection. It binds directly to the allosteric site on the reverse transcriptase and inhibits the activity of both RNA- and DNA-dependent DNA polymerases. This study compared the pharmacokinetics and relative bioavailability of a test and reference formulation of nevirapine 200-mg tablets after single oral doses in healthy Chinese men to meet regulatory criteria for marketing of the new generic formulation. This single-dose, randomized-sequence, open-label, 2-way crossover study was conducted at the Nanjing First Hospital of Nanjing Medical University, Nanjing, China. Healthy male Chinese volunteers were randomized in a 1∶1 ratio to receive a single 200-mg (3.2-mg/kg) tablet of the test or reference formulation, followed by a 2-week washout period and administration of the alternate formulation. The study drugs were administered after a 10-hour overnight fast. Concentrations of nevirapine were assayed using an HPLC-UV method. For analysis of nevirapine pharmacokinetic parameters, blood samples were obtained before dosing and at regularly scheduled intervals over 168 hours after administration. The 2 formulations would be assumed to be bioequivalent for regulatory purposes if the 90% CIs for the log-transformed ratios of nevirapine AUC and C(max) were within the range established by the US Food and Drug Administration (0.80-1.25). Tolerability was evaluated throughout the study based on vital signs, physical examinations, 12-lead ECGs, and subject interviews concerning adverse events (AEs). Twenty Chinese male subjects were enrolled in and completed the study. Their mean age was 23 years (range, 21-25 years), mean weight was 63 kg (range, 56-70 kg), and mean height was 171 cm (range, 166-176 cm). No period or sequence effect was observed. The mean (SD) t(½) was 38.12 (2.23) hours for the test tablet and 36.79 (5.06) hours for the

  4. Emergence of hyper-resistant Escherichia coli MG1655 derivative strains after applying sub-inhibitory doses of individual constituents of essential oils

    Beatriz eChueca


    Full Text Available The improvement of food preservation by using essential oils (EOs and their individual constituents (ICs is attracting enormous interest worldwide. Until now, researchers considered that treatments with such antimicrobial compounds did not induce bacterial resistance via a phenotypic (i.e. transient response. Nevertheless, the emergence of genotypic (i.e. stable resistance after treatment with these compounds had not been previously tested. Our results confirm that growth of Escherichia coli MG1655 in presence of sub-inhibitory concentrations of the ICs carvacrol, citral, and (+-limonene oxide do not increase resistance to further treatments with either the same IC (direct resistance or with other preservation treatments (cross-resistance such as heat or pulsed electric fields (PEF. Bacterial mutation frequency was likewise lower when those IC’s were applied; however, after 10 days of re-culturing cells in presence of sub-inhibitory concentrations of the ICs, we were able to isolate several derivative strains (i.e. mutants displaying an increased minimum inhibitory concentration to those ICs. Furthermore, when compared to the wild type (WT strain, they also displayed direct resistance and cross-resistance. Derivative strains selected with carvacrol and citral also displayed morphological changes involving filamentation along with cell counts at late-stationary growth phase that were lower than the WT strain. In addition, co-cultures of each derivative strain with the WT strain resulted in a predominance of the original strain in absence of ICs, indicating that mutants would not out-compete WT cells under optimal growth conditions. Nevertheless, growth in the presence of ICs facilitated the selection of these resistant mutants. Thus, as a result, subsequent food preservation treatments of these bacterial cultures might be less effective than expected for WT cultures. In conclusion, this study recommends that treatment with ICs at sub

  5. Adding a single low-dose of primaquine (0.25 mg/kg) to artemether-lumefantrine did not compromise treatment outcome of uncomplicated Plasmodium falciparum malaria in Tanzania: a randomized, single-blinded clinical trial.

    Mwaiswelo, Richard; Ngasala, Billy; Jovel, Irina; Aydin-Schmidt, Berit; Gosling, Roland; Premji, Zul; Mmbando, Bruno; Björkman, Anders; Mårtensson, Andreas


    The World Health Organization (WHO) recently recommended the addition of a single low-dose of the gametocytocidal drug primaquine (PQ) to artemisinin-based combination therapy (ACT) in low transmission settings as a component of pre-elimination or elimination programmes. However, it is unclear whether that influences the ACT cure rate. The study assessed treatment outcome of artemether-lumefantrine (AL) plus a single PQ dose (0.25 mg/kg) versus standard AL regimen for treatment of acute uncomplicated Plasmodium falciparum malaria in Tanzania. A randomized, single-blinded, clinical trial was conducted in Yombo, Bagamoyo district, Tanzania. Acute uncomplicated P. falciparum malaria patients aged ≥1 year, with the exception of pregnant and lactating women, were enrolled and treated with AL plus a single PQ dose (0.25 mg/kg) or AL alone under supervision. PQ was administered together with the first AL dose. Clinical and laboratory assessments were performed at 0, 8, 24, 36, 48, 60, and 72 h and on days 7, 14, 21, and 28. The primary end-point was a polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) on day 28. Secondary outcomes included: fever and asexual parasitaemia clearance, proportion of patients with PCR-determined parasitaemia on day 3, and proportion of patients with Pfmdr1 N86Y and Pfcrt K76T on days 0, 3 and day of recurrent infection. Overall 220 patients were enrolled, 110 were allocated AL + PQ and AL, respectively. Parasite clearance by microscopy was fast, but PCR detectable parasitaemia on day 3 was 31/109 (28.4 %) and 29/108 (26.9 %) in patients treated with AL + PQ and AL, respectively (p = 0.79). Day 28 PCR-adjusted ACPR and re-infection rate was 105/105 (100 %) and 101/102 (99 %) (p = 0.31), and 5/107 (4.7 %) and 5/8 (4.8 %) (p = 0.95), in AL + PQ and AL arm, respectively. There was neither any statistically significant difference in the proportion of Pfmdr1 N86Y or Pfcrt K76T

  6. Double-blind controlled trial of a single dose of the combination ivermectin 400 micrograms/kg plus diethylcarbamazine 6 mg/kg for the treatment of bancroftian filariasis: results at six months.

    Glaziou, P; Moulia-Pelat, J P; Nguyen, L N; Chanteau, S; Martin, P M; Cartel, J L


    In 1993, a three-arm double-blind controlled trial was implemented in French Polynesia to compare the tolerance and efficacy of a single dose of the combination ivermectin (IVR) 400 micrograms/kg plus diethylcarbamazine (DEC) 6 mg/kg vs. IVR 400 micrograms/kg alone vs. DEC 6 mg/kg alone, for treatment of Wuchereria bancrofti carriers. Of the 57 treated male patients in whom microfilaria (mf) densities ranged from 22 to 4709 mg/mL, 3 groups of 19 were randomly selected and allocated to one of the 3 treatments. Side effects were experienced by 34 patients (60%), but none suffered a severe reaction. Grade of reaction did not differ between treatment group, but was significantly correlated with the pretreatment mf density. Six months after treatment, 26%, 32% and 53% of patients were amicrofilaraemic in the DEC, IVR and IVR+DEC groups, respectively. Mf levels were 6.3%, and 3.1% and 1.0% of the pretreatment level, respectively, significantly lower in the IVR+DEC group than in both the IVR and DEC comparison groups. The combination IVR+DEC showed promise in term of sustained mf decrease, and could be an effective alternative for lymphatic filariasis control programmes.

  7. Stability of Vancomycin 25 mg/mL in Ora-Sweet and Water in Unit-Dose Cups and Plastic Bottles at 4°C and 25°C.

    Ensom, Mary H H; Decarie, Diane; Lakhani, Anisha


    Solutions of vancomycin for oral administration are not available commercially in Canada or the United States but are needed for patients who cannot swallow capsules. To evaluate the stability of vancomycin solutions stored in unit-dose cups and plastic bottles under refrigeration (4°C) and at room temperature (25°C) for up to 75 days. Vancomycin 25 mg/mL in Ora-Sweet vehicle and water (1:1 ratio by volume) was dispensed into opaque blue polyethylene unit-dose cups with aluminum seal (14 replicates) or amber plastic prescription bottles (6 replicates). Seven cups and 3 bottles were refrigerated (4°C), and the remainder of the containers were stored at room temperature (25°C). At the time of preparation and at 15, 30, 40, 50, 63, and 75 days, 3 aliquots were collected from one of the cups and from every bottle and were stored frozen (-85°C) until the time of analysis. Physical characteristics were evaluated at each time point, including measurement of pH and visual assessment of colour and precipitation. After thawing, the samples were analyzed in triplicate by a validated stability-indicating high-performance liquid chromatography method. A solution was considered stable if 90% of the initial concentration of vancomycin was maintained. No notable changes in colour, taste, or pH were observed in vancomycin solutions stored in the unit-dose cups at 4°C or 25°C or in the plastic bottles stored at 4°C over the 75-day study period. Starting on day 63, a white precipitate was observed in the solutions stored in plastic bottles at 25°C, but there were no notable changes in taste or pH during the 75-day period. The 95% confidence interval of the slope of the curve relating concentration to time, determined by linear regression, indicated that vancomycin solutions stored in cups or bottles at 4°C would maintain at least 93.6% of the initial vancomycin concentration for 75 days and that solutions stored at 25°C would maintain at least 90.0% of the initial

  8. Open-label, 2-period sequential drug interaction study to evaluate the effect of a 100-mg dose of desvenlafaxine on the pharmacokinetics of tamoxifen when coadministered in healthy postmenopausal female subjects.

    Nichols, Alice I; Lubaczewski, Shannon; Liang, Yali; Matschke, Kyle; Braley, Gabriel; Ramey, Tanya


    Potential drugdrug interactions are a concern for patients taking tamoxifen. This study was designed to determine the effect of coadministering desvenlafaxine on tamoxifen pharmacokinetics. This open-label, 2-period inpatient and outpatient study enrolled healthy, postmenopausal women. Period 1, day 1, subjects were administered tamoxifen 40 mg followed by 23 days of blood sampling for pharmacokinetic analyses. During period 2, subjects received desvenlafaxine 100 mg/d for 28 days; a single dose of tamoxifen 40 mg was administered with desvenlafaxine 100 mg on day 7, followed by 23 days of blood sampling. Pharmacokinetics of tamoxifen and its metabolites (AUC over infinite time (AUC(inf)), AUC to the last measurable concentration (AUC(last)), peak plasma concentration (C(max)) were compared for monotherapy vs. combination therapy using the ratio of adjusted mean differences. A superposition method was used in the statistical analysis of N-desmethyl-tamoxifen and endoxifen to address the carry-over observed for those metabolites. The test for interaction was considered negative if the 90% confidence intervals (CIs) for the ratios were within 80 - 125%. Coadministration of tamoxifen with steady-state desvenlafaxine did not alter tamoxifen AUC(inf), AUC(last), and C(max), as reflected by the ratio of adjusted geometric means (90% CIs) of 100.7% (96.7%, 104.9%), 103.5% (100.2%, 106.9%), and 99.4% (94.0%, 105.2%), respectively. Similarly, coadministration did not alter 4-hydroxy- tamoxifen and N-desmethyl-amoxifen pharmacokinetics. The 11.8% (88.2% (82.6%, 94.2%)) and 8.0% (92.0% (84.7%, 100.0%)) decreases in endoxifen AUC(last) and C(max), respectively, were not significant (90% CIs fell wholly within the prespecified acceptance range). Steady-state desvenlafaxine 100 mg did not affect tamoxifen pharmacokinetics. For women treated with tamoxifen, desvenlafaxine may represent a safe and effective treatment unlikely to alter tamoxifen efficacy.


    Thuraganur Kapanigowda


    Full Text Available AIMS AND OBJECTIVES Saddle block anaesthesia is most commonly used technique for perineal surgeries, i.e. haemorrhoids, fissure-in-ano, etc., as it is most economical and easy to administer. Spinal anaesthesia by bupivacaine may be too short for providing postoperative analgesia. Hence, various adjuvants have been used with Local anaesthetics to provide good intraoperative anaesthesia and to prolong postoperative analgesia. The aim of our study was to evaluate the effects of intrathecal administration of dexmedetomidine 10 µg on low dose bupivacaine 0.5% (5 mg, to know the onset and duration of sensory and motor blockade, the haemodynamic effects, duration of analgesia and the occurrence of side effects. METHODOLOGY This prospective randomized double blind study included 60 patients. Patients were randomly allocated into two groups of 30 patients each. Group D received 5 mg of 0.5% hyperbaric with dexmedetomidine 10 µg (0.5 mL and Group N received 5 mg of 0.5% hyperbaric bupivacaine with 0.5 mL of normal saline. The onset of sensory and motor block, haemodynamic effects, duration of analgesia and occurrence of side effects were noted. RESULTS The mean time taken for the onset of sensory block was 6.36±1.2 min and 8.23±1.7 significantly rapid with D Group compared to group N. The total duration of analgesia (360±15 min and 210±30 min in Group D and Group N respectively, P <0.000 and time to first rescue analgesic (370.85±15 min, 230.8±15 min in Group D and Group N respectively, P <0.001 were increased significantly by addition of dexmedetomidine without significant motor block and with minimal side effects. CONCLUSION Dexmedetomidine added intrathecally for saddle block had favourable effects on onset of sensory and total duration of analgesia and rescue analgesia.

  10. Estudo comparativo da eficácia de isotionato de pentamidina administrada em três doses durante uma semana e de N-metil-glucamina 20mgSbV/kg/dia durante 20 dias para o tratamento da forma cutânea da leishmaniose tegumentar americana A comparative study between the efficacy of pentamidine isothionate given in three doses for one week and N-methil-glucamine in a dose of 20mgSbV/day for 20 days to treat cutaneous leishmaniasis

    Carmen Déa Ribeiro de Paula


    Full Text Available Setenta e nove pacientes com leishmaniose tegumentar americana, forma cutânea, foram divididos em dois grupos: o grupo experimental (I, formado por 38 pessoas que receberam isotionato de pentamidina, 4mg/kg/dia, três aplicações, IM, durante uma semana, e o grupo controle (II, formado por 41 doentes tratados com N-metilglucamina, 20mgSbV/kg/dia por 20 dias, EV. Foram identificados, por técnica de anticorpos monoclonais, 21 isolados com predominância de Leishmania (Viannia braziliensis. Encontrou-se cura clínica em 71,05% do grupo experimental e 73,17% do grupo controle (p=0,47. Alterações de ECG foram mais freqüentes utilizando antimonial pentavalente, com significância (pSeventy-nine patients with cutaneous leishmaniasis were included in this study. The experimental group (n = 38 was treated with pentamidine isothionate in a dose of 4mg/kg/day on alternate days, for one week. The control group (n = 41 was treated with N-methylglucamine in a dose of 20mgSbV/kg/day for 20 days. Twenty-one isolates were identified using monoclonal antibody technique. We characterized Leishmania (Viannia braziliensis, most frequently. There was a cure rate of 71.05% of the patients in the experimental group and 73.17% in the control group (p = 0.47.We found a statistical significance regarding frequency of ECG alterations between the experimental and control group (p<0.05. In our study pentamidine was as effective as antimonial for the treatment of american cutaneous leishmaniasis. It proved to be a safer drug considering heart toxicity. Moreover, it requires less time to complete the treatment.

  11. Comparison of rizatriptan 5 mg and 10 mg tablets and sumatriptan 25 mg and 50 mg tablets.

    Kolodny, A; Polis, A; Battisti, W P; Johnson-Pratt, L; Skobieranda, F


    This randomized, double-blind, two-attack, placebo-controlled, crossover study explored the efficacy and tolerability of rizatriptan 10 mg compared with sumatriptan 50 mg as well as rizatriptan 5 mg compared with sumatriptan 25 mg in the acute treatment of migraine. Following randomization to one of six possible treatment sequences, patients (n = 1447) treated two sequential attacks, of moderate or severe intensity, separated by at least 5 days. Patients assessed pain severity, migraine-associated symptoms, and functional disability at 0.5, 1, 1.5, and 2 h post treatment. Compared with placebo, all treatments were effective. On the primary endpoint of time to pain relief, rizatriptan 10 mg was not statistically different from sumatriptan 50 mg [odds ratio (OR) 1.10, P = 0.161], and rizatriptan 5 mg was statistically superior to sumatriptan 25 mg (OR 1.22, P = 0.007). In general, rizatriptan 10 mg and 5 mg treatment resulted in improvement compared with the corresponding doses of sumatriptan on measures of pain severity, migraine symptoms, and functional disability and the 5-mg dose reached statistical significance on almost all measures. All treatments were generally well tolerated.

  12. Quantification of Niacin and Its Metabolite Nicotinuric Acid in Human Plasma by LC-MS/MS: Application to a Clinical Trial of a Fixed Dose Combination Tablet of Niacin Extended-Release/Simvastatin (500 mg/10 mg in Healthy Chinese Volunteers

    Pingping Zhang


    Full Text Available Our paper aimed to develop rapid, sensitive, and specific LC-MS/MS method for the quantification of niacin (NA and its metabolite nicotinuric acid (NUA in human plasma. Following protein precipitation with acetonitrile, the NA, NUA, and internal standard (5-fluorouracil were separated on a Zorbax 300SB-C8 column (250 mm × 4.6 mm, 5 μm with a mobile phase consisting of methanol-2 mM ammonium acetate (3 : 97, v/v at a flow rate of 1 mL/min (split 1 : 1. A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated in negative ion mode. The linear concentration ranges of the calibration curves were 5–800 ng/mL for NA and NUA. The intra-assay RSD for quality control (QC samples were from 5.0% to 8.7% for NA, and 5.5% to 7.6% for NUA. The interassay RSD for QC samples were from 2.8% to 9.4% for NA, and 3.7% to 5.8% for NUA. The relative errors for QC samples were from −2.2% to 2.3% for NA, and −0.6% to 3.2% for NUA. The method was successfully applied to the investigation of the pharmacokinetic profiles of NA, NUA in human after single dose administration of Niacin extended-release/Simvastatin tablet (500 mg/10 mg.

  13. Milnacipran and venlafaxine at flexible doses (up to 200 mg/day in the outpatient treatment of adults with moderate-to-severe major depressive disorder: a 24-week randomized, double-blind exploratory study

    Jean-Pierre Olié


    Full Text Available Jean-Pierre Olié1, David Gourion2, Agnès Montagne3, Michel Rostin4, Marie-France Poirier11Service de Santé Mentale et Thérapeutique, Centre Hospitalier Sainte-Anne, Paris, France; 217 rue des Marronniers, 75016 Paris, France; 3Pierre Fabre Médicament, Labège, France; 4Pierre Fabre Médicament, Castres, FranceAbstract: The objective of this exploratory, multicenter, randomized, double-blind study, was to evaluate the efficacy and safety/tolerability of milnacipran and venlafaxine administered at flexible doses (100, 150 or 200 mg/day, bid administration for 24 weeks (including 4 weeks up titration period in the outpatient treatment of adults presenting with a moderate or severe episode of major depressive disorder (MDD without high suicidal risk (MINI-DSM IV-TR. Of the 195 patients included, 134 (68.7% completed the study. At baseline the two groups were similar, except there was a higher proportion of patients whose episode was severe-DSM IV in the milnacipran group (63.3% versus 54.0% in the venlafaxine group. The initial MADRS score (mean 31.0 decreased progressively during the study, and this decrease was in the two treatment groups (n = 177: 90 milnacipran; 87 venlafaxine at week 24 (observed case/OC, mean change –23.1 milnacipran; –22.4 venlafaxine. The rate of MADRS response (reduction ≥ 50% at week 8 and week 24-last observation carried forward/LOCF was similar in the two groups (week 8: 64.4% milnacipran; 65.5% venlafaxine; week 24: 70% milnacipran; 77% venlafaxine, as was the rate of MADRS remission (score ≤ 10 (week 8: 42.2% milnacipran; 42.5% venlafaxine; week 24: 52.2% milnacipran; 62.1% venlafaxine. In both groups, the most common adverse events were: nausea, dizziness, headache, hyperhidrosis and, in males, genito-urinary problems. The overall safety/tolerability and efficacy profiles of milnacipran and venlafaxine administered at flexible dosages (up to 200 mg/day were similar in the long term treatment of adults

  14. Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: a randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers.

    Parrillo-Campiglia, Susana; Ercoli, Mónica Cedres; Umpierrez, Ofelia; Rodríguez, Patricia; Márquez, Sara; Guarneri, Carolina; Estevez-Parrillo, Francisco T; Laurenz, Marilena; Estevez-Carrizo, Francisco E


    Imatinib is a tyrosine kinase inhibitor that has been established as a highly effective therapy for chronic myelogenous leukemia and gastrointestinal stromal tumors. A new generic, once-daily 400-mg tablet of imatinib has been developed by a pharmaceutical company in Argentina, where the regulatory standard for marketing authorization of an imatinib generic is in vitro dissolution testing. The aim of this study was to assess the bioequivalence of a new generic film-coated test tablet formulation versus a film-coated reference tablet formulation of imatinib 400 mg. The local manufacturer seeks to validate the in vitro performance of this new formulation with a bioequivalence study. A randomized, open-label, single-dose, fasting, 2-period, 2-sequence crossover design with a 2-week washout period was used in this study. The study population consisted of healthy male South American (Uruguayan) volunteers, who were assigned in a 1:1 ratio to a randomized sequence (test-reference or reference-test). In each period, the test or reference formulation was administered after an overnight fast. During the 72-hour follow-up period, participants were monitored for vital signs and symptoms. Blood samples were collected at 15 time points, including baseline, until 72 hours. Physical examination and laboratory tests (blood, urine) were repeated 1 week after study completion. A noncompartmental model was used to determine the pharmacokinetic parameters of imatinib. The 90% CIs of the test/reference ratios for AUC(0-infinity) and C(max) were determined; the test and reference formulations were considered bioequivalent if the 90% CIs were between 0.80 and 1.25. Adverse events were assessed by a nurse who administered a questionnaire while the healthy volunteers were admitted in the unit. The bioequivalence study was conducted in 30 Uruguayan male volunteers. Demographic characteristics (mean [SD]) included age, 27.8 (6.5) years; weight, 71.2 (9.8) kg; height, 1.71 (0.09) m; and body

  15. A single-arm phase III study exploring the efficacy and safety of LNG-IUS 8, a low-dose levonorgestrel intrauterine contraceptive system (total content 13.5 mg), in an Asia-Pacific population.

    Fan, Guangsheng; Kang, Sukho; Ren, Mulan; Weisberg, Edith; Lukkari-Lax, Eeva; Roth, Katrin; Shin, SoYoung


    The objective was to evaluate the efficacy and safety of a low-dose levonorgestrel intrauterine system with total content 13.5 mg (average approximately 8 μg/24 h over the first year; LNG-IUS 8; Jaydess®) in an Asia-Pacific population. An open-label, single-arm phase III study conducted at 25 centers in China, Australia and Korea assessed LNG-IUS 8 use over 3 years in nulliparous and parous women (N=1114) aged 18-40 years with regular menstrual cycles (21-35 days). Primary outcome was pregnancy rate, expressed as the Pearl Index. Secondary outcomes included 3-year cumulative failure rate, treatment-emergent adverse events (TEAEs), discontinuation rate, bleeding profile and placement pain. The full analysis set comprised 925 women (mean age 31.6 years, 6.4% nulliparous). Overall unadjusted Pearl Index was 0.35 (95% confidence interval 0.15-0.70); the 3-year cumulative failure rate was 0.9% (95% confidence interval 0.4-1.9). TEAEs and study drug-related TEAEs were reported in 70.1% and 31.2% of women, respectively. Overall, 27.9% of women discontinued the study, 16.9% due to adverse events. Frequent or prolonged bleeding (World Health Organization criteria) decreased from the first to the twelfth 90-day reference intervals (from 5.0% to 0.7% and from 44.1% to 3.0%, respectively), and the percentage of women with amenorrhea increased over time (from 0.4% to 10.8%). Pain on placement was reported as "none" or "mild" in 91.9% of women. LNG-IUS 8 was an effective and well-tolerated contraceptive method, providing another option for women in the Asia-Pacific region. In this phase III study, LNG-IUS 8 was shown to be highly effective and well tolerated in an Asia-Pacific population and was not associated with any new or unexpected safety events. LNG-IUS 8 provides another contraceptive option for women in the Asia-Pacific region. Copyright © 2016. Published by Elsevier Inc.

  16. The long-term pharmacokinetics and safety of adding low-dose ritonavir to a nelfinavir 1,250 mg twice-daily regimen in HIV-infected patients

    Justesen, U S; Hansen, I M; Andersen, A B;


    1250 mg twice-daily regimen with plasma viral load HIV-1 RNA copies/mL were randomized to continue treatment or to have ritonavir 100 mg twice-daily added. Safety, including fasting lipid levels, was evaluated at weeks 4, 12 and 24. Patients who were randomized to have ritonavir added (n=9......OBJECTIVES: To evaluate the long-term pharmacokinetics and safety of adding ritonavir 100 mg twice-daily to a nelfinavir 1250 mg twice-daily regimen in HIV-infected patients. METHODS: This was a prospective, randomized, open-label, controlled 24-week study. Sixteen patients receiving a nelfinavir...

  17. Eficacia clínica de oxicodona: La presentación de 5 mg en el esquema terapéutico del ascensor analgésico Clinical Effectiveness of oxicodone: The 5 mg dose in the analgesic elevator therapeutic scheme

    M. A. Vidal


    ía eliminar el principal obstáculo para llevar a la práctica el "Ascensor Analgésico".Introduction. Oxicodone has been a semisynthetic opioide derived from thebaine with múltiple actions similar to morphine, used actually clinical for more than 80 years. Its main therapeutic action is the analgesia; and to a lesser extent sedative action. To dose lower than the necessary one to produce analgesia, can act on the center of the cough. The objective of this article is to make a review of the characteristics of oxicodone: its pharmacological properties, tolerability and mainly its clinical effectiveness in the different types of pain and with the different presentations that exist at the moment in the market. The reviewed articles come from the data base of Medline and Cochrane. Clinical effectiveness. Numerous studies guarantee the effectiveness of oxicodone in the treatment of the different types of pain. Nevertheless these studies have their limitations. The studies that are based on the use of oxicodone in nononcological chronic pain are positive comparative studies to placebo. As far as the oncological pain, the comparative clinical tests from morphine and hidromorphone, oxicodone has presented advantages in effectiveness, and safety. Also revisions have been carried out on the matter in which it scores at oxicodone like a good alternative to morphine. Discussion. Oxicodone is a good alternative for the treatment of the moderate-severe pain, for a program of opioids rotation of since it has an excellent balance between analgesia and toxicity. Oxicodone prolonged release 5 mg, is very useful like initial dose to titrate opioids, being climbed dose at 48 hours, with which the incidence of indirect effect is diminished and diminishes the risk of therapeutic abandonment that these entail. With this approach one would be able to eliminate the main obstacle to put in practice the "Analgesic Elevator" theory.

  18. Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40mg Sb v/kg/dia, de 12/12h, por 30 dias na forma cutaneo-mucosa de leishmaniose

    Raimunda N.R. Sampaio


    Full Text Available Foi avaliada a função renal de 11 pacientes com leishmaniose cutâneo-mucosa tratados com antimonial pentavalente na dose de 40mg SbV/kg/dia aplicada de 12/12 horas, em esquema contínuo, durante trinta dias. No estudo, um paciente apresentou insuficiência renal reversível e dois desenvolveram alterações enzimáticas hepáticas e eletrocardiográficas sendo o esquema terapêutico interrompido. Nos demais pacientes observou-se efeitos nefrotóxicos tais como diminuição da taxa de filtração glomerular, diminuição da capacidade de concentração urinária, avaliada por um jejum hídrico de 16 horas e aumento na fração de excreção de sódio. No exame do sedimento urinário observou-se um aumento no número de leucócitos e cilindros. Os resultados encontrados neste estudo sugerem que o tratamento com antimonial pentavalente na dose de 40mg SbV/kg/dia foi menos tolerado em virtude de seus efeitos tóxicos, não parecendo apresentar índice de cura superior ao esquema atualmente preconizado de 20mg SbV/kg/dia.The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40mg/kg/day of pentavalent antimony (SbV, in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxics effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40mg Sb/kg/day was less tolerated on account of its renal toxics

  19. Cardiac dose-response relationships of oral and intravenous pindolol

    Carruthers, S. George


    1 The dose-response curve of pindolol on exercise heart rate has been constructed from observations in healthy male subjects studied 2 h after oral doses of pindolol 0.25 mg, 0.5 mg, 1 mg, 2.5 mg, 5 mg, 10 mg and 20 mg. This dose-response curve has been compared with historical controls who received atenolol, oxprenolol, practolol, propranolol and sotalol.

  20. Three-way, three-period, crossover bioequivalence study of single oral dose of three brands of 300 mg phenytoin sodium tablets marketed in India, on healthy Indian human volunteers

    Maulik S Doshi


    Full Text Available Objective: To compare the bioavailability of two brands of phenytoin sodium tablets available in the Indian market using Eptoin TM as the reference. Materials and Methods: A randomized, assessor-blind, three-way crossover design study was carried out over a period of 6 months after approval from the Institutional Review Board (IRB. Twenty-two healthy male participants received a single oral 300 mg oral tablet of either of the formulations with a 2-week washout. Blood samples were collected predose and at regular intervals postdose. Plasma phenytoin levels were estimated by high-performance liquid chromatography. Calculation of C max , AUC 0-t , and AUC 0-∞ was done by the linear trapezoidal rule and 90-110% margin (90% confidence interval (CI was used to assess bioequivalence. Results: Twenty volunteers completed the study. It was seen that the log-transformed values of C max , AUC 0-t , and AUC 0-∞ of the test formulations were not within the specified limits. Conclusion: Bioinequivalence of available phenytoin brands indicates that switching brands could lead to variations in blood concentrations and thus impact safety and efficacy. If a brand switch is done for any reason, stringent drug-level monitoring is advised.

  1. Vitamin K prophylaxis for premature infants: 1 mg versus 0.5 mg.

    Costakos, Dennis T; Greer, Frank R; Love, Laureen A; Dahlen, Lynn R; Suttie, John W


    We studied babies (22 to 32 weeks gestational age) of mothers wishing to breast-feed. Group 1 received 1 mg of vitamin K and Group 2 received 0.5 mg of vitamin K. The Day 2 plasma levels of vitamin K were 1900 to 2600 times higher on average, and the Day 10 vitamin K levels 550 to 600 times higher on average, relative to normal adult plasma values, whether an initial prophylaxis dose of 0.5 mg or 1 mg was used. We conclude that 0.5 mg as the initial dose of vitamin K intramuscularly or intravenously would likely be more than adequate to prevent hemorrhagic disease of the newborn, and that 0.3 mg/per kg may be used for babies with birth weights below 1000 g. To decrease vitamin K intakes in this population, new preparations of total parenteral nutrition multivitamins are needed.

  2. High-Dose Statins Boost Survival

    ... atorvastatin (Lipitor) or 20 to 40 mg of rosuvastatin (Crestor) daily. Examples of moderate doses include 10 to ... of Lipitor and 5 to 10 mg of Crestor, the study reported. Unlike some previous studies, this ...

  3. Eficácia do regime terapêutico empregando a associação de pantoprazol, claritromicina e amoxicilina, durante uma semana, na erradicação do Helicobacter pylori em pacientes com úlcera péptica Efficacy of the dosing regimen of pantoprazole 40 mg, amoxicillin 1000 mg and clarithromycin 500 mg, twice daily for 7 days, in the eradication of Helicobacter pylori in patients with peptic ulcer

    Luiz Gonzaga Vaz Coelho


    Full Text Available OBJETIVO: Estudo multicêntrico, aberto, delineado para determinar a eficácia da associação de pantoprazol, claritromicina e amoxicilina, na erradicação do Helicobacter pylori em pacientes portadores de úlcera péptica. MATERIAL E MÉTODOS: Setenta e um pacientes (36 mulheres, 35 homens, idade média 41,9 anos provenientes de três centros universitários brasileiros (Belo Horizonte e Porto Alegre com úlcera péptica confirmada à endoscopia e infecção por H. pylori comprovada por, no mínimo, dois testes diagnósticos. Os pacientes foram tratados com a associação de pantoprazol 40 mg, claritromicina 500 mg e amoxicilina 1,0 g, administrada duas vezes ao dia, durante 7 dias. RESULTADOS: Ao final do tratamento, os pacientes foram reexaminados para avaliação dos sintomas gastrointestinais, presença de eventos adversos e aderência ao tratamento. Nova endoscopia com biopsias e teste respiratório com 13C-uréia foram repetidos 60 dias após o término do tratamento para determinação das taxas de erradicação do microrganismo. Foram considerados H. pylori negativos os pacientes com, pelo menos, o teste respiratório com 13C-uréia e mais um teste (teste da urease ou histologia negativos. Ao final do estudo 60/69 (87%, 95% = 78,9-94,8 pacientes erradicaram o H. pylori na análise por protocolo e 60/71 (84,5%, 95% = 76-92,9 na análise por intenção de tratamento. Um paciente interrompeu o tratamento devido à diarréia. Doze pacientes (16,9% apresentaram sintomas adversos e considerados de leve intensidade. CONCLUSÃO: A associação de pantoprazol, amoxicilina e claritromicina por 7 dias constitui alternativa eficaz e bem tolerada para a erradicação do H. pylori em portadores de úlcera péptica no Brasil.AIM: This is an open label, multicenter trial to determine the efficacy of the association of pantoprazole, clarithromycin and amoxicillin to eradicate Helicobacter pylory in patients with peptic ulcer. MATERIAL AND METHODS

  4. Pharmacokinetics Amlodipine Fixed-dose Combination Amlodipine/Benazepril 5/10 mg Capsule in Healthy Volunteers%苯磺酸氨氯地平/盐酸贝那普利(5/10mg)固定剂量复方胶囊剂中氨氯地平在健康人体内的药动学

    阳剑; 刀婕; 张啟智; 朱荣华; 番云涛; 彭文兴


    目的 研究苯磺酸氨氯地平/盐酸贝那普利(5/10 mg)固定剂量复方胶囊剂中氨氯地平在健康人体内的药动学特征,为该药的临床应用提供依据.方法 24名健康受试者随机分成3组,每组8人,男女各半,分别单次口服复方胶囊剂1、2、3粒(氨氯地平剂量分别为5,10,15 mg),中剂量组连续14 d每日1次口服复方胶囊剂2粒(氨氯地平剂量为10 mg).采用超高效液相色谱-电喷雾串联质谱法(UPLC-ESI-MS/MS)测定健康志愿者单次和多次口服复方胶囊剂后氨氯地平的血药浓度,采用DAS2.0药动学程序(中国药理学会数学药理专业委员会出版,上海,中国)非房室数学模型分析方法计算主要药动学参数.结果 健康志愿者单次口服复方胶囊剂1、2、3粒后氨氯地平(5,10,15 mg)的主要药动学参数t1/2分别为(33.5±6.2)、(36.1±7.6)和(39.8±12.5)h,tmax分别为(6.0±1.1)、(7.0±3.4)和(5.6±3.0)h,ρmax分别为(4.37±1.37)、(7.23±1.81)和(14.71 ±3.14) ng·mL-1,AUC0→144分别为(167.7±35.9) 、(283.8 ±47.6)和(574.9±159.0)ng· h·mL-1,AUC0→∞分别为(176.8 ±40.2)、(304.1±54.8)和(628.2±197.5) ng·h·mL-1,V/F分别为(1 389.6±231.5)、(1 724.4±269.2)和(1414.2±342.6)L,MRT0.144分别为(47.8±4.0)、(51.1±9.9)和(52.9±13.9)h,CL/F分别为(29.5±6.5)、(34.0±7.2)和(25.9±7.6) L·h-1.氨氯地平在5 ~15 mg内,其ρmax、AUC0-144、AUC0-∞与剂量相关,但其与剂量不成正比关系;统计分析结果表明口服3种剂量氨氯地平的达峰时间无显著性差异(P>0.05),低、中、高剂量氨氯地平的消除半衰期、V/F、MRT0-144、CL/F相近(P>0.05),t1/2与MRT0-144有逐渐增加的趋势,其中高剂量组t1/2较低、中剂量组分别增加了约6和3h.受试者连续给药14 d后氨氯地平血药浓度达稳态,达到稳态后的ρmaxss为(24.03±5.56) ng· mL-1;ρminss为(15.64±3.93) ng· mL-1;AUC0-24ss为(463.7 ±121.1)ng·h·mL-1,DF为(0.4±0.1).连续

  5. Phase II study of irinotecan (CPT-11) administered every 2 weeks as treatment for patients with colorectal cancer resistant to previous treatment with 5-fluorouracil-based therapies: comparison of two different dose schedules (250 and 200 mg/m2) according to toxicity prognostic factors.

    Saigi, Eugeni; Salut, Antonieta; Campos, Juan Manuel; Losa, Ferran; Manzano, Hermini; Batiste-Alentorn, Eduard; Acusa, Angels; Vélez de Mendizabal, Edelmira; Guasch, Inmaculada; Antón, Isabel


    Our objective was to assess the antitumoral activity and toxicity of irinotecan (CPT-11) 60-min i.v. infusion every 2 weeks as second-line monotherapy of advanced colorectal cancer. Two doses were studied (250 and 200 mg/m) according to the risk of developing toxicity. Two groups of patients were studied: high-risk group (HR, 200 mg/m, n = 45; Karnofsky score 60-80% and/or the record of prior pelvic irradiation) and low-risk-group (LR, 250 mg/m, n = 51; Karnofsky score >80% and without prior pelvic irradiation). The mean number of cycles per patient was 7: 6.6 (HR group) and 8.3 (LR group). Median RDI was 0.96. The overall response rate was 8.9% [95% confidence interval (CI) 2.5-21.2%; HR group] and 15.7% (95% CI 7.0-28.5%; LR group), respectively. The LR group showed two complete responses and a higher percentage of stable disease (56.9 versus 33.3% in HR group). The median survival was 7.1 months (95% CI 5.2-8.9 months, HR group) and 11.7 months (95% CI 8.4-15.1 months, LR group). The median time to disease progression was 3.2 months (95% CI 1.0-5.4 months, HR group) and 5.3 months (95% CI 3.8-6.7 months, LR group). Both CPT-11 treatments were well tolerated. Grade 3/4 toxicity incidence was low, e.g. granulocytopenia (7% of patients in HR group and 9% in LR group) and delayed diarrhea (18% of patients in HR group and 14% in LR group). We conclude that the treatment of patients with the adjusted dose of CPT-11 according to prognostic factors for toxicity resulted in the improved toxicity profile, but showed poorer efficacy outcome. Therefore, the dose reduction in patients with low performance and treated with radiotherapy needs further investigation to provide some new insights on the benefit:risk ratio of such treatment.

  6. Evaluating dose response from flexible dose clinical trials

    Baron David


    Full Text Available Abstract Background The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related. Methods To evaluate dose effect in response on primary efficacy scales from 2 randomized, double-blind, flexible-dose trials of patients with bipolar mania who received olanzapine (N = 234, 5–20 mg/day, or patients with schizophrenia who received olanzapine (N = 172, 10–20 mg/day, we used marginal structural models, inverse probability of treatment weighting (MSM, IPTW methodology. Dose profiles for mean changes from baseline were evaluated using weighted MSM with a repeated measures model. To adjust for selection bias due to non-random dose assignment and dropouts, patient-specific time-dependent weights were determined as products of (i stable weights based on inverse probability of receiving the sequence of dose assignments that was actually received by a patient up to given time multiplied by (ii stable weights based on inverse probability of patient remaining on treatment by that time. Results were compared with those by unweighted analyses. Results While the observed difference in efficacy scores for dose groups for the unweighted analysis strongly favored lower doses, the weighted analyses showed no strong dose effects and, in some cases, reversed the apparent "negative dose effect." Conclusion While naïve comparison of groups by last or modal dose in a flexible-dose trial may result in severely biased efficacy analyses, the MSM with IPTW estimators approach may be a valuable method of removing these biases and evaluating potential dose effect, which may prove useful for planning confirmatory trials.

  7. Methotrexate Dosing Regimen for Plaque-type Psoriasis: A Systematic Review of the Use of Test-dose, Start-dose, Dosing Scheme, Dose Adjustments, Maximum Dose and Folic Acid Supplementation.

    Menting, Stef P; Dekker, Paul M; Limpens, Jacqueline; Hooft, Lotty; Spuls, Phyllis I


    There is a range of methotrexate dosing regimens for psoriasis. This review summarizes the evidence for test-dose, start-dose, dosing scheme, dose adjustments, maximum dose and use of folic acid. A literature search for randomized controlled trials and guidelines was performed. Twenty-three randomized controlled trials (29 treatment groups) and 10 guidelines were included. Two treatment groups used a test-dose, 5 guidelines recommend it. The methotrexate start-dose in randomized controlled trials varied from 5 to 25 mg/week, most commonly being either 7.5 mg or 15 mg. Guidelines vary from 5 to 15 mg/week. Methotrexate was administered as a single dose or in a Weinstein schedule in 15 and 11 treatment-groups, respectively; both recommended equally in guidelines. A fixed dose (n = 18), predefined dose (n = 3), or dose adjusted on clinical improvement (n = 8) was used, the last also being recommended in guidelines. Ten treatment groups used folic acid; in 2 it was allowed, in 14 not mentioned, and in 3 no folic acid was used. Most guidelines recommend the use of folic acid. Authors' suggestions for methotrexate dosing are given.

  8. Cytarabine Dose for Acute Myeloid Leukemia

    Lowenberg, Bob; Pabst, Thomas; Vellenga, Edo; van Putten, Wim; Schouten, Harry C.; Graux, Carlos; Ferrant, Augustin; Sonneveld, Pieter; Biemond, Bart J.; Gratwohl, Alois; de Greef, Georgine E.; Verdonck, Leo F.; Schaafsma, Martijn R.; Gregor, Michael; Theobald, Matthias; Schanz, Urs; Maertens, Johan; Ossenkoppele, Gert J.


    BACKGROUND Cytarabine (ara-C) is an important drug in the treatment of acute myeloid leukemia (AML). High-dose cytarabine (2000 to 3000 mg per square meter of body-surface area) is toxic but results in higher rates of relapse-free survival than does the conventional dose of 100 to 400 mg per square

  9. Mifepristone 5 mg versus 10 mg for emergency contraception: double-blind randomized clinical trial

    Carbonell JL


    Full Text Available Josep Lluis Carbonell,1 Ramon Garcia,2 Adriana Gonzalez,2 Andres Breto,2 Carlos Sanchez2 1Mediterranea Medica Clinic, Valencia, Spain; 2Eusebio Hernandez Gynecology and Obstetrics Teaching Hospital, Havana, Cuba Purpose: To estimate the efficacy and safety of 5 mg and 10 mg mifepristone for emergency contraception up to 144 hours after unprotected coitus. Methods: This double-blind randomized clinical trial was carried out at Eusebio Hernandez Hospital (Havana, Cuba. A total of 2,418 women who requested emergency contraception after unprotected coitus received either 5 mg or 10 mg mifepristone. The variables for assessing efficacy were the pregnancies that occurred and the fraction of pregnancies that were prevented. Other variables assessed were the side effects of mifepristone, vaginal bleeding, and changes in the date of the following menstruation. Results: There were 15/1,206 (1.2% and 9/1,212 (0.7% pregnancies in the 5 mg and 10 mg group, respectively (P=0.107. There were 88% and 93% prevented pregnancies in the 5 mg and 10 mg group, respectively. The side effect profiles were similar in both groups. Delayed menstruation ≥7 days was experienced by 4.9% and 11.0% of subjects in the 5 mg and 10 mg group, respectively (P=0.001. There was a significant high failure rate for women weighing >75 kg in the 5 mg group. Conclusion: It would be advisable to use the 10 mg dose of mifepristone for emergency contraception as there was a trend suggesting that the failure rate of the larger dose was lower. Keywords: mifepristone, emergency contraception

  10. Prolactin response to low dose sulpiride.


    1 Prolactin levels in response to sulpiride were studied in healthy volunteers. 2 Oral doses of 1 mg-50 mg sulpiride or placebo were given. 3 A 3 mg sulpiride dose produced similar levels to those achieved with both 10 mg and 50 mg. 4 Circadian effects were studied showing no significant differences in the prolactin response to sulpiride. 5 Acute or chronic responses showed an attenuation with chronic sulpiride treatment to 50% of the peak levels attained with acute treatment. 6 These results...

  11. Consumption of high-dose vitamin C (1250 mg per day) enhances functional and structural properties of serum lipoprotein to improve anti-oxidant, anti-atherosclerotic, and anti-aging effects via regulation of anti-inflammatory microRNA.

    Kim, Seong-Min; Lim, So-Mang; Yoo, Jeong-Ah; Woo, Moon-Jea; Cho, Kyung-Hyun


    Background Although the health effects of vitamin C are well known, its physiological effect on serum lipoproteins and microRNA still remain to be investigated, especially daily consumption of a high dosage. Objectives To investigate the physiological effect of vitamin C on serum lipoprotein metabolism in terms of its anti-oxidant and anti-glycation activities, and gene expression via microRNA regulation. Methods We analyzed blood parameters and lipoprotein parameters in young subjects (n = 46, 22 ± 2 years old) including smokers who consumed a high dose of vitamin C (1250 mg) daily for 8 weeks. Results Antioxidant activity of serum was enhanced with the elevation of Vit C content in plasma during 8 weeks consumption. In the LDL fraction, the apo-B48 band disappeared at 8 weeks post-consumption in all subjects. In the HDL fraction, apoA-I expression was enhanced by 20% at 8 weeks, especially in male smokers. In the lipoprotein fraction, all subjects showed significantly reduced contents of advanced glycated end products and reactive oxygen species (ROS). Triglyceride (TG) contents in each LDL and HDL fraction were significantly reduced in all groups following the Vit C consumption, suggesting that the lipoprotein was changed to be more anti-inflammatory and atherogenic properties. Phagocytosis of LDL, which was purified from each individual, into macrophages was significantly reduced at 8-weeks post-consumption of vitamin C. Anti-inflammatory and anti-senescence effects of HDL from all subjects were enhanced after the 8-weeks consumption. The expression level of microRNA 155 in HDL3 was reduced by 49% and 75% in non-smokers and smokers, respectively. Conclusion The daily consumption of a high dose of vitamin C for 8 weeks resulted in enhanced anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers.

  12. Treatment of patients with essential hypertension: amlodipine 5 mg/benazepril 20 mg compared with amlodipine 5 mg, benazepril 20 mg, and placebo.

    Kuschnir, E; Acuña, E; Sevilla, D; Vasquez, J; Bendersky, M; Resk, J; Glazer, R


    This multicenter, double-masked, randomized, parallel-group study compared the efficacy, tolerability, and safety of amlodipine 5 mg/benazepril 20 mg, amlodipine 5 mg, benazepril 20 mg, and placebo in patients with essential hypertension. After a placebo run-in period, 308 patients (all white) were randomized to treatment groups and took medication once daily for 8 weeks. Blood pressure was measured after 4 and 8 weeks of treatment in the 23- to 26-hour period after dosing. Patients wore a noninvasive blood pressure monitor for 24 hours before randomization and before the final visit. Investigators recorded adverse experiences at randomization and at study weeks 4 and 8, and obtained specimens for laboratory testing at randomization and at study week 8. Three hundred seven patients were evaluated for efficacy, and 308 for tolerability and safety. At end point (the last postrandomization measurement for each patient), the reduction in mean sitting diastolic blood pressure with the amlodipine 5 mg/benazepril 20 mg treatment was statistically significantly greater than with any comparative therapy. The results of 24-hour monitoring showed that the amlodipine/benazepril treatment, unlike monotherapy, maintained the hourly mean diastolic blood pressure at amlodipine 5 mg/benazepril 20 mg versus 67.5%, 53.3%, and 15.8% with amlodipine, benazepril, and placebo, respectively. This difference between the amlodipine/benazepril treatment group and each comparative single-agent treatment group was statistically significant. Drug-related adverse events occurred in 15.6% of patients in the amlodipine/benazepril group and in 24.7%, 6.5%, and 11.7% of patients in the amlodipine, benazepril, and placebo groups, respectively. Edema occurred less often in the amlodipine/benazepril group than in the amlodipine group. Overall, once-daily therapy with amlodipine 5 mg/benazepril 20 mg provided an antihypertensive effect that was statistically and clinically superior to amlodipine 5 mg

  13. Once daily dose gentamicin in neonates - is our dosing correct?

    Serane, Tiroumourougane V; Zengeya, Stanley; Penford, Gemma; Cooke, Jane; Khanna, Gitika; McGregor-Colman, Elle


    The aim of this paper is to study the safety and efficacy (measured by therapeutic level) of once daily gentamicin in neonates >or=32 weeks of gestation and or=32 weeks of gestation and 2 mg/L. Only 39 (60%) had peak and trough levels within the therapeutic range. All babies who had audiometric evaluation (62 out of 65) had normal hearing. Out of the 65 babies, 60 had paired serum creatinine levels estimated and none had evidence of renal dysfunction. Among term neonates, only 2 out of 50 had the trough serum concentration of >2 mg/L. In 38 (76%) of the 50 neonates, the trough serum gentamicin concentration was <2.0 mg/L and the peak level was <10 mg/L. Forty-eight babies had audiometric evaluation which was normal. A dose of 4 mg/kg/day produces serum gentamicin levels outside the therapeutic range in two-fifths of neonates between 32 and 36 +/- 6 weeks. A single dose of 4 mg/kg/day of gentamicin is appropriate for term babies and probably excessive for 32-36 weeks' neonates.

  14. Cytarabine dose for acute myeloid leukemia

    B. Löwenberg (Bob); T. Pabst (Thomas); E. Vellenga (Edo); W. van Putten; H.C. Schouten (Harry); C. Graux (Carlos); A. Ferrant (Augustin); P. Sonneveld (Pieter); B.J. Biemond (Bart); A. Gratwohl (Alois); G.E. de Greef (Georgine); L.F. Verdonck (Leo); M.R. Schaafsma (Martijn); M. Gregor (Michael); M. Theobald; U. Schanz (Urs); J. Maertens (Johan); G.J. Ossenkoppele (Gert)


    textabstractBACKGROUND: Cytarabine (ara-C) is an important drug in the treatment of acute myeloid leukemia (AML). High-dose cytarabine (2000 to 3000 mg per square meter of body-surface area) is toxic but results in higher rates of relapse-free survival than does the conventional dose of 100 to 400 m

  15. Pharmacokinetic Properties of Single- and Multiple-Dose Pitavastatin Calcium Tablets in Healthy Chinese Volunteers

    Zhu Luo, MD


    Conclusions: In healthy Chinese volunteers, single dosing of 1 mg, 2 mg, and 4 mg pitavastatin resulted in linear plasma pharmacokinetic properties. Compared with single dosing, multiple dosing of pitavastatin showed different distribution and elimination characteristics. Sex did not appear to affect the pharmacokinetic properties of pitavastatin. identifier: ChiCTR-OO-13004294.

  16. Sesame allergy threshold dose distribution.

    Dano, D; Remington, B C; Astier, C; Baumert, J L; Kruizinga, A G; Bihain, B E; Taylor, S L; Kanny, G


    Sesame is a relevant food allergen in France. Compared to other allergens there is a lack of food challenge data and more data could help sesame allergy risk management. The aim of this study is to collect more sesame challenge data and investigate the most efficient food challenge method for future studies. Records of patients at University Hospital in Nancy (France) with objective symptoms to sesame challenges were collected and combined with previously published data. An estimation of the sesame allergy population threshold was calculated based on individual NOAELs and LOAELs. Clinical dosing schemes at Nancy were investigated to see if the optimal protocol for sesame is currently used. Fourteen patients (10 M/4 F, 22 ± 14.85 years old) with objective symptoms were added to previously published data making a total of 35 sesame allergic patients. The most sensitive patient reacted to the first dose at challenge of 1.02 mg sesame protein. The ED05 ranges between 1.2 and 4.0 mg of sesame protein (Log-Normal, Log-Logistic, and Weibull models) and the ED10 between 4.2 and 6.2 mg. The optimal food challenge dosing scheme for sesame follows semi-log dose increases from 0.3 to 3000 mg protein. This article provides a valuable update to the existing clinical literature regarding sesame NOAELs and LOAELs. Establishment of a population threshold for sesame could help in increasing the credibility of precautionary labelling and decrease the costs associated with unexpected allergic reactions. Also, the use of an optimal dosing scheme would decrease time spent on diagnostic and thereafter on the economic burden of sesame allergy diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Zolpidem 10 mg given at daytime is not antagonized by 300 mg caffeine in man.

    Mattila, M J; Nurminen, M L; Vainio, P; Vanakoski, J


    Caffeine counteracts various effects of traditional benzodiazepines (BZDs). As zolpidem, a short-acting hypnotic, is an atypical GABAA-BZD agonist, we investigated when caffeine would counteract the effects of zolpidem as well. In daytime study I, zolpidem 10 mg (capsule) and caffeine 150 or 300 mg (in decaffeinated coffee) were given, alone and in combinations, to parallel groups (n = 15-17) of healthy students in double-blind and placebo-controlled manner. Objective and subjective tests were done before and 45 min and 90 min after intake. Ranked delta values (changes from baseline) were analysed by one-way contrast ANOVA and Scheffe's tests. In daytime study II, four healthy subjects took zolpidem 10 mg alone, and together with blinded caffeine 250 mg or (at -45 min) erythromycin 750 mg. Objective and subjective effects were measured and plasma zolpidem concentrations assayed at baseline and 45 min and 90 min after zolpidem intake. In study I, practice effects after placebo (ad + 30%) were seen for letter cancellation and digit symbol substitution but not for flicker fusion tests. Zolpidem alone significantly impaired (P effects of zolpidem and either dose of caffeine matched those measured after zolpidem alone. Zolpidem + caffeine 300 mg was not stronger than zolpidem + caffeine 150 mg in impairing immediate memory and causing subjective sedation. In study II, zolpidem caused objective and subjective sedation; neither caffeine nor erythromycin modulated the effects of zolpidem or plasma zolpidem concentrations. The sedative effects of 10 mg of zolpidem are not antagonized by 150-300 mg of caffeine in pharmacodynamic or pharmacokinetic terms.

  18. Vickers hardness measurement of ion implanted MgO

    Aoki, Y. (TRCRE, JAERI, 1233 Watanuki-machi, Takasaki, Gunma 370-12 (Japan)); Rueck, D.M. (Materialforschung, UNILAC, GSI, D-6100, Darmstadt (Germany)); Vogt, D. (Materialforschung, UNILAC, GSI, D-6100, Darmstadt (Germany)); Leible, K. (Materialforschung, UNILAC, GSI, D-6100, Darmstadt (Germany)); Khubeis, I. (University of Jordan, P.O. Box 13097, Amman (Jordan)); Meyer, O. (INFP, KfK, D-7500, Karlsruhe 1 (Germany))


    The Vickers hardness was measured for single crystals of MgO(100) implanted with 130 keV or 1.8 MeV Ar[sup +] ions and with 400 keV Xe[sup 2+] ions by means of the indentation technique with an applied load of 0.4-30 mN. Implantation with 130 keV Ar[sup +] and 400 keV Xe[sup 2+] gave similar results in hardening of MgO surface layers. In addition, the dose dependence of the measured hardness curve showed that a softening mechanism takes place at high doses. High energy implantation (1.8 MeV Ar[sup +]) made a hardened surface layer on MgO. This hardened layer also became softer at high doses. ((orig.))

  19. Substitution of Mn for Mg in MgB_2*

    Fitzpatrick, Michael D.; Johnston, David C.; Miller, Lance L.; Hill, Julienne M.


    The study of solid solutions in which the Mg in MgB2 is partially replaced by magnetic 3d or 4f atoms can potentially reveal important information on the superconducting state of MgB_2. As an end-member of the hypothetical Mg_1-xMn_xB2 system, MnB2 is isostructural with MgB2 and is an antiferromagnet below TN = 760 K which becomes canted at 157 K. A previous study by Moritomo et al.[1] examined the structure and properties of multi-phase samples with 0.01J. Phys. Soc. Japan b70, 1889 (2001).; “Effects of transition metal doping in MgB2 superconductor", Y. Moritomo at al. arXiv:cond-mat/0104568.

  20. A comparison of roxatidine acetate 150 mg once daily and 75 mg twice daily in gastric ulcer healing.

    Rösch, W


    In 363 outpatients with endoscopically confirmed gastric ulcers the efficacy and safety of roxatidine acetate 150 mg at night was compared to 75 mg twice daily. After 8 weeks' treatment substantial reductions in gastric ulcer diameter were obtained in addition to healing rates of 83.7 and 86% for the twice daily and night-time dosing, respectively. Daily reductions in day and night-time epigastric pain were obtained with no significant differences between treatment groups for pain scores or antacid tablet consumption. Furthermore, cigarette smoking did not influence the healing rates produced by either treatment schedule. 26 patients reported 32 adverse reactions and 5 patients discontinued treatment because of side effects, although only 1 of these was a severe reaction. The present data suggest that a single night-time dose of roxatidine acetate 150 mg is as safe and effective as the twice daily dose regimen for the management of acute gastric ulceration.

  1. Amphotericin B for cryptococcal meningitis in HIV positive patients: Low dose versus high dose

    Rajeshwari S


    Full Text Available Aim: To compare the safety and efficacy of low dose vs high dose of amphotericin B in cryptococcal meningitis associated with HIV infection. Materials and Methods: Retrospective data of patients admitted with clinical diagnosis with or without microbiological evidence of cryptococcal meningitis was collected from Jan 2000-Mar 2006. Patients′ details were collected in a proforma which included patient′s age, weight, signs and symptoms of disease and microbiological report (blood and CSF analysis. Data also included coexisting disease; concomitant medications taken along with amphotericin B. Adverse drug reactions which occurred during the period of treatment were recorded. Patients were grouped as low dose group and high dose group depending on the dose of amphotericin B given for the treatment of cryptococcal meningitis. Patients who received amphotericin B at doses of 0.33 to 0.64 mg/kg body weight per day were categorized under low dose group and patients who received amphotericin B at doses of 0.7 to 1.1 mg/kg/day were categorized under high dose group. All data were pooled and analyzed between the groups using chi square test. Result: Total number of patients included in the study were 38, 26 in the low dose group and 12 in the high dose group. In the low dose group, 20 were males and six were females, in the high dose group eight were males and four were females. The commonest underlying diseases were tuberculosis (17 in low dose group, nine in high dose group, Pneumocystis carinii (jeroveci pneumonia (16 in low dose group, seven in high dose group and oral candidiasis (eight in low dose group, seven in high dose group, Toxoplasmosis (three in low dose group, one in high dose group, hypertension (1 in group A and diabetes mellitus (1 in group B. Concomitant medication received along with amphotericin B for coexisting diseases in both the groups were antitubercular therapy, cotrimoxazole, antiviral therapy and premedications such as

  2. Low dose gossypol for male contraception

    Zhi-PingGU; Bai-YongMAO; Yi-XinWANG; Ren-AnZHANG; Yong-ZhiTAN; Zheng-XingCHEN; LinCAO; Gen-DiYOU; S.J.Segal


    Aim:To ascertain whether the side effects of gossypol, hypokalemia and irreversibility, could be avoided on dose reduction. Methods: Seventy-seven male volunteers were divided into 3 groups: control (22 cases), 10mg gossypol (29 cases) and 12.5mg (26 cases). Senun levels of testosterone, FSH and LH were measured by RIA and potassium by flame photometry. Sperm counts and motility were examined before and regularly after treatment for the evaluation of contraceptive efficacy. Results: The average sperm density and motility started to decrease significantly by the end of month 2 of medication and gradually reached the infertility levels (<4 million/mL) in both treated groups. After that the 10mg group was asked to take the same dose every other day for up to a total observation period of 16-18 months for the maintenance of infertility. Subjects in the 12.5mg group did not take gossypol any more so as to observe the length of the loading dose required, but in a few, a maintenance dose of 12.5mg every other day was instituted for a few more months. In both treated groups, none of the spouses was pregnant during the maintenance dose period. Senun levels of potassium, FSH, LH and testosterone were not significantly changed and not a single volunteer complained of myoasthenia. After cessation of drug administratioin, the semen data returned to pretreatment levels.Conclusion: A regimen with 10 or 12.5mg of gossypol as the daily loading dose and 35 or 43.75mg as the weekly maintenance dose could induce infertility in male volunteers without developing hypokalemia or irreversibility.(Asian J Androl 2000 Dec;2:283-287)

  3. Antioxidant status in MgO nanoparticle-exposed rats.

    Kiranmai, G; Reddy, A Rama Narsimha


    In this present study, antioxidant status was evaluated in rat serum following exposure to magnesium oxide (MgO) nanoparticles. The lungs of rats were intratracheally instilled with (single dose) phosphate-buffered saline (PBS) + 1% of Tween 80 (solvent control) or MgO or carbonyl iron (negative control) or quartz particles (positive control) at a dose of 1 and 5 mg/kg of body weight. The blood samples were collected at 1, 7, and 30 days of postinstillation of nanoparticles after their exposure, and different parameters were estimated to assess the oxidative stress induced by the instillation of MgO. Exposure of rats to MgO produced a significant (p MgO nanoparticle-exposed rats indicates the reduction in antioxidant defense mechanisms due to the instillation of MgO. These results indicate that exposure to MgO nanoparticles induces oxidative stress by reducing the total antioxidant capacity in rats. The findings suggest possible occupational health hazard in chronic exposures.

  4. Miconazole nitrate vaginal suppository 1,200 mg versus oral fluconazole 150 mg in treating severe vulvovaginal candidiasis.

    Fan, Shangrong; Liu, Xiaopingliu; Liang, Yiheng


    Miconazole is a synthetic imidazole antifungal that has a broad spectrum of activity against Candida albicans and non-albicans Candida species. The aim of this study was to evaluate the efficacy and safety of miconazole nitrate vaginal suppository and oral fluconazole in treating severe vulvovaginal candidiasis (SVVC). In this prospective, randomized case control study, 577 cases of consecutive patients with SVVC were studied at the Gynecological Clinic of Peking University Shenzhen Hospital from January 1, 2009 through December 31, 2010. Patients with SVVC were treated with two doses of miconazole nitrate vaginal suppository 1,200 mg or two doses of fluconazole 150 mg. The patients were followed up for 7-14 and 30-35 days following the second dose of therapy. The mycological cure rates of the patients on days 7-14 of follow-up were 75.9% (220/290) and 84.0% (241/287) in the miconazole and fluconazole groups, respectively (p 0.05). The study demonstrated that two doses of miconazole nitrate vaginal suppository 1,200 mg were as effective as two doses of an oral fluconazole 150 mg regimen in the treatment of patients with SVVC. © 2015 S. Karger AG, Basel.




    Objective: To compare the efficacy of salbutamol as a fixed dose Ventolin Nebule (2.5 mg) and as variable dose respirator solution (0.1 mg/kg bodyweight). Design: Multicentre, randomised, double-blind, parallel group comparison. Setting: The Emergency Departments of the Royal Children's Hospital, Me

  6. Mg-aminoclay as stabilizer for synthesizing highly stable and reactive nZVI for decontamination

    Hwang, Yuhoon; Lee, Young-Chul; Mines, Paul D.

    Despite the large surface area and superior reactivity of nZVI, its limited stability is a major obstacle for in situ subsurface remediation. In this study, Mg-aminoclay (MgAC) was applied for the first time as a stabilizer in nZVI synthesis. With increased doses of Mg-aminoclay, nZVI particle gr...

  7. nduced hyperlipidemic rats. Methods: Column chromatographic fractionation of butanol fraction of total methanol extract of leaves of Bauhinia variegata (Linn. yields four sub-fractions (sub-fraction A-D. All sub-fractions tested for their anti-hyperlipidemic activity. Sub-fractions administered at a dose of 65 mg/kg (oral to the Triton WR-1339 induced hyperlipidemic rats and total cholesterol, triglycerides, HDL, LDL and VLDL

    Deepak Kumar


    Full Text Available Objective: To investigate the effect and evaluation of Anti-hyperlipidemic activity guided subfraction isolated from total methanolic extract of Bauhinia variegata (Linn. leaves on Triton WR-1339 induced hyperlipidemic rats. Methods: Column chromatographic fractionation of butanol fraction of total methanol extract of leaves of Bauhinia variegata (Linn. yields four subfractions (sub-fraction A-D. All sub-fractions tested for their anti-hyperlipidemic activity. Subfractions administered at a dose of 65 mg/kg (oral to the Triton WR-1339 induced hyperlipidemic rats and total cholesterol, triglycerides, HDL, LDL and VLDL level in the blood were checked. Results: Sub-fraction D showed significant reduction (P<0.05 among four sub-fraction in comparison with standard drug fenofibrate. Conclusions: From the above study it could be concluded that butanol sub-fraction D of Bauhinia variegata (Linn. not only have resulted in significant reduction in cholesterol, triglyceride, LDL, VLDL level but also increases the HDL level at a reduced dose level.

  8. Single Daily Dosing of Gentamicin: Pharmacokinetic Comparison of Two Dosing Methodologies for Postpartum Endometritis

    C. Liu


    Full Text Available Objective: We compared the pharmacokinetics of two methods for dosing gentamicin for the treatment of postpartum endometritis with the goal of achieving adequate peak serum concentrations (>12 mg/L and prolonged trough levels below 2 mg/L.

  9. Chloroquine is grossly under dosed in young children with malaria

    Ursing, Johan; Eksborg, Staffan; Rombo, Lars


    BACKGROUND: Plasmodium falciparum malaria is treated with 25 mg/kg of chloroquine (CQ) irrespective of age. Theoretically, CQ should be dosed according to body surface area (BSA). The effect of dosing CQ according to BSA has not been determined but doubling the dose per kg doubled the efficacy of...

  10. [The variance of melphalan doses related to kilogram of body weight and the consequences].

    Vokurka, S


    Melphalan is an important cytotoxic drug. The empirical practice of body surface area-based (BSA) dosing (mg/m2) of melphalan has been critically analyzed in several observations. BSA-based dosing leads to significant variability in doses administered per kilogram of body weight (mg/kg), contributes to increased oral toxicity and probably does not have any significant effect on treatment results within equally BSA (mg/m2) dosed melphalan regimens.

  11. Genetic warfarin dosing: tables versus algorithms.

    Finkelman, Brian S; Gage, Brian F; Johnson, Julie A; Brensinger, Colleen M; Kimmel, Stephen E


    The aim of this study was to compare the accuracy of genetic tables and formal pharmacogenetic algorithms for warfarin dosing. Pharmacogenetic algorithms based on regression equations can predict warfarin dose, but they require detailed mathematical calculations. A simpler alternative, recently added to the warfarin label by the U.S. Food and Drug Administration, is to use genotype-stratified tables to estimate warfarin dose. This table may potentially increase the use of pharmacogenetic warfarin dosing in clinical practice; however, its accuracy has not been quantified. A retrospective cohort study of 1,378 patients from 3 anticoagulation centers was conducted. Inclusion criteria were stable therapeutic warfarin dose and complete genetic and clinical data. Five dose prediction methods were compared: 2 methods using only clinical information (empiric 5 mg/day dosing and a formal clinical algorithm), 2 genetic tables (the new warfarin label table and a table based on mean dose stratified by genotype), and 1 formal pharmacogenetic algorithm, using both clinical and genetic information. For each method, the proportion of patients whose predicted doses were within 20% of their actual therapeutic doses was determined. Dosing methods were compared using McNemar's chi-square test. Warfarin dose prediction was significantly more accurate (all p algorithm (52%) than with all other methods: empiric dosing (37%; odds ratio [OR]: 2.2), clinical algorithm (39%; OR: 2.2), warfarin label (43%; OR: 1.8), and genotype mean dose table (44%; OR: 1.9). Although genetic tables predicted warfarin dose better than empiric dosing, formal pharmacogenetic algorithms were the most accurate. Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  12. [Fluconazole 1200mg or 800mg for cryptococcal meningitis treatment in Ivory Coast].

    Kouakou, G A; Ello, N F; Kassi, N A; Keita, M; Doumbia, A; Mossou, C; Kassi, F K; Tanon, A; Ehui, E; Eholié, S P


    Assessing the use of high-dose fluconazol monotherapy (1200mg or 800mg) in the treatment and prognosis of HIV-associated cryptococcal meningitis in Ivory Coast. A retrospective study carried out from August 2008 to August 2011 based on patients charts suffering from CM in the Abidjan Tropicals and Infectious Disease Unit. Mortality rate and associated factors were analyzed. Forty-six cases of cryptococcal meningitis (2.5% of hospitalizations) were included. The sex-ratio was of 1.2. The median age was 40.5 [35-47] years. The symptomatology was subacute (93.5%). The main clinical symptoms were syndrome of pure meningeal irritation (65%), fever (100%); 35% of patients had encephalomeningits. Twenty-one (45.7%) was ART-naïve patients. Fluconazole 1200mg was prescribed to 29 (63%) patients. Therapeutic lumbar punctures were performed in 42 (91.3) patients. The mortality rate was 50%. Significant predictors of mortality were encephalomeningitis and therapeutic lumbar puncture. Cryptococcal meningitis associated mortality remains high despite the use of high-dose fluconazole monotherapy. Therapeutic lumbar punctures help to improving the prognosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. Do geriatrics require dose titration for antidiabetic agents?

    R Shastry


    Full Text Available Objective: To evaluate the antidiabetic drug dosage differences between geriatric and nongeriatric diabetics with reference to duration of disease and creatinine clearance (Crcl. Materials and Methods: Prospective study conducted for 6 months in a tertiary care hospital. Patients with type 2 diabetes mellitus were grouped into geriatric (age ≥60 years and nongeriatric (age <60 years. Patients′ demographic data, duration of diabetes, medication, and serum creatinine were recorded. Crcl was calculated using Cockcroft-Gault formula. Doses of sulfonylureas (SU were converted into equivalent doses, taking glibenclamide as standard. Univariate analysis was done for comparison of drug doses between groups. Result: A total of 320 geriatric and 157 nongeriatric diabetics completed the study. The duration of diabetes and Crcl adjusted dose reduction of glibenclamide (mean dose: Geriatrics 7.2±0.4 mg, nongeriatrics 9.6±0.7 mg; P=0.01 and gliclazide (mean dose: Geriatrics 85.5±11.5 mg, nongeriatrics 115.3±32.7 mg; P=0.42 was 25%, glimepiride (mean dose: Geriatrics 1.62±0.13 mg, nongeriatrics 2.1±0.18 mg; P=0.06 was 22%. Glipizide did not require dose reduction. Mean converted equivalent dose of sulfonylurea monotherapy was significantly lower in geriatrics than nongeriatrics (3.2±0.5 vs 6.4±1.02 mg; P=0.01 and showed 50% dose reduction. Mean dose of metformin was lower in geriatrics (901±32.2 mg vs 946.7±45.8 mg; P=0.45 and showed 5% reduction in dosage. There was no difference in the mean drug doses of thiazolidinediones and insulin between the groups. Conclusion: A substantial dose reduction of glibenclamide (25%, gliclazide (25%, glimepiride (22%, and metformin (5% in geriatrics compared to nongeriatrics was observed. Smaller dosage formulations like 0.75 mg glibenclamide, 0.5 mg glimepiride, 20 mg gliclazide, and 250 mg metformin may be of value in geriatric diabetic practice.

  14. MG132 Induced Apoptosis Pathway in HL-60 Cells and Impact of Allogeneic Mixed Lymphocyte Reaction

    Yong-ming Zhou; Wei Guo; Hao Zhou; Jin-hua Zhang; Zhi-ping Liu; Mei-xia Yu


    Objective: To investigate the proteasome inhibitor MG132-induced apoptosis pathway in HL-60 cells and the role of allogeneic mixed lymphocyte reaction.Methods: Cell apoptosis was analyzed by flow cytometry. The expressions of p21 protein, p27 protein and p53 protein in HL-60 cells treated with MG132 were measured by Western blot. The proliferation of, peripheral blood mononuclear cells (PBMNCs) after treatment with 75 Gy irradiated HL-60 cells treated with MG132 was measured with CCK-8.Results: High-dose MG132 induced apoptosis in HL-60 cells. No significant change was observed in MG132-induced apoptosis after inhibiting caspase-8 and caspase-9 pathway. The expressions of p21 protein and p27 protein increased in MG132-induced apoptosis. HL-60 cells treated with low-dose MG132 improved the proliferation of PBMNCs from healthy volunteers.Conclusion: High-dose MG132 induced apoptosis and directly killed HL-60 cells. MG132 induced apoptosis in a caspase-8- and caspase-9-independent pathway. p21 protein and p27 protein were involved in MG132-induced apoptosis in HL-60 cells. HL-60 cells treated with Low-dose MG132 improved the effect of promoting the proliferation of PBMNCs from healthy volunteers.

  15. Acoustic dose and acoustic dose-rate.

    Duck, Francis


    Acoustic dose is defined as the energy deposited by absorption of an acoustic wave per unit mass of the medium supporting the wave. Expressions for acoustic dose and acoustic dose-rate are given for plane-wave conditions, including temporal and frequency dependencies of energy deposition. The relationship between the acoustic dose-rate and the resulting temperature increase is explored, as is the relationship between acoustic dose-rate and radiation force. Energy transfer from the wave to the medium by means of acoustic cavitation is considered, and an approach is proposed in principle that could allow cavitation to be included within the proposed definitions of acoustic dose and acoustic dose-rate.

  16. Comparison of 1 mg and 2 mg overnight dexamethasone suppression tests for the screening of Cushing's syndrome in obese patients.

    Sahin, Mustafa; Kebapcilar, Levent; Taslipinar, Abdullah; Azal, Omer; Ozgurtas, Taner; Corakci, Ahmet; Akgul, Emin Ozgur; Taslipinar, Mine Yavuz; Yazici, Mahmut; Kutlu, Mustafa


    Obesity is currently a major public health problem and one of the potential underlying causes of obesity in a minority of patients is Cushing's syndrome (CS). Traditionally, the gold standard screening test for CS is 1 mg dexamethasone overnight suppression test. However, it is known that obese subjects have high false positive results with this test. We have therefore compared the 1 mg and 2 mg overnight dexamethasone suppression tests in obese subjects. Patients whose serum cortisol after ODST was >50 nM underwent and a low-dose dexamethasone suppression test (LDDST); 24-hour urine cortisol was collected for basal urinary free cortisol (UFC). For positive results after overnight 1-mg dexamethasone suppression test we also performed the overnight 2-mg dexamethasone suppression test. We prospectively evaluated 100 patients (22 men and 78 women, ranging in age from 17 to 73 years with a body mass index (BMI) >30 kg/m2 who had been referred to our hospital-affiliated endocrine clinic because of simple obesity. Suppression of serum cortisol to rate in 1 mg overnight test and 2% in 2 mg overnight test (p=0.001). There was no correlation between the cortisol levels after ODST and other parameters. Our results indicate that the 2 mg overnight dexamethasone suppression test (ODST) is more convenient and accurate than 1-mg ODST as a screening test for excluding CS in subjects with simple obesity.

  17. Perbandingan Efektivitas Pemberian Efedrin Oral Dosis 25 mg dengan 50 mg Preoperatif terhadap Kejadian Hipotensi Pascaanestesi Spinal pada Seksio Sesarea

    Selly Oktarina Rosita


    Full Text Available Oral ephedrine is one alternative to prevent hypotension with less adverse effects. The purpose of this study was to determine the effective dose of oral ephedrine given 30–45 minutes before spinal anesthesia to reduce incidence of hypotension. The research was a single-blind randomized experimental study involving 32 pregnant women, ASA II, who underwent caesarean section with spinal anesthesia at Dr. Hasan Sadikin Hospital Bandung from March to May 2012. Subjects were divided into two groups, 25 mg ephedrine and 50mg ephedrine groups. Data was analyzed using Mann Whitney and chi-square test, p<0.05 was considered significant. Statistical analysis showed there was a significant difference (p=0.049 in incidence of hypotension between 25 mg group and 50mg group. 25mg group required more intravenous ephedrine after spinal anesthesia (p=0.040. The conclusion of this study was that oral 50mg ephedrine given 30–45 minutes before performing spinal anesthesia will reduce the incidence of hypotension after spinal anesthesia in comparison to oral 25mg ephedrine. In 25mg group, the amount of ephedrine intravenous administered is higher compared with 50mg group.

  18. Assessment of pulmonary toxicity of MgO nanoparticles in rats.

    Gelli, Kiranmai; Porika, Mahendar; Anreddy, Rama Narsimha Reddy


    In this study, we have evaluated the pulmonary toxicity of MgO nanoparticles (MgO NPs) in rats following their exposure. NPs in phosphate buffered saline + 1% Tween 80 were exposed via intratracheal instillation at a doses of 1 mg/kg or 5 mg/kg into rat lungs and evaluated for various tissue damage markers like alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid and histopathology of lungs at 1, 7, and 30 days of post-exposure intervals. A dose-dependant increase in ALP and LDH activity was observed in BAL fluids of rat lungs than sham control at all post-exposure periods (P MgO NPs. In conclusion, MgO NPs exposure produced a dose-dependent pulmonary toxicity in rats and was comparable with that of Quartz particles.

  19. Low dose spinal anesthesia for knee arthroscopy

    Lakhin R.E.


    Full Text Available Objective: to evaluate the nature of unilateral spinal anesthesia using various modes of administration of low doses of hyperbaric bupivacaine. Materials and Methods. Prospectively, the randomized study included 56 patients undergoing knee arthroscopy. In the control group bupivacaine of 5mg was administered simultaneously, in the main group — fractionally by 2.5 mg. The development of thermal and pain blocks from different sides was investigated. The data were statistically processed. Results. In the control group, the positioning of the patient usually began after the entire dose of anesthetic had been administered. In the case of temperature paresthesia in the area of the sacral segments of the full anesthesia throughout underlying limb was not always achieved. In 6 cases of block was not sufficient. In the main group patient positioning was performed after the administration of 2.5 mg of anesthetic and evaluate temperature paresthesia and in 2 cases the total dose was increased to 7.5 mg. The successful development of sensory block at fractional administration was significantly higher than in the single-step introduction. Conclusion. Temperature paresthesia occurs within the first minute and is an early predictor of developing spinal anesthesia. The area of arising paresthesia shows preferential distribution of the anesthetic. In the application of low dose local anesthetic the desired upper level of anesthesia via the patient positioning and dose adjustment may be achieved.

  20. Comparison of ruminant anthelmintics, using multiple dose administration.

    Hass, D K; Holloway, E L; Brown, L J


    Eleven ruminant anthelmintics were administered to lambs over a 30-day period, using medicated feeds or multiple oral doses. Fenbendazole and its sulfinyl analog, oxfendazole, were effective (greater than 90%) in the control of clinical parasitism at feeding levels of 5 mg/kg of feed. Parbendazole and albendazole were effective at daily oral dose levels of 1 mg/kg of body weight and at feeding dose levels of 10 mg/kg of feed, respectively. Levamisole, mebendazole, and oxibendazole were ineffective in controlling intense natural parasitic infections of sheep at daily oral dose levels equal to or less than 1 mg/kg of body weight and/or a feeding level equal to or less than 10 mg/kg of feed.

  1. Bioequivalence of ondansetron oral soluble film 8 mg (ZUPLENZ) and ondansetron orally disintegrating tablets 8 mg (ZOFRAN) in healthy adults.

    Dadey, Eric


    Oral formulations of ondansetron are used to prevent nausea and vomiting associated with chemotherapy, radiotherapy, and surgery. An oral soluble film formulation of ondansetron (OND OSF) was developed using MonoSol Rx's proprietary PharmFilm technology and was formulated to dissolve rapidly on the tongue, without the need for water. This product provides an oral antiemetic treatment option for patients who experience difficulty swallowing. The purpose of this study was to compare the bioequivalence of OND OSF 8 mg (ZUPLENZ, Monosol Rx, Warren, NJ) with ondansetron orally disintegrating tablets (OND ODT) 8 mg (ZOFRAN, GlaxoSmithKline, Research Triangle Park). In 3 individual open-label, randomized studies, healthy adult subjects received a single dose of OND OSF 8 mg and a single dose of OND ODT 8 mg, under fasted conditions (study 1, n = 48), fed conditions (study 2, n = 48), and fasted with and without water (study 3, n = 18). Each dosing period was followed by a 3- or 7-day washout period. Ondansetron pharmacokinetics were assessed predose to 24 hours postdose for the single 8-mg doses of OND OSF and OND ODT. All analyses were conducted on natural log-transformed pharmacokinetic parameters for OND OSF and OND ODT. Under both fasted and fed conditions, the 90% confidence interval for the comparisons of OND OSF and OND ODT plasma ondansetron area under the curve from time 0 to the last measured concentration (AUC0-t), area under the concentration vs. time curve from time 0 to infinity (AUC0-∞), and maximum plasma concentration (Cmax) were within the 80%-125% range, indicating bioequivalence between the formulations. With features designed to make it portable and easy to take, OND OSF 8 mg provides an alternative treatment option, particularly for patients with dysphagia and others who find it difficult to take oral tablets.

  2. Dose escalation of a curcuminoid formulation

    Crowell James


    Full Text Available Abstract Background Curcumin is the major yellow pigment extracted from turmeric, a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential. However, few systematic studies of curcumin's pharmacology and toxicology in humans have been performed. Methods A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of standardized powder extract, uniformly milled curcumin (C3 Complex™, Sabinsa Corporation. Healthy volunteers were administered escalating doses from 500 to 12,000 mg. Results Seven of twenty-four subjects (30% experienced only minimal toxicity that did not appear to be dose-related. No curcumin was detected in the serum of subjects administered 500, 1,000, 2,000, 4,000, 6,000 or 8,000 mg. Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg. Conclusion The tolerance of curcumin in high single oral doses appears to be excellent. Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, these findings warrant further investigation for its utility as a long-term chemopreventive agent.

  3. Evaluation of the relative thermoluminescence efficiency of LiF:Mg,Ti and LiF:Mg,Cu,P TL detectors to low-energy heavy ions

    Gieszczyk, W.; Bilski, P.; Olko, P.


    The most popular types of LiF-based thermoluminescent (TL) detectors, LiF:Mg,Ti (MTS-N) and LiF:Mg,Cu,P (MCP-N), have been investigated, with respect to their dose (fluence) response and relative TL efficiency to different ion species. The detectors were irradiated using the nitrogen, iron, krypt...

  4. Mg spin affects adenosinetriphosphate activity

    Tulub, Alexander A


    The Schlegel-Frisch ab initio molecular dynamics (ADMP) (DFT:B3LYP), T = 310 K, is used to study complexation between adenosinetriphosphate (ATP), ATP subsystem, and magnesium cofactor [Mg(H2O)6]2+, Mg subsystem, in a water pool, modeled with 78 water molecules, in singlet (S) and triplet (T) states. The computations prove that the way of ATP cleavage is governed by the electron spin of Mg. In the S state Mg prefers chelation of \\gamma-\\beta-phosphate oxygens (O1-O2), whereas in the T state it chelates \\beta-\\alpha-phosphate oxygens (O2-O3) or produces a single-bonded intermediate. Unlike the chelates, which initiate ionic reaction paths, the single-bonded intermediate starts off a free-radical path of ATP cleavage, yielding a highly reactive adenosinemonophosphate ion-radical, .AMP-, earlier observed in the CIDNP (Chemically Induced Dynamic Nuclear Polarization) experiment (A.A. Tulub, 2006). The free-radical path is highly sensitive to Mg nuclear spin, which through a hyperfine interaction favors the produc...

  5. Supplementary iron dose in pregnancy anemia prophylaxis.

    Reddaiah, V P; Raj, P P; Ramachandran, K; Nath, L M; Sood, S K; Madan, N; Rusia, U


    This study was conducted to determine the optimum dose of supplemental iron for prophylaxis against pregnancy anemia. One hundred and ten pregnant women were randomly allocated to three groups: Group A receiving equivalent of 60 mg, group B 120 mg and Group C 240 mg, elemental iron as ferrous sulphate daily; the content of folic acid was constant in all the three groups (0.5 mg). These women had at least consumed 90 tablets in 100 +/- 10 days. Blood was drawn at the beginning and at the end of the treatment. Fifty percent were anemic (less than 11 g/100 ml). The hemoglobin levels rose similarly in all groups and the differences were statistically not significant. Fifty-six percent had depleted iron stores (serum ferritin value less than 12 micrograms/l) at the beginning of the study. Following therapy a statistically significant increase in iron stores was observed in group B and C as compared to group A. The difference between group B and C was not significant. The side effects increased with increasing doses of iron; 32.4%, 40.3% and 72% in group A, B and C respectively. Based on these findings, the authors advocate that optimum dose of iron should be 120 mg instead of 60 mg as is currently being used in the National Nutritional Anemia Prophylaxis Programme.

  6. Benchmark Dose Modeling

    Finite doses are employed in experimental toxicology studies. Under the traditional methodology, the point of departure (POD) value for low dose extrapolation is identified as one of these doses. Dose spacing necessarily precludes a more accurate description of the POD value. ...

  7. Irradiation dose determination below room temperature

    Ramos-Bernal, S. E-mail:; Cruz, E.; Negron-Mendoza, A.; Bustos, E


    The measurements presented were undertaken to provide quantitative information on the low temperature irradiation of thermoluminiscence phosphors. The crystals used were (a) LiF co-doped with Mg, Cu and P, and (b) CaSO{sub 4} doped with Dy. The absorbed dose values in the interval studied showed a linear behavior at low doses and low temperature. The aim of this work is to test if these crystals can be used to measure the dose absorbed by solids at low temperature.

  8. Phenytoin dose adjustment in epileptic patients.

    Mawer, G E; Mullen, P W; Rodgers, M; Robins, A J; Lucas, S B


    1 A preliminary survey showed that many outpatients with partially controlled epilepsy had serum concentrations of phenytoin below the recommended therapeutic range (10-20 μg/ml). A phenytoin tolerance test was devised with the intention of predicting a more adequate daily dose for such a patient. 2 Fifteen patients were each given an oral test dose of 600 mg phenytoin sodium and the serum concentration of phenytoin was measured at intervals over 48 h; the concentration rose during the first 4 h and decayed between 12-48 h as an almost linear function of time. 3 The serum concentration/time curves were fitted by an interative computer program based on the Michaelis-Menten equation. The mean saturated rate of elimination of phenytoin was 435 mg/day and the serum concentration (K(m)) corresponding with 50% saturation was 3.8 μg/ml. The mean calculated dose of phenytoin sodium required for a steady state serum concentration of 10-20 μg/ml was 345-400 mg/day. 4 The Michaelis-Menten principle was used to predict steady state serum phenytoin concentrations in individual patients receiving daily doses of phenytoin sodium adjusted by steps of 100 mg. The serum concentrations tended to be either too low or too high. The steep relationship between phenytoin concentration and dose indicates that when the concentration reaches 5-10 μg/ml it is then appropriate to adjust dose by small steps of about 25 mg.

  9. CsMgPO4

    Nikolay S. Slobodyanik


    Full Text Available Caesium magnesium orthophosphate is built up from MgO4 and PO4 tetrahedra (both with . m. symmetry linked together by corners, forming a three-dimensional framework. The Cs atoms have .m. site symmetry and are located in hexagonal channels running along the a- and b-axis directions.

  10. Estradiol valerate and alcohol intake: dose-response assessments

    Quirarte, Gina L; Reid, Larry D; de la Teja, I Sofía Ledesma; Reid, Meta L; Sánchez, Marco A; Díaz-Trujillo, Arnulfo; Aguilar-Vazquez, Azucena; Prado-Alcalá, Roberto A


    Background An injection of estradiol valerate (EV) provides estradiol for a prolonged period. Recent research indicates that a single 2.0 mg injection of EV modifies a female rat's appetite for alcoholic beverages. This research extends the initial research by assessing 8 doses of EV (from .001 to 2.0 mg/female rat), as well assessing the effects of 2.0 mg EV in females with ovariectomies. Results With the administration of EV, there was a dose-related loss of bodyweight reaching the maximum loss, when it occurred, at about 4 days after injections. Subsequently, rats returned to gaining weight regularly. Of the doses tested, only the 2.0 mg dose produced a consistent increase in intake of ethanol during the time previous research indicated that the rats would show enhanced intakes. There was, however, a dose-related trend for smaller doses to enhance intakes. Rats with ovariectomies showed a similar pattern of effects, to intact rats, with the 2 mg dose. After extensive histories of intake of alcohol, both placebo and EV-treated females had estradiol levels below the average measured in females without a history of alcohol-intake. Conclusion The data support the conclusion that pharmacological doses of estradiol can produce enduring changes that are manifest as an enhanced appetite for alcoholic beverages. The effect can occur among females without ovaries. PMID:17335585

  11. Efficacy and safety of a larger dose (16 mg) of candesartan cilexetil in 65 patients with mild to moderate essential hypertension%高剂量坎地沙坦西酯16 mg治疗轻中度原发性高血压65例临床观察

    张明辉; 赵秀丽; 周延明; 李嘉静; 周辉; 王淑民; 武峰


    目的:评价16 mg坎地沙坦西酯治疗轻中度原发性高血压患者的有效性和安全性.方法:采用随机、双盲、平行对照的研究方法,入选患者65例,随机接受坎地沙坦西酯16 mg·d-1(n=33)或8 mg·d-1(n=32)治疗,共8周,并对其中的37例患者于治疗前后进行24 h动态血压监测.结果:治疗8周末,16 mg组和8 mg组的收缩压分别下降(10.9±11.5)mmHg和(11.5±15.1)mmHg,舒张压分别下降(12.9±11.3)mmHg和(10.5±7.8)mmHg;两组的降压总有效率分别为70%和61.3%.动态血压监测显示,16 mg组和8 mg组的收缩压谷峰比值分别为73%和47%,舒张压为65%和47%.两组的不良事件发生率无统计学差异.结论:高剂量坎地沙坦西酯16 mg·d-1治疗轻中度原发性高血压安全有效,患者耐受性好.

  12. Effects of different doses of dexamethasone plus flunixin meglumine on survival rate in lethal endotoxemia

    Er A.; Uney K.; Altan F.; Cetin G.; Yazar E.; Elmas M.


    Effects of different doses of dexamethasone plus flunixin meglumine on survival rate were investigated in lethal endotoxemia. A total of 60 Balb/C female mice were divided into 4 equal groups. Lethal endotoxemia (80-100%) was induced by lipopolysaccharide injection (Group 1, 1 mg, intraperinoneally). At 4 hours after the lipopolysaccharide injection; low-dose dexamethasone (0.6 mg/kg, SID, 5 days, intramuscularly) + flunixin meglumine (2 mg/kg, SID, 5 days, subcutaneously), normal-dose dexame...

  13. Low dose metoprolol in acute myocardial infarction.

    Kumar, K P; Krishnaswami, S; Prasad, N K; Rath, P C; Jose, J


    A study of the effects of low dose Metoprolol was undertaken in 37 patients with acute myocardial infarction. These patients were randomly divided into three groups depending on the dose of the drug per kg body weight. Group I, consisting of 18 patients, received 0.36 to 0.65 mg per kg per day, Group II (10 patients) received 0.66 to 0.99 mg/kg/day, and Group III (9 patients) 1 to 1.81 mg/kg/day. To assess the degree of beta blockade achieved, the parameters that were evaluated were the fall in blood pressure and heart rate. There was a fall in systolic blood pressure which ranged from 7 to 17%, and fall in heart rate of 6.6 to 12.8% in the 3 groups over the 48-hour study period. These observations were compared with the results obtained from the Goteberg Metoprolol trial and Metoprolol in acute myocardial infarction (MIAMI) trials wherein 200 mg of Metoprolol per day were used. Our preliminary observations suggest that Indian patients may not need such a high dose, and Metoprolol at 50-100 mg per day would probably be sufficient to get the desired effect.

  14. Retrospective study comparing low-dose versus standard dose of bortezomib in patients with multiple myeloma

    Marcela Espinoza Zelada


    Full Text Available INTRODUCTION Bortezomib is a selective inhibitor of the proteosoma that is used in multiple myeloma. In combination with other antineoplastic drugs, it has a well-documented impact in progression-free survival rates and overall survival rates with standard doses (1.3-1.5 mg/m2. However, up to 88% of patients on standard doses have unwanted side effects (neutropenia, neuropathy or anemia. Standard dose (1.3 mg/m2 is used in almost all patients and low dose (0.7-0.8 mg/m2 is reserved for patients with kidney disease and neuropathy. OBJECTIVE We aim to describe clinical, cytological, and cytometric outcomes, as well as overall survival and side effects of low dose versus standard dose of bortezomib in our institution. METHODS Retrospective, descriptive study based on data recovered from clinical charts of 48 multiple myeloma patients treated in our hospital between 2011 and 2013. We included data on age, gender, type of multiple myeloma, serum albumin, serum creatinine, beta 2 microglobulin, calcemia, imaging studies, disease stage, pre-and post-therapy bone marrow studies, adverse events and rate of progression. We also recorded events like date of death or of the last medical appointment. RESULTS Forty-eight multiple myeloma patients were treated with bortezomib-cyclophosphamide-dexamethasone. Twenty-one patients received low dose and 27 patients were treated with the standard dose. No statistical differences between the two groups were found for clinical response (p=0.6, cytological response (p=0.28, flow cytometric response (p= 0.3, rate of adverse effects and overall survival rates. CONCLUSION This retrospective analysis suggests that lower doses of bortezomib have similar effects in disease control measured by flow cytometry and cytology compared to standard doses in multiple myeloma patients.

  15. Toxicity of Nitro-Heterocyclic and Nitroaromatic Energetic Materials to Terrestrial Plants in a Natural Sandy Loam Soil


    TNB, RDX, HMX, and heavy metals to cucumber and radish. They determined that toxicity was mostly related to TNT and TNB, with a LOEC of 7 to 19 mg kg...species exposed to TNB, 2,4-DNT, and 2,6-DNT. Hormesis has been reported in plants exposed to heavy metals and aromatic hydrocarbons (Stebbing, 1982...Watermilfoil and duckweed ), and terrestrial plant species (i.e., yellow nutsedge, poplar, lettuce, and tall fescue (Schott and Worthley, 1974; Palazzo and

  16. Coronary vasodilatory action after a single dose of nicorandil

    H. Suryapranata (Harry); P.W.J.C. Serruys (Patrick); P.J. de Feyter (Pim); P.D. Verdouw (Pieter); P.G. Hugenholtz (Paul)


    textabstractCoronary hemodynamics and vasodilatory effects on major epicardial arteries were investigated after a single dose of nicorandil in 22 patients undergoing cardiac catheterization for suspected coronary artery disease. Nicorandil, 20 mg, was administered sublingually to 11 consecutive pati

  17. Coronary vasodilatory action after a single dose of nicorandil

    H. Suryapranata (Harry); P.W.J.C. Serruys (Patrick); P.J. de Feyter (Pim); P.D. Verdouw (Pieter); P.G. Hugenholtz (Paul)


    textabstractCoronary hemodynamics and vasodilatory effects on major epicardial arteries were investigated after a single dose of nicorandil in 22 patients undergoing cardiac catheterization for suspected coronary artery disease. Nicorandil, 20 mg, was administered sublingually to 11 consecutive pati

  18. Clobazam single or divided dose against diazepam in anxiety neurosis.

    Channabasavanna, S M; Pinto Pereira, L M


    One-hundred-and-fifteen patients diagnosed as anxiety neurotics randomly received in a double blind study 20 mg clobazam (Frisium) as a single nightly dose (37 patients) or 10 mg b.d. (38 patients) or diazepam 5 mg b.d. (40 patients) for six weeks, followed by two weeks on placebo. Both the single and divided doses of clobazam were therapeutically equivalent to diazepam. After drug withdrawal, all three treatment groups continued to improve. Patients on clobazam showed better motor performance than the diazepam series. Patients on clobazam divided dose performed significantly better than those on diazepam. Minor side-effects occurred in all patients. From the results clobazam as a single dose of 20 mg has good anxiolysis without any hungover effect.


    Ravindra Waykar et al


    Full Text Available Generic drugs are lower-cost versions of patent-expired original brand-name medications. According to guidelines of regulatory agencies of the Canada, US and European Union, a generic drug must be “identical, or bioequivalent to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use”. Bioequivalence is decreed when the ratio of the generic to the reference compound for the area-under-the-curve and maximum plasma concentration (Cmax fall within a 0.80–1.25 range. The present study was to develop Olanzapine Tablets and compare pharmacokinetic profile of Zyprexa 10 mg film-coated tablets, Zyprexa Velotabs 10 mg orodispersible tablets and Olanzapine 10mg tablets. Multi media dissolution studies in 0.1N HCl, pH 4.5 acetate buffer and pH 6.8 phosphate buffer were carried out for Reference (Zyprexa Velotab 10 mg and Zyprexa 10 mg and test product (i.e. Olanzapine 10 mg. A single centre, open-label, single-dose, randomised, 3-way crossover bioequivalence study, performed under fasting conditions. Based on the results obtained, it can be concluded that the test olanzapine (Treatment A is bioequivalent to both references Zyprexa Velotab (Treatment B and Zyprexa (Treatment C following a 10 mg dose under fasting conditions. All formulations were well tolerated, with no major side effects and no relevant differences in safety profiles were observed between the preparations, particularly with respect to the number and pattern of adverse event.

  20. Antagonism by idazoxan at low dose but not high dose, of the natriuretic action of moxonidine.

    Allan, D. R.; Penner, S. B.; Smyth, D. D.


    1. Recent studies concerning the imidazoline receptor have utilized idazoxan as a specific imidazoline receptor antagonist. The aim of the present study was to describe the in vivo effects of various doses of idazoxan on renal function, in the presence and absence of moxonidine, an I1 imidazoline receptor agonist. 2. In anaesthetized, unilaterally nephrectomized (7 to 10 days) Sprague Dawley rats, an intrarenal infusion of moxonidine (3 nmol kg-1 min-1) increased urine flow rate, sodium excretion and osmolar clearance without altering free water clearance. Pretreatment with intravenous idazoxan at 0.1 and 0.3 mg kg-1 produced a dose-related decrease in the renal actions of moxonidine. However, a higher dose of idazoxan (1 mg kg-1) was not as effective as the 0.3 mg kg-1 dose in blocking the effects of moxonidine. 3. In a separate series of experiments, the direct renal actions of idazoxan alone were investigated. Idazoxan at 0.3 mg kg-1 failed to alter urine flow rate and sodium excretion. However, idazoxan at 1 mg kg-1 produced a significant increase in urine flow rate and sodium excretion in association with an increase in osmolar clearance. 4. These results do not prove but are consistent with low doses of idazoxan antagonizing the sites stimulated by moxonidine (renal imidazoline receptors). However, at higher doses, idazoxan may function as a partial agonist and/or interact with other receptors to increase urine flow rate, independent of imidazoline receptor blockade. These studies underscore the importance of the dose of idazoxan administered when this antagonist is used as a tool to investigate imidazoline receptors. PMID:8825339

  1. Phase I dose intensification study of 2-weekly epirubicin with GM-CSF in advanced cancer.

    Michael, M; Toner, G C; Olver, I N; Fenessy, A; Bishop, J F


    This study investigated dose intensification of epirubicin administered as a 2-weekly regimen with granulocyte-macrophage colony-stimulating factor (GM-CSF) support. The aim was to define the maximally tolerated dose of epirubicin and to assess the efficacy of GM-CSF to ameliorate its toxicity. Patients with anthracycline-responsive advanced malignancies were eligible. Six dose levels, commencing at 90 mg/m2, of epirubicin administered every 2 weeks for four courses were planned with GM-CSF 10 micrograms/kg/day administered for 10 days from the second day of each course. Six patients were to be entered at each dose level, and escalation to the next level was based upon toxicity criteria. Twelve patients were entered, six at dose level 1 (90 mg/m2) and six at dose level 2 (120 mg/m2). Prospectively defined haematological dose-limiting toxicities were noted in one patient at dose level 1 and in five patients at dose level 2. Further dose escalation was not attempted. Significant nonhaematological toxicities included febrile neutropenia in two and four patients at dose levels 1 and 2, respectively. This study has demonstrated that epirubicin can be safely administered at 2 week intervals with GM-CSF at a dose of 90 mg/m2, equivalent to the previously reported maximum tolerated dose intensity of 45 mg/m2/week. Neutropenia was dose-limiting despite the use of GM-CSF.

  2. Removal of borate by coprecipitation with Mg/Al layered double hydroxide

    Kurashina, Masashi; Inoue, Tatsuki; Tajima, Chihiro; Kanezaki, Eiji


    Borate has been used for various industrial products and excessive dose of boron is harmful to humans. We investigated the removal of borate by direct coprecipitation with Mg/Al layered double hydroxide. In this study, the maximum removal of boron was 90% when Mg 30 mmol and Al 15 mmol at pH = 10 were used for 498 mg/l as B. The boron adsorption isotherms could be fitted to Langmuir model. The calculated constant Ws, saturation limit of boron adsorption, is 25 ± 2 mg/g and it is larger than that of ion exchange reaction (Ws = 15±1 mg/g).

  3. Comparative bioequivalence studies of tramadol hydrochloride sustained-release 200 mg tablets

    Suhas, Khandave; Satish ,Sawant; Santosh ,Joshi; Bansal,Yatish Kumar; Sonal Sushil Kadam,


    Suhas S Khandave1, Satish V Sawant1, Santosh S Joshi1, Yatish K Bansal2, Sonal S Kadam21Accutest Research Laboratories (I) Private Limited, Koparkhirne, Navi Mumbai, Maharashtra, India; 2Ipca Laboratories Limited, Kandivli Mumbai, Maharashtra, IndiaBackground: Tramadol hydrochloride is available as 50 mg immediate-release (IR) and 100 mg, 200 mg, and 300 mg sustained-release (SR) tablets. The recommended dose of tramadol is 50–100 mg IR tablets every 4–6 hours. The tramado...

  4. Bioequivalence study of 400 and 100 mg imatinib film-coated tablets in healthy volunteers.

    Ostrowicz, Andrzej; Mikołajczak, Przemysław L; Wierzbicka, Marzena; Boguradzki, Piotr


    The aim of the study was to investigate the bioavailability of a generic product of 100 mg and 400 mg imatinib film-coated tablets (test) as compared to that of a branded product (reference) at the same strength to determine bioequivalence. The secondary objective of the study was to evaluate tolerability of both products. An open-label, randomized, crossover, two-period, single-dose, comparative study was conducted in 43 (Imatynib-Biofarm 100 mg film-coated tablet) and in 42 (Imatynib-Biofarm 400 mg film-coated tablet), brand name Imatenil, Caucasian healthy volunteers in fed conditions. A single oral dose administration of the test or reference product was separated by 14-day washout period. The imatinib and its metabolite N-desmethyl imatinib concentrations were determined using a validated LC MS/MS method. The results of the single-dose study in healthy volunteers indicated that the film-coated tablets of Imatynib-Biofarm 100 mg and 400 mg film-coated tablets manufactured by Biofarm Sp. z o.o. (test products) are bioequivalent to those of Glivec 100 mg and 400 mg film-coated tablets manufactured by Novartis Pharma GmbH (reference products). Both products in the two doses of imatinib were well tolerated.

  5. Pb low doses induced genotoxicity in Lactuca sativa plants.

    Silva, S; Silva, P; Oliveira, H; Gaivão, I; Matos, M; Pinto-Carnide, O; Santos, C


    Soil and water contamination by lead (Pb) remains a topic of great concern, particularly regarding crop production. The admissible Pb values in irrigation water in several countries range from ≈0.1 to ≈5 mg L(-1). In order to evaluate putative effects of Pb within legal doses on crops growth, we exposed Lactuca sativa seeds and seedlings to increasing doses of Pb(NO3)2 up to 20 mg L(-1). The OECD parameter seed germination and seedling/plant growth were not affected by any of the Pb-concentrations used. However, for doses higher than 5 mg L(-1) significant DNA damage was detected: Comet assay detected DNA fragmentation at ≥ 5 mg L(-1) and presence of micronuclei (MN) were detected for 20 mg L(-1). Also, cell cycle impairment was observed for doses as low as 0.05 mg L(-1) and 0.5 mg L(-1) (mostly G2 arrest). Our data show that for the low doses of Pb used, the OECD endpoints were not able to detect toxicity, while more sensitive endpoints (related with DNA damage and mitotic/interphase disorders) identified genotoxic and cytostatic effects. Furthermore, the nature of the genotoxic effect was dependent on the concentration. Finally, we recommend that MN test and the comet assay should be included as sensitive endpoints in (eco)toxicological assays.

  6. Times to pain relief and pain freedom with rizatriptan 10 mg and other oral triptans

    Ng-Mak, D S; Hu, X. H.; Chen, Y.; Ma, L.; Solomon, G


    Background: In the clinical trial setting, oral rizatriptan 10 mg has greater efficacy than other oral triptans in freedom from migraine headache pain 2 h after dosing. Objective: The study objective is to compare the effectiveness of rizatriptan 10 mg and other oral triptans for acute migraine attack in a naturalistic setting. Methods: A total of 673 patients took rizatriptan 10 mg or their usual-care oral triptans for two migraine attacks in a sequential, cross-over manner and recorded outc...

  7. The effect of single dose versus two doses of praziquantel on Schistosoma haematobium infection and pathology among school-aged children in Mali

    Sacko, M.; Magnussen, Pascal; Traoré, M.


    The aim of this study was to assess the effect of two doses of 40 mg/kg praziquantel with 2 weeks interval versus a standard single dose of 40 mg/kg on cure rates, egg reduction, intensity of infection, and micro-haematuria in Schistosoma haematobium infections. A randomised controlled interventi...

  8. Relative safety profiles of high dose statin regimens

    Carlos Escobar


    Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.Keywords: statins, high doses, tolerability, liver, muscle

  9. High doses of carbamazepine for refractory partial epilepsy Altas doses de carbamazepina para epilepsia parcial refratária

    Cristiana Borges Pereira


    Full Text Available Forty-eight patients with partial seizures were analysed during treatment with 1200 mg/d or more of carbamazepine (CBZ. Thirty-three were on monotherapy and fifteen on polytherapy. The other drugs were kept unchanged in the patients on polytherapy. The dose of CBZ was increased if no control was observed and the patient had no side effects. The doses used ranged between 1200 and 1900 mg/day (1200 mg/day, n=18; 1300mg/day, n=1; 1400 mg/day, n=7; 1600 mg/day, n=9; 1700 mg/day, n=4; 1800 mg/day, n=8; 1900 mg/day, n=1. Anticonvulsant plasma levels were taken to confirm patient compliance. The average plasma level was 9.6 ug/mL. The period of follow up varied from 3 to 96 months (M=25.6. Seizure's control was observed in 7 (14.48% patients taking 1200 mg/day and in 2 (4.16% patients taking 1400 mg/day of CBZ. Thirty-nine patients did not show any control (81.21%. Ten patients (20.81% had signs of intoxication. When patients have no improvement with 1400 mg/day, it is difficult to obtain any control despite the use of higher doses of CBZ, which frequently expose the patient to significant side effects.Foram analisados 48 pacientes epilépticos com crises parciais que faziam uso de carbamazepina (CBZ em doses iguais ou superiores a 1200 mg por dia. Trinta e três estavam em monoterapia e 15 em politerapia. As outras medicações foram mantidas constantes durante a manipulação da dose de CBZ nos pacientes em politerapia. O critério utilizado para o aumento da dose de CBZ foi a falta de controle clínico e a ausência de efeitos colaterais (independente da dosagem sérica. A dose máxima variou de 1200 a 1900 mg/dia (1200 mg, n=18; 1300 mg/dia, n=1; 1400 mg/dia, n=7; 1600 mg/dia, n=9; 1700 mg/dia, n=4; 1800 mg/dia, n=8 ; 1900 mg/dia, n=1. Dosagens séricas de anticonvulsivantes eram utilizadas no sentido de confirmar a aderência ao tratamento. A média das dosagens disponíveis foi de 9,6 ug/mL. O tempo de seguimento variou de 3 a 96 meses (M=25

  10. Chloral hydrate sedation in radiology: retrospective audit of reduced dose

    Bracken, Jennifer [Children' s University Hospital, Radiology Department, Dublin (Ireland); Royal Children' s Hospital, Department of Medical Imaging, Parkville, Victoria (Australia); Heaslip, Ingrid; Ryan, Stephanie [Children' s University Hospital, Radiology Department, Dublin (Ireland)


    Chloral hydrate (CH) is safe and effective for sedation of suitable children. The purpose of this study was to assess whether adequate sedation is achieved with reduced CH doses. We retrospectively recorded outpatient CH sedations over 1 year. We defined standard doses of CH as 50 mg/kg (infants) and 75 mg/kg (children >1 year). A reduced dose was defined as at least 20% lower than the standard dose. In total, 653 children received CH sedation (age, 1 month-3 years 10 months), 42% were given a reduced initial dose. Augmentation dose was required in 10.9% of all children, and in a higher proportion of children >1 year (15.7%) compared to infants (5.7%; P < 0.001). Sedation was successful in 96.7%, and more frequently successful in infants (98.3%) than children >1 year (95.3%; P = 0.03). A reduced initial dose had no negative effect on outcome (P = 0.19) or time to sedation. No significant complications were seen. We advocate sedation with reduced CH doses (40 mg/kg for infants; 60 mg/kg for children >1 year of age) for outpatient imaging procedures when the child is judged to be quiet or sleepy on arrival. (orig.)

  11. Low-dose rituximab is effective in pemphigus

    Horvath, B.; Huizinga, J.; Pas, H. H.; Mulder, A. B.; Jonkman, M. F.


    Background Rituximab, an anti-CD20 antibody, was shown in open series studies to be effective in treating pemphigus at a dose of 4 x 375 mg m(-2) as approved for B-cell malignancies. Objectives We investigated whether a lower dose of rituximab is also effective for pemphigus. Methods Patients with p

  12. Opioid Abstinence Reinforcement Delays Heroin Lapse during Buprenorphine Dose Tapering

    Greenwald, Mark K.


    A positive reinforcement contingency increased opioid abstinence during outpatient dose tapering (4, 2, then 0 mg/day during Weeks 1 through 3) in non-treatment-seeking heroin-dependent volunteers who had been maintained on buprenorphine (8 mg/day) during an inpatient research protocol. The control group (n = 12) received $4.00 for completing…

  13. Formation of Mg2Ni with enhanced kinetics: Using MgH2 instead of Mg as a starting material

    Zhao, Bin; Fang, Fang; Sun, Dalin; Zhang, Qingan; Wei, Shiqiang; Cao, Fenglei; Sun, Huai; Ouyang, Liuzhang; Zhu, Min


    At a temperature over the decomposition point (375 °C) of MgH2, the formation of Mg2Ni is greatly enhanced from the 2MgH2+Ni system, as compared to the 2Mg+Ni system. In support of this finding, in-situ observation of X-ray absorption fine structure of the two systems indicates that MgNi bonds form faster in the 2MgH2+Ni system than in the 2Mg+Ni system. Furthermore, theoretical modeling also shows that Mg atoms are readily released from MgH2 using much less energy and thus are more available to react with Ni once the dehydrogenation of MgH2 occurs, as compared to normal Mg.

  14. Sustained effect after lowering high-dose infliximab in patients with rheumatoid arthritis: a prospective dose titration study.

    Bemt, B.J. van den; Broeder, AA den; Snijders, G.F.; Hekster, Y.A.; Riel, P.L.C.M. van; Benraad, B.; Wolbink, G.J.; Hoogen, F.H.J. van den


    OBJECTIVES: In clinical trials only a small subset of patients with rheumatoid arthritis (RA) benefits from higher than standard dose of infliximab (>3 mg/kg/8 weeks). However, dose escalation of infliximab is frequently applied in clinical practice. Individual adjustment of infliximab treatment




    The effect of preoperative low-dose aspirin (1 mg/kg of body weight) and intraoperative low-dose aprotinin (2 million kallikrein inactivator units) treatment on perioperative blood loss and blood requirements in patients who undergo internal mammary artery bypass operations is unknown. Therefore, we

  16. Effects of nifedipine GITS 20 mg or enalapril 20 mg on blood pressure and inflammatory markers in patients with mild-moderate hypertension.

    Agabiti Rosei, Enrico; Morelli, Patrizia; Rizzoni, Damiano


    Calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors and other drug classes either alone or in combination have been recommended for the treatment of hypertension. Nifedipine gastrointestinal therapeutic system (GITS) 20 mg is a new low-dose formulation with an improved tolerability. The aim of the present study was to compare the effects of nifedipine GITS 20 mg and enalapril 20 mg on blood pressure and circulating adhesion molecules in hypertensive patients. This randomized, double-blind, multicentre trial compared the blood pressure lowering effects of a 12-week treatment of nifedipine GITS 20 mg vs enalapril 20 mg in 264 patients with mild-to-moderate hypertension. Nifedipine GITS 20 mg induced a reduction of clinic blood pressure, which was similar to that observed with enalapril 20 mg. Nifedipine GITS and enalapril lowered mean sitting diastolic blood pressure by 11.8 and 12.4 mmHg, respectively, while systolic blood pressure was reduced by 15.3 and 16.3 mmHg, respectively. Ambulatory blood pressure monitoring-derived blood pressure data showed similar results in both groups without any statistically significant differences between treatments. Both enalapril and nifedipine tended to reduce ICAM-1 and E-selectin, while only nifedipine reduced von Willebrand factor. Both treatments were well tolerated. Our findings demonstrate a similar antihypertensive effectiveness of a low dose (20 mg) of nifedipine GITS in comparison with a standard dose of enalapril (20 mg). Given its clinical efficacy and good tolerability, low-dose nifedipine GITS may be considered a valuable treatment option for hypertensive patients.

  17. Synthesis and characterization of LiF: Mg, Ti for ionizing radiations dosimetry; Sintesis y caracterizacion de LiF: Mg, Ti para dosimetria de radiaciones ionizantes

    Lozano R, I. B.


    Among the different thermoluminescence materials (Tl), the LiF:Mg, Ti is the most used for dosimetric purposes, because its equivalence to the human tissue, it has an effective atomic number of 8.14, the best known commercial dosemeter of this kind is the TLD-100. However, because this dosimeter is an imported product, is quite expensive for many research groups and hospitals. The purpose of this work is the optimization of its synthesis, as the dosimetric characterization, so it can replace the imported dosimeters. The synthesis of LiF:Mg, Ti is a careful process, since one of the reagents, the ion fluorine is highly corrosive. In this work the synthesis of the LiF:Mg, Ti was done by the molten substance method, was used LiF of analytical grade and the magnesium (Mg) and titanium (Ti) activators were incorporated in aqueous solution. For to optimize the handle of the material Tl, we elaborated pellets and teflon (Ptfe) was used as agglutinate material, in a 2:3 proportion. First was prepared the LiF, incorporating just Mg as dopant with a concentration of 400 parts per million (ppm). After the Ti with concentrations from 15 to 120 ppm was incorporated keeping fixed the concentration of Mg (400 ppm). The morphological and structural characterization of the Tl material were made by scanning electron microscopy and X-ray diffraction. The optimal concentration of Ti, was determined as a function of the radiation dose sensibility of the Tl material. The material prepared with 60 ppm of the Ti showed a higher sensibility. However, also the rest of the preparations had the requirements recommended by the international agencies to be used in ionizing radiations dosimetry. For the dosimetric characterization were used samples with 400 ppm of Mg, 400 ppm Mg and 30 ppm Ti, 400 ppm Mg and 60 ppm Ti. The LiF:Mg showed its dosimetric peak at 240 C, while the LiF:Mg, Ti (30 ppm and 60 ppm Ti) showed their dosimetric peak at 220 C and 222 C respectively. The study of the Tl

  18. Sugammadex 4.0 mg kg-1 reversal of deep rocuronium-induced neuromuscular blockade

    Yu, Buwei; Wang, Xiangrui; Hansen, Søren Helbo


    Objective: Maintenance of deep Neuro Muscular Blockade (NMB) until the end of surgery may be beneficial in some surgical procedures. The selective relaxant binding agent sugammadex rapidly reverses deep levels of rocuronium-induced NMB. The purpose of this study was to evaluate the efficacy...... and safety of sugammadex 4.0 mg kg-1 for reversal of deep rocuronium-induced NMB in Chinese and Caucasian patients. Methods: This was an open-label, multicenter, prospective Phase III efficacy study in adult American Society of Anesthesiologists Class 1-3 patients scheduled for surgery under general...... anesthesia and requiring deep NMB. All patients received intravenous propofol and opioids for induction and maintenance of anesthesia, and a single intubation dose of rocuronium 0.6 mg/kg, with maintenance doses of 0.1-0.2 mg/kg as required. Sugammadex 4.0 mg/kg was administered after the last dose...

  19. Safety and tolerability of donepezil 23 mg in moderate to severe Alzheimer's disease

    Zou Heng


    Full Text Available Abstract Background Donepezil 23 mg/d, recently approved in the United States for treatment of moderate to severe Alzheimer's disease (AD, was developed to address the need for an additional treatment option for patients with advanced AD. This report, based on a pivotal phase 3 study, presents a detailed analysis of the safety and tolerability of increasing donepezil to 23 mg/d compared with continuing 10 mg/d. Method Safety analyses comprised examination of the incidence, severity, and timing of treatment-emergent adverse events (AEs and their relationship to treatment initiation; changes in weight, electrocardiogram, vital signs, and laboratory parameters; and the incidence of premature study discontinuation. The analysis population (n = 1434 included all randomized patients who took at least 1 dose of study drug and had a postbaseline safety assessment. To further examine the effect of transition from a lower to a higher donepezil dose, a pooled analysis of safety data from 2 phase 3 trials of donepezil 5 mg/d and 10 mg/d was also performed. Results The safety population comprised 1434 patients: donepezil 23 mg/d (n = 963; donepezil 10 mg/d (n = 471; completion rates were 71.1% and 84.7%, respectively. The most common AEs were nausea, vomiting, and diarrhea (donepezil 23 mg/d: 11.8%, 9.2%, 8.3%; donepezil 10 mg/d: 3.4%, 2.5%, 5.3%, respectively. AEs that contributed most to early discontinuations were vomiting (2.9% of patients in the 23 mg/d group and 0.4% in the 10 mg/d group, nausea (1.9% and 0.4%, diarrhea (1.7% and 0.4%, and dizziness (1.1% and 0.0%. The percentages of patients with AEs in the 23 mg/d group, as well as the timing, type, and severity of these AEs, were similar to those seen in previous donepezil trials with titration from 5 to 10 mg/d. Serious AEs were uncommon (23 mg/d, 8.3%; 10 mg/d, 9.6%. Discussion The 23 mg/d dose of donepezil was associated with typical cholinergic AEs, particularly gastrointestinal-related AEs

  20. Thermodynamic modeling of the La-Mg-Y system and Mg-based alloys database

    DU Zhenmin; GUO Cuiping; LI Changrong; ZHANG Weijing


    As an example of the La-Mg-Y system, the method how to set up the thermodynamic model of individual phases was introduced in the process of thermodynamic optimization. The solution phases (liquid, body-centered cubic,face-centered cubic, hexagonal close-packed and double hexagonal close-packed) were modeled with the Redlich-Kister equation. The compound energy model has been used to describe the thermodynamic functions of the intermetallic compounds in the La-Mg-Y systems. The compounds Mg2Y, Mg24Y5, Mg12La, Mg17La2, Mg41La5, Mg3La and Mg2La in the La-Mg-Y system were treated as the formulae (Mg, Y)2(La,Mg, Y), Mg24(La,Mg, Y)4Y, Mg12(La, Y), Mg17(La, Y)2,Mg41(La,Y)5, Mg3(La,Mg,Y) and Mg2(La,Y), respectively. A model (La,Mg,Y)0.5(La,Mg,Y)0.5 was applied to describe the compound MgM formed by MgLa and MgY in order to cope with the order-disorder transition between body-centered cubic solution (A2) and MgM with CsCl-type structure (B2) in the La-Mg-Y system. The Gibbs energies of individual phases were optimized in the La-Mg, La-Y and La-Mg-Y systems by CALPHAD technique. The projection of the liquidus surfaces for the La-Mg-Y system was predicted. The Mg-based alloys database including 36 binary and 15 ternary systems formed by Mg, Al, Cu, Ni, Mn, Zn and rare earth elements was set up in SGTE standard.

  1. [Mechanism of HL-60 cells apoptosis induced by proteasome inhibitor MG132].

    Zhou, Yong-Ming; Yu, Mei-Xia; Qiu, Yu-Zhen; Xing, Xiao-Lei; Yao, Chun-Hong; Bai, Ru-Jun


    The purpose of this study was to elucidate the apoptosis, apoptotic pathway of HL-60 cells induced by proteasome inhibitor MG132 and its effect on allogeneic mixed lymphocyte reaction. Apoptosis of HL-60 cells was detected by flow cytometry, the expression of P21, P27 and P53 proteins in HL-60 cells treated with MG132 was assayed by Western blot. The HL-60 cells were treated with 1 µmol/L MG132 for 48 h, and irradiated by 75 Gy of (60)Co γ-ray, but their antigenicity was preserved. The effect of irradiated HL-60 cells treated with MG132 on proliferation of peripheral blood mononuclear cells (PBMNC) was measured by CCK-8 method. The results showed that the apoptotic rate of MG132-treated HL-60 cells increased in dose-and time-dependent manner. No significant changes in MG132-induced apoptosis were observed after inhibiting caspase-8 and caspase-9 pathway. The expression of P21 and P27 protein increased after treatment of HL-60 cells with MG132. CCK-8 test showed that HL-60 cells induced with low-dose of MG132 displayed the enhancing effect on proliferation of PBMNC. It is concluded that high dose of MG132 can induce the apoptosis of HL-60 cells, and has direct killing effect on HL-60 cells, but this inducing apoptotic effect on HL-60 cells can not be realized through caspase-8 and caspase-9 pathway. The P21 and P27 protein may be involved in MG132 induced HL-60 cell apoptosis. Low dose of MG132 promotes the proliferation of PBMNC in healthy individuals and enhance the immunity of organism.

  2. Dose-finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia.

    Deenik, Wendy; van der Holt, Bronno; Verhoef, Gregor E G; Smit, Willem M; Kersten, Marie J; Kluin-Nelemans, Hanneke C; Verdonck, Leo F; Ferrant, Augustin; Schattenberg, Anton V M B; Janssen, Jeroen J W M; Sonneveld, Pieter; van Marwijk Kooy, Marinus; Wittebol, Shulamit; Willemze, Roelof; Wijermans, Pierre W; Westveer, Petra H M; Beverloo, H Berna; Valk, Peter; Löwenberg, Bob; Ossenkoppele, Gert J; Cornelissen, Jan J


    The HOVON cooperative study group performed a feasibility study of escalated imatinib and intravenous cytarabine in 165 patients with early chronic-phase chronic myeloid leukemia (CML). Patients received 2 cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) days 1-7) in conjunction with imatinib (200 mg, 400 mg, 600 mg, or 800 mg), according to predefined, successive dose levels. All dose levels proved feasible. Seven dose-limiting toxicities (DLTs) were observed in 302 cycles of chemotherapy, which were caused by streptococcal bacteremia in 5 cases. Intermediate-dose cytarabine (1000 mg/m(2)) prolonged time to neutrophil recovery and platelet recovery compared with a standard dose (200 mg/m(2)). High-dose imatinib (600 mg or 800 mg) extended the time to platelet recovery compared with a standard dose (400 mg). More infectious complications common toxicity criteria (CTC) grade 3 or 4 were observed after intermediate-dose cytarabine compared with a standard-dose of cytarabine. Early response data after combination therapy included a complete cytogenetic response in 48% and a major molecular response in 30% of patients, which increased to 46% major molecular responses at 1 year, including 13% complete molecular responses. We conclude that combination therapy of escalating dosages of imatinib and cytarabine is feasible. This study was registered at as no. CKTO-2001-03.

  3. Risperidone Dosing in Children and Adolescents with Autistic Disorder: A Double-Blind, Placebo-Controlled Study

    Kent, Justine M.; Kushner, Stuart; Ning, Xiaoping; Karcher, Keith; Ness, Seth; Aman, Michael; Singh, Jaskaran; Hough, David


    Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism. Patients (N = 96; 5-17 years), received risperidone (low-dose: 0.125 mg/day [20 to 45 kg] or high-dose: 1.25 mg/day [20 to 45 kg]) or placebo. Mean baseline (range 27-29) to endpoint change…

  4. A comparison of high-dose and low-dose tranexamic acid antifibrinolytic protocols for primary coronary artery bypass surgery

    Stephen M McHugh


    Full Text Available Background and Aims: Tranexamic acid (TA is used for prophylactic antifibrinolysis in coronary artery bypass surgeries to reduce bleeding. We evaluated the efficacy of two different doses of TA for prophylactic antifibrinolysis in patients undergoing primary coronary artery bypass grafting (CABG surgery in this retrospective cohort study at a tertiary care referral centre. Methods: One-hundred eighty-four patients who underwent primary CABG with cardiopulmonary bypass (CPB via sternotomy between January 2009 and June 2011 were evaluated. Pre-operative patient characteristics, intraoperative data, post-operative bleeding, transfusions, organ dysfunction and 30-day mortality were compared between high-dose TA (30 mg/kg loading dose followed by infusion of 15 mg/kg/h until the end of surgery along with 2 mg/kg priming dose in the bypass circuit and low-dose TA (15 mg/kg loading dose followed by infusion of 6 mg/kg/h until the end of surgery along with 1 mg/kg priming dose in the bypass circuit groups. Univariate comparative analysis of all categorical and continuous variables was performed between the two groups by appropriate statistical tests. Linear and logistic regression analyses were performed to control for the effect of confounding on the outcome variables. Results: Chest tube output, perioperative transfusion of blood products and incidence of re-exploration for bleeding did not differ significantly (P> 0.05 between groups. Post-operative complications and 30-day mortality were comparable between the groups. The presence of cardiogenic shock and increased pre-operative creatinine were found to be associated with increased chest tube output on the post-operative day 2 by multivariable linear regression model. Conclusions: Low-dose TA protocol is as effective as high-dose protocol for antifibrinolysis in patients undergoing primary CABG with CPB.



    SUMMARY One-hundred-and-fifteen patients diagnosed as anxiety neurotics randomly received in a double blind study 20 mg clobazam (Frisium) as a single nightly dose (37 patients) or 10 mg b.d. (38 patients) or diazepam 5 mg b.d. (40 patients) for six weeks, followed by two weeks on placebo. Both the single and divided doses of clobazam were therapeutically equivalent to diazepam. After drug withdrawal, all three treatment groups continued to improve. Patients on clobazam showed better motor pe...

  6. Energetic dose: Beyond fire and flint?

    Linder, G.; Rattner, B.; Cohen, J.


    Nutritional and bioenergetic interactions influence exposure to environmental chemicals and may affect the risk realized when wildlife are exposed in the field. Here, food-chain analysis focuses on prairie voles (Microtus ochrogaster) and the evaluation of chemical risks associated with paraquat following 10-d dietary exposures. Reproductive effects were measured in 60-d trials that followed exposures to paraquat-tainted feed: control (untainted feed); 21 mg paraquat/kg feed; 63 mg paraquat/kg feed; and feed-restricted control (untainted feed restricted to 60% baseline consumption). Reproductive success was evaluated in control and treated breeding pairs, and a preliminary bioenergetics analysis was completed in parallel to derive exposure dose. Although reproductive performance differed among groups, feed-restriction appeared to be the dominant treatment effect observed in these 10-d feeding exposure/limited reproductive trials. Exposure dose ranged from 3.70-3.76 to 9.41-11.51 mg parquat/kg BW/day at 21 and 63 mg paraquat/kg feed stock exposures, respectively. Energetic doses as ug paraquat/kcal yielded preliminary estimates of energetic costs associated with paraquat exposure, and were similar within treatments for both sexes, ranging from 4.2-5.5 and 13.1-15.0 ug paraquat/kcal for voles exposed to 21 mg/kg feed stock and 63 mg/kg feed stock, respectively. Given the increasing likelihood that environmental chemicals will be found in wildlife habitat at 'acceptable levels', the critical role that wildlife nutrition plays in evaluating ecological risks should be fully integrated into the assessment process. Tools applied to the analysis of risk must gain higher resolution than the relatively crude methods we currently bring to the process.

  7. Tardive dyskinesia with low dose amisulpride.

    Tharoor, Hema; Padmavati, R


    In recent years, there has been an increasing trend to use amisulpride in the treatment of dysthymia and also as an adjunct treatment in patients with major depression. At low doses (50 mg), amisulpride preferentially blocks presynaptic auto receptors, enhances dopamine release, and therefore acts as a dopaminergic compound able to resolve the dopaminergic hypo activity that characterizes depression. Based on experimental data, amisulpride is the drug of choice for dopaminergic transmission disorders, both in depression and in schizophrenia. This case highlights the development of dyskinesia in a depressed patient treated with low dose amisulpride and fluvoxamine.


    Jiang, Weilin; Jung, Hee Joon; Kovarik, Libor; Wang, Zhaoying; Roosendaal, Timothy J.; Zhu, Zihua; Edwards, Danny J.; Hu, Shenyang Y.; Henager, Charles H.; Kurtz, Richard J.; Wang, Yongqiang


    As a candidate material for fusion reactor applications, silicon carbide (SiC) undergoes transmutation reactions under high-energy neutron irradiation with magnesium as the major metallic transmutant; the others include aluminum, beryllium and phosphorus in addition to helium and hydrogen gaseous species. Calculations by Sawan et al. predict that at a dose of ~100 dpa (displacements per atom), there is ~0.5 at.% Mg generated in SiC. The impact of these transmutants on SiC structural stability is currently unknown. This study uses ion implantation to introduce Mg into SiC. Multiaxial ion-channeling analysis of the as-produced damage state indicates a lower dechanneling yield observed along the <100> axis. The microstructure of the annealed sample was examined using high-resolution scanning transmission electron microscopy. The results show a high concentration of likely non-faulted tetrahedral voids and possible stacking fault tetrahedra near the damage peak. In addition to lattice distortion, dislocations and intrinsic and extrinsic stacking faults are also observed. Magnesium in 3C–SiC prefers to substitute for Si and it forms precipitates of cubic Mg2Si and tetragonal MgC2. The diffusion coefficient of Mg in 3C–SiC single crystal at 1573 K has been determined to be 3.8 ± 0.4E-19 m2/s.

  9. Fesoterodine dose response in subjects with overactive bladder syndrome.

    Khullar, Vik; Rovner, Eric S; Dmochowski, Roger; Nitti, Victor; Wang, Joseph; Guan, Zhonghong


    To compare the efficacy of fesoterodine 4 mg versus 8 mg in treating subjects with overactive bladder (OAB) syndrome. This is a pooled analysis of data from 2 randomized placebo (PBO)-controlled phase III trials. Eligible subjects with frequency and urgency or urgency urinary incontinence (UUI) were randomized to PBO or fesoterodine 4 or 8 mg for 12 weeks. Subjects assessed efficacy using 3-day bladder diaries recording the time of each void, urgency, and incontinence episode. Endpoints included treatment response (based on a 4-point Treatment Benefit scale) and change from baseline in micturitions, UUI episodes, mean volume voided, urgency episodes, and continent days. We assessed tolerability and safety by evaluating adverse events, residual urine volume, laboratory parameters, and treatment withdrawals. At the end of treatment, both doses of fesoterodine showed statistically significant improvements in all efficacy endpoints versus PBO (P Fesoterodine 8 mg performed significantly better than fesoterodine 4 mg in improving all diary variables (P fesoterodine than with PBO included dry mouth, constipation, and urinary tract infection. Both fesoterodine 4 and 8 mg are effective in improving OAB symptoms. The higher 8-mg dose provides additional benefit compared with the lower dose in improving most bladder diary variables, thus offering the possibility of dose flexibility and titration.

  10. Preparation and Hydrogen Storage Properties of Mg-Rich Mg-Ni Ultrafine Particles

    Jianxin Zou


    Full Text Available In the present work, Mg-rich Mg-Ni ultrafine powders were prepared through an arc plasma method. The phase components, microstructure, and hydrogen storage properties of the powders were carefully investigated. It is found that Mg2Ni and MgNi2 could be obtained directly from the vapor state reactions between Mg and Ni, depending on the local vapor content in the reaction chamber. A nanostructured MgH2 + Mg2NiH4 hydrogen storage composite could be generated after hydrogenation of the Mg-Ni ultrafine powders. After dehydrogenation, MgH2 and Mg2NiH4 decomposed into nanograined Mg and Mg2Ni, respectively. Thermogravimetry/differential scanning calorimetry (TG/DSC analyses showed that Mg2NiH4 phase may play a catalytic role in the dehydriding process of the hydrogenated Mg ultrafine particles.

  11. Maternal high-dose folic acid during pregnancy and asthma medication in the offspring

    Zetstra-van der Woude, Priscilla A.; De Walle, Hermien E. K.; Hoek, Annemieke; Bos, H. Jens; Boezen, H. Marike; Koppelman, Gerhard H.; de Jong-van den Berg, Lolkje T. W.; Scholtens, Salome


    Purpose Low-dose folic acid supplementation (0.5 mg) taken during pregnancy has been associated with an increased risk for childhood asthma. The effect of high-dose folic acid (5 mg) advised to women at risk for having a child with neural tube defect has not been assessed so far. Our aim was to inve

  12. Tenoxicam 20 mg or 40 mg after thoracotomy: a prospective, randomized, double-blind, placebo-controlled study.

    Merry, A F; Sidebotham, D A; Middleton, N G; Calder, M V; Webster, C S


    Forty-five adults undergoing thoracotomy were randomized to receive placebo, tenoxicam 20 mg or tenoxicam 40 mg IV during chest wall closure. All patients received intraoperative fentanyl and intercostal blocks followed by morphine by patient-controlled analgesia. Patient numbers 13 to 45 also received thoracic epidural analgesia by continuous infusion of bupivacaine 0.125%, patient numbers 25 to 45 having fentanyl 2 microg/ml added to the epidural infusion. Efficacy parameters and adverse reactions were assessed over the first 24 hours postoperatively. On a 100 mm visual analogue scale, mean (SD) pain at rest (adjusted area under curve for hours 1 to 24) was 25.8 (12.5), 17.4 (14.8) and 16.5 (13.3) mm for groups receiving placebo, 20 mg and 40 mg tenoxicam, respectively (ANOVA: P<0.05). There were no significant differences between study groups postoperatively in pain on coughing, opioid consumption, blood gas measurements, nausea, vomiting, sedation, blood loss, haemoglobin or serum creatinine. One patient in each tenoxicam group reported epigastric pain, rated moderate. These data support the inclusion of tenoxicam 20 mg IV in the management of pain at rest for patients undergoing thoracotomy, but do not show additional benefit for a higher dose.

  13. Pegvisomant bioavailability of single 30 mg/mL subcutaneous injection compared to two 15 mg/mL subcutaneous injections: a pharmacokinetic, safety and tolerability study.

    Jen, Juif; LaBadie, Robert R; Liang, Yali; Crownover, Penelope H; Gao, Xiang; Hey-Hadavi, Juliana H


    The study was conducted to evaluate the pharmacokinetics (PK), relative bioavailability (relBA), safety and tolerability of two single-dose pegvisomant subcutaneous (SC) administrations: one injection of 30 mg/mL (1 × 30 mg/mL) versus two injections of two 15 mg/mL (2 × 15 mg/mL). This was a 2-period, single-dose, crossover study in 14 healthy male and female subjects. All subjects received both administrations during the two treatment periods separated by a two-week washout. Serum samples were collected intensively up to 360 h post injection and were assayed by a validated enzyme linked immunosorbent assay (ELISA) for pegvisomant. PK parameters including AUC and Cmax were derived by noncompartmental analyses. Mixed effects model was used to obtain bioavailability estimates. Safety and tolerability were assessed by clinical monitoring, including adverse events, laboratory assessments and injection site reactions. All subjects completed the study. The relBA of 1 × 30 mg/mL relative to 2 × 15 mg/mL was 123.89% with a 90% CI (112.91-135.93%). Adjusted for the difference in actual pegvisomant amounts in both formulations the dose-adjusted relBA reduced to 112.97% with a 90% CI (103.09-123.80%). Single injection with a higher drug concentration in injection solution might have a role in this 13% higher bioavailability for 1 × 30 mg/mL administration. Other PK parameters for the two administrations were comparable. No laboratory abnormalities, vital signs, ECG, or injection site reactions of clinical concern were observed in either treatment. Comparable BA, safety and tolerability of the new 30 mg/mL strength to the currently marketed 15 mg/mL strength were established in this study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Improved efficacy of intramuscular weekly administration of clodronate 200 mg (100 mg twice weekly) compared with 100 mg (once weekly) for increasing bone mineral density in postmenopausal osteoporosis.

    Frediani, Bruno; Bertoldi, Ilaria; Pierguidi, Serena; Nicosia, Antonella; Picerno, Valentina; Filippou, Georgios; Cantarini, Luca; Galeazzi, Mauro


    Clodronate is a bisphosphonate used for the treatment of postmenopausal osteoporosis and all conditions characterized by excess bone resorption. We have previously reported that intramuscular (IM) therapy with clodronate at a dose of 100 mg/week displays significant effects on bone mineral density (BMD) although a plateau effect is observed after 1 year of treatment. Previous reports indicate that the densitometric effects of bisphosphonates directly correlate with the drug dosage and suggest that using IM clodronate at doses higher than 100 mg/week may result in improved efficacy. However, to the best of our knowledge, this has never been proved. The primary endpoint of the study was the effect on BMD of IM clodronate 100 mg once weekly or 100 mg twice weekly in patients with postmenopausal osteoporosis. The incidence of non-traumatic vertebral fractures and adverse events was also reported. The present study was a randomized, open-label, parallel-group trial conducted between January 2007 and December 2009 in the Osteoporosis and Osteoarticular Instrumental Diagnosis Centre (University of Siena, Siena, Italy). The study involved 60 women, aged 57-78 years, with a history of postmenopausal osteoporosis for more than 5 years. Patients were randomized to receive IM clodronate 100 mg once weekly (Group A, 30 patients) or 100 mg twice weekly (Group B, 30 patients), for 2 years. Significant increases compared with baseline in BMD were observed for both groups at 1 and 2 years, with significantly higher increases for Group B compared with Group A. Group B displayed a BMD increase (± SD) at the lumbar spine of +4.0 % (± 2.1) and +5.9 % (± 2.0) at 1 and 2 year(s), respectively, compared with +2.8 % (± 1.7) and +3.5 % (± 2.2), respectively, observed for Group A. Similarly, Group B showed better performance compared with Group A for BMD increase at the femoral neck, with an observed increase of +3.5 % (± 1.7) and +5.4 % (± 1.8) at 1 and 2 year(s), respectively

  15. Toxicity from repeated doses of acetaminophen in children: assessment of causality and dose in reported cases.

    Heard, Kennon; Bui, Alison; Mlynarchek, Sara L; Green, Jody L; Bond, G Randall; Clark, Richard F; Kozer, Eran; Koff, Raymond S; Dart, Richard C


    Liver injury has been reported in children treated with repeated doses of acetaminophen. The objective of this study was to identify and validate reports of liver injury or death in children younger than 6 years who were administered repeated therapeutic doses of acetaminophen. We reviewed US Poison Center data, peer-reviewed literature, US Food and Drug Administration Adverse Event Reports, and US Manufacturer Safety Reports describing adverse effects after acetaminophen administration. Reports that described hepatic abnormalities (description of liver injury or abnormal laboratory testing) or death after acetaminophen administration to children younger than 6 years were included. The identified reports were double abstracted and then reviewed by an expert panel to determine if the hepatic injury was related to acetaminophen and whether the dose of acetaminophen was therapeutic (≤75 mg/kg) or supratherapeutic. Our search yielded 2531 reports of adverse events associated with acetaminophen use. From these cases, we identified 76 cases of hepatic injury and 26 deaths associated with repeated acetaminophen administration. There were 6 cases of hepatic abnormalities and no deaths associated with what our panel determined to be therapeutic doses. A large proportion of cases could not be fully evaluated due to incomplete case reporting. Although we identified numerous examples of liver injury and death after repeated doses of acetaminophen, all the deaths and all but 6 cases of hepatic abnormalities involved doses more than 75 mg/kg per day. This study suggests that the doses of less than 75 mg/kg per day of acetaminophen are safe for children younger than 6 years.

  16. Radio-photoluminescence of highly irradiated LiF:Mg,Ti and LiF:Mg,Cu,P detectors

    Mrozik, Anna; Marczewska, Barbara; Obryk, Barbara; Hodyr, Krzysztof; Gieszczyk, Wojciech


    The radio-photoluminescent (RPL) characteristics of LiF:Mg,Ti (MTS) and LiF:Mg,Cu,P (MCP) thermoluminescent detectors, routinely used in radiation protection dosimetry, were investigated after irradiation with ultra-high electron doses ranging up to 1 MGy. The photoluminescence of both types of LiF detectors was stimulated by a blue light (460 nm) and measured within a spectral window around 530 nm. The RPL dose response was found to be linear up to 50 kGy and sublinear in the range of 50 kGy to 1 MGy for MCP detectors and linear up to 3 kGy and next sublinear in the range from 5 kGy to 1 MGy for MTS detectors. For both type of LiF detectors RPL signal is saturated for doses higher than 100 kGy. The observed differences between MCP and MTS may suggest, that the RPL effect in LiF is not entirely governed by intrinsic defects (F2 and F3+ centers), but impurities may also have a significant influence. Due to the non-destructive character of the RPL measurement, it is suggested to apply combined RPL/TL readouts, ...

  17. Highly (100) oriented MgO growth on thin Mg layer in MTJ structure

    Jimbo, K [Department of Physical Electronics, Tokyo Institute of Technology, 2-12-1-S3-42 O-okayama, Meguro, Tokyo 152-8552 (Japan); Nakagawa, S, E-mail:


    In order to apply Stress Assisted Magnetization Reversal (SAMR) method to perpendicular magnetoresistive random access memory (p-MRAM) with magnetic tunnel junction (MTJ) using MgO (001) oriented barrier layer, multilayer of Ta/ Terfenol-D/ Mg/ MgO and Ta/ Terfenol-D/ MgO were prepared. While the MgO layer, deposited directly on the Terfenol-D layer, did not show (100) orientatin, very thin metallic Mg layer, deposited prior to the MgO deposition, was effective to attain MgO (100) orientation. The crystalline orientation was very weak without Mg, however, the multilayer with Mg showed very strong MgO(100) peak and the MgO orientation was shifted depending on the Mg thickness.

  18. Effect of combination tablets containing amlodipine 10 mg and irbesartan 100 mg on blood pressure and cardiovascular risk factors in patients with hypertension

    Yagi S


    Full Text Available Shusuke Yagi,1 Akira Takashima,1 Minoru Mitsugi,2 Toshihiro Wada,2 Junko Hotchi,1 Ken-ichi Aihara,3 Tomoya Hara,1 Masayoshi Ishida,1 Daiju Fukuda,4 Takayuki Ise,1 Koji Yamaguchi,1 Takeshi Tobiume,1 Takashi Iwase,1 Hirotsugu Yamada,1 Takeshi Soeki,1 Tetsuzo Wakatsuki,1 Michio Shimabukuro,4 Masashi Akaike,5 Masataka Sata11Department of Cardiovascular Medicine, Graduate School of Health Biosciences, University of Tokushima, Tokushima, 2Department of Internal Medicine, Shikoku Central Hospital, Shikokuchuo, 3Department of Medicine and Bioregulatory Sciences, 4Department of Cardio-Diabetes Medicine, 5Department of Medical Education, Graduate School of Health Biosciences, University of Tokushima, Tokushima, JapanBackground: Hypertension is one of the major risk factors for cardiovascular and cerebrovascular disease and mortality. Patients who receive insufficient doses of antihypertensive agents or who are poorly adherent to multidrug treatment regimens often fail to achieve adequate blood pressure (BP control. The aim of this study was to determine the efficacy of an angiotensin II receptor blocker (ARB and calcium channel blocker (CCB combination tablet containing a regular dose of irbesartan (100 mg and a high dose of amlodipine (10 mg with regard to lowering BP and other risk factors for cardiovascular disease.Methods: We retrospectively evaluated data from 68 patients with essential hypertension whose treatment regimen was changed either from combination treatment with an independent ARB and a low-dose or regular-dose CCB or from a combination tablet of ARB and a low-dose or regular-dose CCB to a combination tablet containing amlodipine 10 mg and irbesartan 100 mg, because of incomplete BP control. Previous treatments did not include irbesartan as the ARB.Results: The combination tablet decreased systolic and diastolic BP. In addition, it significantly decreased serum uric acid, low-density lipoprotein cholesterol, and increased high

  19. Effects of voluntary dose escalation in a placebo-controlled, flexible-dose trial of fesoterodine in subjects with overactive bladder.

    Staskin, David; Khullar, Vik; Michel, Martin C; Morrow, Jon D; Sun, Franklin; Guan, Zhonghong; Dmochowski, Roger


    To characterize the response to fesoterodine treatment for overactive bladder (OAB) in subjects who did or did not choose to dose escalate in a flexible-dose study. Subjects were randomized to fesoterodine 4  mg or placebo. At week 2, subjects could remain on 4  mg (non-escalators) or choose to increase to 8  mg (escalators) for the remaining 10 weeks (sham escalation for placebo). Subjects completed 3-day bladder diaries at baseline, week 2 and week 12 noting micturitions, urgency episodes, and urgency urinary incontinence (UUI) episodes. Sixty-three per cent of 438 subjects randomized to fesoterodine and 73% of 445 randomized to placebo dose escalated. At baseline, fesoterodine escalators had significantly more micturitions and urgency episodes than fesoterodine non-escalators (P fesoterodine non-escalators versus escalators (P fesoterodine non-escalators and escalators (P > 0.05). The placebo escalator group did not demonstrate a similar response over placebo non-escalators following the dose escalation decision point. A rapid and robust response to fesoterodine 4  mg was demonstrated in non-escalators. Subjects who chose to dose escalate to fesoterodine 8  mg at week 2 showed significant improvement by week 12 versus baseline and week 2 (prior to escalation), as well as versus placebo. Dose escalation to 8  mg fesoterodine provided subjects with efficacy and tolerability similar to those who were satisfied with the 4-mg dose. Copyright © 2011 Wiley Periodicals, Inc.

  20. Fabrication and superconducting properties of internal Mg diffusion processed MgB2 wires using MgB4 precursors

    Xu, Da; Wang, Dongliang; Yao, Chao; Zhang, Xianping; Ma, Yanwei; Oguro, Hidetoshi; Awaji, Satoshi; Watanabe, Kazuo


    Monofilament MgB2/Nb/Monel wires were fabricated using three different MgB4 precursors by an internal Mg diffusion (IMD) process. The wire geometry and heat-treatment conditions were optimized in order to improve the critical current density (J c) of the MgB2 wire. The influences of the quality of MgB4 powders, such as the particle size and MgO impurity, on the microstructure and superconducting properties of the wires were discussed. Although there were small amounts of voids, unreacted MgB4 particles and MgO impurity existed in the superconducting layers, and the transport layer J c of the wire with the MgB4 precursor reached 3.0 × 104 A cm-2 at 4.2 K and 10 T, which was comparable to that of IMD-processed wires fabricated using boron precursors. Both the non-barrier J c and engineering J c of MgB2 wire made using a MgB4 precursor were enhanced due to the improved grain connectivity and the enlarged fill factor.

  1. Determination of the 36Mg(n ,γ )37Mg reaction rate from Coulomb dissociation of 37Mg

    Shubhchintak; Chatterjee, R.; Shyam, R.


    We use the Coulomb dissociation (CD) method to calculate the rate of the 36Mg(n ,γ )37Mg radiative capture reaction. The CD cross sections of the 37Mg nucleus on a 208Pb target at the beam energy of 244 MeV/nucleon, for which new experimental data have recently become available, were calculated within the framework of a finite-range distorted-wave Born approximation theory that is extended to include the projectile deformation effects. Invoking the principle of detailed balance, these cross sections are used to determine the excitation function and subsequently the rate of the 36Mg(n ,γ )37Mg reaction. We compare these rates to those of the 36Mg(α ,n )39Si reaction calculated within a Hauser-Feshbach model. We find that for T9 as large as up to 1.0 (in units of 109 K) the 36Mg(n ,γ )37Mg reaction is much faster than the 36Mg(α ,n )39Si one. The inclusion of the effects of 37Mg projectile deformation in the breakup calculations enhances the (n ,γ ) reaction rate even further. Therefore, it is highly unlikely that the (n ,γ )β -decay r -process flow will be broken at the 36Mg isotope by the α process.

  2. Subantimicrobial dose doxycycline for acne and rosacea.

    Bikowski, Joseph B


    Acne vulgaris and rosacea present therapeutic challenges due to their chronicity, potential for disfigurement, and psychosocial impact. Although pathophysiologically distinct, both conditions have major inflammatory components. Consequently, topical and systemic antimicrobial agents are routinely prescribed for extended periods. Emergence of resistant strains of Propionibacterium acnes, adverse events, and compliance issues associated with chronic systemic tetracycline use have led to new treatment approaches. At subantimicrobial doses, tetracyclines reduce inflammation via anticollagenolytic, antimatrix-degrading metalloproteinase, and cytokine down-regulating properties. Subantimicrobial dose (SD) doxycycline (Periostat 20 mg) has clinical utility in periodontitis and has been investigated in a double-blind, placebo-controlled trial in the treatment of moderate facial acne as well as in an open label study in the treatment of rosacea. The results of subantimicrobial dose doxycycline treatment in early trials support its benefits and further investigation in acne and rosacea.

  3. The coordination of Mg in foraminiferal calcite

    Branson, Oscar; Redfern, Simon A. T.; Tyliszczak, Tolek; Sadekov, Aleksey; Langer, Gerald; Kimoto, Katsunori; Elderfield, Henry


    The Mg/Ca ratio of foraminiferal calcite is a widely accepted and applied empirical proxy for ocean temperature. The analysis of foraminifera preserved in ocean sediments has been instrumental in developing our understanding of global climate, but the mechanisms behind the proxy are largely unknown. Analogies have been drawn to the inorganic precipitation of calcite, where the endothermic substitution of Mg for Ca is favoured at higher temperatures. However, evidence suggests that foraminiferal Mg incorporation may be more complex: foraminiferal magnesium is highly heterogeneous at the sub-micron scale, and high Mg areas coincide with elevated concentrations of organic molecules, Na, S and other trace elements. Fundamentally, the incorporation mode of Mg in foraminifera is unknown. Here we show that Mg is uniformly substituted for Ca within the calcite mineral lattice. The consistency of Mg-specific X-ray spectra gathered from nano-scale regions across the shell (‘test’) reveals that the coordination of Mg is uniform. The similarity of these spectra to that produced by dolomite shows that Mg is present in an octahedral coordination, ideally substituted for Ca in a calcite crystal structure. This demonstrates that Mg is heterogeneous in concentration, but not in structure. The degree of this uniformity implies the action of a continuous Mg incorporation mechanism, and therefore calcification mechanism, across these compositional bands in foraminifera. This constitutes a fundamental step towards a mechanistic understanding of foraminiferal calcification processes and the incorporation of calcite-bound palaeoenvironment proxies, such as Mg.

  4. Phase I Study of Continuous Weekly Dosing of Dimethylamino Benzoylphenylurea (BPU) in Patients with Solid Tumours

    Messersmith, Wells A.; Rudek, Michelle A.; Baker, Sharyn D.; Zhao, Ming; Collins, Connie; Colevas, A. Dimitrios; Donehower, Ross C.; Carducci, Michael A.; Wolff, Antonio C.


    A phase I study of Dimethylamino Benzoylphenylurea (BPU), a tubulin inhibitor, was performed using a weekly continuous schedule. Patients with refractory solid tumours received oral BPU once weekly without interruption at doses ranging from 5 to 320mg using an accelerated titration design. Nineteen subjects received 54 cycles of BPU. Early pharmacokinetic findings of decreased clearance with increasing dose and plasma accumulation led to the expansion of the 320mg dose level. Two subjects the...

  5. Highway driving in the elderly the morning after bedtime use of hypnotics: a comparison between temazepam 20 mg, zopiclone 7.5 mg, and placebo.

    Leufkens, Tim R M; Vermeeren, Annemiek


    A major problem related to hypnotic drug use is residual sedation the morning after bedtime administration. This constitutes a particular safety hazard for patients who have to drive a car the next morning. Information on the severity of residual effects is mainly derived from studies conducted with young healthy volunteers. However, most users of hypnotics are older people who may be more sensitive to drug effects. The aim of this study was to evaluate the residual effects the morning after evening doses of temazepam 20 mg and zopiclone 7.5 mg on driving performance in healthy elderly drivers. Eighteen healthy elderly drivers (10 females and 8 males; mean age, 64.3 years) participated in a double-blind, 3-way crossover study. Treatments were single oral doses of temazepam 20 mg, zopiclone 7.5 mg, and placebo administered at bedtime. Subjects performed a standardized highway driving test between 10 and 11 hours after hypnotic intake. Before and after the driving test, cognitive performance was assessed. Driving performance did not differ between temazepam and placebo but was significantly impaired after zopiclone 7.5 mg (P hypnotics. Temazepam 20 mg is unlikely to impair driving 10 hours or more after bedtime administration in healthy elderly aged 75 years or younger. Zopiclone 7.5 mg moderately impairs driving in the elderly at least until 11 hours after administration. The magnitude of impairing effects in the elderly was comparable with those found previously in younger volunteers.

  6. Modeling and stabilities of Mg/MgH2 interfaces: A first-principles investigation

    Tang, Jia-Jun; Yang, Xiao-Bao; Chen, Li-Juan; Zhao, Yu-Jun


    We have theoretically investigated the modeling and the structural stabilities of various Mg/MgH2 interfaces, i.e. Mg(10bar 10)/MgH2(210), Mg(0001)/MgH2(101) and Mg(10bar 10)/MgH2(101), and provided illuminating insights into Mg/MgH2 interface. Specifically, the main factors, which impact the interfacial energies, are fully considered, including surface energies of two phases, mutual lattice constants of interface model, and relative position of two phases. The surface energies of Mg and MgH2, on the one hand, are found to be greatly impacting the interfacial energies, reflected by the lowest interfacial energy of Mg(0001)/MgH2(101) which is comprised of two lowest energy surfaces. On the other hand, it is demonstrated that the mutual lattice constants and the relative position of two phases lead to variations of interfacial energies, thus influencing the interface stabilities dramatically. Moreover, the Mg-H bonding at interface is found to be the determinant of Mg/MgH2 interface stability. Lastly, interfacial and strain effects on defect formations are also studied, both of which are highly facilitating the defect formations. Our results provide a detailed insight into Mg/MgH2 interface structures and the corresponding stabilities.

  7. Modeling and stabilities of Mg/MgH2 interfaces: A first-principles investigation

    Jia-Jun Tang


    Full Text Available We have theoretically investigated the modeling and the structural stabilities of various Mg/MgH2 interfaces, i.e. Mg(101¯0/MgH2(210, Mg(0001/MgH2(101 and Mg(101¯0/MgH2(101, and provided illuminating insights into Mg/MgH2 interface. Specifically, the main factors, which impact the interfacial energies, are fully considered, including surface energies of two phases, mutual lattice constants of interface model, and relative position of two phases. The surface energies of Mg and MgH2, on the one hand, are found to be greatly impacting the interfacial energies, reflected by the lowest interfacial energy of Mg(0001/MgH2(101 which is comprised of two lowest energy surfaces. On the other hand, it is demonstrated that the mutual lattice constants and the relative position of two phases lead to variations of interfacial energies, thus influencing the interface stabilities dramatically. Moreover, the Mg-H bonding at interface is found to be the determinant of Mg/MgH2 interface stability. Lastly, interfacial and strain effects on defect formations are also studied, both of which are highly facilitating the defect formations. Our results provide a detailed insight into Mg/MgH2 interface structures and the corresponding stabilities.

  8. Efficacy of reduced dose of pegfilgrastim in Japanese breast cancer patients receiving dose-dense doxorubicin and cyclophosphamide therapy.

    Mizuno, Yoshio; Fuchikami, Hiromi; Takeda, Naoko; Iwai, Masaru; Sato, Kazuhiko


    This retrospective study aimed to evaluate the efficacy of a 3.6-mg dose of pegfilgrastim for primary prophylaxis in Japanese breast cancer patients receiving dose-dense chemotherapy. Patients treated with adjuvant or neoadjuvant chemotherapy for early-stage breast cancer at the Tokyo-West Tokushukai Hospital were included in this analysis. Because 6 mg pegfilgrastim has not yet been approved for use in Japan, we compared the outcomes of a dose-dense doxorubicin and cyclophosphamide regimen plus 3.6 mg pegfilgrastim support with a conventional dose epirubicin and cyclophosphamide regimen. The incidence of febrile neutropenia, relative dose intensity, dose delay, dose reduction, regimen change and hospitalization because of neutropenia were assessed. From November 2013 to March 2016, 97 patients with stage I-III invasive breast cancer were analyzed (dose-dense doxorubicin and cyclophosphamide plus 3.6-mg pegfilgrastim group, n  =  41; epirubicin and cyclophosphamide group, n  =  56; median ages, 49.0 and 48.5 years, respectively). Febrile neutropenia occurred during the first chemotherapy cycle in 7 of 56 patients (12.5%) in the epirubicin and cyclophosphamide group and 0 of 41 patients in the dose-dense doxorubicin and cyclophosphamide group (P  =  0.02). The average relative dose intensities were 97.9% and 96.8%, respectively (P  =  0.28), with corresponding dose delay rates of 4.9% (2/41) and 16.1% (9/56), respectively (P  =  0.11) and dose reduction rates of 0% (0/41) and 7.1% (4/56), respectively (P  =  0.16). Our results indicate the efficacy of a 3.6-mg pegfilgrastim dose for the primary prevention of febrile neutropenia in dose-dense doxorubicin- and cyclophosphamide-treated Japanese breast cancer patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail:

  9. Evaluation of a vancomycin dosing protocol for intensive care unit patients

    Brinkman, I.; Verstappen, G.; Veeger, N.; Boerma, E. C.; Buter, H.


    Vancomycin is a glycopeptide antibiotic that needs to be dosed to achieve target trough levels of 15-20 mg/l. Dosing can be challenging in ICU patients. To optimise therapy, in ICU-pharmacy collaboration, a dosing protocol was introduced on the ICU of the Medical Center Leeuwarden, the Netherlands.




    in 235 patients who underwent transurethral surgery, perioperative oral ciprofloxacin prophylaxis was given as a single dose 500 mg versus a 3-day regimen. Out of 180 evaluable patients, 84 received a single dose and 96 received a 3-day course. In the single dose prophylaxis group there were 5 failu




    in 235 patients who underwent transurethral surgery, perioperative oral ciprofloxacin prophylaxis was given as a single dose 500 mg versus a 3-day regimen. Out of 180 evaluable patients, 84 received a single dose and 96 received a 3-day course. In the single dose prophylaxis group there were 5




    in 235 patients who underwent transurethral surgery, perioperative oral ciprofloxacin prophylaxis was given as a single dose 500 mg versus a 3-day regimen. Out of 180 evaluable patients, 84 received a single dose and 96 received a 3-day course. In the single dose prophylaxis group there were 5 failu

  13. Resveratrol Induces Apoptosis in Human Osteosarcoma MG63 Cells

    Yan Liu; Xin Wang; Yuxin Xie; Jingui Zhang; Qingshan Wang; Xianhui Xu


    OBJECTIVE To investigate apoptosis in human osteosarcoma MG63 cells induced by resveratrol and the molecular mechanism involved.METHODS MG63 cells were treated with different concentrations of resveratrol and transmission electron microscopy was used to observe morphological changes occurring in apoptosis.The MTT method was used to determine the inhibitory rate and flow cytometry was used to assess apoptosis and to analyze the expression of the p21ciP1/WAF1 and survivin proteins;the expression of p21ciP1/WAF1 and survivin mRNAs was analyzed by the reverse transcriptase polymerase chain reaction (RT-PCR).RESULTS After resveratrol treatment,the growth of the MG63 cells was significantly inhibited in a time- and dose-dependent fashion.By transmission electron microscopy,the cells displayed morphological changes characteristic of apoptosis,including formation of cytoplasmic vacuoles,chromatin condensation and margination.Flow cytometry showed that the growth of the cells was inhibited after resveratrol (10 mg/L and 20 mg/L) treatment.The inhibitory rates were (11.9 ±0.63)% and (19.7 ± 0.88)%respectively.The quantity of treated cells in G0/G1 transition was increased,but the number in the S phase and G2/M transition was decreased.A subdiploid peak was observed.The expression of p21ciP1/WAF1 was up-regulated while survivin was down-regulated.CONCLUSION Resveratrol can inhibit growth and induce apoptosis of MG63 cells.Its molecular mechanism might be related to modulation of survivin and p21ciP1/WAF1 expression.

  14. Vancomycin Utilization Evaluation: Are We Dosing Appropriately?

    Ladan Ayazkhoo


    Full Text Available Background: Inappropriate use of vancomycin not only increase health care costs but also contribute to the emergence of resistant organisms. Higher trough serum vancomycin concentrations (>10mg/L has been recommended for avoidance of development of resistance. We aim to compare the administered dose with recommended doses based on guideline-recommended weight-based dosing.Methods: In a cross sectional study, all patients who received vancomycin between July and October 2013, in infectious disease, internal medicine wards and emergency department of a teaching hospital in Tehran, Iran were entered to the study. Indication of vancomycin and necessary data for dose calculation including height and serum creatinine were recorded. Prescribed doses were compared with recommended doses in guidelines and calculated Glomerular filtration rate (GFR for each patient.Results: One hundred and four patients (45 females and 59 males recruited in the study. Our results indicated that, from all administered doses of vancomycin, 64.4% and 88.8% differs significantly (more than 20% based on American Pharmacist Association (AphA vancomycin monograph and guideline-recommended, weight-based vancomycin dosing (for adults, respectively.Conclusion: Underdosing of vancomycin is a major risk factor for developing resistance of gram positive organisms to this glycopeptide. Our results showed that more than half of patients receiving vancomycin are in the risk of low drug levels based on guidelines. So, having a comprehensive plan for the proper use of this drug especially designing effective internal guidelines can prevent emergence of resistance to vancomycin in future.

  15. Analysis of dosimetric peaks of MgB4O7:Dy (40% Teflon versus LiF:Mg,Ti TL detectors

    Paluch-Ferszt Monika


    Full Text Available Magnesium tetraborate doped with dysprosium (MgB4O7:Dy is known as a good thermoluminophor for personal dosimetry of gamma ray and X-ray radiation because of its high sensitivity and close tissue equivalence. This material can be produced by different routes. The sintered pastilles of magnesium tetraborate mixed with Teflon (40% used in this work were manufactured at the Federal University of Sergipe, Department of Physics by the solid-state synthesis. Magnesium tetraborate was already used for high-dose dosimetry, exhibiting linearity for a wide range of doses. In this work, the authors examined its main characteristics prior to potential use of detectors in everyday dosimetry, comparing this material to a widely used LiF:Mg,Ti phosphor. The following tests influencing dosimetric peaks of MgB4O7:Dy were presented: (1 the shape of the glow curves, (2 annealing conditions and post-irradiation annealing and its influence for background of the detectors, (3 the choice of the heating rates at the read-out and (4 the threshold dose, that is, the lowest possible dose to be measured. Similar tests were performed with LiF:Mg,Ti detectors, produced and widely used in Poland. The results were compared and discussed.

  16. Controllable dose; Dosis controlable

    Alvarez R, J.T.; Anaya M, R.A. [ININ, A.P. 18-1027, 11801 Mexico D.F. (Mexico)]. E-mail:


    With the purpose of eliminating the controversy about the lineal hypothesis without threshold which found the systems of dose limitation of the recommendations of ICRP 26 and 60, at the end of last decade R. Clarke president of the ICRP proposed the concept of Controllable Dose: as the dose or dose sum that an individual receives from a particular source which can be reasonably controllable by means of any means; said concept proposes a change in the philosophy of the radiological protection of its concern by social approaches to an individual focus. In this work a panorama of the foundations is presented, convenient and inconveniences that this proposal has loosened in the international community of the radiological protection, with the purpose of to familiarize to our Mexican community in radiological protection with these new concepts. (Author)

  17. Dose intensification of etoposide in the BEAM ABMT protocol for malignant lymphoma.

    Mills, W; Strang, J; Goldstone, A H; Linch, D C


    We have previously demonstrated a dose response relationship in Hodgkin's disease for the combination of BCNU, VP16, Ara C and Melphalan, with the superior efficacy of the BEAM regimen requiring haemopoietic support, compared with miniBEAM. To further exploit this, we have attempted to escalate the VP16 dose in BEAM. The standard etoposide dose is 200 mg/m2 IV for four days. Thirty seven patients with refractory lymphoma received 400 mg/m2/day of etoposide, and 13 patients 600 mg/m2/day, in addition to BCNU, cytarabine, and melphalan. Toxicity and outcome parameters were compared in the preceding 40 patients, who received 200 mg/m2/day etoposide. The toxic mortality with 400 mg/m2/day of etoposide (3%) was identical to that for the standard BEAM regimen (5%). Two procedure related deaths occurred in the highest VP16 dose group (15%). The morbidity of the lower etoposide dose regimens was comparable, but 600 mg/m2/day induced significantly greater gastrointestinal toxicity. Twelve of the 13 patients receiving this dose suffered grade II-IV mucositis, with stomatitis, dysphagia and prolonged diarrhoea; 5 haemodynamically significant gastrointestinal haemorrhage, and 1 fatal toxic colitis. Granulocyte colony stimulating factor did not influence the nonhaematological toxicity. The three month response rates were similar (91%) in all dose cohorts. The maximum tolerable etoposide dose within the BEAM regimen is thus 400 mg/m2 for four days.

  18. Acute and subchronic effects of bilastine (20 and 40 mg) and hydroxyzine (50 mg) on actual driving performance in healthy volunteers.

    Conen, Silke; Theunissen, Eef L; Van Oers, Anita C M; Valiente, Román; Ramaekers, Johannes G


    Bilastine is a new second-generation H1 antagonist. Although bilastine has been demonstrated to produce little or no performance impairment in laboratory tests, it cannot be excluded that it produces impairments in real-life performance such as driving. This study aims to assess the effects of two doses of bilastine (20 and 40 mg) on actual driving after single and repeated administration. Hydroxyzine 50 mg was included as an active control. Twenty-two participants (11 females, 11 males) were tested in a placebo-controlled, randomized, double-blind, four-way cross-over design. Participants were treated with once-daily doses for eight consecutive days. On day 1 and 8 of each treatment period participants performed an actual highway driving test. The primary variable was standard deviation of lateral position (SDLP), a measure of weaving. Results demonstrated that hydroxyzine significantly increased SDLP on days 1 and 8 of treatment. Bilastine did not affect SDLP. It is concluded that hydroxyzine produces severe driving impairment after single doses and that this impairment only partly mitigates over time due to a lack of complete tolerance. Bilastine did not produce any driving impairment after single and repeated doses and can be safely used in traffic in doses up to 40 mg.

  19. Corrosion behavior of Mg and Mg-Zn alloys in simulated body fluid

    GAO Jia-cheng; WU Sha; QIAO Li-ying; WANG Yong


    The corrosion behavior of Mg and Mg-Zn in simulated body fluid was studied.The mass loss of pure Mg,Mg-Zn-Zr and Mg-Zn-Zr-Y in simulated body fluid was measured using photovoltaic scale meter.Corrosion rate was determined through electrochemical tests.Finally,the corrosion mechanism was tbermodynamically studied.The results show that the corrosion rate decreases with the lapse of time for both pure Mg and Mg alloys.The purer the alloy,the borer the corrosion resistance exhibits.The corrosion behavior of Mg alloy is improved by the addition of trace Y.

  20. High-dose metoclopramide + lorazepam versus low-dose metoclopramide + lorazepam + dehydrobenzperidol in the treatment of cisplatin-induced nausea and vomiting

    Herrstedt, Jørn; Hannibal, J; Hallas, Jesper;


    In a randomized double-blind, cross-over trial of 34 patients receiving cisplatin-based chemotherapy (20-100 mg/m2), the antiemetic effect of high-dose metoclopramide (HDM) (10 mg/kg iv. loading dose + 7 hours continuous infusion) + lorazepam (L) (2.5 mg x 4 po) was compared with low.......01). Sedation was seen in all but 1 patient, and was graded as severe in 6 patients receiving the HDM and in 2 patients receiving the LDM regimen. No extrapyramidal adverse reactions were seen. We conclude that high-dose metoclopramide + lorazepam is a safe antiemetic regimen and significantly superior to low...

  1. A cost-minimization analysis of combination therapy in hypertension: fixed-dose vs extemporary combinations

    Marco Bellone


    Full Text Available BACKGROUND: Cardiovascular disease management and prevention represent the leading cost driver in Italian healthcare expenditure. In order to reach the target blood pressure, a large majority of patients require simultaneous administration of multiple antihypertensive agents.OBJECTIVE: To assess the economic impact of the use of fixed dose combinations of antihypertensive agents, compared to the extemporary combination of the same principles.METHODS: A cost minimization analysis was conducted to determine the pharmaceutical daily cost of five fixed dose combinations (olmesartan 20 mg + amlodipine 5 mg, perindopril 5 mg + amlodipine 5 mg, enalapril 20 mg + lercanidipine 10 mg, felodipine 5 mg + ramipril 5 mg, and delapril 30 mg + manidipine 10 mg compared with extemporary combination of the same principles in the perspective of the Italian NHS. Daily acquisition costs are estimated based on current Italian prices and tariffs.RESULTS: In three cases the use of fixed‑dose combination instead of extemporary combination induces a lower daily cost. Fixed combination treatment with delapril 30 mg + manidipine 10 mg induces greater cost savings for the National Health System (95,47 €/pts/year, as compared to free drugs combination therapy.CONCLUSIONS: Compared with free drug combinations, fixed‑dose combinations of antihypertensive agents are associated with lower daily National Health Service acquisition costs.

  2. Aspirin, salicylate, sulfite and tartrazine induced bronchoconstriction. Safe doses and case definition in epidemiological studies.

    Corder, E H; Buckley, C E


    Allergic-like reactions to chemical components of foods and medicines may be common. The prevalence of idiosyncratic reactions to aspirin, salicylate, metabisulfite and tartrazine is not known. We used a tertiary referral clinic population to estimate safe exposure doses for epidemiological studies. A 15% decrease in the amount of air expired in one second was defined a positive response. The median effective molar doses of the agents were remarkably similar: metabisulfite 0.19 mM, 34.4 mg [95% confidence interval (CI) 0.14, 0.27 mM]; tartrazine 0.10 M, 55.0 mg (95% CI 0.05, 0.21 mM); aspirin 0.09 mM, 16.5 mg (95% CI 0.04, 0.19 mM); and salicylate 0.11 mM, 15.3 mg (95% CI 0.05, 0.27 mM). Doses to which the most sensitive (5%) and practically all (95%) susceptible persons might respectively respond are: metabisulfite 4.6 mg, 255.8 mg; tartrazine 3.4 mg, 885.6 mg; aspirin 0.8 mg, 332.3 mg; and salicylate 2.6 mg, 89.9 mg. Doses within these ranges can be used in epidemiological studies.

  3. β-Carotene Conversion to Vitamin A Decreases As the Dietary Dose Increases in Humans12

    Novotny, Janet A.; Harrison, Dawn J.; Pawlosky, Robert; Flanagan, Vincent P.; Harrison, Earl H.; Kurilich, Anne C.


    It has been suggested that high doses of β-carotene limit its conversion to vitamin A, yet this effect has not been well established in humans. A feeding study was conducted in a randomized crossover design in which volunteers consumed 2 doses of deuterium-labeled β-carotene on 2 occasions, with β-carotene and vitamin A response assessed by plasma area under the concentration time curve (AUC). Seven volunteers (4 men, 3 women) consumed each of 2 doses of β-carotene-d8 and provided serial blood samples for 37 d after each dose. β-Carotene doses were 20 and 40 mg. Plasma β-carotene-d8 was assessed by HPLC-MS. Plasma retinol (ROH)-d4, which was derived from the β-carotene-d8, was evaluated by GC-MS after saponification to convert retinyl esters to ROH prior to the formation of the trimethylsilylether. The plasma AUC for β-carotene-d8 increased 2-fold from the 20-mg dose to the 40-mg dose. The plasma AUC for ROH-d4 increased 36% from the 20-mg dose to the 40-mg dose. These results establish that, in humans, β-carotene conversion to vitamin A decreases as the dietary dose increases. PMID:20237064

  4. Pharmacokinetics, Pharmacodynamics, and Safety of Single-Dose Canagliflozin in Healthy Chinese Subjects.

    Chen, Xia; Hu, Pei; Vaccaro, Nicole; Polidori, David; Curtin, Christopher R; Stieltjes, Hans; Sha, Sue; Weiner, Sveta; Devineni, Damayanthi


    Canagliflozin, an orally active sodium-glucose cotransporter 2 inhibitor, is approved in many countries as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The recommended dose of canagliflozin is 100 or 300 mg once daily. This Phase I study was conducted to evaluate the pharmacokinetics, pharmacodynamics, and safety profile of canagliflozin in healthy Chinese subjects. In this double-blind, single-dose, 3-way crossover study, 15 healthy subjects were randomized (1:1:1) to receive single oral doses of canagliflozin 100 mg, canagliflozin 300 mg, or placebo. Pharmacokinetic, pharmacodynamic, and safety assessments were made at prespecified time points. All participants are healthy Chinese adults. Mean AUC and Cmax of canagliflozin increased in a dose-dependent manner after single-dose administration (AUC0-∞, 10,521 ng · h/mL for 100 mg, 33,583 ng · h/mL for 300 mg; Cmax, 1178 ng/mL for 100 mg, 4113 ng/mL for 300 mg). The mean apparent t½ and the median Tmax of canagliflozin were independent of dose (t½, 16.0 hours for 100 mg, 16.2 hours for 300 mg; Tmax, ~1 hour). Mean CL/F and renal clearance of canagliflozin were comparable between the 2 doses. Mean plasma metabolite to parent molar ratios for Cmax and AUC0-∞ were similar with both doses. Canagliflozin decreased the 24-hour mean renal threshold for glucose, calculated by using measured creatinine clearance to estimate the glomerular filtration rate (67.9 and 60.7 mg/dL for canagliflozin 100 and 300 mg, respectively) and 24-hour increased urinary glucose excretion (33.8 and 42.9 g for canagliflozin 100 and 300 mg, respectively) in a dose-dependent manner; the 24-hour plasma glucose profile remained largely unchanged. No deaths, hypoglycemic events, or discontinuations due to adverse events were observed. Pharmacokinetics (AUC and Cmax) of canagliflozin increased in a dose-dependent manner after single oral doses of canagliflozin (100 and 300 mg) in

  5. Effects of alfaxalone administered intravenously to healthy yearling loggerhead sea turtles (Caretta caretta) at three different doses.

    Phillips, Brianne E; Posner, Lysa P; Lewbart, Gregory A; Christiansen, Emily F; Harms, Craig A


    OBJECTIVE To compare physiologic and anesthetic effects of alfaxalone administered IV to yearling loggerhead sea turtles (Caretta caretta) at 3 different doses. DESIGN Randomized crossover study. ANIMALS 9 healthy yearling loggerhead sea turtles. PROCEDURES Animals received each of 3 doses of alfaxalone (3 mg/kg [1.4 mg/lb], 5 mg/kg [2.3 mg/lb], or 10 mg/kg [4.5 mg/lb]) administered IV in randomly assigned order, with a minimum 7-day washout period between doses. Endotracheal intubation was attempted following anesthetic induction, and heart rate, sedation depth, cloacal temperature, and respirations were monitored. Times to first effect, induction, first voluntary muscle movement, first respiration, and recovery were recorded. Venous blood gas analysis was performed at 0 and 30 minutes. Assisted ventilation was performed if apnea persisted 30 minutes following induction. RESULTS Median anesthetic induction time for all 3 doses was 2 minutes. Endotracheal intubation was accomplished in all turtles following induction. Heart rate significantly increased after the 3- and 5-mg/kg doses were administered. Median intervals from alfaxalone administration to first spontaneous respiration were 16, 22, and 54 minutes for the 3-, 5-, and 10-mg/kg doses, respectively, and median intervals to recovery were 28, 46, and 90 minutes, respectively. Assisted ventilation was required for 1 turtle after receiving the 5-mg/kg dose and for 5 turtles after receiving the 10-mg/kg dose. The 10-mg/kg dose resulted in respiratory acidosis and marked hypoxemia at 30 minutes. CONCLUSIONS AND CLINICAL RELEVANCE IV alfaxalone administration to loggerhead sea turtles resulted in a rapid anesthetic induction and dose-dependent duration of sedation. Assisted ventilation is recommended if the 10 mg/kg dose is administered.


    Saroj Nepal , Suhrid Banskota , Nirmal Marasini, Biki Gupta , Shyam Prasad Lohani , Shova Basnet and Bal Mukunda Regmi*


    The objective of the study was to compare the bioavailability of a single oral 100 mg dose of two brands of phenytoin sodium formulations available in the Nepalese market. Formulation B was taken as test drug and compared with the innovator brand which was taken as reference standard. A randomized, two-way crossover study was done in six healthy adult male rabbits. All six rabbits received a single oral 100 mg dose of both the formulations with a two-week washout period between the formulatio...

  7. Can a nonequivalent choice of dosing regimen bias the results of flexible dose double blind trials? The CATIE schizophrenia trial.

    Rosenheck, Robert A; Davis, Vicki G; Davis, Sonia M; Stroup, Scott; McEvoy, Joseph; Swartz, Marvin; Lieberman, Jeffrey


    One of the major challenges in the design of double-blind flexible-dosing clinical trials comparing active drugs is the selection of dosing regimens that are equivalent across drugs. This study uses data from the CATIE schizophrenia trial to evaluate the hypothesis that drugs that were dosed somewhat higher in the trial than in typical practice would show greater efficacy and more side effects, especially at high capsule levels, than drugs that were dosed at lower relative strengths. CATIE was a large (N=1460) randomized trial comparing 5 antipsychotics in patients with chronic schizophrenia. The blind was maintained in CATIE by prescribing identical-looking capsules of each medication. Dosing was flexible, such that PIs could prescribe from one to four capsules per day, and could modify the dose based on a patient's symptoms and side effects. Capsule strengths for olanzapine (7.5 mg) and quetiapine (200 mg) were relatively higher than for risperidone (1.5 mg), perphenazine (8 mg) or ziprasidone (40 mg). Proportional hazards models of time to all cause discontinuation and mixed regression models for continuous measures of symptoms, quality of life and side effects were used to test for interactions between randomly assigned drug and number of capsules prescribed per visit. We hypothesized that if a dosing bias was present, the flex-dosing design would result in a significant interaction such that drugs with higher relative dosing per capsule would be more effective and have more side effects than drugs with lower relative dosing and that this effect would be greatest at the largest prescribed dosing regimen (4 capsules). There were no significant interactions between drug assignment and number of capsules in the proportional hazards analyses of time to all cause discontinuation (p=.77, excluding ziprasidone and .74 in the ziprasidone cohort) or in the mixed model analysis of PANSS symptoms (p=.49), quality of life (p=.45); or measures of tardive dyskinesia (AIMS, p

  8. Comparative bioequivalence studies of tramadol hydrochloride sustained-release 200 mg tablets

    Suhas S Khandave


    Full Text Available Suhas S Khandave1, Satish V Sawant1, Santosh S Joshi1, Yatish K Bansal2, Sonal S Kadam21Accutest Research Laboratories (I Private Limited, Koparkhirne, Navi Mumbai, Maharashtra, India; 2Ipca Laboratories Limited, Kandivli Mumbai, Maharashtra, IndiaBackground: Tramadol hydrochloride is available as 50 mg immediate-release (IR and 100 mg, 200 mg, and 300 mg sustained-release (SR tablets. The recommended dose of tramadol is 50–100 mg IR tablets every 4–6 hours. The tramadol SR 200 mg tablet is a better therapeutic option, with a reduced frequency of dosing, and improved patient compliance and quality of life. The present study evaluated the bioequivalence of a generic tramadol SR 200 mg tablet.Methods: A comparative in vitro dissolution study was performed on the test and reference products, followed by two separate single-dose bioequivalence studies under fasting and fed conditions and one multiple-dose bioequivalence study under fasting conditions. These bioequivalence studies were conducted in healthy human subjects using an open-label, randomized, two-treatment, two-period, two-sequence, crossover design. The oral administration of the test and reference products was done on day 1 for both the single-dose studies and on days 1–5 for the multiple-dose study in each study period as per the randomization code. Serial blood samples were collected at predefined time points in all the studies. Analysis of plasma concentrations of tramadol and O-desmethyltramadol (the M1 metabolite was done by a validated liquid chromatography-mass spectrometry analytical method. The standard acceptance criterion of bioequivalence was applied on log-transformed pharmacokinetic parameters for tramadol and its M1 metabolite.Results: The ratios for geometric least-square means and 90% confidence intervals were within the acceptance range of 80%–125% for log-transformed primary pharmacokinetic parameters for tramadol and its M1 metabolite in all the three studies

  9. Effectiveness of Valganciclovir 900mg Versus 450mg for Cytomegalovirus Prophylaxis in Renal Transplantation: A Systematic Review and Meta-Analysis.

    Xin, Wang; Hui, Yang; Xiaodong, Zhang; Xiangli, Cui; Shihui, Wang; Lihong, Liu


    Valganciclovir 900 mg/day is approved for cytomegalovirus (CMV) prophylaxis, but 450 mg/day is seems also effective. We systematically reviewed the efficacy and safety of low-dose versus high-dose valganciclovir prophylaxis in renal transplantation recipients. An electronic search was conducted up to November 29, 2016. The primary outcomes were incidences of CMV, CMV disease, mortality and opportunistic infection. The second outcomes were acute rejection, allograft loss, adverse drug reaction (ADR). 7 cohort studies, all with high quality involving (1431 patients) were included. There was no significant difference of the incidence of following CMV disease (1271 patients, odds ratio [OR] 0.74, 95% confidence interval [CI], 0.38-1.43, p=0.36), acute rejection (1343 patients, OR 0.77, 95%CI 0.53-1.14, p=0.19), allograft loss (1271 patients, OR 0.64, 95%CI 0.31-1.35, p=0.24), mortality (1271 patients, OR 0.55, 95%CI 0.20-1.47, p=0.23) and opportunistic infections (OI) (985 patients, OR 0.76, 95%CI 0.52-1.10, p=0.14) between the low-dose and the high-dose valganciclovir  prophylaxis. And no significant difference was observed for premature valganciclovir discontinuation (1010 patients, OR 0.81, 95%CI 0.52-1.25, p=0.33) and the incidence of leukopenia (1082 patients, OR 0.65, 95%CI 0.34-1.22, p=0.18) between the two regimens. 450 mg and 900 mg doses of valganciclovir are equipotent for CMV universal prophylaxis. CMV 450 mg prophylaxis should be used for renal transplant recipients. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  10. Non-resonant microwave absorption studies of superconducting MgB2 and MgB2 + MgO

    Janhavi P Joshi; Subhasis Sarangi; A K Sood; Dilip Pal; S V Bhat


    Non-resonant microwave absorption (NRMA) studies of superconducting MgB2 and a sample containing ∼ 10% by weight of MgO in MgB2 are reported. The NRMA results indicate near absence of intergranular weak links in the pure MgB2 sample. A linear temperature dependence of the lower critical field c1 is observed indicating a non- wave superconductivity. However, the phase reversal of the NRMA signal which could suggest wave symmetry is also not observed. In the MgB2 + MgO sample, much larger low field dependent absorption is observed indicating the presence of intergranular weak links. The hysteretic behavior of NRMA is compared and contrasted in the two samples. In the pure MgB2 sample, a large hysteresis is observed between the forward and the reverse scans of the magnetic field indicating strong pinning of flux lines. This hysteresis saturates a few degrees below c while in the MgB2 + MgO sample, a much slower increase of hysteresis with decreasing temperature is observed, a signature of weaker pinning.

  11. Gut microbiota and tacrolimus dosing in kidney transplantation.

    John R Lee

    Full Text Available Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5 or did not require such an increase (Dose Stable Group, n=14. We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2 ± 1.1 mg/day vs. 3.8 ± 0.8 mg/day, respectively, P=0.61, two-way between-group ANOVA using contrasts but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6 ± 2.4 mg/day vs. 3.3 ± 1.5 mg/day, respectively, P<0.001. Our systematic characterization of the gut microbial composition identified that fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was 11.8% in the Dose Escalation Group and 0.8% in the Dose Stable Group (P=0.002, Wilcoxon Rank Sum test, P<0.05 after Benjamini-Hochberg correction for multiple hypotheses. Fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was positively correlated with future tacrolimus dosing at 1 month (R=0.57, P=0.01 and had a coefficient ± standard error of 1.0 ± 0.6 (P=0.08 after multivariable linear

  12. Two separate dose-dependent effects of paroxetine

    Nielsen, Anette Green; Pedersen, Rasmus Steen; Nøhr-Jensen, Lene


    PURPOSE: To investigate paroxetine's putative dose-dependent impact on pupil reaction and inhibition of the O-demethylation of tramadol. METHODS: Twelve healthy CYP2D6 extensive metabolizers participated in this double-blinded randomized five-way placebo controlled cross-over study; they received...... placebo, 10, 20, 30, and 50 mg paroxetine as single oral doses at bedtime. Next morning the pupil was measured followed by oral intake of 50 mg of tramadol, and urine was collected for 8 h. Three hours after ingestion of tramadol a second measurement of the pupil was performed. Enantioselective urine...... concentrations of (+/-)-tramadol and (+/-)-O-desmethyltramadol (M1) were determined. RESULTS: With placebo, the median maximum pupil diameter was 6.43 mm (range 5.45-7.75 mm) before tramadol and 6.22 mm (4.35-7.65 mm) after 50 mg of tramadol (P = 0.4935). Paroxetine resulted in a statistically significant, dose...

  13. Two separate dose-dependent effects of paroxetine

    Nielsen, Anette Green; Pedersen, Rasmus Steen; Noehr-Jensen, Lene;


    PURPOSE: To investigate paroxetine's putative dose-dependent impact on pupil reaction and inhibition of the O-demethylation of tramadol. METHODS: Twelve healthy CYP2D6 extensive metabolizers participated in this double-blinded randomized five-way placebo controlled cross-over study; they received...... placebo, 10, 20, 30, and 50 mg paroxetine as single oral doses at bedtime. Next morning the pupil was measured followed by oral intake of 50 mg of tramadol, and urine was collected for 8 h. Three hours after ingestion of tramadol a second measurement of the pupil was performed. Enantioselective urine...... concentrations of (+/-)-tramadol and (+/-)-O-desmethyltramadol (M1) were determined. RESULTS: With placebo, the median maximum pupil diameter was 6.43 mm (range 5.45-7.75 mm) before tramadol and 6.22 mm (4.35-7.65 mm) after 50 mg of tramadol (P = 0.4935). Paroxetine resulted in a statistically significant, dose...

  14. Dose-dependent expression of neuronopathy after experimental pyridoxine intoxication.

    Xu, Y; Sladky, J T; Brown, M J


    We examined the sequence of nervous system abnormalities that resulted when rats were given excess amounts of vitamin B6 (pyridoxine). High doses of pyridoxine (1,200 or 600 mg/kg/d) for 6 to 10 days caused a neuronopathy with necrosis of dorsal root ganglion (DRG) sensory neurons, accompanied by centrifugal axonal atrophy and breakdown of peripheral and central sensory axons. Large diameter neurons with long processes and large cytoplasmic volumes were especially affected. Smaller doses (300 to 150 mg/kg/d) for up to 12 weeks had minor effects on DRG neurons, but produced a neuropathy with axonal atrophy and degeneration. Guinea pigs given 1,800 mg/kg/d developed sensory neuronopathy, whereas mice given similar or higher doses did not have neuropathologic abnormalities. Multiple factors including rate of administration, differential neuronal vulnerability, and species susceptibility have bearing on the final expression of pyridoxine neurotoxicity.

  15. The optimal succinylcholine dose for intubating emergency patients: retrospective comparative study

    M. Magdy Hussien


    Full Text Available Background : Succinylcholine remains the drug of choice for satisfactory rapid-sequence tracheal intubation. It is not clear from the literature why the 1 mg/kg dose of succinylcholine has been traditionally used. The effective dose (ED95 of succinylcholine is less than 0.3 mg/kg. The dose of 1 mg/kg represents 3.5 to 4 times the ED95. Objectives : To compare the effect of the traditionally used 1 mg/kg of succinylcholine with lower doses of 0.6 mg/kg and 0.45 mg/kg on intubation condition regarding the onset time, duration of action, duration of abdominal fasciculation, and the intubation grading. Methods : This retrospective comparative study was carried into three groups of ASA III & IV (American Society of Anesthesiologist's Physical Status III and IV non-prepared emergency patients who were intubated at emergency department of Hamad General Hospital, Doha, Qatar during January 1st 2007 to August 31, 2010. The Institutional Research Board (IRB approval was obtained. This study was limited to 88 patients who received fentanyl 1 µg/kg followed by etomidate 0.3 mg/kg intravenously as induction agents and succinylcholine as a muscle relaxant agent in doses of 0.45 mg/kg, 0.6 mg/kg, or 1 mg/kg. Results : Increasing the succinylcholine dosage shortened the onset time, prolonged the duration of action, and prolonged the duration of abdominal fasciculation significantly (P<.001. Tracheal intubation was 100% successful in the three groups of patients. Conclusion : Succinylcholine dose of 0.45 mg/kg provides an optimal intubation condition in ASA III & IV emergency non-prepared patients. Duration of action of succinylcholine is dose dependent; reducing the dose allows a more rapid return of spontaneous respiration and airway reflexes.

  16. Antenatal steroids: can we optimize the dose?

    Romejko-Wolniewicz, Ewa; Teliga-Czajkowska, Justyna; Czajkowski, Krzysztof


    Purpose of review The beneficial effects of antenatal steroids in women at risk of preterm birth are evident. A dose of 24 mg appears sufficient, but there are insufficient data to recommend betamethasone or dexamethasone, a single steroid dose, the optimal interval between doses and repeated courses, the gestational age at which treatment is beneficial and the long-term effects of steroid treatment. This review addresses these aspects of antenatal steroid treatment. Recent findings Although the 12-h and 24-h dosing intervals are equivalent with respect to prevention of respiratory distress syndrome, the former enables the completion of treatment in 50% more neonates delivered prematurely. Reducing the single steroid dose in patients at risk for premature birth reduces the associated maternal side effects. An inverse relationship has been demonstrated between the number of corticosteroid courses and foetal growth. The reduced size of exposed foetuses has been attributed to birth at earlier gestational ages and decreased foetal growth. Evidence suggests that antenatal exposure to synthetic glucocorticoids in term-born children has long-lasting effects, which may have important implications in the recommendation of steroids before elective caesarean at term. Summary The short-term and long-term effects of the dosage regimen on the pregnant mother and foetus remain unclear. PMID:24463225

  17. Lack of effect of beta-blocker on flat dose response to thiazide in hypertension: efficacy of low dose thiazide combined with beta-blocker.


    Increasing the dose of a thiazide diuretic used alone in patients with essential hypertension has little further effect on blood pressure but increases the deleterious metabolic consequences of the diuretic. The effect of a beta-blocker on this flat dose response is not known. In two randomised crossover studies the effect of 12.5 mg, 25 mg, and 50 mg hydrochlorothiazide combined with 400 mg acebutolol was assessed. The mean fall in supine blood pressure was about 15% and was the same whateve...

  18. Utirik Atoll Dose Assessment

    Robison, W.L.; Conrado, C.L.; Bogen, K.T


    On March 1, 1954, radioactive fallout from the nuclear test at Bikini Atoll code-named BRAVO was deposited on Utirik Atoll which lies about 187 km (300 miles) east of Bikini Atoll. The residents of Utirik were evacuated three days after the fallout started and returned to their atoll in May 1954. In this report we provide a final dose assessment for current conditions at the atoll based on extensive data generated from samples collected in 1993 and 1994. The estimated population average maximum annual effective dose using a diet including imported foods is 0.037 mSv y{sup -1} (3.7 mrem y{sup -1}). The 95% confidence limits are within a factor of three of their population average value. The population average integrated effective dose over 30-, 50-, and 70-y is 0.84 mSv (84, mrem), 1.2 mSv (120 mrem), and 1.4 mSv (140 mrem), respectively. The 95% confidence limits on the population-average value post 1998, i.e., the 30-, 50-, and 70-y integral doses, are within a factor of two of the mean value and are independent of time, t, for t > 5 y. Cesium-137 ({sup 137}Cs) is the radionuclide that contributes most of this dose, mostly through the terrestrial food chain and secondarily from external gamma exposure. The dose from weapons-related radionuclides is very low and of no consequence to the health of the population. The annual background doses in the U. S. and Europe are 3.0 mSv (300 mrem), and 2.4 mSv (240 mrem), respectively. The annual background dose in the Marshall Islands is estimated to be 1.4 mSv (140 mrem). The total estimated combined Marshall Islands background dose plus the weapons-related dose is about 1.5 mSv y{sup -1} (150 mrem y{sup -1}) which can be directly compared to the annual background effective dose of 3.0 mSv y{sup -1} (300 mrem y{sup -1}) for the U. S. and 2.4 mSv y{sup -1} (240 mrem y{sup -1}) for Europe. Moreover, the doses listed in this report are based only on the radiological decay of {sup 137}Cs (30.1 y half-life) and other

  19. The conduction bands of MgO, MgS and HfO2

    Boer, P.K. de; Groot, R.A. de


    Electronic structure calculations for MgO, MgS and HfO2 are reported. It is shown that the conduction bands of MgO and MgS have predominantly anion character, contrary to the common picture of the conduction band being derived from cation states. In transition metal oxides, unoccupied anion states a

  20. TRPM6 forms the Mg2+ influx channel involved in intestinal and renal Mg2+ absorption.

    Voets, T.; Nilius, B.; Hoefs, S.J.G.; Kemp, J.W.C.M. van der; Droogmans, G.; Bindels, R.J.M.; Hoenderop, J.G.J.


    Mg2+ is an essential ion involved in a multitude of physiological and biochemical processes and a major constituent of bone tissue. Mg2+ homeostasis in mammals depends on the equilibrium between intestinal Mg2+ absorption and renal Mg2+ excretion, but little is known about the molecular nature of

  1. Patient-optimized doses of fesoterodine improve bladder symptoms in an open-label, flexible-dose study.

    Wyndaele, Jean-Jacques; Goldfischer, Evan R; Morrow, Jon D; Gong, Jason; Tseng, Li-Jung; Choo, Myung-Soo


    To assess changes in overactive bladder (OAB) symptoms and patient-reported outcomes in a post hoc analysis in which subjects from a 12-week, open-label, flexible-dose fesoterodine study were stratified according to whether they opted for dose escalation. Subjects with OAB (eight or more micturitions and three or more urgency episodes per 24 h) who reported dissatisfaction with tolterodine within 2 years of screening received fesoterodine 4 mg once daily for 4 weeks, with an optional dose increase to 8 mg after week 4 based on discussion of efficacy and tolerability between the subject and investigator. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and Urgency Perception Scale (UPS) at baseline and weeks 4 and 12, and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. Subjects rated treatment satisfaction at week 12. Dose escalation to 8 mg at week 4 was chosen by 255 (50%) of 513 subjects. At baseline, subjects who opted for dose escalation at week 4 (escalators) had significantly higher means for all diary variables except urgency urinary incontinence (UUI) episodes, significantly greater OAB-q Symptom Bother scores and significantly lower OAB-q health-related quality of life (HRQL) scores (all P fesoterodine significantly improved OAB symptoms and patient-reported outcomes in subjects who chose to remain on the initial 4-mg dose, as well as in the 50% of subjects who escalated to the 8-mg dose after 4 weeks. Non-escalators had significantly fewer OAB symptoms at baseline and significantly greater improvements than escalators before dose escalation. Escalators showed increased symptom relief after dose escalation; improvements in most outcomes were similar among non-escalators and escalators by week 12. Flexible-dose fesoterodine was well tolerated, with similar adverse-event profiles observed in the escalator and non-escalator groups. These results may help clinicians to identify patients more likely to

  2. Safety and pharmacokinetics of 120 mg/kg versus 60 mg/kg weekly intravenous infusions of alpha-1 proteinase inhibitor in alpha-1 antitrypsin deficiency: a multicenter, randomized, double-blind, crossover study (SPARK).

    Campos, Michael A; Kueppers, Friedrich; Stocks, James M; Strange, Charlie; Chen, Junliang; Griffin, Rhonda; Wang-Smith, Laurene; Brantly, Mark L


    Augmentation therapy with the approved dose of 60 mg/kg weekly intravenous (IV) alpha-1 proteinase inhibitor (alpha1-PI), achieves a trough serum level of 11 μM in individuals with alpha-1 antitrypsin deficiency (AATD), yet this is still below the level observed in healthy individuals. This study assessed the safety and pharmacokinetic profile of weekly infusions of a 120 mg/kg dose of alpha1-PI in 30 adults with AATD. Subjects with symptomatic, genetically determined (genotypes PI*ZZ, PI*Z(null), PI*(null)(null) or PI*(Z)Mmalton) AATD were randomly assigned to weekly infusions of 60 or 120 mg/kg alpha1-PI (Prolastin-C®) for 8 weeks before crossing over to the alternate dose for 8 weeks. Adverse events (AEs) (including exacerbations), vital signs, pulmonary function tests, and laboratory assessments were recorded. Pharmacokinetic measurements included AUC0-7days, Cmax, trough, tmax, and t1/2, based on serum alpha1-PI concentrations. In total for both treatments, 112 AEs were reported, with exacerbation of COPD being the most frequent, consistent with the subjects' diagnoses. Mean steady-state serum alpha1-PI concentrations following 120 mg/kg weekly IV alpha1-PI were higher than with the 60 mg/kg dose and mean trough concentrations were 27.7 versus 17.3 μM, respectively. Dose proportionality was demonstrated for AUC0-7days and Cmax, with low inter-subject variability. The 120 mg/kg alpha1-PI weekly dose was considered to be safe and well tolerated, and provided more favorable physiologic alpha1-PI serum levels than the currently recommended 60 mg/kg dose. The effect of this dosing regimen on slowing and/or preventing emphysema progression in subjects with AATD warrants further investigation.

  3. Dose-related selection of fluoroquinolone-resistant Escherichia coli.

    Olofsson, Sara K; Marcusson, Linda L; Strömbäck, Ann; Hughes, Diarmaid; Cars, Otto


    To investigate the effects of clinically used doses of norfloxacin, ciprofloxacin and moxifloxacin on survival and selection in Escherichia coli populations containing fluoroquinolone-resistant subpopulations and to measure the value of the pharmacodynamic index AUC/mutant prevention concentration (MPC) that prevents the growth of pre-existing resistant mutants. Mixed cultures of susceptible wild-type and isogenic single (gyrA S83L) or double (gyrA S83L, Delta marR) fluoroquinolone-resistant mutants were exposed to fluoroquinolones for 24 h in an in vitro kinetic model. Antibiotic concentrations modelled pharmacokinetics attained with clinical doses. All tested doses eradicated the susceptible wild-type strain. Norfloxacin 200 mg administered twice daily selected for both single and double mutants. Ciprofloxacin 250 mg administered twice daily eradicated the single mutant, but not the double mutant. For that, 750 mg administered twice daily was required. Moxifloxacin 400 mg once daily eliminated the single mutant, but did not completely remove the double mutant. The MPC of ciprofloxacin was determined and based on those dose simulations that eradicated mutant subpopulations, an AUC/MPC(wild-type) of 35 prevented selection of the single mutant, whereas an AUC/MPC(single mutant) of 14 (equivalent to an AUC/MPC(wild-type) of 105) prevented selection of the double mutant. All tested clinical dosing regimens were effective in eradicating susceptible bacteria, but ciprofloxacin 750 mg twice daily was the only dose that prevented the selection of single- and double-resistant E. coli mutants. Thus, among approved fluoroquinolone dosing regimens, some are significantly more effective than others in exceeding the mutant selection window and preventing the enrichment of resistant mutants.

  4. Comparative study of pharmacokinetics/ pharmacodynamics of ciprofloxacin between 400 mg intravenously every 8 h and 400 mg intravenously every 12 h in patients with gram negative bacilli bacteremia.

    Saengsuwan, Phanvasri; Jaruratanasirikul, Sutep; Jullangkoon, Monchana; Aeinlang, Nanchanit


    To compare the ratio of the area under the concentration-time curve at 24 hours to the minimum inhibitory concentration value (24-h AUC/MIC) of ciprofloxacin between 400 mg intravenously every 8 h and 400 mg intravenously every 12 h. A prospective, randomized, two-way crossover study of 10 patients with gram-negative bacilli bacteremia was conducted. All patients were randomized to receive ciprofloxacin in both regimens consecutively: (i) 400 mg intravenously every 8 h for four doses; (ii) 400 mg intravenously every 12 h for four doses. Ciprofloxacin pharmacokinetic studies were carried out after the start of both regimens. For the ciprofloxacin 400 mg intravenously every 8 h regimen, the 24-h AUC/MIC at MICs of 0.5 and 1 microg/ml were 218.63 +/- 78.75 and 109.31 +/- 39.37, respectively. For the ciprofloxacin 400 mg intravenously every 12 h regimen, the 24-h AUC/MIC at MICs of 0.5 and +/- microg/ml were 144.07 +/- 57.02 and 72.03 +/- 28.51, respectively. After 14 days of ciprofloxacin treatment, the gram-negative bacilli infections were eradicated in all patients. Moreover, during both regimens, no adverse events related to the use of ciprofloxacin were observed. Both ciprofloxacin 400 mg every 8 h and 400 mg every 12 h regimens can provide good coverage for pathogens with the susceptibility breakpoint of ciprofloxacin with an MIC of 0.5 microg/ml. For pathogens with an MIC of 1.0 microg/ml, only ciprofloxacin 400 mg every 8 h regimen can provide a 24-h AUC/MIC ratio greater than 100.

  5. Efficacy of prednisone 1–4 mg/day in patients with rheumatoid arthritis: a randomised, double-blind, placebo controlled withdrawal clinical trial


    Objective: A randomised double-blind placebo controlled withdrawal clinical trial of prednisone versus placebo in patients with rheumatoid arthritis (RA), treated in usual clinical care with 1–4 mg/day prednisone, withdrawn to the same dose of 1 mg prednisone or identical placebo tablets. Methods: All patients were from one academic setting and all trial visits were conducted in usual clinical care. Patients were taking stable doses of 1–4 mg prednisone with stable clinical status, documented...

  6. Assessment of internal doses

    Rahola, T; Falk, R; Isaksson, M; Skuterud, L


    There is a definite need for training in dose calculation. Our first course was successful and was followed by a second, both courses were fully booked. An example of new tools for software products for bioassay analysis and internal dose assessment is the Integrated Modules for Bioassay Analysis (IMBA) were demonstrated at the second course. This suite of quality assured code modules have been adopted in the UK as the standard for regulatory assessment purposes. The intercomparison measurements are an important part of the Quality Assurance work. In what is known as the sup O utside workers ' directive it is stated that the internal dose measurements shall be included in the European Unions supervision system for radiation protection. The emergency preparedness regarding internal contamination was much improved by the training with and calibration of handheld instruments from participants' laboratories. More improvement will be gained with the handbook giving practical instructions on what to do in case of e...

  7. Hydrogen storage systems from waste Mg alloys

    Pistidda, C.; Bergemann, N.; Wurr, J.; Rzeszutek, A.; Møller, K. T.; Hansen, B. R. S.; Garroni, S.; Horstmann, C.; Milanese, C.; Girella, A.; Metz, O.; Taube, K.; Jensen, T. R.; Thomas, D.; Liermann, H. P.; Klassen, T.; Dornheim, M.


    The production cost of materials for hydrogen storage is one of the major issues to be addressed in order to consider them suitable for large scale applications. In the last decades several authors reported on the hydrogen sorption properties of Mg and Mg-based systems. In this work magnesium industrial wastes of AZ91 alloy and Mg-10 wt.% Gd alloy are used for the production of hydrogen storage materials. The hydrogen sorption properties of the alloys were investigated by means of volumetric technique, in situ synchrotron radiation powder X-ray diffraction (SR-PXD) and calorimetric methods. The measured reversible hydrogen storage capacity for the alloys AZ91 and Mg-10 wt.% Gd are 4.2 and 5.8 wt.%, respectively. For the Mg-10 wt.% Gd alloy, the hydrogenated product was also successfully used as starting reactant for the synthesis of Mg(NH2)2 and as MgH2 substitute in the Reactive Hydride Composite (RHC) 2LiBH4 + MgH2. The results of this work demonstrate the concrete possibility to use Mg alloy wastes for hydrogen storage purposes.

  8. Coherent interface structures and intergrain Josephson coupling in dense MgO/Mg2Si/MgB2 nanocomposites

    Ueno, Katsuya; Nagashima, Yukihito; Seto, Yusuke; Matsumoto, Megumi; Sakurai, Takahiro; Ohta, Hitoshi; Takahashi, Kazuyuki; Uchino, Takashi


    Many efforts are under way to control the structure of heterointerfaces in nanostructured composite materials for designing functionality and engineering application. However, the fabrication of high-quality heterointerfaces is challenging because the crystal/crystal interface is usually the most defective part of the nanocomposite materials. In this work, we show that fully dense insulator (MgO)/semiconductor(Mg2Si)/superconductor(MgB2) nanocomposites with atomically smooth and continuous interfaces, including epitaxial-like MgO/Mg2Si interfaces, are obtained by solid phase reaction between metallic magnesium and a borosilicate glass. The resulting nanocomposites exhibit a semiconductor-superconducting transition at 36 K owing to the MgB2 nanograins surrounded by the MgO/Mg2Si matrix. This transition is followed by the intergrain phase-lock transition at ˜24 K due to the construction of Josephson-coupled network, eventually leading to a near-zero resistance state at 17 K. The method not only provides a simple process to fabricate dense nanocomposites with high-quality interfaces, but also enables to investigate the electric and magnetic properties of embedded superconducting nanograins with good intergrain coupling.

  9. The Coordination of Mg in Foraminiferal Calcite

    Branson, O.; Redfern, S. A.; Tyliszczak, T.; Sadekov, A.; Langer, G.; Elderfield, H.


    The Mg/Ca ratio in calcite shells ('tests') of foraminifera is an empirical ocean temperature proxy widely used to interpret palaeoclimates. We explore the distribution and local environment of Mg in foram tests using STXM and NEXAFS spectroscopy to test the fundamental assumptions behind the proxy, and shed light on the mechanisms underpinning this vital oceanographic tool. Throughout the development of the Mg/Ca proxy, it has been assumed that Mg in foraminifera tests substitutes directly into the calcite lattice (1). This assumption is based on XRD analyses of various high-Mg biogenic carbonates, where Mg concentrations are manifest in the shifted position of diffraction peaks (2, 3). The extrapolation of this trend to foraminiferal calcite links the proxy to inorganic precipitation experiments, and provides a theoretical mechanistic framework to understand the link between Mg/Ca and temperature: the substitution of Mg is endothermic, and favoured at higher temperatures. However, the concentration of Mg in most foraminifera (0-10 mmol/mol Mg/Ca) is below the detection limit of XRD methods, and the analogy to inorganic systems has not been explicitly tested. Electron microprobe (4-6), LA-ICP-MS (7) and high-resolution nanoSIMS mapping (Sadekov, unpub.) of foraminifera tests have revealed the presence of high 'trace element' bands running in plane with the test surface, enriched in Mg, Sr, S, organic molecules and other trace elements. This emphasises a key question highlighted by Dodd (1) when the proxy was still in its infancy: how is Mg incorporated into mineral skeletons? By direct substitution into the calcite lattice, interstitially in a separate distinct mineral phase, or associated with organic compounds? We address this fundamental question using scanning transmission X-ray microscopy (STXM) and X-ray absorption spectroscopy at ALS beamline 11.0.2 to examine the distribution and local atomic environment of Mg in two contrasting species of foraminifera

  10. Dose Reduction Techniques



    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the smart things that protect the worker but do not hinder him while the task is being accomplished. In addition, we should not demand that large amounts of money be spent for equipment that has marginal value in order to save a few millirem. We have broken the handout into sections that should simplify the presentation. Time, distance, shielding, and source reduction are methods used to reduce dose and are covered in Part I on work execution. We then look at operational considerations, radiological design parameters, and discuss the characteristics of personnel who deal with ALARA. This handout should give you an overview of what it takes to have an effective dose reduction program.

  11. Physical dependence potential of daily tramadol dosing in humans

    Lofwall, Michelle R.; Mintzer, Miriam Z.; Bigelow, George E.; Strain, Eric C.


    Rationale Tramadol is an atypical, mixed-mechanism analgesic involving both opioid and catecholamine processes that appears to have low abuse potential and may be useful as a treatment for opioid dependence. Objectives The current study assessed the level of physical dependence and opioid blockade efficacy produced by daily maintenance on oral tramadol. Methods Nine residential opioid-dependent adults were maintained on two doses of daily oral tramadol (200 and 800 mg) for approximately 4-week intervals in a randomized, double-blind, crossover design. The acute effects of intramuscular placebo, naloxone (0.25, 0.5, and 1.0 mg), and hydromorphone (1.5, 3.0, and 6.0 mg) were tested under double-blind, randomized conditions. Outcomes included observer- and subject-rated measures and physiologic indices. Results Challenge doses of naloxone resulted in significantly higher mean peak withdrawal scores compared to placebo. Withdrawal intensity from naloxone was generally greater during 800 versus 200 mg/day tramadol maintenance. Mean peak ratings of agonist effects were elevated at higher hydromorphone challenge doses, but did not differ significantly between tramadol doses. Physiologic measures were generally affected by challenge conditions in a dose-dependent manner, with few differences between tramadol maintenance dose conditions. Conclusions Chronic tramadol administration produces dose-related opioid physical dependence, without producing dose-related attenuation of agonist challenge effects. Tramadol may be a useful treatment for patients with low levels of opioid dependence or as a treatment for withdrawal during opioid detoxification, but does not appear to be effective as a maintenance medication due to a lack of opioid cross-tolerance. PMID:20589494

  12. Kinetics and disposition of orally dosed sodium chlorate in sheep

    Experiments were conducted in sheep to determine excretory characteristics of sodium chlorate after a single oral dose. In Exp. 1 lambs (n = 16; age = 8.1 ± 1.7 d; BW = 8.2 ± 1.1 kg; mean ± SD) were dosed orally with 0, 30, 60, or 90 mg/kg BW of sodium chlorate. Twenty-four h after exposure chlorate...

  13. Dose reconstruction of X-ray irradiation of the larynx

    Takacsi-Nagy, L.; Weisz, C.; Zarand, P.; Nemeth, G.


    The authors have determined the dose distribution in the neck for parallel opposed and three field orthovoltage X-ray irradiation techniques of cc. laringis. LiF:Mg, Ti rods and pellets combined with film densitometry were used. Absorbed dose measured in the region of vocal chords is about 20% lower than that assessed by assuming full backscatter (perpendicular incidence) and by using standard isodose tables.

  14. Existing form and effect of zirconium in pure Mg, Mg-Yb, and Mg-Zn-Yb alloys

    YU Wenbin; HE Hong; LI Chunmei; LI Qing; LIU Zhiyi; QIN Bing


    The existing form and grain refining effects of small zirconium addition in pure Mg, Mg-Yb and Mg-Zn binary alloys, and Mg-Zn-Yb ternary alloy (ZK60-Yb) were investigated. The results show that Zr element exists mainly in single and cluster particles of pure α-Zr or Zn-Zr compounds inside grains and at grain boundaries. Only the particles located in the interior of grains can act as the nucleus for α-Mg growth and effectively promote the formation of Fine equiaxed grains. The broken and dispersed Zr-rich particles produced during the hot extrusion process can form nebulous banded structure in which these free particles may act as obstacles to dislocation motion in wrought magnesium alloys.

  15. Minimal doses of hydroxyurea for sickle cell disease

    C.S.P. Lima


    Full Text Available The use of hydroxyurea (HU can improve the clinical course of sickle cell disease. However, several features of HU treatment remain unclear, including the predictability of drug response and determination of adequate doses, considering positive responses and minimal side effects. In order to identify adequate doses of HU for treatment of sickle cell disease, 10 patients, 8 with sickle cell anemia and 2 with Sß thalassemia (8SS, 2Sß, were studied for a period of 6 to 19 months in an open label dose escalation trial (10 to 20 mg kg-1 day-1. Hemoglobin (Hb, fetal hemoglobin (Hb F and mean corpuscular volume (MCV values and reticulocyte, neutrophil and platelet counts were performed every two weeks during the increase of the HU dose and every 4 weeks when the maximum HU dose was established. Reduction in the number of vasoocclusive episodes was also considered in order to evaluate the efficiency of the treatment. The final Hb and Hb F concentrations, and MCV values were significantly higher than the initial values, while the final reticulocyte and neutrophil counts were significantly lower. There was an improvement in the concentration of Hb (range: 0.7-2.0 g/dl at 15 mg HU kg-1 day-1, but this concentration did not increase significantly when the HU dose was raised to 20 mg kg-1 day-1. The concentration of Hb F increased significantly (range: 1.0-18.1% when 15 mg HU was used, and continued to increase when the dose was raised to 20 mg kg-1 day-1. The final MCV values increased 11-28 fl (femtoliters. However, reticulocyte (range: 51-205 x 109/l and neutrophil counts (range: 9.5-1.3 x 109/l obtained at this dose were significantly lower than those obtained with 15 mg kg-1 day-1. All patients reported a decrease in frequency or severity of vasoocclusive episodes. These results suggest that a hydroxyurea dose of 15 mg kg-1 day-1 seems to be adequate for treatment of sickle cell disease in view of the minimal side effects observed and the improvement

  16. Low dose of lipopolysaccharide pretreatment can alleviate the inflammatory response in wound infection mouse model

    Dong Wang; Yang Liu; Yan-Rui Zhao; Jun-Lin Zhou


    Purpose:To assess the effects of lipopolysaccharide (LPS) pretreatment on wound infection mouse model and evaluate the biological safety of the optimal pretreatment dose in vivo.Methods:Mice were pretreated with LPS of different doses at 48 and 24 h before femoral medial longitudinal incision was made and infected with different bacteria.Results:It is showed that 0.5 mg/kg/time of LPS pretreatment can significantly alleviate the inflammation in mouse model infected with methicillin-resistances Staphylococcus aureus,methicillin-sensitive S.aureus,Pseudomonas aeruginosa,or Escherichia coli compared with doses of 0.25 mg/kg/time,1 mg/kg/time,and 1.5 mg/kg/time.Conclusions:LP5 pretreatment can alleviate the inflammation in mouse model and the optimal dose is 0.5 mg/kg/time,and meanwhile it does not damage organs' function.

  17. Dose requirement and complications of diluted and undiluted propofol for deep sedation in endoscopic retrograde cholangiopancreatography

    SomchaiAmornyotin; WichitSrikureja; WiyadaChalayonnavin; SiripornKongphlay


    BACKGROUND: In general, the dose requirement and complications of propofol are lower when used in the diluted form than in the undiluted form. The aim of this study was to determine the dose requirement and complications of diluted and undiluted propofol for deep sedation in endoscopic retrograde cholangiopancreatography. METHODS: Eighty-six patients were randomly assigned to either group D (diluted propofol) or U (undiluted propofol). All patients were sedated with 0.02-0.03 mg/kg midazolam (total dose ≤2 mg for age RESULTS:  All endoscopies were completed successfully. Mean propofol doses per body weight and per body weight per hour in groups D and U were 3.0 mg/kg, 6.2 mg/kg per hour and 4.7 mg/kg, 8.0 mg/kg per hour, respectively. The mean dose of propofol, expressed as total dose, dose/kg or dose/kg per hour and the recovery time were not significantly different between the two groups. Sedation-related adverse events during and immediately after the procedure were higher in group U (42.9%) than in group D (18.2%) (P=0.013). CONCLUSIONS: Propofol requirement and recovery time in the diluted and undiluted propofol groups were comparable. However, the sedation-related hypotension was significantly lower in the diluted group than the undiluted group.

  18. Single dose dipyrone for acute postoperative pain.

    Edwards, Jayne; Meseguer, Fuensanta; Faura, Clara; Moore, R Andrew; McQuay, Henry J; Derry, Sheena


    Dipyrone (metamizole) is a non-steroidal anti-inflammatory drug used in some countries to treat pain (postoperative, colic, cancer, and migraine); it is banned in others because of an association with life-threatening blood agranulocytosis. This review updates a 2001 Cochrane review, and no relevant new studies were identified, but additional outcomes were sought. To assess the efficacy and adverse events of single dose dipyrone in acute postoperative pain. The earlier review searched CENTRAL, MEDLINE, EMBASE, LILACS and the Oxford Pain Relief Database to December 1999. For the update we searched CENTRAL, MEDLINE,EMBASE and LILACS to February 2010. Single dose, randomised, double-blind, placebo or active controlled trials of dipyrone for relief of established moderate to severe postoperative pain in adults. We included oral, rectal, intramuscular or intravenous administration of study drugs. Studies were assessed for methodological quality and data extracted by two review authors independently. Summed total pain relief over six hours (TOTPAR) was used to calculate the number of participants achieving at least 50% pain relief. Derived results were used to calculate, with 95% confidence intervals, relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over six hours. Use and time to use of rescue medication were additional measures of efficacy. Information on adverse events and withdrawals was collected. Fifteen studies tested mainly 500 mg oral dipyrone (173 participants), 2.5 g intravenous dipyrone (101), 2.5 g intramuscular dipyrone (99); fewer than 60 participants received any other dose. All studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen, dexketoprofen, ketorolac, pethidine, tramadol, suprofen); eight used placebo controls.Over 70% of participants experienced at least 50% pain relief over 4 to 6 hours with oral dipyrone 500 mg compared to 30

  19. Multiple-dose pharmacokinetics confirm no accumulation and dose proportionality of the novel promotile drug tegaserod (HTF 919).

    Appel-Dingemanse, S; Hirschberg, Y; Osborne, S; Pommier, F; McLeod, J


    To evaluate the steady-state pharmacokinetics (PK) and dose proportionality of the selective 5-HT4 receptor partial agonist tegaserod (HTF 919) in healthy subjects. Eighteen subjects were given 2, 6, or 12-mg doses of tegaserod twice daily (b.i.d.) for 5 days, with PK and safety assessments made during the 12 h or 24 h following first administration, and 12 h after the final dose. Tegaserod was rapidly absorbed [time to reach measured maximum plasma concentration after multiple administrations (tmax,ss) 1 h]. Steady-state PK were consistent with single-dose PK characteristics supporting that there was no accumulation of tegaserod in plasma based on systemic exposure. Mean measured maximum plasma concentration after multiple administrations (Cmax,ss) and area under the plasma concentration-time curve over one dosing interval (tau, 0-12 h after drug administration, AUC tau) were between 0.7 +/- 0.3 ng/ml and 5.6 +/- 2.9 ng/ml and 2.4 +/- 1.3 and 20.4 +/- 14.0, respectively, indicating dose-proportional PK of tegaserod in the range 2-12 mg b.i.d. Tegaserod was safe and well tolerated. No serious adverse events were reported. Tegaserod exhibits no accumulation and dose-proportional PK after multiple doses.

  20. The relationship between terazosin dose and blood pressure response in hypertensive patients.

    Achari, R; Hosmane, B; Bonacci, E; O'Dea, R


    A double-blind, randomized, placebo-controlled, multicenter study was conducted to describe the dose-response curve for terazosin on blood pressure. A total of 128 patients with mild to moderate essential hypertension (supine diastolic blood pressure, 100 to 114 mmHg) participated in the study. The study consisted of a 4-week single-blind placebo lead-in period and a 14-week double-blind treatment period. Patients were randomized in equal numbers to four parallel treatment groups: terazosin 1, 2, and 5 mg; terazosin 2, 5, and 10 mg; terazosin 20, 40, and 80 mg; and placebo. The 24-hour ambulatory blood pressure measurements were performed at the end of the placebo lead-in period and at the end of each 4-week fixed-dose period. The nonlinear, mixed-effect model computer program was used to analyze the dose-response relationship. There was a strong dose-response relationship between fall in blood pressure and the 1 to 10 mg terazosin dose, as well as a plateauing of response for terazosin doses above 10 mg. The maximum antihypertensive response (Emax) to terazosin was 10.7 mmHg for systolic blood pressure and 8.0 mmHg for diastolic blood pressure. The daily dose of terazosin, which produced 50% of the maximum response (ED50), was 3.0 mg for systolic blood pressure and 1.5 mg for diastolic blood pressure. The results of this study suggest that although some patients may benefit from terazosin doses of greater than 10 mg, doses up to 10 mg will maximize therapeutic benefit for most patients, with acceptable side effects.

  1. [Calculation of the first dose of amikacine: evaluation of the current dosage recommendations].

    Jean-Bart, E; Debeurme, G; Ducher, M; Bourguignon, L


    Aminoglycosides, including amikacin, are antibiotics with major interest in the management of sepsis, but with a high potential toxicity. The French national recommendations revised in 2011 recommend a dose of amikacin ranging from 15 to 30 mg/kg. The objective was to assess if such a dose interval allows reaching the efficiency target concentrations of 64 mg/L without exceeding the toxic threshold of 2.5mg/L. From a cohort of 100 patients treated with amikacin, the individual pharmacokinetic parameters were estimated using pharmacokinetic software (MM-USCPACK). Peak and residual concentrations obtained after simulated doses ranging from 15 to 30 mg/kg were estimated and compared with the effective and toxic thresholds. The optimum dose to achieve precisely the efficiency target was calculated for each patient. Patients studied had a mean age of 79 years, mean weight of 58 kg, and mean creatinine clearance of 45 mL/min. The dose of 30 mg/kg allows the achievement of an effective peak in 98.7% of patients, but led to a potentially toxic through for 72.4% of them. The optimal dose was at mean of 1264 mg, significantly different than doses calculated with weight (P<0.0001). A weak correlation was found between weight and the optimal dose. A fixed dose of 30 mg/kg seems to be effective for most patients, but often excessive and leads to a toxic residual to 72% of patients, whereas 15 mg/kg was insufficient for most patients. The low correlation between optimal dose and patient weight shows that weight does not explain fully the interindividual variability.

  2. Effect of low dose pioglitazone on glycemic control and insulin resistance in Type 2 diabetes: A randomized, double blind, clinical trial.

    Rajagopalan, Sujit; Dutta, Pinaki; Hota, Debasish; Bhansali, Anil; Srinivasan, Anand; Chakrabarti, Amitava


    This study shows that pioglitazone 7.5 mg/day as an add-on therapy in Southeast Asian patients with Type 2 diabetes is safer and equally efficacious as the 15- and 30-mg doses of pioglitazone. Hence it is prudent to start pioglitazone therapy at a lower dose of 7.5 mg/day.

  3. Dose Reduction Techniques

    Waggoner, L O


    As radiation safety specialists, one of the things we are required to do is evaluate tools, equipment, materials and work practices and decide whether the use of these products or work practices will reduce radiation dose or risk to the environment. There is a tendency for many workers that work with radioactive material to accomplish radiological work the same way they have always done it rather than look for new technology or change their work practices. New technology is being developed all the time that can make radiological work easier and result in less radiation dose to the worker or reduce the possibility that contamination will be spread to the environment. As we discuss the various tools and techniques that reduce radiation dose, keep in mind that the radiological controls should be reasonable. We can not always get the dose to zero, so we must try to accomplish the work efficiently and cost-effectively. There are times we may have to accept there is only so much you can do. The goal is to do the sm...

  4. T dose Vaccine Policy

    National Programme of Immunization (NPI), measles remains a disturbing cause ... or as a supplement is expected to offer a second opportunity to children who ... available in 1963, the world welcomed it with joy .... one dose of vaccine were not always protected from .... begins a long story Starting now is still early enough.

  5. Dose escalation studies with caspofungin against Candida glabrata.

    Domán, Marianna; Kovács, Renátó; Perlin, David S; Kardos, Gábor; Gesztelyi, Rudolf; Juhász, Béla; Bozó, Aliz; Majoros, László


    Echinocandins are recommended as first-line agents against invasive fungal infections caused by Candida glabrata, which still carry a high mortality rate. Dose escalation of echinocandins has been suggested to improve the clinical outcome against C. glabrata. To address this possibility, we performed in vitro and in vivo experiments with caspofungin against four WT C. glabrata clinical isolates, a drug-susceptible ATCC 90030 reference strain and two echinocandin-resistant strains with known FKS mutations. MIC values for the clinical isolates in RPMI 1640 were ≤ 0.03 mg l(-1 ) but increased to 0.125-0.25 mg l(-1 )in RPMI 1640+50% serum. In RPMI 1640+50% serum, the replication of C. glabrata was weaker than in RPMI 1640.Caspofungin in RPMI 1640 at 1 and 4 mg l(-1) showed a fungicidal effect within 7 h against three of the four clinical isolates but was only fungistatic at 16 and 32 mg l(-1) (paradoxically decreased killing activity). In RPMI 1640+50% serum, caspofungin at ≥ 1 mg l(-1) was rapidly fungicidal (within 3.31 h) against three of the four isolates. In a profoundly neutropenic murine model, all caspofungin doses (1, 2, 3, 5 and 20 mg kg(-1) daily) decreased the fungal tissue burdens significantly (P caspofungin dose escalation does not improve efficacy.

  6. Pregnancy-induced changes in the long-term pharmacokinetics of 1.1 mg vs. 5 mg folic acid: a randomized clinical trial.

    Shere, Mahvash; Nguyen, Patricia; Tam, Carolyn; Stern, Seth; Kapur, Bhushan; O'Connor, Deborah L; Koren, Gideon


    The objective of this randomized clinical trial was to compare steady-state gestational RBC and plasma folate concentrations in pregnant women supplementing daily with 1.1 mg (regular dose) vs. 5 mg (high dose) folic acid. Thirty-seven pregnant women, who were not previously taking folic acid, were enrolled in this open-label, 2-arm, randomized clinical trial after informed consent. Participants were randomly assigned either 1.1 or 5 mg of folic acid-containing prenatals until gestational age (g.a.) 30 weeks. Plasma and RBC folate concentrations were measured at baseline, g.a.6 weeks, g.a.12 weeks, and g.a.30 weeks using a chemiluminescent immunoassay. Results showed sustained significant increase in RBC folate in the 5 mg group between g.a.6 weeks and g.a.30 weeks (P pregnancy alter long-term folate pharmacokinetics. Despite supplementation over an extended period of time, steady-state does not seem to be achieved in either dose group within our study.

  7. The paradox of human equivalent dose formula: A canonical case study of abrus precatorius aqueous leaf extract in monogastric animals

    Saganuwan Alhaji Saganuwan


    Full Text Available There is abundant literature on the toxicity of A. precatorius seeds. However there is a need to define the toxicity limit of the Abrus precatorius leaf in monogastric animals. Human Equivalent Dose (HED which is equal to animal dose multiplied by animal km (metabolism constant divided by human km was used to project the LD50 of fifteen monogastric animals , where human km factor is body weight (kg divided by body surface area (m2. Human Equivalent No-observable Adverse Effect Doses were determined by multiplying the animal no-observable adverse effect dose by animal weight (Wa divided by human weight (Wh. The LD50 of the aqueous leaf extract of Abrus precatorius in mice was estimated to be between 2559.5 and 3123.3 mg/kg body weight. The LD50 extrapolated from mouse to rat (1349.3-1646.6 mg/kg, hamster (1855.3-2264.1 mg/kg, guinea pig (1279.5-1561.4 mg/kg, rabbit (618.4-754.7 mg/kg, monkey (593.7-724.5 mg/kg, cat (392.7-479.2 mg/kg, dog and baboon (371.1-452.8 mg/kg, child (297-362 mg/kg and adult human (197.8-241.5 mg/kg body weight respectively could be a reality. The therapeutic safe dose range for the animals was 1-12.5 mg/kg body weight for a period of 7 days, but at a dose (≤ 200 mg/kg body weight the leaf extract showed haematinic effect. However, at a higher dose (> 200 mg/kg, the extract showed haemolytic activity in rats, whereas at a dose (≥25.0 mg/kg, the leaf extract might be organotoxic in hamster, guinea pig, rabbit, monkey, cat, dog, baboon, child and adult human if administered orally for a period of 7 days.

  8. Dose-response effect of the lercanidipine/enalapril combination: a pooled analysis.

    Rizzoni, Damiano


    The dose-effect relationship of fixed-dose combinations of anti-hypertensive drugs has been only poorly explored. This pooled analysis investigates the dose-response relationship of fixed-dose lercanidipine + enalapril in patients with mild-to-moderate hypertension. This was an individual patient data analysis of four randomized studies (n = 2340). The primary efficacy variable was the change from baseline in sitting diastolic blood pressure (SDBP). Secondary variables were change from baseline in sitting systolic BP (SSBP), proportion of responder patients, and safety. All fixed-dose combinations were superior to placebo in the reduction of SDBP. The greatest effect was observed with the market-available combination lercanidipine 20 mg/enalapril 20 mg (-15.3 mmHg vs. baseline; p < 0.05). The reduction in SDBP associated with the other two marketed fixed combinations of lercanidipine/enalapril were -10.7 mmHg for the 10 mg/20 mg combination and -9.8 mmHg for the 10 mg/10 mg combination (p < .05 for both comparisons). Similar findings were reported for SSBP reduction: the greatest effect was observed with lercanidipine 20 mg/enalapril 20 mg (-19.2 mmHg). The reduction in SSBP was -12.5 mmHg for the 10 mg/20 mg combination and -11.1 mmHg for the 10 mg/10 mg combination (p < .05 for all comparisons). The highest responder rate was reported with lercanidipine 20 mg/enalapril 20 mg (75.0%); this figure was 56.1% with the 10 mg/20 mg and 53.0% with the 10/10 mg combination. No safety concerns were reported. This pooled analysis of four randomized studies shows evidence of a dose-response effect in BP reduction with different fixed combinations of lercanidipine + enalapril. To our knowledge, this is the first analysis investigating the dose-response effect of a specific fixed-dose combination of anti-hypertensive agents. Further studies on this intriguing topic are however necessary.

  9. Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial.

    Eltahir A G Khalil

    Full Text Available BACKGROUND: Anti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL but the appropriate single dose is unknown. METHODOLOGY: A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1-5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT PCR. PRINCIPAL FINDINGS: The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73-93%, 40% (95%CI 19-64%, and 58% (95%CI 41-73% in patients treated with multiple doses (n = 63, and single doses of 7·5 (n = 21 or 10 mg/kg (n = 40, respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label. CONCLUSIONS: The tested AmBisome regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified. TRIALS REGISTRATION: www.clinicaltrials.govNCT00832208.

  10. A randomized, controlled trial of 3.0 mg of Liraglutide in weight management

    Pi-Sunyer, Xavier; Astrup, Arne; Fujioka, Ken


    Background Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, ...

  11. Rectangular nanovoids in helium-implanted and thermally annealed MgO(100)

    Kooi, B.J.; Veen, A. van; Hosson, J.Th.M. De; Schut, H.; Fedorov, A.V.; Labohm, F.


    Cleaved MgO(100) single crystals were implanted with 30 keV 3He ions with doses varying from 1×10^19 to 1×10^20 m-2 and subsequently thermally annealed from 100 to 1100 °C. Transmission electron microscopy observations revealed the existence of sharply rectangular nanosize voids at a depth slightly

  12. Thermoluminescence characteristics of MgSO sub 4 :Dy,Mn phosphor

    Luo Da Ling; Deng Zou Ping; Li Guo Zhen


    The MgSO sub 4 :Dy,Mn thermoluminescence (TL) phosphors have been prepared by co-doping with various concentrations of activators the Dy and Mn. The dose-responses to gamma-rays are studied by deconvolution of the TL glow curves. It is found that the TL sensitivity of the MgSO sub 4 :Dy,Mn phosphor is comparable to that of the phosphor LiF:Mg,Ti. Besides, there is only one main dosimetric peak at 383 deg. C in its TL glow curve. The trap parameters of the dosimetric peak were obtained as activation energy E approx 1.972 eV, the frequency-factor s approx 4.294x10 sup 1 sup 4 s sup - sup 1 and the kinetic order b approx 2 by fitting the glow curves with general-order kinetics. The area of this dosimetric peak is approx 90% of the integral area of the whole glow curve for a gamma dose range of 0.1 Gy-20 kGy. The dose response of MgSO sub 4 :Dy,Mn to gamma-rays in this dose range is supralinear. There are no radiation damage effects observed in TL glow curves above 1 kGy as that occurred in LiF dosimeters.

  13. Pharmacology of rising oral doses of 5-hydroxytryptophan with carbidopa.

    Smarius, L J C A; Jacobs, G E; Hoeberechts-Lefrandt, D H M; de Kam, M L; van der Post, J P; de Rijk, R; van Pelt, J; Schoemaker, R C; Zitman, F G; van Gerven, J M A; Gijsman, H J


    5-hydroxytryptophan (5-HTP) is a direct 5-hydroxytryptamine (5-HT) precursor used to assess central serotonergic function. Its use has been limited by a narrow window between neuroendocrine changes and side effects, and variable kinetics related to inconsistent administration modes. By combining 5-HTP with carbidopa (CBD), increased bioavailability for brain penetration and decreased peripheral side effects would be expected, due to reduced peripheral decarboxylation of 5-HTP to 5-HT. A double-blind, placebo-controlled, single rising dose, four-way crossover trial with placebo randomisation was performed in 15 healthy male volunteers to investigate the neuroendocrine dose-response relationship at various 5-HTP levels; the tolerability and subjective effects of oral 5-HTP at 100, 200 and 300 mg combined with CBD and the pharmacokinetic properties of the 5-HTP/CBD-challenge. Dose-dependent increases in average cortisol concentrations were observed. Mean response (area-under-the-curve) over the first 4 hours (SD): 172.0 nmol/L (22.3) for placebo, 258.3 nmol/L (72.6) for 100 mg, 328.47 nmol/L (84.6) for 200 mg and 387.3 nmol/L (82.4) for 300 mg 5-HTP. Similar dose-dependent increases for prolactin were seen while adreno-corticotrophic hormone response was more variable. 5-HTP kinetics were adequately described using a one-compartment model with first-order absorption and a lag time (mean oral clearance 28 L/h interindividual coefficient of variation 31%). Nausea and vomiting occurred dose-dependently as most frequent side effects, resulting in dose-related dropout of 6.6% at 100 mg and 45.5% at 300 mg 5-HTP. Orally administered 5-HTP combined with CBD is an effective serotonergic challenge test, exhibiting dose-related plasma concentrations and neuroendocrine responsiveness. Frequent occurrence of nausea and vomiting limits the applicability of this challenge at 5-HTP doses above 100 mg.

  14. A comparison of roxatidine acetate 150 mg once daily and 75 mg twice daily in duodenal ulcer healing.

    Hentschel, E; Schütze, K


    A randomised multicentre, double-blind study of the efficacy and safety of roxatidine acetate 150 mg at bedtime or 75 mg twice a day was conducted in 300 outpatients with endoscopically confirmed duodenal ulcers. After 14 days' treatment with roxatidine acetate substantial reductions in ulcer sizes had been obtained, in addition to healing rates of 87 to 89%, with no significant differences between the dosage regimens. There were graded reductions in day and night-time assessment of epigastric pain for both treatment groups and no differences in the mean numbers of antacid tablets consumed. In addition, cigarette smoking did not influence the healing rates produced by either treatment schedule. 11 patients reported 12 mild adverse reactions, with gastrointestinal symptoms the most frequent, and no clinically significant alterations in laboratory values. The present data suggests that a single bedtime dose of roxatidine acetate 150 mg produces effective duodenal ulcer healing and pain relief equivalent to that produced by a twice daily dosage regimen.

  15. Determinants of thiopental induction dose requirements.

    Avram, M J; Sanghvi, R; Henthorn, T K; Krejcie, T C; Shanks, C A; Fragen, R J; Howard, K A; Kaczynski, D A


    Dose requirements for thiopental anesthetic induction have significant age- and gender-related variability. We studied the association of the patient characteristics age, gender, weight, lean body mass, and cardiac output with thiopental requirements. Doses of thiopental, infused at 150 mg/min, required to reach both a clinical end-point and an electroencephalographic (EEG) end-point were determined in 30 males and 30 females, aged 18-83 yr. Univariate least squares linear regression analysis revealed outliers in the relationships of age, weight, lean body mass, and cardiac output to thiopental dose at clinical and EEG endpoints. Differential weighting of data points minimized the effect of outliers in the construction of a robust multiple linear regression model of the relationship between several selected independent variables and the dependent variables thiopental dose at clinical and EEG endpoints. The multiple linear regression model for thiopental dose at the clinical end-point selecting the regressor variables age, weight, and gender (R2 = 0.76) was similar to that for age, lean body mass, and gender (R2 = 0.75). Thiopental dose at the EEG endpoint was better described by models selecting the variables age, weight, and cardiac output (R2 = 0.88) or age, lean body mass, and cardiac output (R2 = 0.87). Although cardiac output varied with age, age always remained a selected variable. Because weight and lean body mass differed with gender, their selection as variables in the model eliminated gender as a selected variable or minimized its importance.

  16. UHV and Ambient Pressure XPS: Potentials for Mg, MgO, and Mg(OH)2 Surface Analysis

    Head, Ashley R.; Schnadt, Joachim


    The surface sensitivity of x-ray photoelectron spectroscopy (XPS) has positioned the technique as a routine analysis tool for chemical and electronic structure information. Samples ranging from ideal model systems to industrial materials can be analyzed. Instrumentational developments in the past two decades have popularized ambient pressure XPS, with pressures in the tens of mbar now commonplace. Here, we briefly review the technique, including a discussion of developments that allow data collection at higher pressures. We illustrate the information XPS can provide by using examples from the literature, including MgO studies. We hope to illustrate the possibilities of ambient pressure XPS to Mg, MgO, and Mg(OH)2 systems, both in fundamental and applied studies.

  17. Exercise and sport performance with low doses of caffeine.

    Spriet, Lawrence L


    Caffeine is a popular work-enhancing supplement that has been actively researched since the 1970s. The majority of research has examined the effects of moderate to high caffeine doses (5-13 mg/kg body mass) on exercise and sport. These caffeine doses have profound effects on the responses to exercise at the whole-body level and are associated with variable results and some undesirable side effects. Low doses of caffeine (caffeine doses (1) do not alter the peripheral whole-body responses to exercise; (2) improve vigilance, alertness, and mood and cognitive processes during and after exercise; and (3) are associated with few, if any, side effects. Therefore, the ergogenic effect of low caffeine doses appears to result from alterations in the central nervous system. However, several aspects of consuming low doses of caffeine remain unresolved and suffer from a paucity of research, including the potential effects on high-intensity sprint and burst activities. The responses to low doses of caffeine are also variable and athletes need to determine whether the ingestion of ~200 mg of caffeine before and/or during training and competitions is ergogenic on an individual basis.

  18. Diffusion of Ca and Mg in Calcite

    Cygan, R.T.; Fisler, D.K.


    The self-diffusion of Ca and the tracer diffusion of Mg in calcite have been experimentally measured using isotopic tracers of {sup 25}Mg and {sup 44}Ca. Natural single crystals of calcite were coated with a thermally-sputtered oxide thin film and then annealed in a CO{sub 2} gas at one atmosphere total pressure and temperatures from 550 to 800 C. Diffusion coefficient values were derived from the depth profiles obtained by ion microprobe analysis. The resultant activation energies for Mg tracer diffusion and Ca self-diffusion are respectively: E{sub a}(Mg) = 284 {+-} 74 kJ/mol and E{sub a}(Ca) = 271 {+-} 80 kJ/mol. For the temperature ranges in these experiments, the diffusion of Mg is faster than Ca. The results are generally consistent in magnitude with divalent cation diffusion rates obtained in previous studies and provide a means of interpreting the thermal histories of carbonate minerals, the mechanism of dolomitization, and other diffusion-controlled processes. The results indicate that cation diffusion in calcite is relatively slow and cations are the rate-limiting diffusing species for the deformation of calcite and carbonate rocks. Application of the calcite-dolomite geothermometer to metamorphic assemblages will be constrained by cation diffusion and cooling rates. The direct measurement of Mg tracer diffusion in calcite indicates that dolomitization is unlikely to be accomplished by Mg diffusion in the solid state but by a recrystallization process.

  19. A Phase I Dose-Escalation Study of Antibody BI-505 in Relapsed/Refractory Multiple Myeloma

    Hansson, Markus; Gimsing, Peter; Badros, Ashraf;


    , at escalating doses from 0.0004 to 20 mg/kg, with extension of therapy until disease progression for responding or stable patients receiving 0.09 mg/kg or higher doses. RESULTS: A total of 35 patients were enrolled. The most common adverse events were fatigue, pyrexia, headache, and nausea. Adverse events were...

  20. Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort

    Chatzidionysiou, Katerina; Lie, Elisabeth; Nasonov, Evgeny;


    BACKGROUND: The approved dose of rituximab (RTX) in rheumatoid arthritis is 1000 mg × 2, but some data have suggested similar clinical efficacy with 500 mg × 2. The purpose of this study was to compare the effectiveness of the regular and low doses given as first treatment course. METHODS: Twelve...

  1. Measurement of entrance skin dose and estimation of organ dose during pediatric chest radiography.

    Kumaresan, M; Kumar, Rajesh; Biju, K; Choubey, Ajay; Kantharia, S


    Entrance skin dose (ESD) was measured to calculate the organ doses from the anteroposterior (AP) and posteroanterior (PA) chest x-ray projections for pediatric patients in an Indian hospital. High sensitivity tissue-equivalent thermoluminescent dosimeters (TLD, LiF: Mg, Cu, P chips) were used for measuring entrance skin dose. The respective organ doses were calculated using the Monte Carlo method (MCNP 3.1) to simulate the examination set-up and a three-dimensional mathematical phantom for representing an average 5-y-old Indian child. Using this method, conversion coefficients were derived for translating the measured ESD to organ doses. The average measured ESDs for the chest AP and PA projections were 0.305 mGy and 0.171 mGy, respectively. The average calculated organ doses in the AP and the PA projections were 0.196 and 0.086 mSv for the thyroid, 0.167 and 0.045 mSv for the trachea, 0.078 and 0.043 mSv for the lungs, 0.110 and 0.013 mSv for the liver, 0.002 and 0.016 mSv for the bone marrow, 0.024 and 0.002 mSv for the kidneys, and 0.109 and 0.023 mSv for the heart, respectively. The ESD and organ doses can be reduced significantly with the proper radiological technique. According to these results, the chest PA projection should be preferred over the AP projection in pediatric patients. The estimated organ doses for the chest AP and PA projections can be used for the estimation of the associated risk.

  2. Two prospective dosing methods for nortriptyline.

    Perry, P J; Browne, J L; Alexander, B; Tsuang, M T; Sherman, A D; Dunner, F J


    This study compared two prospective pharmacokinetic dosing methods to predict steady-state concentrations of nortriptyline. One method required multiple determinations of the nortriptyline plasma concentration to estimate the drug's steady-state concentration. The second method required a single nortriptyline concentration drawn at a fixed time, preferably 36 hours, following a nortriptyline test dose. The 36-hour nortriptyline plasma concentrations (NTP 36h) were substituted into the straight-line equation of Cssav = 17.2 + 3.74 (NTP 36h), where Cssav is the average steady-state concentration for a 100 mg/day dose of nortriptyline. No differences were noted between the observed steady-state nortriptyline concentration of 121 +/- 19 ng/ml, the 36-hour single-point prediction mean concentration of 121 +/- 21 ng/ml, or the multiple-point prediction mean concentration of 122 +/- 19 ng/ml. Because of the similar findings between the two methods, the clinical advantages and disadvantages of each kinetic approach are discussed to put these prospective dosing protocols into their proper perspective.

  3. Effects of proton radiation dose, dose rate and dose fractionation on hematopoietic cells in mice

    Ware, J.H.; Rusek, A.; Sanzari, J.; Avery, S.; Sayers, C.; Krigsfeld, G.; Nuth, M.; Wan, X.S.; Kennedy, A.R.


    The present study evaluated the acute effects of radiation dose, dose rate and fractionation as well as the energy of protons in hematopoietic cells of irradiated mice. The mice were irradiated with a single dose of 51.24 MeV protons at a dose of 2 Gy and a dose rate of 0.05-0.07 Gy/min or 1 GeV protons at doses of 0.1, 0.2, 0.5, 1, 1.5 and 2 Gy delivered in a single dose at dose rates of 0.05 or 0.5 Gy/min or in five daily dose fractions at a dose rate of 0.05 Gy/min. Sham-irradiated animals were used as controls. The results demonstrate a dose-dependent loss of white blood cells (WBCs) and lymphocytes by up to 61% and 72%, respectively, in mice irradiated with protons at doses up to 2 Gy. The results also demonstrate that the dose rate, fractionation pattern and energy of the proton radiation did not have significant effects on WBC and lymphocyte counts in the irradiated animals. These results suggest that the acute effects of proton radiation on WBC and lymphocyte counts are determined mainly by the radiation dose, with very little contribution from the dose rate (over the range of dose rates evaluated), fractionation and energy of the protons.

  4. Comparison of the Efficacy and Safety of 2 Acetaminophen Dosing Regimens in Febrile Infants and Children: A Report on 3 Legacy Studies

    Zimmerman, Brenda; Gelotte, Cathy; Kuffner, Edwin K.


    OBJECTIVE Compare efficacy and safety of 10 to 15 mg/kg with 20 to 30 mg/kg acetaminophen in febrile children 6 months to ≤ 11 years from 3 double-blind, randomized, single or multiple dose studies. METHODS Doses were compared on sum of the temperature differences (SUMDIFF), maximum temperature difference (MAXDIFF), temperature differences at each time point, and dose by time interactions. Alanine aminotransferase (ALT) was evaluated in the 72-hour duration study. RESULTS A single dose of acetaminophen 20 to 30 mg/kg produced a greater effect on temperature decrement and duration of antipyretic effect over 8 hours than a single dose of 10 to 15 mg/kg. When equivalent total doses (i.e., 2 doses of 10 to 15 mg/kg given at 4-hour intervals and 1 dose of 20 to 30 mg/kg) were given over the initial 8-hour period, there were no significant temperature differences. Over a 72-hour period, 10 to 15 mg/kg acetaminophen administered every 4 hours maintained a more consistent temperature decrement than 20 to 30 mg/kg acetaminophen administered every 8 hours. Following doses of 60 to 90 mg/kg/day for up to 72 hours, no child had a clinically important increase in ALT from baseline. The number of children with reported adverse events was similar between doses. CONCLUSIONS Data demonstrate the antipyretic effect of acetaminophen is dependent on total dose over a given time interval. These 3 studies provide clinical evidence that the recommended standard acetaminophen dose of 10 to 15 mg/kg is a safe and effective dose for treating fever in pediatric patients when administered as a single dose or as multiple doses for up to 72 hours. PMID:28337078

  5. Evaluation of LiF:Mg,Ti (TLD-100 for Intraoperative Electron Radiation Therapy Quality Assurance.

    Raffaele Liuzzi

    Full Text Available Purpose of the present work was to investigate thermoluminescent dosimeters (TLDs response to intraoperative electron radiation therapy (IOERT beams. In an IOERT treatment, a large single radiation dose is delivered with a high dose-per-pulse electron beam (2-12 cGy/pulse during surgery. To verify and to record the delivered dose, in vivo dosimetry is a mandatory procedure for quality assurance. The TLDs feature many advantages such as a small detector size and close tissue equivalence that make them attractive for IOERT as in vivo dosimeters.LiF:Mg,Ti dosimeters (TLD-100 were irradiated with different IOERT electron beam energies (5, 7 and 9 MeV and with a 6 MV conventional photon beam. For each energy, the TLDs were irradiated in the dose range of 0-10 Gy in step of 2 Gy. Regression analysis was performed to establish the response variation of thermoluminescent signals with dose and energy.The TLD-100 dose-response curves were obtained. In the dose range of 0-10 Gy, the calibration curve was confirmed to be linear for the conventional photon beam. In the same dose region, the quadratic model performs better than the linear model when high dose-per-pulse electron beams were used (F test; p<0.05.This study demonstrates that the TLD dose response, for doses ≤10 Gy, has a parabolic behavior in high dose-per-pulse electron beams. TLD-100 can be useful detectors for IOERT patient dosimetry if a proper calibration is provided.

  6. Solvation of Mg in Helium-4: Are there Meta-stable Mg Dimers ?

    Krotscheck, Eckhard


    Experiments on the formation of magnesium complexes in $^4$He nanodroplets were interpreted as the observation of the formation of weakly bound magnesium complexes. We present results for single Mg and Mg dimer solvation using the hypernetted chain / Euler-Lagrange method as well as path integral Monte Carlo simulations. We find that the phonon-mediated, indirect Mg-Mg interaction adds an oscillatory component to the direct Mg-Mg interaction. We undertake a step-by-step examination of the ingredients of the calculation of the phonon-induced interaction, comparing the results of semi-analytic HNC-EL calculations for bulk and single impurity results with experiments as well as Monte Carlo data. We do not find evidence for a sufficiently strong secondary minimum in the effective Mg-Mg interaction to support a metastable state.

  7. The role of MgO content in ex situ MgB2 wires

    Kovac, P.; Hugek, I.; Meligek, T.;


    An experimental study of the effect of MgO content in the MgB2 powder used for ex situ made composite wires was carried out. Two single-core MgB2/Fe/Cu wires were made using commercial MgB2 powders from Alfa Aesar containing different fraction of MgO. Critical temperature and critical currents...... of as-deformed and heat-treated wires were measured. The differences between the wires are discussed and correlated with the MgO content. It was found that by increasing the amount of MgO, the inter-grain connectivity worsens, but well distributed and low size MgO particles improve flux pinning....

  8. Weight-Based Adaptation of TNF-Antagonist Induction versus Maintenance Dose

    Marco A. Muster


    Full Text Available Biologics are highly specific and exhibit few problems in regard to overdosages. In clinical practice, induction schemes with an initial loading dose and a subsequent lower maintenance dose have been established and are of higher efficacy for psoriasis than starting directly with the maintenance dose. As obese patients sometimes respond less well to standard dosages, increases of the maintenance dose, but not the loading doses, have been tried with variable success. In our study, we increased the loading (160 mg instead of 80 mg but not the maintenance dose of adalimumab in an obese patient with severe psoriasis resistant to previous biologics and methotrexate. Within 12 weeks, both PASI (11 to 1.6 and DLQI (22/30 to 5/30 decreased. This strategy might be an effective and less costly alternative to doubling the maintenance doses, and could be further evaluated for psoriasis patients refractory to previous treatments.

  9. Doses from radiation exposure

    Menzel, H G


    Practical implementation of the International Commission on Radiological Protection's (ICRP) system of protection requires the availability of appropriate methods and data. The work of Committee 2 is concerned with the development of reference data and methods for the assessment of internal and external radiation exposure of workers and members of the public. This involves the development of reference biokinetic and dosimetric models, reference anatomical models of the human body, and reference anatomical and physiological data. Following ICRP's 2007 Recommendations, Committee 2 has focused on the provision of new reference dose coefficients for external and internal exposure. As well as specifying changes to the radiation and tissue weighting factors used in the calculation of protection quantities, the 2007 Recommendations introduced the use of reference anatomical phantoms based on medical imaging data, requiring explicit sex averaging of male and female organ-equivalent doses in the calculation of effecti...

  10. Entrance surface dose according to dose calculation: Head and wrist

    Sung, Ho Jin [Dept. Radiology, Chonnam National University Hospital, Gwangju (Korea, Republic of); Han, Jae Bok; Song, Jong Nam; Choi, Nam Gil [Dept. of Radiological Science, Dongshin University, Naju (Korea, Republic of)


    This study were compared with the direct measurement and indirect dose methods through various dose calculation in head and wrist. And, the modified equation was proposed considering equipment type, setting conditions, tube voltage, inherent filter, added filter and its accompanied back scatter factor. As a result, it decreased the error of the direct measurement than the existing dose calculation. Accordingly, diagnostic radiography patient dose comparison would become easier and radiographic exposure control and evaluation will become more efficient. The study findings are expected to be useful in patients' effective dose rate evaluation and dose reduction.

  11. Multiple-dose pharmacokinetics of fesoterodine sustained-release in healthy Korean volunteers.

    Shin, Dongseong; Shin, Kwang-Hee; Lee, SeungHwan; Lim, Kyoung Soo; Cho, Joo-Youn; Jang, In-Jin; Shin, Sang-Goo; Yu, Kyung-Sang


    Fesoterodine is a pro-drug of the active metabolite 5-hydroxymethyl tolterodine (5-HMT), a muscarinic receptor antagonist. This study aimed to evaluate the safety profile and pharmacokinetic characteristics of multiple oral doses of sustained-release fesoterodine (fesoterodine SR) in healthy Korean males. A randomized, double-blind, placebo-controlled, multiple-dose study with two oral doses (4 mg and 8 mg) was conducted in healthy Korean male participants. The study drug was administered once daily for 5 days. The plasma concentration of 5-HMT was measured up to 72 hours after the last drug administration. The CYP2D6 genotype was analyzed using polymerase chain reaction (PCR) methods to assess the effect of genetic polymorphisms on the pharmacokinetic parameters. 20 participants completed the study. The mean (SD) areas under the plasma concentration-time curves during the dosing interval (AUCτ) of the 4 mg and 8 mg dose groups were 26.1 (8.0) and 64.2 (30.5) μg·h/ml and the mean peak concentrations (Cmax) were 2.6 (0.7) and 6.0 (2.0) μg/ml, respectively, at steady-state. The mean AUCτ and Cmax of 5-HMT increased in approximately the same proportion as the dose increased. Fesoterodine SR was well tolerated without any serious adverse events or abnormal clinical laboratory findings. Systemic 5-HMT exposure showed dose-proportional characteristics in the 4 mg to 8 mg dose range in healthy Korean males. Thus, 4 mg or 8 mg doses of fesoterodine SR taken once-daily were tolerable in healthy Korean males.

  12. Efficacy of single large doses of caspofungin in a neutropenic murine model against the "psilosis" group.

    Berényi, Réka; Kovács, Renátó; Domán, Marianna; Gesztelyi, Rudolf; Kardos, Gábor; Juhász, Béla; Perlin, David; Majoros, László


    We compared the in vivo efficacy of single large dose of caspofungin to that of daily smaller caspofungin doses (with same cumulative doses) against C. albicans (echinocandin susceptible and resistant isolates) and the “psilosis� group in a neutropenic murine model. Seven treatment groups were formed for C. orthopsilosis, C. metapsilosis and C. albicans (no treatment, 1, 2 and 3 mg/kg caspofungin daily for five days; single 5, 10 and 15 mg/kg caspofungin doses). For C. parapsilosis there were five treatment groups (no treatment, 3 and 4 mg/kg caspofungin daily for five days; single 15 and 20 mg/kg caspofungin). Tissue burdens of C. orthopsilosis and C. parapsilosis were significantly decreased by daily 3 mg/kg and 10 or 15 mg/kg single caspofungin doses (Pcaspofungin doses (Pcaspofungin were comparable or sometimes superior to the lower, daily-dose regimen against the “psilosis� group supporting further studies with this therapeutic strategy.

  13. Effects of low-dose midazolam with propofol in patient-controlled sedation (PCS) for apicectomy.

    Küçükyavuz, Zuhal; Cambazoğlu, Mine


    We studied the effects of low-dose midazolam with propofol for patient control sedation (PCS) in 30 healthy (ASA grade I) patients who were randomly allocated into two equal groups (n = 15 in each). They were given a propofol infusion of 2mg/kg/h after a bolus dose of 0.7 mg/kg. The second group was given the 2mg/kg/h propofol infusion after a dose of midazolam 0.03 mg/kg and a bolus dose of propofol 0.7 mg/kg. The standard dose for PCS was propofol 0.2mg/kg in both groups. Clinical data were taken and haemodynamic variables, and oxygen saturation were recorded before and on the 5th, 10th, 20th, and 30th minutes during the operations. The level of sedation, amnesia and conditions of each patient were evaluated during the study. Patients' satisfaction was recorded using a modified visual analogue scale (VAS). All results were evaluated statistically. We conclude that low-dose midazolam with propofol during PCS neither reduced oxygen saturation nor prolonged the time of discharge. Low-dose midazolam with propofol also improved the acceptability and comfort for patients and made the operation easier, which makes it preferable to propofol alone.

  14. Low-dose norfloxacin and ciprofloxacin therapy worsen leptospirosis in hamster.

    Wu, Dianjun; Zhang, Wenlong; Wang, Tingting; Lin, Tao; Jin, Xuemin; Xie, Xufeng; Guo, Jian; Cao, Yongguo; Wu, Rui


    Antibiotics play an important role in the treatment of leptospirosis. Many antibiotics at appropriate concentrations improved the survival rate and alleviated tissue injury, while, when dosing strategies fall below subtherapeutic levels, worse therapeutic effects are seen. In the present study, we investigated the efficacy of low-dose norfloxacin (10, 20 and 30 mg/kg) and ciprofloxacin (1, 2 and 5 mg/kg) against leptospirosis in a hamster model using Leptospira interrogans serovar Icterohaemorrhagiae. The histopathology and bacterial loads of target organs (liver, kidney and lung) were also studied by treatment with norfloxacin at the dose of 10 mg/kg in this model. Using RT-PCR, the expression of inflammatory factor IL-1β and TNF-α was analyzed by comparing the norfloxacin and untreated group. All untreated animals, serving as a negative control, displayed 50% survival rate, while hamsters treated with norfloxacin at the dose of 10 and 20 mg/kg and ciprofloxacin at the dose of 1 and 2 mg/kg showed a lower survival rate than the untreated group. Furthermore, norfloxacin at the dose of 10 mg/kg increased bacterial loads and aggravated tissue injury of target organs. The delayed induction of IL-1β and TNF-α was found in tissues of norfloxacin group. Our study indicates an increased risk associated with low-dose norfloxacin and ciprofloxacin in leptospirosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. First dose in man


    Du er blevet ansat som læge i et lægemiddelfirma med ansvar for planlægning og sikkerhed i fase 1 forsøg. Firmaet har udviklet tre dopamin D2-receptor antagonister til behandling af skizofreni. Lægemidlerne har undergået et omfattende farmakologisk, toksikologisk og farmaceutisk afprøvningsprogra...... fase 1 forsøg alias »First dose in man«....

  16. Forty-eight weeks treatment with clevudine 30 mg qd versus lamivudine 100 mg qd for chronic hepatitis B infection: a double-blind randomized study.

    Lau, George K K; Leung, Nancy


    Clevudine is a pyrimidine analogue with potent activity against hepatitis B virus (HBV) replication in vitro. In a previous pivotal phase III clinical study, 24 weeks treatment with clevudine 30 mg has been shown to profoundly suppress HBV replication and normalize serum alanine aminotransferase level. In this study, we compare the efficacy and safety of clevudine (30 mg daily) versus lamivudine (100 mg daily) for 48 weeks in treatment-naive chronic hepatitis B e antigen (HBeAg) positive patients. Ninety-two chronic HBeAg positive patients were randomized to receive clevudine 30 mg daily or lamivudine 100 mg daily in a 1:1 ratio. The clevudine group demonstrated greater viral suppression at week 48 when compared with the lamivudine group (median reduction: 4.27 vs. 3.17 log(10) copies/ml at week 48, pviral rebound during lamivudine therapy but no resistance was found in the clevudine group during 48-week treatment period. A 48-week dosing with clevudine 30 mg daily was superior to lamivudine 100 mg daily in suppressing HBV replication, with no emergence of viral breakthrough in patients with HBeAg positive chronic hepatits B.

  17. Efficacy of imatinib dose escalation in Chinese gastrointestinal stromal tumor patients

    Jian Li; Ji-Fang Gong; Jie Li; Jing Gao; Nai-Ping Sun; Lin Shen


    AIM:To investigate the efficacy and safety of imatinib dose escalation in Chinese patients with advanced gastrointestinal stromal tumor (GIST).METHODS:Advanced GIST patients previously failing 400 mg imatinib treatment were enrolled in this study.Patients received imatinib with dose escalation to 600mg/d,and further dose escalation to 800 mg/d if imatinib 600 mg/d failed.Progression-free survival,overall survival,clinical efficacy,c-kit/PDGFRA genotype and safety were evaluated.RESULTS:52 patients were enrolled in this study.For the 47 evaluable patients receiving imatinib (600 mg/d),the disease control rate was 40.4%,and the median progression-free survival for all patients was 17 wk (95% CI:3.9-30.1).The median overall survival after dose escalation was 81 wk (95% CI:36.2-125.8).Adverse events,mainly edema,fatigue,granulocytopenia and skin rash were tolerable.However,further dose escalation (800 mg/d) in 14 cases was ineffective,with disease progression and severe adverse events.Among 30 cases examined for gene mutations,patients with exon 9 mutations experienced a better progression-free survival of 47 wk.CONCLUSION:Imatinib dose escalation to 600 mg/d is more appropriate for Chinese patients and may achieve further survival benefit.

  18. Aging Behavior of Mg-Y-Zr and Mg-Nd-Zr Cast Alloys


    Aging behavior of Mg-3.6Y-0.5Zr and Mg-2.7Nd-0.5Zr alloys was investigated by microhardness measurement and transmission electron microscopy. In the case of Mg-Y-Zr alloy, the presence of β″ phase, a major strengthener, having base centered orthorhombic structure with its lattice constants of aβ″=0.64 nm, bβ″=2.22 nm,and cβ″=0.52 nm was identified. In the case of Mg-Nd-Zr alloy aged at 250℃, the presence ofβ″ and β′phases was identified. The crystal structure ofβ″ phase was found to be DO19 and its orientation relationships with Mg matrix were [0001]β″//[0001]Mg and [01-10]β″//[0110]Mg. The β′ phase had face centered cubicstructure and its orientation relationships with Mg matrix were [011]β′//[0001]Mg and [-11-1]β′//[-2110]Mg.The Mg-2.7Nd-0.5Zr alloy showed higher hardness compared with Mg-3.6Y-0.5Zr alloy.

  19. In vitro and in vivo comparison of binary Mg alloys and pure Mg.

    Myrissa, Anastasia; Agha, Nezha Ahmad; Lu, Yiyi; Martinelli, Elisabeth; Eichler, Johannes; Szakács, Gábor; Kleinhans, Claudia; Willumeit-Römer, Regine; Schäfer, Ute; Weinberg, Annelie-Martina


    Biodegradable materials are under investigation due to their promising properties for biomedical applications as implant material. In the present study, two binary magnesium (Mg) alloys (Mg2Ag and Mg10Gd) and pure Mg (99.99%) were used in order to compare the degradation performance of the materials in in vitro to in vivo conditions. In vitro analysis of cell distribution and viability was performed on discs of pure Mg, Mg2Ag and Mg10Gd. The results verified viable pre-osteoblast cells on all three alloys and no obvious toxic effect within the first two weeks. The degradation rates in in vitro and in vivo conditions (Sprague-Dawley® rats) showed that the degradation rates differ especially in the 1st week of the experiments. While in vitro Mg2Ag displayed the fastest degradation rate, in vivo, Mg10Gd revealed the highest degradation rate. After four weeks of in vitro immersion tests, the degradation rate of Mg2Ag was significantly reduced and approached the values of pure Mg and Mg10Gd. Interestingly, after 4 weeks the estimated in vitro degradation rates approximate in vivo values. Our systematic experiment indicates that a correlation between in vitro and in vivo observations still has some limitations that have to be considered in order to perform representative in vitro experiments that display the in vivo situation.

  20. Estimation of the Dose and Dose Rate Effectiveness Factor

    Chappell, L.; Cucinotta, F. A.


    Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

  1. Dose reduction in evacuation proctography

    Hare, C.; Halligan, S.; Bartram, C.I.; Gupta, R.; Walker, A.E.; Renfrew, I. [Intestinal Imaging Centre, St. Mark' s Hospital, London (United Kingdom)


    The goal of this study was to reduce the patient radiation dose from evacuation proctography. Ninety-eight consecutive adult patients referred for proctography to investigate difficult rectal evacuation were studied using a digital imaging system with either a standard digital program for barium examinations, a reduced dose digital program (both with and without additional copper filtration), or Video fluoroscopy. Dose-area products were recorded for each examination and the groups were compared. All four protocols produced technically acceptable examinations. The low-dose program with copper filtration (median dose 382 cGy cm{sup 2}) and Video fluoroscopy (median dose 705 cGy cm{sup 2}) were associated with significantly less dose than other groups (p < 0.0001). Patient dose during evacuation proctography can be reduced significantly without compromising the diagnostic quality of the examination. A digital program with added copper filtration conveyed the lowest dose. (orig.)

  2. Low-dose naloxone provides an abuse-deterrent effect to buprenorphine

    Webster LR


    Full Text Available Lynn R Webster,1 Michael D Smith,1 Cemal Unal,2 Andrew Finn3 1PRA Health Sciences, Salt Lake City, UT, USA; 2Biometrical Solutions LLC, Raleigh, NC, USA; 3BioDelivery Sciences International, Inc., Raleigh, NC, USA Abstract: In developmental research, plasma buprenorphine concentrations comparable to a 2 mg buprenorphine–naloxone (BN sublingual tablet have been achieved with a 0.75 mg dose of BN buccal film, a small, bioerodible polymer film for application to mucosal membranes. This was a randomized, double-blind, placebo-controlled, single-dose, four-period crossover study in opioid-dependent subjects with chronic pain receiving >100 mg oral morphine equivalents daily who experienced withdrawal following a naloxone challenge dose. The objective of the study was to determine if intravenous (IV naloxone doses of 0.1 and 0.2 mg would produce a withdrawal response when coadministered with a 0.75 mg IV dose of buprenorphine. Fifteen subjects receiving 90–1,260 mg oral morphine equivalents per day enrolled and completed the study. Precipitated withdrawal occurred in 13% (2/15 of placebo-treated subjects and 47% (7/15 of buprenorphine-treated subjects. When combined with the 0.75 mg dose of buprenorphine, a 0.1 mg dose of naloxone increased the incidence of precipitated withdrawal to 60%, and a 0.2 mg dose of naloxone increased the incidence to 73%. By 15 minutes postdose, the mean change in Clinical Opioid Withdrawal Scale (COWS score from predose was 3.0 for placebo, 6.9 for buprenorphine, 9.8 for BN 0.1 mg, and 12.4 for BN 0.2 mg. The mean COWS score with each active treatment was significantly greater than placebo (P<0.001, and the mean COWS score for each of the naloxone-containing treatments was significantly greater than for buprenorphine alone (P<0.001. Naloxone doses as low as 0.1 mg added an abuse-deterrent effect to a 0.75 mg IV dose of buprenorphine. Keywords: opioid dependence, withdrawal symptoms, abuse-deterrent, buprenorphine

  3. The Mg impurity in nitride alloys

    Zvanut, M. E.; Willoughby, W. R.; Sunay, U. R. [Department of Physics, University of Alabama at Birmingham, Birmingham AL (United States); Koleske, D. D.; Allerman, A. A. [Sandia National Laboratory, Albuquerque NM (United States); Wang, Ke; Araki, Tsutomu [Department of Photonics, Ritsumeikan University, Kusatsu, Shiga (Japan); Nanishi, Yasushi [Department of Photonics, Ritsumeikan University, Kusatsu, Shiga, Japan and WCU Program, Department of Materials Science and Engineering, Seoul National University, Seoul (Korea, Republic of)


    Although several magnetic resonance studies address the Mg acceptor in GaN, there are few reports on Mg doping in the alloys, where hole production depends strongly on the Al or In content. Our electron paramagnetic resonance (EPR) measurements of the p-type alloys suggest that the Mg impurity retains the axial symmetry, characteristic of a p-type dopant in both alloys; however, In and Al produce additional, different characteristics of the acceptor. In InGaN, the behavior is consistent with a lowering of the acceptor level and increasing hole density as In concentration increases. For AlGaN, the amount of neutral Mg decreases with increasing Al content, which is attributed to different kinetics of hydrogen diffusion thought to occur in samples with higher Al mole fraction.

  4. Thermodynamic optimization of Mg-Nd system

    MENG Fan-gui; LIU Hua-shan; LIU Li-bin; JIN Zhan-peng


    Based on the reported experimental data, the phase diagram of Mg-Nd binary system was optimized using the CALPHAD approach. Gibbs energies of the disordered BCC_A2 and ordered BCC_B2 phases were modeled with a single expression based on a 2-sublattice model. Liquid and terminal solutions, such as dHCP and HCP, were modeled as substitutional solutions. Intermediate phases Mg2Nd, Mg3Nd and Mg41Nd5 were treated as stoichiometric compounds. The optimization was carried out in the Thermo-Calc package. A set of thermodynamic parameters is obtained. Calculated phase diagram, enthalpies of formation and Gibbs energies of formation are in reasonable agreement with the experimental data.

  5. Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults.

    Brown, Randall T; Nicholas, Christopher R; Cozzi, Nicholas V; Gassman, Michele C; Cooper, Karen M; Muller, Daniel; Thomas, Chantelle D; Hetzel, Scott J; Henriquez, Kelsey M; Ribaudo, Alexandra S; Hutson, Paul R


    Psilocybin is a psychedelic tryptamine that has shown promise in recent clinical trials for the treatment of depression and substance use disorders. This open-label study of the pharmacokinetics of psilocybin was performed to describe the pharmacokinetics and safety profile of psilocybin in sequential, escalating oral doses of 0.3, 0.45, and 0.6 mg/kg in 12 healthy adults. Eligible healthy adults received 6-8 h of preparatory counseling in anticipation of the first dose of psilocybin. The escalating oral psilocybin doses were administered at approximately monthly intervals in a controlled setting and subjects were monitored for 24 h. Blood and urine samples were collected over 24 h and assayed by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for psilocybin and psilocin, the active metabolite. The pharmacokinetics of psilocin were determined using both compartmental (NONMEM) and noncompartmental (WinNonlin) methods. No psilocybin was found in plasma or urine, and renal clearance of intact psilocin accounted for less than 2% of the total clearance. The pharmacokinetics of psilocin were linear within the twofold range of doses, and the elimination half-life of psilocin was 3 h (standard deviation 1.1). An extended elimination phase in some subjects suggests hydrolysis of the psilocin glucuronide metabolite. Variation in psilocin clearance was not predicted by body weight, and no serious adverse events occurred in the subjects studied. The small amount of psilocin renally excreted suggests that no dose reduction is needed for subjects with mild-moderate renal impairment. Simulation of fixed doses using the pharmacokinetic parameters suggest that an oral dose of 25 mg should approximate the drug exposure of a 0.3 mg/kg oral dose of psilocybin. Although doses of 0.6 mg/kg are in excess of likely therapeutic doses, no serious physical or psychological events occurred during or within 30 days of any dose. NCT02163707.

  6. Intravenous Iron Therapy in Patients with Iron Deficiency Anemia: Dosing Considerations

    Koch, Todd A.; Myers, Jennifer; Goodnough, Lawrence Tim


    Objective. To provide clinicians with evidence-based guidance for iron therapy dosing in patients with iron deficiency anemia (IDA), we conducted a study examining the benefits of a higher cumulative dose of intravenous (IV) iron than what is typically administered. Methods. We first individually analyzed 5 clinical studies, averaging the total iron deficit across all patients utilizing a modified Ganzoni formula; we then similarly analyzed 2 larger clinical studies. For the second of the larger studies (Study 7), we also compared the efficacy and retreatment requirements of a cumulative dose of 1500 mg ferric carboxymaltose (FCM) to 1000 mg iron sucrose (IS). Results. The average iron deficit was calculated to be 1531 mg for patients in Studies 1–5 and 1392 mg for patients in Studies 6-7. The percentage of patients who were retreated with IV iron between Days 56 and 90 was significantly (p < 0.001) lower (5.6%) in the 1500 mg group, compared to the 1000 mg group (11.1%). Conclusions. Our data suggests that a total cumulative dose of 1000 mg of IV iron may be insufficient for iron repletion in a majority of patients with IDA and a dose of 1500 mg is closer to the actual iron deficit in these patients. PMID:26257955

  7. High-dose acetylcysteine in idiopathic pulmonary fibrosis.

    Demedts, M.; Behr, J.; Buhl, R.; Costabel, U.; Dekhuijzen, P.N.R.; Jansen, H.M.L.; MacNee, W.; Thomeer, M.; Wallaert, B.; Laurent, F.; Nicholson, A.G.; Verbeken, E.K.; Verschakelen, J.; Flower, C.D.; Capron, F.; Petruzzelli, S.; Vuyst, P. De; Bosch, J.M. van den; Rodriguez-Becerra, E.; Corvasce, G.; Lankhorst, I.L.M.; Sardina, M.; Montanari, M.


    BACKGROUND: Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis. METHODS: We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) add

  8. Low-Dose Pyridoxine Masks Pyridoxine-Dependent Seizures


    A 4-month-old male infant with pyridoxine dependency and seizures from birth was controlled with extremely low-dose pyridoxine (0.5 mg/day) given as a vitamin supplement, in a report from Joana de Gusmao Children’s Hospital, Florianopolis, Brazil.

  9. High-dose acetylcysteine in idiopathic pulmonary fibrosis.

    Demedts, M.; Behr, J.; Buhl, R.; Costabel, U.; Dekhuijzen, P.N.R.; Jansen, H.M.L.; MacNee, W.; Thomeer, M.; Wallaert, B.; Laurent, F.; Nicholson, A.G.; Verbeken, E.K.; Verschakelen, J.; Flower, C.D.; Capron, F.; Petruzzelli, S.; Vuyst, P. De; Bosch, J.M. van den; Rodriguez-Becerra, E.; Corvasce, G.; Lankhorst, I.L.M.; Sardina, M.; Montanari, M.


    BACKGROUND: Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis. METHODS: We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) add

  10. High-dose acetylcysteine in idiopathic pulmonary fibrosis.

    Demedts, M.; Behr, J.; Buhl, R.; Costabel, U.; Dekhuijzen, P.N.R.; Jansen, H.M.L.; MacNee, W.; Thomeer, M.; Wallaert, B.; Laurent, F.; Nicholson, A.G.; Verbeken, E.K.; Verschakelen, J.; Flower, C.D.; Capron, F.; Petruzzelli, S.; Vuyst, P. De; Bosch, J.M. van den; Rodriguez-Becerra, E.; Corvasce, G.; Lankhorst, I.L.M.; Sardina, M.; Montanari, M.


    BACKGROUND: Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis. METHODS: We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily)

  11. MgH{sub 2} as dopant for improved activation of commercial Mg ingot

    Jain, P., E-mail: [Hydrogen Research Institute, Université du Québec à Trois-Rivières, 3351 des Forges, Trois-Rivières, Québec G9A 5H7 (Canada); Lang, J. [Hydrogen Research Institute, Université du Québec à Trois-Rivières, 3351 des Forges, Trois-Rivières, Québec G9A 5H7 (Canada); Skryabina, N.Y. [Department of Physics, Perm State University, 15, Bukireva, 614990 Perm (Russian Federation); Fruchart, D. [Institut Néel, BP 166, 38042 Grenoble Cedex 9 (France); Santos, S.F [CECS, Federal University of ABC, Rua Santa Adélia 166, Santo André, SP 09210-170 (Brazil); Binder, K.; Klassen, T. [Institute of Materials Technology, Helmut-Schmidt-University, University of the Federal Armed Forces, Holstenhofweg 85, 22043 Hamburg (Germany); Huot, J., E-mail: [Hydrogen Research Institute, Université du Québec à Trois-Rivières, 3351 des Forges, Trois-Rivières, Québec G9A 5H7 (Canada)


    Highlights: •We propose a simple method to reduce production cost of light weight materials for hydrogen storage applications. •Cheaper Mg ingot rather than expensive MgH{sub 2} is used as starting material. •Effect of MgH{sub 2} as catalytic powder for improved activation behavior of Mg is demonstrated. -- Abstract: In this paper, we propose a method to decrease the activation time (first hydrogenation) of commercial Mg. This new alternative processing route uses a combination of cold rolling and short time ball milling to obtain full hydrogen capacity quickly in the first hydrogenation. As ball milling of ductile materials leads to particle agglomeration, brittle Mg plates produced by repetitive cold rolling were used as starting material. These rolled plates were then ball milled for 30 min with and without the addition of 5 wt% Mg or MgH{sub 2} powders. All the synthesized samples were investigated for hydrogen storage, absorption–desorption behavior and microstructure using X-ray diffraction (XRD), Scanning Electron Microscopy (SEM) and pressure-composition temperature (PCT) methods. Results showed slow activation behavior for cold rolled Mg plates, which was slightly improved after milling. Further improvement was obtained by adding 5 wt% of Mg powder during ball milling. In contrast, when the plates were ball milled with 5 wt% of MgH{sub 2} powder a drastic improvement in activation behavior was observed with hydrogen capacity reaching up to 6.2 wt% in comparison to 2.74 wt% for undoped and 3.57 wt% for Mg doped samples. These results reveal that ball milling with ductile Mg powder deforms only the surface of Mg plates while brittle MgH{sub 2} powders causes fracturing and cracks, increasing the surface area and generating heterogeneous nucleation sites within the bulk material.

  12. Evaluation of enzyme dose and dose-frequency in ameliorating substrate accumulation in MPS IIIA Huntaway dog brain.

    King, Barbara; Marshall, Neil; Beard, Helen; Hassiotis, Sofia; Trim, Paul J; Snel, Marten F; Rozaklis, Tina; Jolly, Robert D; Hopwood, John J; Hemsley, Kim M


    Intracerebrospinal fluid (CSF) infusion of replacement enzyme is under evaluation for amelioration of disease-related symptoms and biomarker changes in patients with the lysosomal storage disorder mucopolysaccharidosis type IIIA (MPS IIIA; ; NCT#01155778; #01299727). Determining the optimal dose/dose-frequency is important, given the invasive method for chronically supplying recombinant protein to the brain, the main site of symptom generation. To examine these variables, we utilised MPS IIIA Huntaway dogs, providing recombinant human sulphamidase (rhSGSH) to young pre-symptomatic dogs from an age when MPS IIIA dog brain exhibits significant accumulation of primary (heparan sulphate) and secondary (glycolipid) substrates. Enzyme was infused into CSF via the cisterna magna at one of two doses (3 mg or 15 mg/infusion), with the higher dose supplied at two different intervals; fortnightly or monthly. Euthanasia was carried out 24 h after the final injection. Dose- and frequency-dependent reductions in heparan sulphate were observed in CSF and deeper layers of cerebral cortex. When we examined the amount of immunostaining of the general endo/lysosomal marker, LIMP-2, or quantified activated microglia, the higher fortnightly dose resulted in superior outcomes in affected dogs. Secondary lesions such as accumulation of GM3 ganglioside and development of GAD-reactive axonal spheroids were treated to a similar degree by both rhSGSH doses and dose frequencies. Our findings indicate that the lower fortnightly dose is sub-optimal for ameliorating existing and preventing further development of disease-related pathology in young MPS IIIA dog brain; however, increasing the dose fivefold but halving the frequency of administration enabled near normalisation of disease-related biomarkers.

  13. Safety and pharmacokinetics of higher doses of caspofungin in healthy adult participants.

    Migoya, Elizabeth M; Mistry, Goutam C; Stone, Julie A; Comisar, Wendy; Sun, Peng; Norcross, Alisha; Bi, Sheng; Winchell, Gregory A; Ghosh, Kalyan; Uemera, Naoto; Deutsch, Paul J; Wagner, John A


    Caspofungin was the first in a new class of antifungal agents (echinocandins) indicated for the treatment of primary and refractory fungal infections. Higher doses of caspofungin may provide another option for patients who have failed caspofungin or other antifungal therapy. This study evaluated the safety, tolerability, and pharmacokinetics of single 150- and 210-mg doses of caspofungin in 16 healthy participants and 100 mg/d for 21 days in 20 healthy participants. Other than infusion site reactions and 1 reversible elevation in alanine aminotransferase (≥2× and caspofungin was generally well tolerated. Geometric mean AUC(0-∞) after single 150- and 210-mg doses was 279.7 and 374.9 µg·h/mL, respectively; peak concentrations were 29.4 and 33.5 µg/mL, respectively; and 24-hour postdose concentrations were 2.8 and 4.2 µg/mL, respectively. Steady state was achieved in the third week of dosing. Following multiple 100-mg doses of caspofungin, day 21 geometric mean AUC(0-24) was 227.4 µg·h/mL, peak concentration was 20.9 µg/mL, and trough concentration was 4.7 µg/mL. Beta-phase t(1/2) was ~8 to ~13 hours. Caspofungin pharmacokinetics at these higher doses were dose proportional to and consistent with those observed at lower doses, suggesting a modest nonlinearity of increased accumulation with dose, which was considered not clinically meaningful.

  14. The influence of Mg-Zr master alloy microstructure on the corrosion of Mg

    Gandel, D. S.; Easton, M. A.; Gibson, M. A.; Abbott, T.; Birbilis, N.

    In this study, sixteen Mg-Zr alloys were produced to investigate the role of Zr on corrosion of Mg. Alloys were produced using two different commercial Mg-Zr master alloys commonly used for grain refining Mg, but which contain different Zr particle size distributions. It is seen that the master alloy with a smaller Zr particle size leads to an alloy containing more Zr in solid solution. The ratio of Zr in solid solution and in particle form was observed to have a marked effect on the corrosion of Mg.

  15. Features of Mg2Si Layer Growth in Si/Mg2Si Multilayers

    L.E. Konotopskyi


    Full Text Available Features of magnesium siliced layer growth in Si/Mg2Si multilayers in initial state and after thermal annealing were studied by methods of transmission electron microscopy and X-Ray scattering. As-deposited magnesium silicide layers are amorphous with nanocrystal inclusions of metastable h-Mg2Si. Formation of Mg2Si in hexagonal modification occurs under the influence of stress produced by silicon layers. At T = 723 К Mg2Si layers finished crystallizes in hexagonal modification, with some coarsening of grains. That is accompanied with 7.3 % reduction in period of the Si/Mg2Si multilayer.

  16. Influence of Mg Content on Deformability of AlMg Alloys during Extrusion

    Leśniak D.


    Full Text Available In this study the research on deformability of AlMg alloys with high Mg contents in extrusion was carried out. The different shapes from AlMg alloys containing 3.5%, 4.5% and 5.5% of Mg were extruded on 500 T semi-industrial press by using one-hole and multi-hole flat dies. The extrudates surface quality was under investigations in relation with the temperature-speed parameters of the extrusion process. The metal exit speed was estimated depending on the extrudates shape, wall thickness and Mg content. The alloy’s border solidus and liquidus temperatures were also determined.

  17. Dose-dependent impulse control disorders in piribedil overdose.

    Giugni, Juan Carlos; Tschopp, Lorena; Escalante, Victoria; Micheli, Federico


    We describe a 73-year-old female patient with Parkinson disease who developed impulse control disorders (ICDs) and dopamine dysregulation syndrome (DDS) owing to piribedil overdose. She was initially put on piribedil 150 mg; and owing to disease progression, levodopa was added 4 years later. Three years later, piribedil was raised to 200 mg; but presumably owing to a misunderstanding, she took 400 mg/d, which was well tolerated and produced an improvement in her parkinsonian symptoms.However, over the next few weeks, she started shopping compulsively, buying unnecessary clothes and food. In addition, she visited her dog's veterinarian several times a day with nonsense queries. She began to have financial problems and family disruption. During an examination, mild dyskinesia was evident.We diagnosed ICDs and most likely dopamine dysregulation syndrome DDS. Piribedil doses were decreased to 200 mg/d and levodopa increased up to 750 mg/d, with a clear improvement in compulsive behavior without worsening of the dyskinesia.Our case shows that even in cases in which regular doses of dopamine agonists are harmless, dose increments can induce these unwanted effects.

  18. Elevated temperature properties of Mg- 12Li-Al-MgO composites

    WEI Xiao-wei; HUANG Qing-min


    The compressive creep of Mg-12Li-Al-MgO particulate composites was investigated, which were produced by the reaction of reinforcement materials (B2O3) with Mg-12Li-Al alloy melt in the temperature range of 100-190 ℃ and under different compressive stress in the range of 40-70 MPa with special apparatus. The content of MgO particulates is about 0, 5%, 10%,15%(volume fraction) in Mg-12Li-Al alloy respectively. The results reveal that the creep resistance of the particulate composites is increased with increasing the content of MgO particulates and considerable improvementin creep resistance is observed in Mg-12Li-Al-MgO composites. However, over all range of temperatures and stresses, the creep data for these composites can be correlated using an empirical equation εs =Aσnexp(-Q/RT), where n is 4.93 and Q is about 78.1 kJ/mol for Mg-14Li-Al alloy and n is between 7.48 and 9.47 and Q is 111.2-137.3 kJ/mol for Mg-12Li-Al-MgO composites. The different compressive creep behavior of the composites is associated with the different material constant A. The compressive creep rate is controlled by the lattice diffusion of Li and dislocation climb.

  19. Ultrafast Synthesis and Related Phase Evolution of Mg2Si and Mg2Sn Compounds

    Zhang, Qiang; Lu, Qiangbing; Yan, Yonggao; Su, Xianli; Tang, Xinfeng


    Both Mg2Si and Mg2Sn compounds were synthesized by an ultra-fast self-propagating high-temperature synthesis (SHS) method. The data regarding SHS were obtained via theoretical calculation combined with experiments, showing that the adiabatic temperature T ad and ignition temperature T ig of Mg2Si are a little higher than those of Mg2Sn. The mechanism of phase evolution and the concomitant microstructure evolution during the synthesis process of Mg2Si and Mg2Sn compounds were investigated by adopting SHS technique coupled with a sudden quenching treatment. Differential scanning calorimetry (DSC), field emission scanning electron microscopy (FESEM), and x-ray powder diffraction (XRD) results indicate that Mg2Si compound can be directly synthesized through the reaction of Mg and Si elements at around 850 K. Correspondingly, the formation of Mg2Sn needs to undergo melting of Sn and the subsequent feeble reaction between Mg and Sn elements before the large scale transformation at 730 K. As the groundwork, this research embodies great significance for future study on the ultrafast SHS process of the ternary Mg2Si1-x Sn x solid solutions.

  20. In vitro evaluation of carbamazepine 200 mg tablets.

    Kibwage, I O; Nguyo, M


    A comparative in-vitro performance of carbamazepine 200mg tablet products available on the Kenyan market was evaluated. The products which include the innovator product, Tegretol, have similar quality consonant with pharmacopoeial specifications. A batch of one of the products had a carbamazepine content of 106.6% label claim which was outside the upper limits of 105%. One product packaged in multiple-unit containers of a 1000, had an unacceptable high friability of 6.82% loss in weight. All products had good dissolution profiles and released at least 70% of the dose within 45 minutes. Drug dissolution from tablets was found to vary between batches for one product. At each sampling time, most generics had wide variations in amount of dissolved drug. The effect of such variations on tablet efficacy cannot be ascertained in the absence of bioavailability data.

  1. establishment of background radiation dose rate in the vicinity of the ...


    radiation dose rate data prior to commencement of uranium mining activities. Twenty stations in seven ... exploration activities in this period of rising uranium demand .... Magnesium Borate (MgB407) (Mathur 1983). In this study, calcium ...

  2. Formation and Corrosion Resistance of Mg-Al Hydrotalcite Film on Mg-Gd-Zn Alloy

    Ba, Z. X.; Dong, Q. S.; Kong, S. X.; Zhang, X. B.; Xue, Y. J.; Chen, Y. J.


    An environment-friendly technique for depositing a Mg-Al hydrotalcite (HT) (Mg6Al2(OH)16-CO3ṡ4H2O) conversion film was developed to protect the Mg-Gd-Zn alloy from corrosion. The morphology and chemical compositions of the film were analyzed by scanning electronic microscope (SEM) equipped with energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD) and Raman spectroscopy (RS), respectively. The electrochemical test and hydrogen evolution test were employed to evaluate the biocorrosion behavior of Mg-Gd-Zn alloy coated with the Mg-Al HT film in the simulated body fluid (SBF). It was found that the formation of Mg-Al HT film was a transition from amorphous precursor to a crystalline HT structure. The HT film can effectively improve the corrosion resistance of magnesium alloy. It indicates that the process provides a promising approach to modify Mg-Gd-Zn alloy.

  3. Effect of graded doses and a high dose of microbial phytase on the digestibility of various minerals in weaner pigs

    Kies, A.K.; Kemme, P.A.; Sebek, L.B.J.; Diepen, van J.T.M.; Jongbloed, A.W.


    An experiment with 224 weaner pigs (initial BW of 7.8 kg) was conducted to determine the effect of dose of dietary phytase supplementation on apparent fecal digestibility of minerals (P, Ca, Mg, Na, K, and Cu) and on performance. Four blocks, each with 8 pens of 7 pigs, were formed. Eight dietary tr

  4. Pharmacogenetically based dosing of thiopurines in childhood acute lymphoblastic leukemia

    Levinsen, Mette; Rotevatn, Elisabeth Orskov; Rosthøj, Susanne


    BACKGROUND: Previous studies have indicated that patients with thiopurine methyltransferase (TPMT) low activity (TPMT(LA)) have reduced risk of relapse but increased risk of second malignant neoplasm (SMN) compared to patients with TPMT wild-type (TPMT(WT)) when treated with 6 MP maintenance...... therapy starting doses of 75 mg/m(2)/day. To reduce SMN risk, 6MP starting doses were reduced to 50 mg/m(2)/day for patients with TPMT heterozygosity in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2000 protocol. PROCEDURE: We explored the pattern of SMN and relapse in the NOPHO...... relapse or SMN, the risk of SMN versus leukemia relapse was significantly lower in the ALL2000 cohort for patients with a 6MP starting dose

  5. Thermoluminescence studies of γ-irradiated ZnO:Mg{sup 2+} nanoparticles

    Pushpa, N. [Department of Physics, Bangalore University, Bangalore 560 056 (India); Kokila, M.K., E-mail: [Department of Physics, Bangalore University, Bangalore 560 056 (India); Nagabhushana, K.R. [Department of Physics - S & H, PES University, Bangalore 560 085 (India)


    Pure and Mg{sup 2+} doped ZnO nanoparticles are synthesized by solution combustion method. X-ray diffraction studies of the samples confirm hexagonal phase. Crystallite size is calculated using Scherer formula and found to be ∼30 nm for undoped ZnO and 34–38 nm for Mg{sup 2+} doped ZnO. A broad PL emission in the range 400–600 nm with peaks at 400, 450, 468, 483, 492, 517, 553 nm are observed in both pure and Mg{sup 2+} doped nanoparticles. Near band edge emission of ZnO is observed at 400 nm. The broad band emissions are due to surface defects. PL emission intensity is found to increase with Mg{sup 2+} concentration up to 1.5 mol% and then decreases due to concentration quenching. Samples are irradiated with γ-rays in a dose range 0.05–8 kGy. Gamma irradiation doesn’t affect PL properties. Undoped samples exhibit unstructured low intense TL glow with peak at 720 K. Whereas Mg{sup 2+} doped samples exhibit well structured TL glow curves with peak at ∼618 K. TL glow peak intensity of Mg{sup 2+} doped samples increases with Mg{sup 2+} concentration up to 2 mol%, thereafter decreases. TL curves of Mg{sup 2+} (2 mol%) doped ZnO exhibit two glows, a high intense peak at 618 K and a weak one with peak at ∼485 K. TL intensity of Mg{sup 2+} (2 mol%) doped ZnO samples increases with gamma dose up to 1 kGy and then decreases. Kinetic parameters of TL glows are calculated by deconvolution technique. Activation energy and frequency factor are found to be 1.5 eV and 3.38 × 10{sup 11} s{sup −1} respectively.

  6. Melting relations in the MgO-MgSiO3 system up to 70 GPa

    Ohnishi, Satoka; Kuwayama, Yasuhiro; Inoue, Toru


    Melting experiments in a binary system MgO-MgSiO3 were performed up to 70 GPa using a CO2 laser heated diamond anvil cell. The quenched samples were polished and analyzed by a dualbeam focused ion beam (FIB) and a field emission scanning electron microscope (FE-SEM), respectively. The liquidus phase and the eutectic composition were determined on the basis of textual and chemical analyses of sample cross sections. Our experimental results show that the eutectic composition is the Si/Mg molar ratio of 0.76 at 35 GPa and it decreases with increasing pressure. Above 45 GPa, it becomes relatively constant at about 0.64-0.65 Si/Mg molar ratio. Using our experimental data collected at a wide pressure range up to 70 GPa together with previous experimental data, we have constructed a thermodynamic model of the eutectic composition of the MgO-MgSiO3 system. The eutectic composition extrapolated to the pressure and temperature conditions at the base of the mantle is about 0.64 Si/Mg molar ratio. The modeled eutectic composition is quite consistent with a previous prediction from ab initio calculations (de Koker et al. in Earth Planet Sci Lett 361:58-63, 2013), suggesting that the simple assumption of a non-ideal regular solution model can well describe the melting relation of the MgO-MgSiO3 system at high pressure. Our results show that the liquidus phase changes from MgO-periclase to MgSiO3-bridgmanite at 35 GPa for the simplified pyrolite composition ( 0.7 Si/Mg molar ratio), while MgSiO3-bridgmanite is the liquidus phase at the entire lower mantle conditions for the chondritic composition ( 0.84 Si/Mg molar ratio).

  7. [Doses-related effects of lynestrenol on ovulation (author's transl)].

    Pizarro, M A; Thomas, K; Ferin, J


    8 women, aged 22-28, with normal, ovulatory menstrual cycles, volunteered to take different doses of Lynestrenol to determine its effects on Luteineizing Hormone (LH) secretion, and on plasma progesterone levels. Blood samples were taken in the morning and plasma was immediately separated. Results showed that body temperature varied unpredictably during the cycle, and therefore could not be considered a reliable parameter of ovulation. 0.35 mg of Lynestrenol administered daily was enough to suppress ovulation, as evidenced by the absence of LH during midcycle. Although differences exists in individual reactions, administration of Lynestrenol beyond 0.6 mg. daily always suppresses ovulation because of hypothalamo-pituitary inhibition, while doses below 0.5mg. daily can bring about episodic peaks. It is still not clear how Lynestrenol influences gonadotropins, especially LH, while intermittent bleeding seems to be the only sure side effect.

  8. Phase I study of continuous weekly dosing of dimethylamino benzoylphenylurea (BPU) in patients with solid tumours.

    Messersmith, Wells A; Rudek, Michelle A; Baker, Sharyn D; Zhao, Ming; Collins, Connie; Colevas, A Dimitrios; Donehower, Ross C; Carducci, Michael A; Wolff, Antonio C


    A phase I study of dimethylamino benzoylphenylurea (BPU), a tubulin inhibitor, was performed using a weekly continuous schedule. Patients with refractory solid tumours received oral BPU once weekly without interruption at doses ranging from 5 to 320mg using an accelerated titration design. Nineteen subjects received 54 cycles of BPU. Early pharmacokinetic findings of decreased clearance with increasing dose and plasma accumulation led to the expansion of the 320mg dose level. Two subjects then developed late haematologic dose-limiting toxicities (DLTs) that were associated with the highest plasma exposure to BPU and metabolites. Study enrollment resumed at dose 150mg with real-time pharmacokinetic monitoring. Seven additional subjects (6 evaluable) were treated for a median of 2 cycles (range 1.5-4) without further myelotoxicity. A long half-life and accumulation of BPU and active metabolites were observed, recommending against a continuous administration. Weekly oral BPU therapy should be further tested using an interrupted schedule.

  9. Metoprolol Dose Equivalence in Adult Men and Women Based on Gender Differences: Pharmacokinetic Modeling and Simulations

    Andy R. Eugene


    Full Text Available Recent meta-analyses and publications over the past 15 years have provided evidence showing there are considerable gender differences in the pharmacokinetics of metoprolol. Throughout this time, there have not been any research articles proposing a gender stratified dose-adjustment resulting in an equivalent total drug exposure. Metoprolol pharmacokinetic data was obtained from a previous publication. Data was modeled using nonlinear mixed effect modeling using the MONOLIX software package to quantify metoprolol concentration–time data. Gender-stratified dosing simulations were conducted to identify equivalent total drug exposure based on a 100 mg dose in adults. Based on the pharmacokinetic modeling and simulations, a 50 mg dose in adult women provides an approximately similar metoprolol drug exposure to a 100 mg dose in adult men.

  10. Effect of Admission Oral Diuretic Dose on Response to Continuous versus Bolus Intravenous Diuretics in Acute Heart Failure: An Analysis from DOSE-AHF

    Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.


    Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (<120 mg furosemide equivalent, n=131) outpatient diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486

  11. Dose distributions around selectron applicators

    Pla, C.; Evans, M.D.; Podgorsak, E.B.


    Measured and calculated dose distributions around selectron applicators, loaded with /sup 60/Co high dose rate pellets, are presented. The effect of the stopping screw, spacers, pellets themselves and the applicator wall on the dose distribution is discussed. The measured dose distribution is in almost perfect agreement with the calculated distribution in planes perpendicular to the applicator axis and containing a source. On the applicator axis directly below the applicator the measured dose amounts to about 75% of the calculated value, when only the stopping screw attenuates the beam from a pellet. When the beam is attenuated by spacers in addition to the stopping screw, the discrepancy between the calculated and measured dose may exceed 50%. Clinically relevant source geometries are also discussed. It is shown that for most regions around the applicator the method of a simple addition of dose contributions from individual point sources is an acceptable approximation for the calculation of dose distributions around the selectron applicators.

  12. Low-dose ketoconazole-fluconazole combination versus fluconazole in single doses for the treatment of vaginal candidiasis

    Jan Susilo


    Full Text Available Background: Vaginal candidiasis (VC is one of the most common fungal diseases. Candida albicans is the most common causative fungus and has been isolated from more than 80% of specimens obtained from women with VC. Ketoconazole is the first orally active antifungal, the dosage for VC is 200 mg twice daily for 5 days. Fluconazole is the newer oral antifungal, its dosage for VC is a single oral dose of 150 mg. Since fluconazole 150 mg is considerably expensive, a single dose of 100 mg ketoconazole and 40 mg fluconazole in combination has been tested for the treatment of VC. The results showed that from 11 women with confirmed VC, 1-2 weeks after drug administration, the mycological culture was negative in 8 women, positive in 1 woman, and 2 woman lost to follow-up. This promising result led to the present study with the objective to confirm the efficacy and safety of the above combination in a formal clinical trial.Methods: A total of 165 female patients, aged 18 years or older, with the diagnosis of VC from clinical symptoms (pruritus or burning or excessive discharge and positive microscopic smear (pseudohyphae and/or yeast cells were randomized to receive a single dose of either keto-fluco combination (n = 85 or fluconazole (n = 80, and returnedfor follow-up visit on day 8.Results: Among these patients, 39 patients had negative baseline culture, leaving 126 patients eligible for efficacy evaluation. The mycological eradication in the keto-fluco group was 74.5% (41 patients from a total of 55 patients with available mycological culture, while that in the fluconazole group was 70.2% (40 patients from 57 patients with available culture and this difference was not significant. The clinical favorable response (clinical cure and clinical improvement in the keto-fluco arm (n = 60 was 98.3%, while that in the fluconazole group (n = 66 was 100%. Adverse events were found in 5 patients, 3 patients in the keto-fluco group (3/85 = 3.5% and 2

  13. Hanford Environmental Dose Reconstruction Project

    Finch, S.M.; McMakin, A.H. (comps.)


    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (dose estimates): source terms; environmental transport; environmental monitoring data; demography, food consumption, and agriculture; environmental pathways and dose estimates.

  14. Effect of a single dose of mesoglycan on the human fibrinolytic system, and the profibrinolytic action of nine daily doses.

    Vittoria, A; Messa, G L; Frigerio, C; Celasco, G; Auteri, A


    The profibrinolytic activity of orally administered Mesoglycan was evaluated in 18 patients affected by impaired plasma fibrinolytic activity. Mesoglycan was administered by a single oral dose of 24, 48 or 72 mg on 1 day, and by repeated doses of 48 mg twice a day for 9 consecutive days. After the single administration all the fibrinolytic parameters were significantly and positively influenced with an order of magnitude and a duration of effects proportional to the dose employed. After the repeated administration, a constant and reproducible activation of the fibrinolytic system was observed without any interference with haemocoagulative parameters. These results confirm that Mesoglycan is endowed with a relevant profibrinolytic activity in man after oral administration. The pharmacological activity of Mesoglycan could possibly involve the liberation of a certain amount of plasminogen tissue activator.

  15. Diferentes doses de ciclofosfamida no sistema imune de ovinos

    Garcia Maurício


    Full Text Available O objetivo deste trabalho foi avaliar o efeito de diferentes doses de ciclofosfamida como indutor de imunossupressão experimental em ovinos. Foram empregados 30 animais, divididos em quatro grupos experimentais. Os animais dos grupos I, II e III foram submetidos, respectivamente, às doses de 10, 25 e 40mg kg-1 e os do grupo IV não receberam a droga, permanecendo como controle. Todos os animais foram imunizados com vacina contra a brucelose e, seis dias após a vacinação, foi feita a titulação através da soroaglutinação rápida em placa. Foi feita também a contagem de linfócitos sangüíneos e a dosagem de gamaglobulinas séricas, diariamente, durante uma semana, após a aplicação da ciclofosfamida. Houve óbitos apenas em alguns animais do grupo III (40mg kg-1. Assim, a droga mostrou-se segura com doses inferiores a 25mg kg-1. Quanto à imunossupressão, a mesma pôde ser demonstrada tanto nos animais que receberam 25mg kg-1, quanto aqueles que receberam 40mg/kg, através da análise dos resultados das contagens de linfócitos e dos títulos pós-vacinais anti-brucela. A dose de 25mg kg-1 de ciclofosfamida mostrou-se, assim, a mais adequada para ser usada em modelos de imunodepressão em ovinos, considerando sua ação imunossupressora e sua segurança e toxicidade.

  16. Hydrodechlorination of Tetrachloromethane over Palladium Catalysts Supported on Mixed MgF₂-MgO Carriers.

    Bonarowska, Magdalena; Wojciechowska, Maria; Zieliński, Maciej; Kiderys, Angelika; Zieliński, Michał; Winiarek, Piotr; Karpiński, Zbigniew


    Pd/MgO, Pd/MgF₂ and Pd/MgO-MgF₂ catalysts were investigated in the reaction of CCl₄ hydrodechlorination. All the catalysts deactivated in time on stream, but the degree of deactivation varied from catalyst to catalyst. The MgF₂-supported palladium with relatively large metal particles appeared the best catalyst, characterized by good activity and selectivity to C₂-C₅ hydrocarbons. Investigation of post-reaction catalyst samples allowed to find several details associated with the working state of hydrodechlorination catalysts. The role of support acidity was quite complex. On the one hand, a definite, although not very high Lewis acidity of MgF₂ is beneficial for shaping high activity of palladium catalysts. The MgO-MgF₂ support characterized by stronger Lewis acidity than MgF₂ contributes to very good catalytic activity for a relatively long reaction period (~5 h) but subsequent neutralization of stronger acid centers (by coking) eliminates them from the catalyst. On the other hand, the role of acidity evolution, which takes place when basic supports (like MgO) are chlorided during HdCl reactions, is difficult to assess because different events associated with distribution of chlorided support species, leading to partial or even full blocking of the surface of palladium, which plays the role of active component in HdCl reactions.

  17. Radiation dose to physicians’ eye lens during interventional radiology

    Bahruddin, N. A.; Hashim, S.; Karim, M. K. A.; Sabarudin, A.; Ang, W. C.; Salehhon, N.; Bakar, K. A.


    The demand of interventional radiology has increased, leading to significant risk of radiation where eye lens dose assessment becomes a major concern. In this study, we investigate physicians' eye lens doses during interventional procedures. Measurement were made using TLD-100 (LiF: Mg, Ti) dosimeters and was recorded in equivalent dose at a depth of 0.07 mm, Hp(0.07). Annual Hp(0.07) and annual effective dose were estimated using workload estimation for a year and Von Boetticher algorithm. Our results showed the mean Hp(0.07) dose of 0.33 mSv and 0.20 mSv for left and right eye lens respectively. The highest estimated annual eye lens dose was 29.33 mSv per year, recorded on left eye lens during fistulogram procedure. Five physicians had exceeded 20 mSv dose limit as recommended by international commission of radiological protection (ICRP). It is suggested that frequent training and education on occupational radiation exposure are necessary to increase knowledge and awareness of the physicians’ thus reducing dose during the interventional procedure.

  18. Prospective, randomised trial of the time dependent antiplatelet effects of 500 mg and 250 mg acetylsalicylic acid i. v. and 300 mg p. o. in ACS (ACUTE).

    Zeymer, Uwe; Hohlfeld, Thomas; Vom Dahl, Jürgen; Erbel, Raimund; Münzel, Thomas; Zahn, Ralf; Roitenberg, Alexander; Breitenstein, Stefanie; Pap, Ákos Ferenc; Trenk, Dietmar


    Little is known about the onset of action after intravenous or oral administration of acetylsalicylic acid (ASA) in patients with acute coronary syndromes (ACS). The aim of the study was to compare intravenous 250 or 500 mg acetylsalicylic acid (ASA) with oral 300 mg in ASA naïve patients with ACS concerning the onset of antiplatelet effects measured by time dependent thromboxane inhibition. A total of 270 patients with ACS acid (AA)-induced platelet thromboxane release (TXB2) 5 minutes (min) after study drug administration. Both 250 mg and 500 mg ASA i. v. inhibited TXB2 formation nearly completely (geometric means: from 581.7 and 573.9 ng/ml at baseline to 3.9 and 3.1 ng/ml at 5 min, respectively) compared to 300 mg oral ASA (geometric means: from 652.0 to 223.7 ng/ml) (p-value, ANCOVA: < 0.0001). Similar results were obtained for inhibition of AA-induced platelet aggregation (Multiplate ASPItest; from means 86.41 and 85.72 U to 23.04 and 20.57 U at 5 min, respectively) compared to 300 mg oral ASA from mean 87.18 to 75.56 U (p-value, ANCOVA: <0.0001). The rate of bleedings was low and comparable between the groups. In summary, the administration of a single dose of 250 or 500 mg ASA IV compared to 300 mg orally is associated with a faster and more complete inhibition of thromboxane generation and platelet aggregation. Bleeding complications were comparable between the groups.

  19. Preparation of Metallic Isotope 26Mg

    WuXiaolei; ZhangFuming; GanZaiguo; GuoJunsheng; QinZhi


    Some special isotope material is usually used in nuclear experiments. It can be served as ion beam or target. When new superheavy nuclide 265Bh (Z=107) is synthesized, a reaction of 243Am target with 26Mg ion beamis selected to produce new isotope 265Bh. The preparation and production of this rare and extremely expensive isotope 26 Mg used for ion beam substance will be a key problem in synthesizing experiment of 265Bh. Theavailable chemical form of isotope 26Mg in commercial product usually is oxide or other compound, which are not required in our experiment. They need to be transformed to metal form as a proper working substance in ion source.

  20. Hydrogenation properties of Mg-Al alloys

    Andreasen, Anders


    In this paper the properties of Mg-Al alloys in relation to hydrogen storage are reviewed. The main topics of this paper are materials preparation, hydrogen capacity, thermodynamics of hydride formation, and the kinetics of hydride formation and decomposition. Hydrogenation of Mg-Al leads...... to disproportionation with the formation of magnesium hydride and metallic aluminum as the final product. Experimental evidence renders this process reversible. It is observed that the enthalpy of hydride formation of magnesium is lowered upon alloying with Al due to a slightly endothermic disproportionation reaction....... Further, it is found that the kinetics of hydrogenation, as well dehydrogenation, may be significantly improved by alloying compared to pure Mg. The expense of these improvements of the hydrogenation/dehydrogenation properties is a lower gravimetric hydrogen density in the hydrogenated product, (C) 2008...

  1. High Spin States in ^24Mg

    Schwartz, J.; Lister, C. J.; Wuosmaa, A.; Betts, R. R.; Blumenthal, D.; Carpenter, M. P.; Davids, C. N.; Fischer, S. M.; Hackman, G.; Janssens, R. V. F.


    The ^12C(^16O,α)^24Mg reaction was used at 51.5MeV to populate high angular momentum states in ^24Mg. Gamma-rays de-exciting high spin states were detected in a 20 detector spectrometer (the AYE-ball) triggered by the ANL Fragment Mass Analyser (FMA). Channel selection, through detection of ^24Mg nuclei with the appropriate time of flight, was excellent. All the known decays from high spin states were seen in a few hours, with the exception of the 5.04 MeV γ-decay of the J^π=9^- state at 16.904 MeV footnote A.E.Smith et al., Phys. Lett. \\underlineB176, (1986)292. which could not be confirmed. The potential of the technique for studying the radiative decay of states with very high spin in light nuclei will be discussed.

  2. Phase equilibrium in Mg-Cu-Y

    Mezbahul-Islam, Mohammad; Medraj, Mamoun


    Magnesium-based bulk metallic glasses (BMG) have potential in applications ranging from biomedical to sports equipment and the Mg-Cu-Y system offers some of the most promising alloys. Phase relations and ternary solubility of the binary and ternary compounds of this system have been experimentally investigated. The Isothermal section of Mg-Cu-Y system at 673 K for the entire composition range has been constructed. Phase relations in the Cu-rich (>66 at.% Cu) region of the Mg-Cu-Y system has been determined for the first time. The homogeneity range of three ternary compounds has been determined. Solidifications behavior of several key alloys have been discussed based on the differential scanning calorimetry (DSC) experiments and thermodynamic calculations. Extensive analysis of the DSC curves has been carried out to relate them to the corresponding phase transformation reactions and temperatures. Some of the most promising metallic glass forming regions have been analyzed using thermodynamic calculations.

  3. Pharmacodynamic effects of standard dose prasugrel versus high dose clopidogrel in non-diabetic obese patients with coronary artery disease.

    Darlington, Andrew; Tello-Montoliu, Antonio; Rollini, Fabiana; Ueno, Masafumi; Ferreiro, José Luis; Patel, Ronakkumar; Desai, Bhaloo; Guzman, Luis A; Bass, Theodore A; Angiolillo, Dominick J


    Increased body weight is independently associated with impaired clopidogrel pharmacodynamic (PD) response. Prasugrel has more potent PD effects compared with clopidogrel, although its PD effects in obese patients are unknown. The aim of this prospective, randomised, study was to compare the PD effects of standard-dose prasugrel [60 mg loading dose (LD)/10 mg daily maintenance dose (MD)] with high-dose clopidogrel (900 mg LD/150 mg daily MD) in non-diabetic obese [body mass index (BMI) ≥30 kg/m²] patients, with coronary artery disease (CAD) on aspirin therapy. PD assessments (baseline, 2 hours post-LD and 6 ± 2 days after MD) were conducted using four platelet function assays, and the platelet reactivity index (PRI) assessed by VASP was used for sample size estimation. A total of 42 patients with a BMI of 36.42 ± 5.6 kg/m² completed the study. There were no differences in baseline PD measures between groups. At 2 hours post-LD, prasugrel was associated with lower PRI compared with clopidogrel (24.3 ± 5.5 vs 58.7 ± 5.7, p≤0.001), with consistent findings for all assays. At one-week, PRI values on prasugrel MD were lower than clopidogrel MD without reaching statistical significance (34.7 ± 5.8 vs 42.9 ± 5.8, p=0.32), with consistent findings for all assays. Accordingly, rates of high on-treatment platelet reactivity were markedly reduced after prasugrel LD, but not after MD. In conclusion, in non-diabetic obese patients with CAD, standard prasugrel dosing achieved more potent PD effects than high-dose clopidogrel in the acute phase of treatment, but this was not sustained during maintenance phase treatment. Whether an intensified prasugrel regimen is required in obese patients warrants investigation.

  4. Comparison of acute alprazolam (0.25, 0.50 and 1.0 mg) effects versus those of lorazepam 2 mg and placebo on memory in healthy volunteers using laboratory and telephone tests.

    Vermeeren, A; Jackson, J L; Muntjewerff, N D; Quint, P J; Harrison, E M; O'Hanlon, J F


    This study was designed to confirm the hypothetical dose-dependent effect of alprazolam on memory and to compare its effects on tests measuring different aspects of cognitive and psychomotor functioning. A secondary purpose was to compare the sensitivity of newly developed telephone tests with a standard laboratory test of memory. Twenty healthy male volunteers (aged 18-35 years) participated in a five-way double-blind crossover design. Treatments were single oral doses of alprazolam (0.25, 0.5 and 1.0 mg), placebo and lorazepam 2.0 mg. The latter was included as an internal control for demonstrating sensitivity of the method. Lorazepam significantly impaired all performance measures except two: verbal fluency and accuracy of music recognition were insensitive to drug effects. Alprazolam had clear dose-dependent effects on different aspects of memory: 0.25 mg did not affect any parameter; 0.5 mg impaired performance in a Word Learning Test and a Spatial Memory Test and also psychomotor performance; 1.0 mg additionally impaired Syntactic Reasoning, Semantic Verification, and Critical Flicker Fusion performance. Alprazolam's effects were not selective for any of the cognitive functions as measured in this study. The telephone tests were clearly less sensitive than the standard test, though sufficient for showing significant effects of alprazolam 1 mg and lorazepam 2 mg.

  5. Prediction of Optimal Reversal Dose of Sugammadex after Rocuronium Administration in Adult Surgical Patients

    Shigeaki Otomo


    Full Text Available The objective of this study was to determine the point after sugammadex administration at which sufficient or insufficient dose could be determined, using first twitch height of train-of-four (T1 height or train-of-four ratio (TOFR as indicators. Groups A and B received 1 mg/kg and 0.5 mg/kg of sugammadex, respectively, as a first dose when the second twitch reappeared in train-of-four stimulation, and Groups C and D received 1 mg/kg and 0.5 mg/kg of sugammadex, respectively, as the first dose at posttetanic counts 1–3. Five minutes after the first dose, an additional 1 mg/kg of sugammadex was administered and changes in T1 height and TOFR were observed. Patients were divided into a recovered group and a partly recovered group, based on percentage changes in T1 height after additional dosing. T1 height and TOFR during the 5 min after first dose were then compared. In the recovered group, TOFR exceeded 90% in all patients at 3 min after sugammadex administration. In the partly recovered group, none of the patients had a TOFR above 90% at 3 min after sugammadex administration. An additional dose of sugammadex can be considered unnecessary if the train-of-four ratio is ≥90% at 3 min after sugammadex administration. This trial is registered with UMIN000007245.

  6. Prediction of Optimal Reversal Dose of Sugammadex after Rocuronium Administration in Adult Surgical Patients

    Iwasaki, Hiroshi


    The objective of this study was to determine the point after sugammadex administration at which sufficient or insufficient dose could be determined, using first twitch height of train-of-four (T1 height) or train-of-four ratio (TOFR) as indicators. Groups A and B received 1 mg/kg and 0.5 mg/kg of sugammadex, respectively, as a first dose when the second twitch reappeared in train-of-four stimulation, and Groups C and D received 1 mg/kg and 0.5 mg/kg of sugammadex, respectively, as the first dose at posttetanic counts 1–3. Five minutes after the first dose, an additional 1 mg/kg of sugammadex was administered and changes in T1 height and TOFR were observed. Patients were divided into a recovered group and a partly recovered group, based on percentage changes in T1 height after additional dosing. T1 height and TOFR during the 5 min after first dose were then compared. In the recovered group, TOFR exceeded 90% in all patients at 3 min after sugammadex administration. In the partly recovered group, none of the patients had a TOFR above 90% at 3 min after sugammadex administration. An additional dose of sugammadex can be considered unnecessary if the train-of-four ratio is ≥90% at 3 min after sugammadex administration. This trial is registered with UMIN000007245. PMID:24672542

  7. Cell response of nanographene platelets to human osteoblast-like MG63 cells.

    Zhang, X; Li, M; Wang, Y B; Cheng, Y; Zheng, Y F; Xi, T F; Wei, S C


    The biologic/cytotoxic effects of dispersed nanographene platelets (NGPs) on human osteosarcoma cells (MG63 cell line) were first studied by examining cell viability, cycle, apoptosis, change in morphology, lactate dehydrogenase (LDH) release, alkaline phosphatase (ALP) activity, and inflammation. The results shown that the cell cytotoxicity of the dispersed NGPs exhibited dose-dependent characters, which had no obvious cytotoxic effects to MG63 cells at the concentration less than 10 μg mL(-1), whereas could postpone cell cycle, promote cell apoptosis, damage cell microstructure, induce serious tumor necrosis factor-α expression and greatly reduce ALP activity of MG63 cells at higher concentration of NGPs (>10 µg mL(-1)). Besides, NGPs had little influence on the LDH leakage. The cytotoxic mechanism of NGPs to MG63 cells was speculated to be intracellular activity with no physical damage of plasma membrane.

  8. Electron beam irradiated HDPE/EVA/Mg(OH)2 composites for flame-retardant electric cables

    Hui LIU; Nabil A. Noman ALKADASI; Yan ZHU; Li-fang TONG; Zheng-ping FANG; Yong-chang WANG


    The mechanical properties and flammability of high-density polyethylene (HDPE)/ethylene vinyl acetate (EVA) mixed with various amounts of magnesium hydroxide (Mg(OH)2) as the filler in composites, irra-diated with electron beam at an irradiation dose of 150 kGy, have been studied. It is found that high-energy electron beam irradiation has significant effects on the mechanical properties of the HDPE/EVA/Mg(OH)2 com-posites. The tensile strength and elastic modulus increased greater than in the unirradiated ones. Meanwhile, with increasing the content of Mg(OH)2 in the composites, the limiting oxygen index (LOI) value increased sharply. The microstructure of the caves of the unirradiated HDPE/EVA/Mg(OH)2 composites show poor interface of composites compared with the irradiated ones, as observed in SEM micrographs.

  9. Comparative study of thermoluminescent properties of LiF: Mg, Cu, P, LiF: Mg, Ti and TLD-100 irradiated with X-rays; Estudio comparativo de las propiedades termoluminiscentes de LiF: Mg, Cu, P, LiF: Mg, Ti y TLD-100 irradiados con rayos X

    Azorin, J.; Rivera, T.; Gonzalez, P.; Ortega, X.; Ginjaume, M. [Universidad Autonoma Metropolitana-Iztapalapa, 09000 Mexico D.F. (Mexico)


    The thermoluminescent properties (Tl) of LiF: Mg, Cu, P, and LiF: Mg, Ti, were investigated both developed in Mexico and comparing them with the properties of TLD-100 when they are exposure to X-rays. The Tl curve of LiF: Mg, Cu, P exhibited two peaks at 200 and 300 Centigrade. Its response Tl in function of dose resulted linear in the interval of 0.5 Gy until 5 Gy and its sensitivity to X-ray was around 25 times greater that of the TLD-100. Also it was measured the Tl response of the three materials in function of photon energy. The results showed that LiF: Mg, Cu, P has potential to be used as X-ray dosemeter. (Author)

  10. Acute cognitive effects of high doses of dextromethorphan relative to triazolam in humans

    Carter, Lawrence P.; Reissig, Chad J.; Johnson, Matthew W.; Klinedinst, Margaret A.; Griffiths, Roland R.


    BACKGROUND Although concerns surrounding high-dose dextromethorphan (DXM) abuse have recently increased, few studies have examined the acute cognitive effects of high doses of DXM. The aim of this study was to compare the cognitive effects of DXM with those of triazolam and placebo. METHODS Single, acute, oral doses of DXM (100, 200, 300, 400, 500, 600, 700, 800 mg/70 kg), triazolam (0.25, 0.5 mg /70 kg), and placebo were administered p.o. to twelve healthy volunteers with histories of hallucinogen use, under double-blind conditions, using an ascending dose run-up design. Effects on cognitive performance were examined at baseline and after drug administration for up to 6 hours. RESULTS Both triazolam and DXM produced acute impairments in attention, working memory, episodic memory, and metacognition. Impairments observed following doses of 100-300 mg/70 kg DXM were generally smaller in magnitude than those observed after 0.5 mg/70 kg triazolam. Doses of DXM that impaired performance to the same extent as triazolam were in excess of 10-30 times the therapeutic dose of DXM. CONCLUSION The magnitude of the doses required for these effects and the absence of effects on some tasks within the 100-300 mg/70 kg dose range of DXM, speak to the relatively broad therapeutic window of over-the-counter DXM preparations when used appropriately. However, the administration of supratherapeutic doses of DXM resulted in acute cognitive impairments on all tasks that were examined. These findings are likely relevant to cases of high-dose DXM abuse. PMID:22989498

  11. Superconductivity in MgB2


    In January of 2001 the superconductivity of the compound MgB2 with a critical temperature Tc of up to 39 K was discovered. This Tc is the highest in all intermetallic compound and alloy superconductors. MgB2 has a simple structure and its manufacturing capital cost is lower, therefore it could become a practical superconductor in the future. The recent progress is reviewed here which covers the progress in electronic structure, high Tc mechanism, superconducting parameters (Debye temperature, specific heat coefficient of electron, critical fields, coherent length, penetration depth, energy gap, critical current and relaxation rate of flux). Moreover the issue on power transmission is discussed.

  12. Electron microscopy observations of MgB 2 wire prepared by an internal Mg diffusion method

    Shimada, Y.; Kubota, Y.; Hata, S.; Ikeda, K.; Nakashima, H.; Matsumoto, A.; Togano, K.; Kumakura, H.


    Microstructure in a high-density MgB2 wire fabricated by an internal Mg diffusion (IMD) process has been investigated by electron microscopy imaging and analysis at different scales. In the IMD process, a pure Mg rod was used as Mg source, and nanosized SiC powders were mixed with amorphous B powders. In the case of a heat treatment at 640 °C for 1 h carried out after rolling and drawing processes, the wire has two microstructural features that degrade critical current density: uncrystallized zones composed mainly of unreacted B and SiC powders, and cracks partly filled with course Mg2Si crystals. Those cracks were formed in the uncrystallized zones as well as in crystallized MgB2 zones. It indicate that the cracks formed by the mechanical milling and drawing remain after the heat treatment.

  13. Efficient hydrogen storage with the combination of lightweight Mg/MgH2 and nanostructures.

    Cheng, Fangyi; Tao, Zhanliang; Liang, Jing; Chen, Jun


    Efficient hydrogen storage plays a key role in realizing the incoming hydrogen economy. However, it still remains a great challenge to develop hydrogen storage media with high capacity, favourable thermodynamics, fast kinetics, controllable reversibility, long cycle life, low cost and high safety. To achieve this goal, the combination of lightweight materials and nanostructures should offer great opportunities. In this article, we review recent advances in the field of chemical hydrogen storage that couples lightweight materials and nanostructures, focusing on Mg/MgH(2)-based systems. Selective theoretical and experimental studies on Mg/MgH(2) nanostructures are overviewed, with the emphasis on illustrating the influences of nanostructures on the hydrogenation/dehydrogenation mechanisms and hydrogen storage properties such as capacity, thermodynamics and kinetics. In particular, theoretical studies have shown that the thermodynamics of Mg/MgH(2) clusters below 2 nm change more prominently as particle size decreases.

  14. Interoceptive conditioning with the nicotine stimulus: extinction learning as a method for assessing stimulus similarity across doses.

    Polewan, Robert J; Savala, Stephanie A; Bevins, Rick A


    Interoceptive conditioning involving the nicotine stimulus likely contributes to chronic tobacco use. To better understand the nature of this interoceptive conditioning, we compared generalization during repeated extinction with generalization in a 'transfer of extinction' test using a wide range of test doses. Rats were first trained in the discriminated goal-tracking task in which nicotine (0.2 or 0.4 mg/kg), but not saline, was paired with repeated intermittent access to sucrose. Across sessions, nicotine acquired control of approach behavior directed at the location of previous sucrose deliveries. Extinction followed with eight 20-min sessions without sucrose access; extinction doses of nicotine ranged from 0.05 to 0.6 mg/kg. In rats trained with 0.4 mg/kg, the 0.1, 0.2, and 0.6 mg/kg doses evoked comparable responding across extinction sessions; substitution was only partial at 0.05 and 0.075 mg/kg (i.e. above saline controls, but less than the training dose). With the 0.2 mg/kg training dose, complete generalization was seen only at the 0.1 and 0.4 mg/kg doses. After extinction, rats were given a transfer test with their training dose. Rats trained with 0.4 mg/kg showed full transfer of extinction learning with 0.1, 0.2, and 0.6 mg/kg (i.e. responding comparable with extinction with the training dose). Partial transfer was observed at 0.075 mg/kg. With the 0.2 mg/kg nicotine dose, only 0.4 mg/kg fully generalized; 0.075, 0.1, and 0.6 mg/kg showed partial transfer. Extinction with 0.05 mg/kg dose did not show transfer to either training dose. These findings indicated that conclusions regarding stimulus similarity across nicotine doses can vary with testing protocol.

  15. Cyclosporine A combined with medium/low dose prednisone in progressive IgA nephropathy.

    Xu, Lin; Liu, Zhong-Cheng; Guan, Guang-Ju; Lv, Xue-Ai; Luo, Qing


    The aim of the present study was to evaluate the efficacy of cyclosporine A (CsA) combined with medium/low dose prednisone in the treatment of progressive immunoglobulin A nephropathy (IgAN). Ninety-six patients who satisfied the inclusion criteria were enrolled in a prospective controlled clinical study. They were assigned into two groups and initially given either 0.6-0.8 mg/kg/day prednisone (maximum 40 mg/day) plus 3 mg/kg/day CsA (CsA group), or 1 mg/kg/day prednisone (maximum 60 mg/day) alone (steroid group). During therapy, the dose of prednisone was reduced in both groups and the dose of CsA was gradually tailed off over the first 3 months and maintained at 2 mg/kg/day in the CsA group. Urinary protein excretion, serum biochemical indexes, clinical efficacy and side effects of CsA were assayed. A significant decline in mean 24-hour urinary protein excretion (p prednisone and CsA (p 0.05). CsA at a dose of 2-3 mg/kg/day in combination with medium/low dose prednisone was effective in inducing remission of IgAN, especially for patients with Lee's Grade III IgAN, and is a safe and effective choice for short-term treatment of patients with progressive IgAN.

  16. A new dosing schedule for gentamicin in blood pythons (Python curtus): a pharmacokinetic study.

    Hilf, M; Swanson, D; Wagner, R; Yu, V L


    Gentamicin is frequently used in the treatment of aerobic Gram-negative infections in reptiles. Pharmacokinetic data to ensure proper dosing are scant, especially for large snakes. A pharmacokinetic study of gentamicin was therefore conducted in four blood pythons. Snakes were given intramuscular injections of either 2.5 mg kg-1 or 3.0 mg kg-1 loading dose followed by 1.5 mg kg-1 at 72 and 96 hours. A linear pharmacokinetic relationship between gentamicin serum concentrations and time was demonstrated in each of the four snakes studied. Peak serum concentrations occurred six to 10 hours after injection and ranged from 4.6 to 8.9 micrograms ml-1. Half-life was variable and ranged from 32 to 110 hours. Total body clearance and apparent volume of distribution varied little between the individual snakes studied. There was no evidence of renal toxicity. For blood pythons a loading dose of 2.5 mg kg-1 followed by 1.5 mg kg-1 at 96 hour intervals is recommended. If higher concentrations are desired, a loading dose of 3.0 mg kg-1 followed by 1.5 mg kg-1 at 96 hours can be given. These dosing schedules will provide serum concentrations in excess of the minimum inhibitory concentrations for most aerobic Gram-negative bacilli that are pathogenic in snakes; gentamicin accumulation with subsequent renal dysfunction should not occur.

  17. Effective dose and dose to crystalline lens during angiographic procedures; Dose effective et dose au cristallin lors de procedures angiographiques

    Pages, J. [QUARAD and Radiology Dept., Vvije Universiteit Brussel (Belgium)


    The highest radiation doses levels received by radiologists are observed during interventional procedures. Doses to forehead and neck received by a radiologist executing angiographic examinations at the department of radiology at the academic hospital (AZ-VUB) have been measured for a group of 34 examinations. The doses to crystalline lens and the effective doses for a period of one year have been estimated. For the crystalline lens the maximum dose approaches the ICRP limit, that indicates the necessity for the radiologist to use leaded glasses. (N.C.)

  18. Dose-dependent effects of hydrocortisone infusion on autobiographical memory recall.

    Young, Kymberly; Drevets, Wayne C; Schulkin, Jay; Erickson, Kristine


    The glucocorticoid hormone cortisol has been shown to impair episodic memory performance. The present study examined the effect of two doses of hydrocortisone (synthetic cortisol) administration on autobiographical memory retrieval. Healthy volunteers (n = 66) were studied on two separate visits, during which they received placebo and either moderate-dose (0.15 mg/kg IV; n = 33) or high-dose (0.45 mg/kg IV; n = 33) hydrocortisone infusion. From 75 to 150 min post-infusion subjects performed an Autobiographical Memory Test and the California Verbal Learning Test (CVLT). The high-dose hydrocortisone administration reduced the percent of specific memories recalled (p = .04), increased the percent of categorical (nonspecific) memories recalled (p cortisol affects accessibility of autobiographical memories in a dose-dependent manner. Specifically, administration of hydrocortisone at doses analogous to those achieved under severe psychosocial stress impaired the specificity and speed of retrieval of autobiographical memories.

  19. Dose assessment of aircrew using passive detectors

    Hajek, M.; Berge, T.; Schoener, W.; Summerer, L.; Vana, N


    Radiation exposure of aircrew is a serious concern which has been given special emphasis in the European Council directive 96/29/Euratom. The cosmic ray induced neutron component can contribute more than 50% to the biologically relevant dose at aviation altitudes. Various computational approaches to route dose assessment, e.g. CARI, are in use nowadays and are compared with experimental data. Measurements of aircrew exposure usually involve extensive instrumentation in order to cover the whole particle spectrum and energy range present inside aircraft. Due to their small size and easy handling, thermoluminescence dosemeters represent an appropriate alternative. Previous measurements onboard aircraft applying the high-temperature ratio method with LiF:Mg,Ti dosemeters for the determination of an 'averaged' linear energy transfer of mixed radiation fields demonstrate the ability of this method to evaluate the dose equivalent, according to the Q(LET{sub (}) relationship proposed by the ICRP. Measurements with CaF{sub 2}:Tm dosemeters are currently in progress and are discussed here. (author)

  20. The reactive Mg-liquid infiltration to obtain long superconducting MgB$_{2}$ cables

    Giunchi, G


    An alternative “in situ” process to the MgB2 wire manufacturing is represented by the Reactive Mg-Liquid Infiltration (Mg-RLI) process [1], in which the precursor wire is constituted by a metallic sheath encasing a central Mg rod, surrounded by the B powders. We demonstrated that this peculiar “internal Mg” assembly is able to produce very dense superconducting material of high critical current density, with an acceptable fill factor, up to 0.28. Furthermore the Mg-RLI allows also to easily dope the MgBB2 material either by carbon or nanoSiC powders. In order to realize long cables with this technique, two different approaches may be applied. The first one relies on the assembly of thin wires, fine enough that the liquid Mg cannot freely percolate along the wire during the reaction, and the second one relies on the assembly of thick hollow wires, reacted with a continuous supply of Mg to avoid deficiency of Mg in some part of the precursor wire. Both techniques have been demonstrated feasible and the ...

  1. The Interplay of Al and Mg Speciation in Advanced Mg Battery Electrolyte Solutions.

    See, Kimberly A; Chapman, Karena W; Zhu, Lingyang; Wiaderek, Kamila M; Borkiewicz, Olaf J; Barile, Christopher J; Chupas, Peter J; Gewirth, Andrew A


    Mg batteries are an attractive alternative to Li-based energy storage due to the possibility of higher volumetric capacities with the added advantage of using sustainable materials. A promising emerging electrolyte for Mg batteries is the magnesium aluminum chloride complex (MACC) which shows high Mg electrodeposition and stripping efficiencies and relatively high anodic stabilities. As prepared, MACC is inactive with respect to Mg deposition; however, efficient Mg electrodeposition can be achieved following an electrolytic conditioning process. Through the use of Raman spectroscopy, surface enhanced Raman spectroscopy, (27)Al and (35)Cl nuclear magnetic resonance spectroscopy, and pair distribution function analysis, we explore the active vs inactive complexes in the MACC electrolyte and demonstrate the codependence of Al and Mg speciation. These techniques report on significant changes occurring in the bulk speciation of the conditioned electrolyte relative to the as-prepared solution. Analysis shows that the active Mg complex in conditioned MACC is very likely the [Mg2(μ-Cl)3·6THF](+) complex that is observed in the solid state structure. Additionally, conditioning creates free Cl(-) in the electrolyte solution, and we suggest the free Cl(-) adsorbs at the electrode surface to enhance Mg electrodeposition.

  2. Effect of Ni on Mg based hydrogen storage alloy Mg3Nd

    TONG Yanqing; OUYANG Liuzhang; ZHU Min


    Magnesium-neodymium based alloys were prepared by induction melting in an alumina crucible under protection of pure argon atmosphere. XRD patterns show that the as-melted Mg-Nd and Mg3NdNi 0.1 diffraction peaks can be excellently indexed with D03 structure (BiF3 type, space group Fm3m ). The lattice constant of Mg3Nd phase is 0.7390 nm, which is determined by XRD analysis using Cohen's extrapolation method. The reversible hydrogen storage capacity reaches 1.95wt.% for Mg3Nd and 2.68wt.% for Mg3NdNi0.1 . The desorption of hydrogen takes place at 291 ℃ for Mg3Nd and at 250 ℃ for Mg3NdNi 0.1 . The alloys could absorb hydrogen at room temperature with rapid hydriding and dehydriding kinetics after only one cycle. The enthalpy (ΔH ) and entropy (ΔS ) of Mg3Nd-H dehydriding reaction were -68.2 kJ·mol-1 H2 and -0.121 kJ·(K·mol)-1 H2 determined by using van't Hoff plot according to the pressure-composition-isotherms (P-C-I) curve measured at different temperatures. Hydrogen absorption kinetic property of Mg3NdNi 0.1 alloy was also measured at room temperature.

  3. Comparing Doping Methodologies in Mg2Si/AgMg System

    Polymeris, G. S.; Theodorakakos, A.; Mars, K.; Godlewska, E.; Lioutas, Ch. B.; Hatzikraniotis, E.; Paraskevopoulos, K. M.


    Morphological and optical characterizations for the Mg2Si samples doped with Ag are presented. Two different doping methodologies with silver, namely in situ and ex situ doping, were studied for the case of Mg2Si of self-propagating high-temperature synthesis. Electron microscopy measurements in both scanning and transmission configurations verified the presence of AgMg precipitates embedded in the Mg2Si matrix and similar results were also yielded by FTIR spectroscopy. Finally, the dependence of silver content in both forms of dopant and inter-metallic constituent is studied upon doping technology.

  4. Confinement of Mg-MgH2 systems into carbon nanotubes changes hydrogen sorption energetics.

    Liang, Jian-jie; Kung, W-C Paul


    The density functional theory (DFT) method was used to study the effect of nanoconfinement on the energetics of Mg-MgH2 systems. Varying levels of loading of the Mg/MgH2 particles into a (10,10) carbon nanotube were examined, and the corresponding energetics were computed. A clear trend was observed that, as the level of loading increases (increasing confinement), the net energy change in the hydrogen sorption/desorption processes decreases to a significant level when the loading approaches the maximum. The confinement was found not to depend on the tube length of the confining nanotubes.

  5. To evaluate the analgesic activity of resveratrol in different doses in animal model

    Tanu Garg


    Conclusions: In the study, resveratrol exhibited analgesic activity in both thermal and chemical pain models in both the doses, and analgesic activity in higher dose (100 mg/kg was comparable to standard drug. [Int J Basic Clin Pharmacol 2016; 5(3.000: 869-872

  6. High-Dose Daunorubicin in Older Patients with Acute Myeloid Leukemia

    Lowenberg, Bob; Ossenkoppele, Gert J.; van Putten, Wim; Schouten, Harry C.; Graux, Carlos; Ferrant, Augustin; Sonneveld, Pieter; Maertens, Johan; Jongen-Lavrencic, Mojca; von Lilienfeld-Toal, Marie; Biemond, Bart J.; Vellenga, Edo; Kooy, Marinus van Marwijk; Verdonck, Leo F.; Beck, Joachim; Doehner, Hartmut; Gratwohl, Alois; Pabst, Thomas; Verhoef, Gregor


    Background A complete remission is essential for prolonging survival in patients with acute myeloid leukemia (AML). Daunorubicin is a cornerstone of the induction regimen, but the optimal dose is unknown. In older patients, it is usual to give daunorubicin at a dose of 45 to 50 mg per square meter o

  7. Sodium fusidate ameliorates the course of diabetes induced in mice by multiple low doses of streptozotocin

    Nicoletti, F; Di Marco, R; Conget, I


    We studied the effects of the immunosuppressant sodium fusidate (fusidin) on murine immunoinflammatory diabetes mellitus (DM) induced by multiple low doses of streptozotocin (SZ). Fusidin was given by gavage to three strains of mice (C57KsJ, C57BL/6, CD1) at doses 10 or 100 mg/kg body weight every...

  8. Treatment of early AIDS dementia in intravenous drug users : High versus low dose peptide T

    Kosten, TR; Rosen, MI; McMahon, TL; Bridge, TP; OMalley, SS; Pearsall, R; OConnor, PG


    This placebo-controlled, double blind, cross-over study tested the efficacy of two different doses of Peptide T in the treatment of nine intravenous drug users with early AIDS dementia who were also receiving methadone and AZT. Subjects received Peptide T doses of either 15 or 1.5 mg daily for four

  9. Bioequivalence studies for two different strengths of montelukast in healthy volunteers: 10 mg film-coated tablets and 5 mg chewable tablets.

    Pedroso, P; Almeida, S; Filipe, A; Neves, R I; Boudreault, S; Jiménez, C


    In order to assess the bioequivalence of 2 different formulations of montelukast, a pivotal trial for the montelukast 10 mg film-coated tablets formulation and a pivotal trial for the montelukast 5 mg chewable tablets formulation were conducted.For the 10 mg study, 34 healthy subjects were enrolled in a single centre, randomised, single-dose, open-label, 2-way crossover study, with a minimum washout period of 7 days, while for the 5 mg study, 42 healthy subjects were included in another study with a similar design. For both studies, plasma samples were collected up to 24 h post-dosing and drug levels were determined by reverse liquid chromatography and detected by tandem mass spectrometry detection.Pharmacokinetic parameters used for bioequivalence assessment, area under the concentration-time curve from time zero to time of last non-zero concentration (AUC0-t) and from time zero to infinity (AUC0-inf) and maximum observed concentration (Cmax), were determined from the drug concentration data using non-compartmental analysis.In the 10 mg study, the 90% confidence intervals obtained by analysis of variance were 99.62-120.51% for Cmax, 102.25-117.37% for AUC0-t and 101.96-116.67% for AUC0-inf, which were within the predefined acceptable range of 80.00-125.00%.In the 5 mg study, the 90% confidence intervals were 91.14-98.46% for Cmax, 93.02-98.42% for AUC0-t and 93.09-98.63% for AUC0-inf, which were within the predefined acceptable range of 80.00-125.00%.Bioequivalence between formulations was concluded both in terms of rate and extent of absorption for both strengths.

  10. Efavirenz 400 mg daily remains non-inferior to 600 mg: 96 week data from the double-blind, placebo-controlled ENCORE1 study

    Dianne Carey


    Full Text Available Introduction: ENCORE1 compared the efficacy and safety of reduced versus standard dose efavirenz (EFV with tenofovir/emtricitabine (TDF/FTC as first-line HIV therapy. The primary analysis at 48 weeks showed 400 mg EFV was safe and virologically non-inferior to 600 mg. This analysis explores over 96 weeks the durability of efficacy and safety. Materials and Methods: A multinational, double-blind, placebo-controlled, non-inferiority trial in treatment-naïve HIV-positive adults randomized to TDF/FTC plus reduced (400 mg, EFV400 or standard dose (600 mg, EFV600 EFV. The difference between proportions of participants with plasma HIV RNA (VL 200 copies/mL (p=0.47 or mean change from baseline VL (p=0.74. Mean change from baseline in CD4 T-cell counts at week 96 remained significantly higher for EFV400 than EFV600 (difference 25 cells/µL; 95% CI 2–48; p=0.03. There was no difference in the frequency or severity of AEs (EFV400 = 89.4%, EFV600 = 89.3%; difference 0.09; 95% CI −4.73 to 4.90; p=0.97. The proportions ever reporting an AE definitely or probably EFV-related were EFV400 (37.7% and EFV600 (47.9% (difference −10.2%; 95% CI −17.9 to −2.51; p=0.01. SAEs did not differ in frequency (EFV400 = 7.5%, EFV600 = 10.4%; difference −2.9%; 95% CI −7.3 to 1.6; p=0.20. Conclusions: Non-inferiority of EFV 400 mg to EFV 600 mg when combined with TDF/FTC as initial HIV therapy was confirmed at week 96. Both doses demonstrated similar safety profiles. These results support the use of a lower EFV dose as part of routine HIV management.

  11. Relative bioavailability of oral low dose methotrexate. A comparison of 2 different formulations.

    Fosså, S D; Tveit, K; Börmer, O; Moxnes, A; Jørgensen, N P; Orjaseter, H; Kristoffersen, D T


    In 39 patients the bioavailability of methotrexate from the two tablets Emthexat 2.5 mg and Methotrexate 2.5 mg was assessed in a double-blind study after a single oral dose of 30 mg/m2 Methotrexate. There was a considerable inter-individual variation of the serum pharmacokinetics in regard to Cmax and tmax, independent on the MTX formulation. Emthexat 2.5 mg tablets and Methotrexate 2.5 mg tablets were bioequivalent according to the definition (AUCE greater than or equal to AUCM X 80%).

  12. Single-dose versus multiple-dose ciprofloxacin plus metronidazole prophylaxis in transrectal ultrasound-guided biopsy of the prostate: a randomized controlled trial.

    Zhoobin Heidari Bateni


    Full Text Available To investigate and compare the infectious and non-infectious complications of single-dose versus multiple-dose antibiotic therapy for trans-rectal ultrasound (TRUS-guided biopsy of the prostate. Patients were enrolled in a prospective randomized study that was designed to investigate the effects of single-dose versus multiple-dose antimicrobial prophylaxis regimen mainly on asymptomatic bacteriuria, urinary tract infection (UTI without fever, fever and urinary septicemia. The single-dose group received one ciprofloxacin 500 mg tablet and two metronidazole 250 mg tablets at 2 hours before the biopsy, while the multiple-doses group received those every 12 hours from 3 days before the biopsy. One-hundred and sixty patients were evaluated in two groups and bacteriuria in urinalysis was encountered in 12 patients (15% in the single-dose group and four patients (5% in the multiple-dose group, with a significant difference (P=0.035. UTI without fever occurred in six patients (7.5% in the single-dose group and one patient (1.25% in the multiple-dose group, with no significant difference (borderline P=0.053. After biopsy, three patients (3.75% returned with fever due to UTI and bacteremia in the single-dose group and none in the multiple-dose group, but with no significant difference (P=0.08. Regarding non-infectious complications, there were no significant differences between the two groups. Using prophylactic antibiotics for prostate biopsy in multiple doses, and at least 3 days before the procedure significantly reduces the rate of bacteriuria compared with a single-dose regimen.

  13. Two Week Oral Dose Range-Finding Toxicity Study of WR269410 in Rats


    male receiving 30.0 mg/kg/day, and in one high dose (18.0 mg/kg/day) female. Cyanosis characterized as blue feet was seen in treatment group 3...8.5 Change Test Article Vehicle Ŕ.5% Na+ carboxymethylcellulose /0.3% Tween 80" to ŕ% Methylcellulose/0.2% Tween 80". Reason: Better

  14. Weekly low-dose mitoxantrone plus doxorubicin as second-line chemotherapy for advanced breast cancer

    M. Bontenbal (Marijke); A.S.Th. Planting (André); C.J. Rodenburg (C.); A. Dees; J. Verweij (Jaap); C.C.M. Bartels (Carina); J. Alexieva-Figusch (Jana); W.L.J. van Putten (Wim); J.G.M. Klijn (Jan)


    textabstractWeekly low dose mitoxantrone (3 mg/m2) plus doxorubicin (8 mg/m2) was administered as second-line chemotherapy to 33 patients with advanced breast cancer. Four out of 28 evaluable patients (14%) obtained a partial response with a median duration of 34 weeks (range 18-67+ weeks), while 8




    Full Text Available Introduction: The effects of different doses of oestrogen on the endometrium of women with premature ovarian failure have been examined in this study. Materials and Methods: Four groups of women of reproductive age were studied; 1 normal fertile controls 2. patients given a standard, variable hormone replacement therapy (HRT 3. a group given a fixed daily dose of 1 mg of oestrogen and 4. a group given a fixed daily dose of 4 mg of oestrogen. Endrometrial diposises were taken at a bout 5-6 days after ovulation and tissue was prepared for light and electron microscopy. Morphometry was used to evaluate quantitatively various features of endometrial luminal epithelial cells. The volume fraction (Vv of nucleus to cell in the standard group was significantly larger than the 4 mg group. Results: The Vv of euchromatin to nucleus was larger in the controls and 4 mg group than the 1 mg subjects. The Vv of mitochondria to cell was largest in the control group. The ratio of desmosomes to surface membrane was increased (P<0.05 in the 1 mg subjects. Conclusion: These results suggest that, while standard HRT is generally a good mimic of controls, the 1 mg fixed dose delayed some membrane features and the fixed 4 mg group showed advancement in some organelle growth.


    Thorup, I.; Würtzen, G.; Carstensen, J.


    Pulegone and menthol, components of peppermint oil, were investigated in rats. The substances were administered by gavage for 28 days at 0, 20, 80, 160 mg pulegone and 0, 200, 400, 800 mg menthol/kg body wt./day, respectively. At the two highest doses, pulegone induced atonia, decreased blood...


    Thorup, I.; Würtzen, G.; Carstensen, J.


    Pulegone and menthol, components of peppermint oil, were investigated in rats. The substances were administered by gavage for 28 days at 0, 20, 80, 160 mg pulegone and 0, 200, 400, 800 mg menthol/kg body wt./day, respectively. At the two highest doses, pulegone induced atonia, decreased blood...

  18. Controlled, dose-response study of sertindole and haloperidol in the treatment of schizophrenia

    Zimbroff, DL; Kane, JM; Tamminga, CA; Daniel, DG; Mack, RJ; Wozniak, PJ; Sebree, TB; Wallin, BA; Kashkin, KB; Adan, F; Ainslie, G; Allan, E; Atri, P; Baker, R; Beitman, B; Brown, G; Canive, J; Carman, J; Dott, S; Edwards, J; Fenton, W; Freidli, J; Funderburg, L; Ereshefsky, L; Gladson, M; Hamilton, J; Haque, S; Hartford, J; Horne, R; Houck, C; Jampala, C; Labelle, A; Larson, G; Lesem, M; Liskow, B; Makela, E; Moore, N; Morphy, M; Posever, T; Risch, S; Rotrosen, J; Sheehan, D; Silverstone, P; Swann, A; Tapp, A; Thomas, M; Volavka, J; Vora, S


    Objective: This multicenter, double-blind, placebo-controlled study evaluated the efficacy and safety of three doses of sertindole (12, 20, and 24 mg/day) and haloperidol (4, 8, and 16 mg/day) in the treatment of psychotic symptoms for 497 hospitalized patients with schizophrenia. Method: The patien

  19. Monte Carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy.

    Daniel G Zhang

    Full Text Available MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF and conventional flattened 6MV photon beams were used. High dose rate (HDR brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL would be needed.

  20. Monte Carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy.

    Zhang, Daniel G; Feygelman, Vladimir; Moros, Eduardo G; Latifi, Kujtim; Zhang, Geoffrey G


    MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd)-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF) and conventional flattened 6MV photon beams were used. High dose rate (HDR) brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL) would be needed.

  1. Effect of Mg-Nb oxides addition on hydrogen sorption in MgH{sub 2}

    Rahman, M.W.; Castellero, A. [Dipartimento di Chimica IFM, NIS Centre of Excellence, Universita di Torino, Via Pietro Giuria 9, 10125 Torino (Italy); Enzo, S. [Dipartimento di Chimica, Universita di Sassari, 07100 Sassari (Italy); Livraghi, S.; Giamello, E. [Dipartimento di Chimica IFM, NIS Centre of Excellence, Universita di Torino, Via Pietro Giuria 9, 10125 Torino (Italy); Baricco, M., E-mail: [Dipartimento di Chimica IFM, NIS Centre of Excellence, Universita di Torino, Via Pietro Giuria 9, 10125 Torino (Italy)


    Highlights: > H{sub 2} sorption reactions in MgH{sub 2} with 1 mol% MgNb{sub 2}O{sub 6}, Mg{sub 4}Nb{sub 2}O{sub 9} and Mg{sub 3}Nb{sub 6}O{sub 11} have been investigated. > Ball-milled samples showed the presence of a mixture of {beta} and {gamma} allotropes of MgH{sub 2}. > The presence of Mg-Nb oxides significantly accelerates the hydrogen absorption and desorption processes. > Experimental results are discussed on the basis of thermodynamic and kinetic arguments. - Abstract: H{sub 2} absorption and desorption reactions in MgH{sub 2} promoted by ball-milling with 1 mol% MgNb{sub 2}O{sub 6}, Mg{sub 4}Nb{sub 2}O{sub 9} and Mg{sub 3}Nb{sub 6}O{sub 11} have been investigated. MgH{sub 2} was milled with the bare oxides for 12 h under a high purity Ar atmosphere. Absorption and desorption reactions in the ball-milled samples were studied by in situ X-ray diffraction (XRD) in isothermal conditions with Anton Paar XRK 900 reaction chamber. XRD patterns for absorption were recorded at 573 K under hydrogen pressure of 0.9 MPa and for desorption at 623 K in vacuum. Experimental data were analysed according to the Rietveld method. Ball-milled samples showed the presence of a mixture of {beta} and {gamma} allotropes of MgH{sub 2}, with significantly broadened diffraction peaks due to reduced crystallite size and strain, together with bare additives. The presence of Mg-Nb oxides significantly accelerates the hydrogen absorption and desorption processes. The amount of hydrogen absorbed in the presence of Mg-Nb-O phases is lower than the maximum stoichiometric capacity, because of the presence of a non-reactive MgO layer on the surface of the powders or at the grain boundaries. Experimental results are discussed on the basis of thermodynamic and kinetic arguments.

  2. Demonstration of the analgesic efficacy and dose-response of acetylsalicylic acid with pseudoephedrine.

    Schachtel, Bernard P; Voelker, Michael; Sanner, Kathleen M; Gagney, Diana; Bey, Mary; Schachtel, Emily J; Becka, Michael


    To determine acute analgesia by acetylsalicylic acid (ASA) when combined with pseudoephedrine (PSE) in patients with upper respiratory tract infection (URTI), we used the sore throat pain model to measure single-dose effects of ASA 500 mg/PSE 30 mg, ASA 1000 mg/PSE 60 mg, and acetaminophen (APAP) 1000 mg/PSE 60 mg (serving as a positive control). Under double-blind, randomized, placebo-controlled conditions, 640 adult patients with confirmed acute pharyngitis and rhinosinusitis associated with URTI rated throat pain intensity and relief at intervals over 6 hours. Efficacy was demonstrated for both doses of ASA/PSE compared with placebo for all end points, including total pain relief and summed pain intensity differences, beginning at 20 minutes on both scales (all P pseudoephedrine.

  3. High-dose desvenlafaxine in outpatients with major depressive disorder.

    Ferguson, James M; Tourian, Karen A; Rosas, Gregory R


    This study investigated the safety and efficacy of long-term treatment with high-dose desvenlafaxine (administered as desvenlafaxine succinate) in major depressive disorder (MDD). In this multicenter, open-label study, adult outpatients with MDD aged 18-75 were treated with flexible doses of desvenlafaxine (200-400 mg/d) for ≤ 1 year. Safety assessments included monitoring of treatment-emergent adverse events (TEAEs), patient discontinuations due to adverse events, electrocardiograms, vital signs, and laboratory determinations. The primary efficacy measure was mean change from baseline in the 17-item Hamilton Rating Scale for Depression [HAM-D(17)] total score. The mean daily desvenlafaxine dose range over the duration of the trial was 267-356 mg (after titration). The most frequent TEAEs in the safety population (n = 104) were nausea (52%) and headache (41%), dizziness (31%), insomnia (29%), and dry mouth (27%). All TEAEs were mild or moderate in severity. Thirty-four (33%) patients discontinued from the study because of TEAEs; nausea (12%) and dizziness (9%) were the most frequently cited reasons. The mean change in HAM-D(17) total score for the intent-to-treat population (n = 99) was -9.9 at the last on-therapy visit in the last-observation-carried-forward analysis and -14.0 at month 12 in the observed cases analysis. Conclusion High-dose desvenlafaxine (200-400 mg/d) was generally safe and effective in the long-term treatment of MDD.

  4. Dosing celecoxib in pediatric patients with juvenile rheumatoid arthritis.

    Krishnaswami, Sriram; Hutmacher, Matt M; Robbins, Jeffery L; Bello, Akintunde; West, Christine; Bloom, Bradley J


    The objective was to derive dosing recommendations for the use of celecoxib in patients with juvenile rheumatoid arthritis (JRA) using pharmacokinetic (PK) and exposure-response data. PK and efficacy data from a randomized, double-blind, 12-week study of celecoxib dosed at 3 and 6 mg/kg twice a day (bid) as an investigational suspension formulation in 152 JRA patients aged 2 to 17 years, PK data from 36 adult RA patients, and relative bioavailability data in healthy adults comparing suspension or capsule sprinkles with the commercial capsule were analyzed. Typical oral clearance (L/h) values were 40% and 24% lower in patients weighing 10 and 25 kg, respectively, compared with a 70-kg patient. Longitudinal, logistic pharmacodynamic models incorporating linear effects of dose/area under the plasma concentration-time curve (AUC) over 0 to 12 hours (AUC(0-12)) suggested that the percentage of responders increased with celecoxib exposure. Systemic exposures (AUC) were similar for the suspension, capsule sprinkles, and intact capsule. Administration of a 50-mg bid capsule (or sprinkles) for patients weighing 10 to 25 kg and 100 mg bid for patients >25 kg was predicted to yield similar exposures and response rates as those observed in the JRA trial. Doses and dosage forms not studied in the JRA trial were approved based on the results of this analysis.

  5. Dose-response study of spinal hyperbaric ropivacaine for cesarean section

    CHEN Xin-zhong; CHEN Hong; LOU Ai-fei; L(U) Chang-cheng


    Background: Spinal hyperbaric ropivacaine may produce more predictable and reliable anesthesia than plain ropivacaine for cesarean section. The dose-response relation for spinal hyperbaric ropivacaine is undetermined. This double-blind,randomized, dose-response study determined the ED50 (50% effective dose) and ED95 (95% effective dose) of spinal hyperbaric ropivacaine for cesarean section anesthesia. Methods: Sixty parturients undergoing elective cesarean section delivery with use of combined spinal-epidural anesthesia were enrolled in this study. An epidural catheter was placed at the L1~L2 vertebral interspace,then lumbar puncture was performed at the L3~L4 vertebral interspace, and parturients were randomized to receive spinal hyperbaric ropivacaine in doses of 10.5 mg, 12 mg, 13.5 mg, or 15 mg in equal volumes of 3 ml. Sensory levels (pinprick) were assessed every 2.5 min until a T7 level was achieved and motor changes were assessed by modified Bromage Score. A dose was considered effective ifan upper sensory level to pin prick ofT7 or above was achieved and no intraoperative epidural supplement was required. ED50 and ED95 were determined with use of a logistic regression model. Results: ED50 (95% confidence interval)of spinal hyperbaric ropivacaine was determined to be 10.37 (5.23~11.59) mg and ED95 (95% confidence interval) to be 15.39(13.81~23.59) mg. The maximum sensory block levels and the duration of motor block and the rate ofhypotension, but not onset of anesthesia, were significantly related to the ropivacaine dose. Conclusion: The ED50 and ED95 of spinal hyperbaric ropivacaine for cesarean delivery under the conditions of this study were 10.37 mg and 15.39 mg, respectively. Ropivacaine is suitable for spinal anesthesia in cesarean delivery.

  6. Preparation of an additive-free sample with a MgH2 phase by planetary ball milling of Mg with10 wt% MgH2

    Hong, Seong-Hyeon; Song, Myoung Youp


    In order to prepare an additive-free sample with a MgH2 phase, 90 wt% Mg+10 wt% MgH2 (named Mg-10MgH2) was milled under hydrogen atmosphere in a planetary ball mill for different durations (2 h, 5 h, and 10 h). The hydrogen absorption and release properties of the prepared samples were investigated and compared with those of purchased pure MgH2 samples. Mg-10MgH2 milled for 5 h had the largest quantity of hydrogen released at 648 K for 100 min of 5.96 wt%. Mg-10MgH2 milled for 5 h released 0.11 wt% H for 10 min, 4.85 wt% H for 30 min, and 5.83 wt% H for 60 min at 648 K at the first cycle. Mg-10MgH2 milled for 5 h absorbed 5.39 wt% H for 5 min and 5.92 wt% H for 60 min at 648 K at the second cycle. Dehydriding curves were also obtained at the first cycle of Mg-10MgH2 samples milled for 5 h using Mg powder with or without sieving (200 mesh). The dehydriding curve at 648 K of a Mg-10MgH2 sample milled for 5 h in the planetary ball mill was compared with that of the sample milled for 24 h in a horizontal ball mill.


    Yuen, Kevin C J; Williams, Gavin; Kushner, Harvey; Nguyen, Dat


    To examine the relationship between dose, clinical response (based on independent evaluation of metabolic, physical, neurologic, and social assessments), and safety of mifepristone treatment in patients with endogenous Cushing syndrome (CS). This post hoc analysis included 40 clinical responders and 50 participants who received a dose of mifepristone (safety population) in the 24-week phase 3 SEISMIC (Study of the Efficacy and Safety of Mifepristone in the Treatment of Endogenous Cushing Syndrome) trial. The dose of mifepristone at the initial clinical response was analyzed, and the rate of serious adverse events (SAEs) and AEs reported in ≥20% of patients were compared to average mifepristone doses over time. Among the clinical responders, 85% and 35% had their initial clinical responses at mifepristone doses ≥600 and ≥900 mg/day, respectively. The SAE rate did not increase with a higher dose over time. The AE rates for fatigue, headache, nausea, and peripheral edema declined significantly at weeks 16 to 24 (all P<.05 vs. weeks 1-2) as the study progressed and mifepristone doses were increased. Other AEs such as hypokalemia, vomiting, and decreased appetite did not significantly increase from weeks 1 to 2 as mifepristone doses were increased. The majority of clinical responders in the SEISMIC trial received mifepristone doses ≥600 mg/day suggesting that higher doses were required to achieve optimal clinical benefit in patients with endogenous CS. Notably, mifepristone dose escalations did not result in any significant or concordant increase in the rates of SAEs and common AEs.

  8. Pharmacokinetics of high-dose intravenous melatonin in humans

    Andersen, Lars P H; Werner, Mads U; Rosenkilde, Mette Marie


    This crossover study investigated the pharmacokinetics and adverse effects of high-dose intravenous melatonin. Volunteers participated in 3 identical study sessions, receiving an intravenous bolus of 10 mg melatonin, 100 mg melatonin, and placebo. Blood samples were collected at baseline and 0, 60......, 120, 180, 240, 300, 360, and 420 minutes after the bolus. Quantitative determination of plasma melatonin concentrations was performed using a radioimmunoassay technique. Pharmacokinetic parameters were estimated by a compartmental pharmacokinetic analysis. Adverse effects included assessments...... of sedation and registration of other symptoms. Sedation, evaluated as simple reaction times, was measured at baseline and 120, 180, 300, and 420 minutes after the bolus. Twelve male volunteers completed the study. Median (IQR) Cmax after the bolus injections of 10 mg and 100 mg of melatonin were 221...

  9. Pharmacokinetics and pharmacodynamics of single and multiple doses of prasugrel in healthy native Chinese subjects

    Yi-min CUI; Zi-ning WANG; Xiao-wen CHEN; Hui-lin ZHANG; Xia ZHAO; Ying ZHOU


    Aim:To characterize the pharmacokinetics (PKs),pharmacodynamics (PDs),and tolerability of different dose regimens of prasugrel in healthy Chinese subjects.Methods:This was a single-centered,open-label,parallel-design study.Subjects received a single loading dose (LD) of prasugrel followed by once-daily maintenance dose (MD) for 10 d.They were enrolled into 3 groups:60 mg LD/10 mg MD; 30 mg LD/7.5 mg MD; 30 mg LD/5 mg MD.Blood samples were collected after the first and last dose.The serum concentration of the active metabolite of prasugrel was determined using a LC/MS/MS method.Platelet aggregation was assessed using the VerifyNow-P2Y12 assay.Results:Thirty-six healthy native Chinese subjects (19 males) aged 18-45 were enrolled; mean age and body weight were similar across the treatment groups (n=12 for each).The metabolite AUC0-4 and Cmax increased dose-proportionally across the dose range of 5 mgto 60 mg.The median Tmax was 0.5 h in all groups.The PD parameters,indicated bythe inhibition of ADp-induced platelet aggregation,were met more rapidly in the 60 mg group than the 30 mg group after the LD (94%-98%).This high degree of inhibition of platelet aggregation was maintained following the 10 mg MD (87%-90%) and was lower in the 7.5 mg and 5 mg MD groups (79%-83% and 64%-67%,respectively).Prasugrel was well tolerated in healthy Chinese subjects for single doses up to 60 mg and a MD of 10 mg for 10 d.Conclusion:The PKs and PDs of the active metabolite of prasugrel were similar to those in Chinese subjects reported by a previous bridging study,which demonstrated that the exposure to the active metabolite in Chinese subjects was higher than in Caucasians.

  10. PABLM. Accumulated Environment Radiation Dose

    Napier, B.A.; Kennedy, W.E.Jr.; Soldat, J.K. [Pacific Northwest Lab., Richland, WA (United States)


    PABLM calculates internal radiation doses to man from radionuclides in food products and external radiation doses from radionuclides in the environment. Radiation doses from radionuclides in the environment may be calculated from deposition on the soil or plants during an atmospheric or liquid release, or from exposure to residual radionuclides after the releases have ended. Radioactive decay is considered during the release, after deposition, and during holdup of food after harvest. The radiation dose models consider exposure to radionuclides deposited on the ground or crops from contaminated air or irrigation water, radionuclides in contaminated drinking water, aquatic foods raised in contaminated water, and radionuclides in bodies of water and sediments where people might fish, boat, or swim. For vegetation, the radiation dose model considers both direct deposition and uptake through roots. Doses may be calculated for either a maximum-exposed individual or for a population group. The program is designed to calculate accumulated radiation doses from the chronic ingestion of food products that contain radionuclides and doses from the external exposure to radionuclides in the environment. A first-year committed dose is calculated as well as an integrated dose for a selected number of years.

  11. Safety and pharmacokinetics of ciprofloxacin dry powder for inhalation in cystic fibrosis: a phase I, randomized, single-dose, dose-escalation study.

    Stass, Heino; Delesen, Heinz; Nagelschmitz, Johannes; Staab, Doris


    Reliable, reproducible deposition to the lung is a major prerequisite for the clinical use of inhaled drugs. Ciprofloxacin dry powder for inhalation (ciprofloxacin DPI; Bayer HealthCare AG, Leverkusen, Germany) is an antibacterial therapy in development using Novartis' PulmoSphere™ technology (Novartis Pharma AG, Basel, Switzerland) for the targeted delivery of ciprofloxacin to the lung via a T-326 inhaler. This randomized, single-blind, placebo-controlled, dose-escalation study investigated the safety, tolerability, and pharmacokinetics of single-dose ciprofloxacin DPI (32.5 mg [n=6] or 65 mg [n=6]) and matching placebo (n=4) in adult patients with cystic fibrosis and stable pulmonary status (forced expiratory volume in 1 sec ≥30%) who were colonized with Pseudomonas aeruginosa. Peak sputum concentrations of 34.9 mg/L (range 2.03-229) and 376 mg/L (8.95-1283) for ciprofloxacin 32.5 mg and 65 mg, respectively, indicated targeting of ciprofloxacin DPI to the lung. This contrasted with low systemic exposure (peak plasma concentrations: 0.0790 mg/L [32.5 mg] and 0.182 mg/L [65 mg]). Single-dose ciprofloxacin DPI 32.5 mg or 65 mg was well tolerated with similar incidences of adverse events across all groups. No deaths, discontinuations, treatment-related serious adverse events, or clinically relevant changes in laboratory parameters, vital signs, or lung function tests were reported. Lung targeting with high pulmonary concentrations of ciprofloxacin combined with low systemic exposure was confirmed. These results support further study of ciprofloxacin DPI as a potentially more convenient alternative to nebulized antibiotic solutions for managing chronic lung infections.

  12. Superiority of fesoterodine 8 mg vs 4 mg in reducing urgency urinary incontinence episodes in patients with overactive bladder: results of the randomised, double-blind, placebo-controlled EIGHT trial.

    Chapple, Christopher; Schneider, Tim; Haab, François; Sun, Franklin; Whelan, Laurence; Scholfield, David; Dragon, Erika; Mangan, Erin


    .4%; fesoterodine 4-mg group, 12.9%; fesoterodine 8-mg group, 26.1%); most cases were mild or moderate in all treatment groups. Rates of serious AEs and discontinuations due to AEs were low in all groups. In a 12-week, prospectively designed, superiority trial, fesoterodine 8 mg showed statistically significantly superior efficacy vs fesoterodine 4 mg and placebo, as measured by reductions in UUI episodes and other diary variables, diary-dry dry rate, and improvements in measures of symptom bother, HRQL, and other PROs; clear evidence of dose-dependent efficacy is unique to fesoterodine among antimuscarinics and other oral agents for the treatment of OAB. Fesoterodine 4 mg was significantly more effective than placebo on all outcomes except for improvements in UPS scores. These data support the benefit of having two doses of fesoterodine in clinical practice, with the recommended starting dose of 4 mg for all patients and the fesoterodine 8-mg dose available for patients who require a higher dose to achieve optimal symptom relief. © 2014 The Authors. BJU International © 2014 BJU International.

  13. Destabilization of Mg Hydride by Self-Organized Nanoclusters in the Immiscible Mg-Ti System

    Asano, Kohta; Westerwaal, Ruud J.; Anastasopol, Anca; Mooij, Lennard P A; Boelsma, Christiaan; Ngene, Peter; Schreuders, Herman; Eijt, Stephan W H; Dam, Bernard


    Mg is an attractive hydrogen storage material not only because of its high gravimetric and volumetric hydrogen capacities but also because of it low material costs. However, the hydride of MgH2 is too stable to release hydrogen under moderate conditions. We demonstrate that the formation of

  14. Energy Bands and Fermi Surface for beta-MgMh and beta-MgTl

    Skriver, Hans Lomholt


    The energy bands of ordered β′-MgHg and β′-MgTl have been calculated by the relativistic linear-muffintin-orbital method. We show how the gross features of the energy bands may be estimated from Wigner-Seitz rules. The densities of states are calculated and the heat capacities derived. The Fermi...

  15. Destabilization of Mg Hydride by Self-Organized Nanoclusters in the Immiscible Mg-Ti System

    Asano, Kohta; Westerwaal, Ruud J.; Anastasopol, Anca; Mooij, Lennard P A; Boelsma, Christiaan; Ngene, Peter; Schreuders, Herman; Eijt, Stephan W H; Dam, Bernard


    Mg is an attractive hydrogen storage material not only because of its high gravimetric and volumetric hydrogen capacities but also because of it low material costs. However, the hydride of MgH2 is too stable to release hydrogen under moderate conditions. We demonstrate that the formation of nanomete

  16. Deferasirox at therapeutic doses is associated with dose-dependent hypercalciuria.

    Wong, Phillip; Polkinghorne, Kevan; Kerr, Peter G; Doery, James C G; Gillespie, Matthew T; Larmour, I; Fuller, Peter J; Bowden, Donald K; Milat, Frances


    Deferasirox is an oral iron chelator used widely in the treatment of thalassemia major and other transfusion-dependent hemoglobinopathies. Whilst initial long-term studies established the renal safety of deferasirox, there are now increasing reports of hypercalciuria and renal tubular dysfunction. In addition, urolithiasis with rapid loss of bone density in patients with β thalassemia major has been reported. We conducted a cross-sectional cohort study enrolling 152 adult patients comprising of β thalassemia major (81.5%), sickle cell disease (8%), thalassemia intermedia (2%), HbH disease (6.5%) and E/β thalassemia (2%). Cases were matched with normal control subjects on age, gender and serum creatinine. Iron chelator use was documented and urine calcium to creatinine ratios measured. At the time of analysis, 88.8% of patients were receiving deferasirox and 11.2% were on deferoxamine. Hypercalciuria was present in 91.9% of subjects on deferasirox in a positive dose-dependent relationship. This was not seen with subjects receiving deferoxamine. At a mean dose of 30.2±8.8mg/kg/day, deferasirox was associated with an almost 4 fold increase in urine calcium to creatinine ratio (UCa/Cr). Hypercalciuria was present at therapeutic doses of deferasirox in a dose-dependent manner and warrants further investigation and vigilance for osteoporosis, urolithiasis and other markers of renal dysfunction.

  17. Manipulation of Mg(2+)-Ca(2+) Switch on the Development of Bone Mimetic Hydroxyapatite.

    Andrés, Nancy C; D'Elía, Noelia L; Ruso, Juan M; Campelo, Adrián E; Massheimer, Virginia L; Messina, Paula V


    Ionic substitution can affect essential physicochemical properties leading to a specific biological behavior upon implantation. Therefore, it has been proposed as a tool to increase the biological efficiency of calcium phosphate based materials. In the following study, we have evaluated the contribution of an important cation in nature, Mg(2+), into the structure of previously studied biocompatible and biodegradable hydroxyapatite (HA) nanorods and its subsequent effect on its chemical, morphology, and bone mimetic articulation. Mg(2+)-substituted HA samples were synthesized by an aqueous wet-chemical precipitation method, followed by an hydrothermal treatment involving a Mg(2+) precursor that partially replace Ca(2+) ions into HA crystal lattice; Mg(2+) concentrations were modulated to obtain a nominal composition similar to that exists in calcified tissues. Hydrothermally synthesized Mg(2+)-substituted HA nanoparticles were characterized by X-ray powder diffraction, FT-NIR and EDX spectroscopies, field emission scanning and high resolution transmission electron microscopies (FE-SEM, H-TEM). Molecular modeling combining ab initio methods and power diffraction data were also performed. Results showed that Mg(2+)-substitution promoted the formation of calcium deficient HA (cdHA) where Mg(2+) replacement is energetically favored at Ca(1) position in a limited and specific amount directing the additional Mg(2+) toward the surface of the crystal. The control of Mg(2+) incorporation into HA nanorods gave rise to a tailored crystallinity degree, cell parameters, morphology, surface hydration, solubility, and degradation properties in a dose-replacement dependent manner. The obtained materials show qualities that conjugated together to drive an optimal in vitro cellular viability, spreading, and proliferation confirming their biocompatibility. In addition, an improved adhesion of osteoblast was evidenced after Mg(2+)-Ca(2+) substitution.

  18. TL and OSL studies of carbon doped magnesium aluminate (MgAl2O4:C)

    Raj, Sanu S.; Mishra, D. R.; Soni, Anuj; Grover, V.; Polymeris, G. S.; Muthe, K. P.; Jha, S. K.; Tyagi, A. K.


    The MgAl2O4:C has been synthesized by using two different methods by electron gun and vacuum assisted melting of MgAl2O4 in presence of graphite. The MgAl2O4:C phosphor thus developed by these two different methods have similar types of the TL/OSL defects with multiple overlapping TL glow peaks from 100 °C to 400 °C. The Computerized Curve De-convolution Analysis (CCDA) has been used to measure TL parameters such as thermal trap depth, frequency factor and order of kinetic associated with charge transfer process in TL phenomenon. The investigated TL/OSL results show that these two methods of incorporating carbon in MgAl2O4 have generated closely resemble the defects of similar types in MgAl2O4:C lattice. However, the MgAl2O4:C synthesized by electron gun shows relatively larger concentration of the TL/OSL defects as compared to MgAl2O4:C synthesized using vacuum assisted melting method. The photo-ionization cross-section (PIC) associated with fastest OSL component of MgAl2O4: C is found to be ∼ 0.5 times than that of fastest OSL component of commercially available dosimetric grade α-Al2O3:C. The MgAl2O4:C thus developed shows good dynamic OSL dose linearity from few mGy to 1 Gy. This work reveals that MgAl2O4:C could be developed as potential tissue equivalent OSL / TL material.

  19. Prevention of Streptozotocin-Induced Diabetic Nephropathy by MG132: Possible Roles of Nrf2 and IκB

    Wang, Yangwei; Tan, Yi; Miao, Lining


    Our previous study showed that proteasomal inhibitor MG132 can prevent diabetic nephropathy (DN) along with upregulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). The present study was to investigate whether MG132 can prevent DN in wild-type and Nrf2-KO mice. Type 1 diabetes was induced in wild-type and Nrf2-KO mice by multiple low doses of streptozotocin. Two weeks after streptozotocin injection, both wild-type and Nrf2-KO mice were randomly divided into four groups: control, MG132, DM, and DM/MG132. MG132 (10 μg/kg/day) or vehicle was administered intraperitoneally for 4 months. Renal function, morphology, and biochemical changes were measured after 4-month treatment with MG132. MG132 treatment suppressed proteasomal activity in the two genotypes. In wild-type mice, MG132 attenuated diabetes-induced renal dysfunction, fibrosis, inflammation, and oxidative damage along with increased Nrf2 and IκB expression. Deletion of Nrf2 gene resulted in a partial, but significant attenuation of MG132 renal protection in Nrf2-KO mice compared with wild-type mice. MG132-increased IκB expression was not different between wild-type and Nrf2-KO mice. This work indicates that MG132 inhibits diabetes-increased proteasomal activity, resulting in Nrf2 and IκB upregulation and renal protection, which could be used as a strategy to prevent diabetic nephropathy. PMID:28373900

  20. Dose-dependent elimination of 8-methoxypsoralen in the mouse

    Cheney, P.; Pacula, C.M.; Gerber, N.; Mays, D.C.


    8-Methoxypsoralen (8-MOP), a photoactive linear furocoumarin, is effective in the treatment of several diseases, including psoriasis, mycosis fungoides and T-cell leukemia. Recently, a specific extraction procedure for /sup 14/C-8-MOP showed that the elimination of 8-MOP in the rat was dose-dependent. Similar pharmacokinetic studies were undertaken in mice. Purity of /sup 14/C-8-MOP, verified by a four-tube countercurrent distribution using hexane (8 ml) and pH 7.4 phosphate buffer (0.1 M 15 ml) as described by Bush, was >98% and distributed with a partition coefficient of 3.86. Male CD-1 mice were each given an i.p. dose of 10 or 50 mg/kg of /sup 14/C-8-MOP (3.4 sacrificed at timed intervals, homogenized in 150 ml of 0.1 M phosphate buffer (pH 7.4) and a portion (0.8 ml) of the homogenate used to quantify 8-MOP as described above. The elimination half-life measured in the first 45 min was 7.4 min at 10 mg/kg and 95 min at 50 mg/kg. A similar half-life of 9.2 min was measured in mice given an i.v. dose 10 mg/kg of 8-MOP. Explanations of dose-dependent elimination include enzyme saturation, product inhibition or both. Between 58-80% of the administered radioactivity was recovered in the urine within 24 hr. Nine peaks of radioactivity were observed in the urine by HPLC, two of which coeluted with 5,8-dihydroxypsoralen and 6-(7-hydroxy-8-methoxycoumaryl)-acetic acid.

  1. Modification effect of lanthanum on primary phase Mg2Si in Mg-Si alloys

    WANG Liping; GUO Erjun; MA Baoxia


    The modifying effect of La addition on primary phase Mg2Si in Mg-5Si alloys was investigated. The results showed that a proper amount of La could effectively modify the primary phase Mg2Si. Based on the present experiment, the optimal modification effect was obtained with an addition of about 0.5 wt.% La. The size of the primary phase Mg2Si was considerably reduced to 25 μm or less and the morphology was modified from a coarse dendritic shape to a polyhedral shape. However, when the addition of La increased to 0.8 wt.% or higher, the primary Mg2Si grew into a coarse dendritic morphology again. Moreover, it was found that some LaSi2 compounds were formed during solidification and the amount of the compounds appeared to increase gradually with increasing La content.

  2. Microstructure and hardness of Mg-based composites reinforced with Mg2Si particles

    Mustafa Aydin; Cem Ozgür; Osman San


    Magnesium powders were mechanically alloyed with SiO2 powder particles having different particle sizes using high-energy ball milling techniques under Ar atmosphere for 1 h. The powders were consolidated with cold pressing under 560 Mpa. They were then sintered at 550℃ for 45 min under Ar atmosphere. The composites obtained on the Mg-SiO2 system were investigated using the Archimedes principle, a differential scanning calorimeter, X-ray diffraction, optic microscopy, and scanning electron microscopy. For the mechanically alloyed powders, the solid-state reaction of the synthesis of Mg2Si and MgO progressed further during sintering of the materials. The results showed that the strengthening mechanisms were dependent on dispersion hardening of fine Mg2Si and MgO particulates dispersed homogeneously in the matrix.

  3. Growth of MgO on multi-layered graphene and Mg in PVA matrix

    Marka, Sandeep K.; Mohiddon, Md. Ahamad; Prasad, Muvva D.; Srikanth, Vadali V. S. S.


    An easy and low temperature in-situ growth of MgO micro-rods on multi-layered graphene (MLG) in poly vinyl alcohol (PVA) matrix is elucidated. MLG decked with nanosized fragments of MgO and PVA are used as the starting materials to form MgO micro-rods (width = ∼1 μm and length = ∼4 μm) and MLG filled PVA composite film. Simple solution mixing, spin coating and simple drying processes are used to obtain the PVA composite. The growth mechanism of MgO micro-rods and the role of PVA in the growth of MgO micro-rods are explained on the basis of the observed morphological, structural and phase characteristics and a further controlled synthesis experiment, respectively.

  4. Pharmacokinetics of terbinafine after single oral dose administration in red-tailed hawks (Buteo jamaicensis).

    Bechert, Ursula; Christensen, J Mark; Poppenga, Robert; Fahmy, Sahar A; Redig, Patrick


    To determine pharmacokinetic parameters of orally administered terbinafine hydrochloride for potential treatment of aspergillosis in raptors, 10 adult red-tailed hawks (Buteo jamaicensis) were used in single dose trials by using 15, 30, and 60 mg/kg doses with a 2-week washout period between trials. After administration of 15 mg/kg terbinafine, mean (+/- SD) plasma concentration peaked in approximately 5 hours at 0.3 +/- 0.24 microg/mL, whereas a 30 mg/kg dose resulted in peak mean (+/- SD) plasma concentration of 1.2 +/- 0.40 microg/mL in 3 hours and a 60 mg/kg dose resulted in mean (+/- SD) concentration of 2.0 +/- 0.75 microg/mL in 5 hours. The volume of distribution decreased with increasing doses, averaging 76.8 +/- 38.06 mL/kg for the 15 mg/kg dose and falling to 55.2 +/- 17.4 mL/kg for the 30 mg/kg dose. This suggests that terbinafine accumulated in deep tissues, limiting further distribution at higher doses. The harmonic mean (+/- SD) half-life was biphasic, with initial values of 14.7 +/- 6.67 hours, 17.5 +/- 8.7 hours, and 13.3 +/- 5.03 hours for 15, 30, and 60 mg/kg doses, respectively. A rapid first-elimination phase was followed by a slower second phase, and final elimination was estimated to be 161 +/- 78.2 and 147 +/- 65.6 hours for 15 and 30 mg/kg doses, respectively. Linearity was demonstrated for the area under the curve but not for peak plasma concentrations for the 3 doses used. Calculations based on pharmacokinetic parameter values indicated that a dosage of 22 mg/kg terbinafine q24h would result in steady-state trough plasma concentrations above the minimum inhibitory concentration of terbinafine (0.8-1.6 microg/mL). This dosage is recommended as a potential treatment option for aspergillosis in raptors. However, additional research is required to determine both treatment efficacy and safety.

  5. Dose dense (CEOP-14) vs dose dense and rituximab (CEOP-14 +R) in high-risk diffuse large cell lymphoma.

    Avilés, Agustin; Nambo, María J; Neri, Natividad; Cleto, Sergio; Castañeda, Claudia; Huerta-Guzmàn, Judith; Murillo, Edgar; Contreras, Margarita; Talavera, Alejandra; González, Martha


    To assess efficacy and toxicity of rituximab and dose chemotherapy in high-risk diffuse large cell lymphoma, we conducted a controlled clinical trial to assess efficacy and toxicity of a dose-dense regimen CEOP- 14 (cyclophosphamide, epirubicin, vincristine, and prednisone every 14 d) compared to CEOP-14 plus rituximab. One hundred and ninety-six patients were randomized to received CEOP-rituximab (cyclophosphamide 1500 mg/m2, epirubicin 120 mg/m2, vincristine, and prednisone at standard dose and rituximab at 375 mg/m2) compared with the same chemotherapy administered every 14 d (CEOP-14). In an intent-to-treat analysis all patients were available for efficacy and toxicity. Complete response in CEOP-14 was observed in 73 cases (74%) and in 75 patients (76%) in the CEOP-R regimen (76%) (p = 0.8). With a median follow-up of 53.4 mo, median has not been reached in time to tumor-progression (TTP) and overall survival (OS). Actuarial curves at 5 yr showed that TTP and OS in patients treated with CEOP-R were 74% and 67%, respectively, that were not statistical different when compared to CEOP-14, 72% and 65%, respectively (p = 0.8). Acute toxicity was mild and well tolerated. The use of a dense-dose regimen is useful and well tolerated in patients with very high risk diffuse large cell lymphoma. The addition of rituximab did not improve outcome in these setting of patients.

  6. Study and characterization of dosimeter LiF:Mg,Cu,P for using in aeronautical dosimetry; Estudo e caracterizacao do dosimetro de LiF:Mg,Cu,P para utilizacao em dosimetria aeronautica

    Flavia, Hanna, E-mail: [Universidade Paulista (UNIP), Sao Jose dos Campos, SP (Brazil); Federico, Claudio; Lelis, Odair; Pereira, Heloisa; Pereira, Marlon, E-mail: [Instituto de Estudos Avancados (EFA-A/IEAV), Sao Jose dos Campos, SP (Brazil). Div. de Fisica Aplicada


    The effects of cosmic ionizing radiation incidents in aircraft components and crews has been a source of concern and motivated increasingly studies and improvements in the area. The low dose rates involved in this radiation field in aircraft flight altitudes imply Dosimetric necessity of using materials with high efficiency of detection, to enable studies lower cumulative doses resulting in shorter routes or lower altitude. The choice of thermoluminescent dosimeters LiF: Mg, Cu, P was done by having a detection efficiency of about fifteen times higher than its predecessor (LiF: Mg, Ti), and therefore, applied in very low doses dosimetry, and environmental dosimetry . The implementation of the use of pair dosimetric TLD-600H and 700H-TLD will serve as support for testing and studies on the effects of low doses of cosmic radiation in environmental dosimetry applied in the aviation environment in the usual flight altitudes. In this paper are presented the results of development of a methodology for dosimetry low doses of gamma radiation and neutrons using the pair dosimetric TLD-600H and 700H-TLD. The results demonstrate a sensitivity of dosimeters well above the dosimeters LiF: Mg, Ti confirming its suitability for dosimetry of low doses.

  7. Neutron dose estimation in a zero power nuclear reactor

    Triviño, S.; Vedelago, J.; Cantargi, F.; Keil, W.; Figueroa, R.; Mattea, F.; Chautemps, A.; Santibañez, M.; Valente, M.


    This work presents the characterization and contribution of neutron and gamma components to the absorbed dose in a zero power nuclear reactor. A dosimetric method based on Fricke gel was implemented to evaluate the separation between dose components in the mixed field. The validation of this proposed method was performed by means of direct measurements of neutron flux in different positions using Au and Mg-Ni activation foils. Monte Carlo simulations were conversely performed using the MCNP main code with a dedicated subroutine to incorporate the exact complete geometry of the nuclear reactor facility. Once nuclear fuel elements were defined, the simulations computed the different contributions to the absorbed dose in specific positions inside the core. Thermal/epithermal contributions of absorbed dose were assessed by means of Fricke gel dosimetry using different isotopic compositions aimed at modifying the sensitivity of the dosimeter for specific dose components. Clear distinctions between gamma and neutron capture dose were obtained. Both Monte Carlo simulations and experimental results provided reliable estimations about neutron flux rate as well as dose rate during the reactor operation. Simulations and experimental results are in good agreement in every positions measured and simulated in the core.

  8. Calcium kinetics with microgram stable isotope doses and saliva sampling

    Smith, S. M.; Wastney, M. E.; Nyquist, L. E.; Shih, C. Y.; Wiesmann, H.; Nillen, J. L.; Lane, H. W.


    Studies of calcium kinetics require administration of tracer doses of calcium and subsequent repeated sampling of biological fluids. This study was designed to develop techniques that would allow estimation of calcium kinetics by using small (micrograms) doses of isotopes instead of the more common large (mg) doses to minimize tracer perturbation of the system and reduce cost, and to explore the use of saliva sampling as an alternative to blood sampling. Subjects received an oral dose (133 micrograms) of 43Ca and an i.v. dose (7.7 micrograms) of 46Ca. Isotopic enrichment in blood, urine, saliva and feces was well above thermal ionization mass spectrometry measurement precision up to 170 h after dosing. Fractional calcium absorptions determined from isotopic ratios in blood, urine and saliva were similar. Compartmental modeling revealed that kinetic parameters determined from serum or saliva data were similar, decreasing the necessity for blood samples. It is concluded from these results that calcium kinetics can be assessed with micrograms doses of stable isotopes, thereby reducing tracer costs and with saliva samples, thereby reducing the amount of blood needed.

  9. Oral desensitization to milk: how to choose the starting dose!

    Mori, Francesca; Pucci, Neri; Rossi, Maria Elisabetta; de Martino, Maurizio; Azzari, Chiara; Novembre, Elio


    Mori F, Pucci N, Rossi ME, de Martino M, Azzari C, Novembre E. Oral desensitization to milk: how to choose the starting dose! Pediatr Allergy Immunol 2010: 21: e450–e453. © 2009 John Wiley & Sons A/S A renewed interest in oral desensitization as treatment for food allergy has been observed in the last few years. We studied a novel method based on the end point skin prick test procedure to establish the starting dose for oral desensitization in a group of 30 children higly allergic to milk. The results (in terms of reactions to the first dose administered) were compared with a group of 20 children allergic to milk as well. Such control group started to swallow the same dose of 0.015 mg/ml of milk. None reacted to the first dose when administered according to the end point skin prick test. On the other side, ten out of 20 children (50%) from the control group showed mild allergic reactions to the first dose of milk. In conclusion the end point skin prick test procedure results safe and easy to be performed in each single child in order to find out the starting dose for oral desensitization to milk, also by taking into account the individual variability. PMID:19624618

  10. Sodium fusidate ameliorates the course of diabetes induced in mice by multiple low doses of streptozotocin

    Nicoletti, F; Di Marco, R; Conget, I


    development of hyperglycaemia acutely induced by one single and high (160 mg/kg) dose of SZ, which is a model of DM primarily due to the toxic action of SZ on the beta cells and does not involve immunopathogenetic mechanisms. On day 14 after SZ, fusidin markedly altered the circulating cytokine profile......We studied the effects of the immunosuppressant sodium fusidate (fusidin) on murine immunoinflammatory diabetes mellitus (DM) induced by multiple low doses of streptozotocin (SZ). Fusidin was given by gavage to three strains of mice (C57KsJ, C57BL/6, CD1) at doses 10 or 100 mg/kg body weight every...

  11. Up-dosing with bilastine results in improved effectiveness in cold contact urticaria

    Krause, K; Spohr, A.; Zuberbier, T.; Church, M. K.; Maurer, M.


    Background Cold contact urticaria (CCU) is characterized by itchy wheal and flare responses due to the release of histamine and other pro-inflammatory mediators after exposure to cold. The treatment of choice is nonsedating antihistamines, dosages of which may be increased up to fourfold if standard doses are ineffective. Here, we assess the effects of a standard 20 mg dose and up-dosing to 40 and 80 mg of bilastine in reducing the symptoms of CCU and inflammatory mediator release following c...

  12. Transfer of Low Dose Aspirin Into Human Milk.

    Datta, Palika; Rewers-Felkins, Kathleen; Kallem, Raja Reddy; Baker, Teresa; Hale, Thomas W


    Aspirin has antipyretic and anti-inflammatory properties and is frequently used by pregnant and lactating women. However, its transfer in human milk when administered at low dose has not been reported. Research aim: This study aimed to evaluate the transfer of acetylsalicylic acid and its metabolite, salicylic acid, into human milk following the use of low dose aspirin. In this study, milk samples were collected at 0, 1, 2, 4, 8, 12, and 24 hours from seven breastfeeding women after a steady-state daily dose of 81 mg of aspirin. Milk levels of acetylsalicylic acid and salicylic acid were determined by liquid chromatography-tandem mass spectrometry. Acetylsalicylic acid levels were below the limit of quantification (0.61 ng/ml) in all the milk samples, whereas salicylic acid was detected at very low concentrations. The average concentration of salicylic acid observed was 24 ng/ml and the estimated relative infant dose was 0.4%. Acetylsalicylic acid transfer into milk is so low that it is undetectable even by highly sophisticated methodology. Salicylic acid does appear in the human milk in comparatively low amounts, which are probably subclinical in infants. Thus, the daily use of an 81-mg dose of aspirin should be considered safe during lactation.

  13. Dose from slow negative muons.

    Siiskonen, T


    Conversion coefficients from fluence to ambient dose equivalent, from fluence to maximum dose equivalent and quality factors for slow negative muons are examined in detail. Negative muons, when stopped, produce energetic photons, electrons and a variety of high-LET particles. Contribution from each particle type to the dose equivalent is calculated. The results show that for the high-LET particles the details of energy spectra and decay yields are important for accurate dose estimates. For slow negative muons the ambient dose equivalent does not always yield a conservative estimate for the protection quantities. Especially, the skin equivalent dose is strongly underestimated if the radiation-weighting factor of unity for slow muons is used. Comparisons to earlier studies are presented.

  14. Long-term retention on treatment with lumiracoxib 100 mg once or twice daily compared with celecoxib 200 mg once daily: A randomised controlled trial in patients with osteoarthritis

    Notter Marianne


    Full Text Available Abstract Background The efficacy, safety and tolerability of lumiracoxib, a novel selective cyclooxygenase-2 (COX-2 inhibitor, has been demonstrated in previous studies of patients with osteoarthritis (OA. As it is important to establish the long-term safety and efficacy of treatments for a chronic disease such as OA, the present study compared the effects of lumiracoxib at doses of 100 mg once daily (o.d. and 100 mg twice daily (b.i.d. with those of celecoxib 200 mg o.d. on retention on treatment over 1 year. Methods In this 52-week, multicentre, randomised, double-blind, parallel-group study, male and female patients (aged at least 40 years with symptomatic primary OA of the hip, knee, hand or spine were randomised (1:2:1 to lumiracoxib 100 mg o.d. (n = 755, lumiracoxib 100 mg b.i.d. (n = 1,519 or celecoxib 200 mg o.d. (n = 758. The primary objective of the study was to demonstrate non-inferiority of lumiracoxib at either dose compared with celecoxib 200 mg o.d. with respect to the 1-year retention on treatment rate. Secondary outcome variables included OA pain in the target joint, patient's and physician's global assessments of disease activity, Short Arthritis assessment Scale (SAS total score, rescue medication use, and safety and tolerability. Results Retention rates at 1 year were similar for the lumiracoxib 100 mg o.d., lumiracoxib 100 mg b.i.d. and celecoxib 200 mg o.d. groups (46.9% vs 47.5% vs 45.3%, respectively. It was demonstrated that retention on treatment with lumiracoxib at either dose was non-inferior to celecoxib 200 mg o.d. Similarly, Kaplan-Meier curves for the probability of premature discontinuation from the study for any reason were similar across the treatment groups. All three treatments generally yielded comparable results for the secondary efficacy variables and all treatments were well tolerated. Conclusion Long-term treatment with lumiracoxib 100 mg o.d., the recommended dose for OA, was as effective and well

  15. Mg based alloys obtained by mechanical alloying

    Ordonez, S. [Univ. de Santiago de Chile (Chile). Fac. de Ingenieria; Garcia, G.; Serafini, D.; San Martin, A.


    In the present work, we studied the production of magnesium alloys, of stoichiometry 2Mg + Ni, by mechanical alloying (MA) and the behavior of the alloys under hydrogen in a Sievert`s type apparatus. The elemental powders were milled under argon atmosphere in a Spex 8000 high energy ball mill. The milled materials were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Only minimum amounts of the Mg{sub 2}Ni intermetallic compound was obtained after 22 h of milling time. Most of the material was sticked to the inner surface of the container as well as to the milling balls. Powders milled only for 12 hours transforms to the intermetallic at around 433 K. Effects of the MA on the hydrogen absorption kinetics were also studied. (orig.) 10 refs.

  16. Bulk amorphous Mg-based alloys

    Pryds, Nini


    The present paper describes the preparation and properties of bulk amorphous quarternary Mg-based alloys and the influence of additional elements on the ability of the alloy to form bulk amorphous. The main goal is to find a Mg-based alloy system which shows both high strength to weight ratio...... and a low glass transition temperature. The alloys were prepared by using a relatively simple technique, i.e. rapid cooling of the melt in a copper wedge mould. The essential structural changes that are achieved by going from the amorphous to the crystalline state through the supercooled liquid state...... are discussed in this paper. On the basis of these measurements phase diagrams of the different systems were constructed. Finally, it is demonstrated that when pressing the bulk amorphous alloy onto a metallic dies at temperatures within the supercooled liquid region, the alloy faithfully replicates the surface...

  17. Novel alginate based coatings on Mg alloys

    Sangeetha, K.; Roy, Abhijit [Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Singh, Satish [Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Lee, Boeun [Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Kumta, Prashant N., E-mail: [Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Department of Chemical Engineering, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Center for Craniofacial Regeneration, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Center for Complex Engineered Multifunctional Materials, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA 15261 (United States)


    Coatings on yttrium doped magnesium (Mg4Y) alloy substrates were prepared using alginate hydrogels by dip coating method to improve the surface bioactive properties of the substrate. Furthermore, composite coatings containing nano-sized calcium phosphate corresponding to hydroxyapatite (HA) phase entrapped within alginate hydrogel were also synthesized on the Mg4Y substrates. Surface characteristics of these coated substrates have been investigated using FTIR-ATR, SEM and EDS. The results show that the coatings with alginate alone are not stable in vitro; however, incorporation of NanoCaPs slightly improves the stability of these coatings. In addition, these composite coatings showed cell attachments with fibronectin incorporation. These results indicate that alginate hydrogels have the potential to be used as bioactive coating materials for different biofunctional applications.

  18. First-dose pharmacokinetics of aminoglycosides in critically ill haematological malignancy patients.

    Blackburn, Laura M; Tverdek, Frank P; Hernandez, Mike; Bruno, Jeffrey J


    The primary objective of this study was to determine the volume of distribution (Vd) (L/kg) of intravenous aminoglycosides (AGs) in critically ill haematological malignancy patients. Secondary objectives were to determine the body weight (actual, ideal, adjusted or lean) that yields the most precise estimate of Vd when normalised in L/kg as well as the frequency that current first-dose strategies result in post-distributional peak concentrations (C(peak)) within the target range (tobramycin 16-24 mg/L; amikacin 32-48 mg/L). In total, 58 AG doses were included (tobramycin, n = 34; amikacin, n = 24). Median Vd was 0.38 L/kg normalised per the most precise dose weight, which was actual body weight (ABW). The median dose was 445 mg (5.8 mg/kg ABW) for tobramycin and 1200 mg (13.8 mg/kg ABW) for amikacin. Target C(peak) (tobramycin 20mg/L; amikacin 40 mg/L) was achieved in only 25% of all AG episodes, with 4% exceeding the target and 71% falling below the target. Twenty-four organisms were isolated in the study sample; target C(peak) achievement (tobramycin 20 mg/L; amikacin 40 mg/L) would yield a peak:minimum inhibitory concentration of 10 in 75% and 52% of organisms, respectively. In conclusion, an increased Vd of AGs was identified in this critically ill haematological malignancy patient sample, and current dosing yielded a suboptimal C(peak) in the majority of patients. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  19. Low-dose hydrocortisone (HC) replacement therapy is associated with improved bone remodeling balance in hypopituitary subjects

    Behan, L A


    The effect of commonly used glucocorticoid replacement regimens on bone health in hypopituitary subjects is not well known. We aimed to assess the effect of 3 hydrocortisone (HC) replacement dose regimens on bone turnover in this group.10 hypopituitary men with severe ACTH deficiency were randomised in a crossover design to 3 HC dose regimens, Dose A (20mg mane, 10mg tarde), Dose B (10mg twice daily) and Dose C (10mg mane, 5mg tarde). Following 6 weeks of each regimen participants underwent fasting sampling of bone turnover markers.Data from matched controls were used to produce a Z score for subject bone formation and resorption markers and to calculate the bone remodeling balance (formation Z score-resorption Z score) and turnover index ((formation Z + resorption Z)\\/2). A positive bone remodeling balance with increased turnover is consistent with a favourable bone cycle. Data are expressed as median (range).The Pro Collagen Type 1 Peptide (PINP) bone formation Z-score was significantly increased in Dose C, (1.805 (-0.6-10.24)) compared to Dose A (0.035 (-1.0-8.1)) p<0.05 while there was no difference in the C-terminal crosslinking telopeptide (CTx) resorption Z score. The bone remodeling balance was significantly lower for dose A -0.02 (-1.05-4.12) compared to dose C 1.13 (0.13-6.4) (p<0.05). Although there was a trend to an increased bone turnover index with the lower dose regimen, this was not statistically significant.Low dose HC replacement (10mg mane\\/5 mg tarde) was associated with increased bone formation and improved bone remodeling balance which is associated with a more favourable bone cycle. This may have a long term beneficial effect on bone health.

  20. A prospective study of mortality from cryptococcal meningitis following treatment induction with 1200 mg oral fluconazole in Blantyre, Malawi.

    Katherine M Gaskell

    Full Text Available We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800 mg oral fluconazole (57% [33/58]. National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200 mg. We assessed whether this has improved outcomes.This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200 mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800 mg/day.47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200 mg, ten-week mortality remained 55% (26/47. This was no better than our previous study (Hazard Ratio [HR] of death on 1200 mg vs. 800 mg fluconazole: 1.29 (95% CI: 0.77-2.16, p = 0.332. There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07-1.03, p = 0.055].There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis.

  1. Electronic structure of MgB2

    P Modak; R S Rao; B K Godwal; S K Sikka


    Results of ab initio electronic structure calculations on the compound MgB2 using the FPLAPW method employing GGA for the exchange-correlation energy are presented. Total energy minimization enables us to estimate the equilibrium volume, / ratio and the bulk modulus, all of which are in excellent agreement with experiment. We obtain the mass enhancement parameter by using our calculated (F) and the experimental specific heat data. The c is found to be 24.7 K.

  2. Orientation relationships between icosahedral clusters in hexagonal MgZn2 and monoclinic Mg4Zn7 phases in Mg-Zn(-Y) alloys

    Rosalie, Julian M.; Somekawa, Hidetoshi; Singh, Alok; Mukai, Toshiji


    Intermetallic precipitates formed in heat-treated and aged Mg-Zn and Mg-Zn-Y alloys have been investigated via electron microscopy. Coarse spheroidal precipitates formed on deformation twin boundaries contained domains belonging to either the MgZn2 hexagonal Laves phase or the monoclinic Mg4Zn7 phase. Both phases are structurally related to the quasi-crystalline phase formed in Mg-Zn-Y alloys, containing icosahedrally coordinated zinc atoms arranged as a series of broad rhombohedral units. This rhombohedral arrangement was also visible in intragranular precipitates where local regions with the structures of hexagonal MgZn2 and Mg4Zn7 were found. The orientation adopted by the MgZn2 and Mg4Zn7 phases in twin-boundary and intragranular precipitates was such that the icosahedral clusters were aligned similarly. These results highlight the close structural similarities between the precipitates of the Mg-Zn-Y alloy system.

  3. Outcome of AIDS-associated cryptococcal meningitis initially treated with 200 mg/day or 400 mg/day of fluconazole

    Morroni C


    Full Text Available Abstract Background AIDS-associated cryptococcal meningitis has a high mortality. Fluconazole was the only systemic antifungal therapy available in our centre. From 1999–2001 we used low-dose fluconazole (200 mg daily initially, and did not offer therapy to patients perceived to have poor prognoses. In 2001 donated fluconazole became available, allowing us to use standard doses (400 mg daily initially. Antiretroviral therapy was not available during the study period. Methods Retrospective chart review of adult patients before and after the fluconazole donation. Results 205 patients fulfilled the inclusion criteria, 77 before and 128 after the donation. Following the donation fewer patients received no antifungal treatment (5% vs 19%, p = 0.002, and more patients received standard-dose fluconazole (90% vs 6%, p 1,000 were independent predictors of in-hospital mortality. Concomitant rifampicin did not affect in-hospital survival. Thirteen patients were referred to the tertiary referral hospital and received initial treatment with amphotericin B for a mean of 6 days – their in-hospital survival was not different from patients who received only fluconazole (p = 0.9. Kaplan-Meier analysis showed no differences in length of survival by initial treatment with standard or low doses of fluconazole (p = 0.27 log rank test; median survival was 76 and 82 days respectively. Conclusion Outcome of AIDS-associated cryptococcal meningitis is similar with low or standard doses of fluconazole. The early mortality is high. Initial therapy with amphotericin B and other measures may be needed to improve outcome.

  4. Ferrous bisglycinate 25 mg iron is as effective as ferrous sulfate 50 mg iron in the prophylaxis of iron deficiency and anemia during pregnancy in a randomized trial.

    Milman, Nils; Jønsson, Lisbeth; Dyre, Pernille; Pedersen, Palle Lyngsie; Larsen, Lise Grupe


    To compare the effects of oral ferrous bisglycinate 25 mg iron/day vs. ferrous sulfate 50 mg iron/day in the prevention of iron deficiency (ID) and iron deficiency anemia (IDA) in pregnant women. Randomized, double-blind, intention-to-treat study. Antenatal care clinic. 80 healthy ethnic Danish pregnant women. Women were allocated to ferrous bisglycinate 25 mg elemental iron (Aminojern®) (n=40) or ferrous sulfate 50 mg elemental iron (n=40) from 15 to 19 weeks of gestation to delivery. Hematological status (hemoglobin, red blood cell indices) and iron status (plasma iron, plasma transferrin, plasma transferrin saturation, plasma ferritin) were measured at 15-19 weeks (baseline), 27-28 weeks and 36-37 weeks of gestation. Occurrence of ID (ferritin ferrous bisglycinate was not inferior to ferrous sulfate. Ferrous bisglycinate in a low dose of 25 mg iron/day appears to be adequate to prevent IDA in more than 95% of Danish women during pregnancy and postpartum.

  5. Organ Doses and Effective Doses in Pediatric Radiography: Patient-Dose Survey in Finland

    Kiljunen, T.; Tietaevaeinen, A.; Parviainen, T.; Viitala, A.; Kortesniemi, M. (Radiation Practices Regulation, Radiation and Nuclear Safety Authority, Helsinki (Finland))


    Background: Use of the effective dose in diagnostic radiology permits the radiation exposure of diverse diagnostic procedures to be quantified. Fundamental knowledge of patient doses enhances the implementation of the 'as low as reasonably achievable' (ALARA) principle. Purpose: To provide comparative information on pediatric examination protocols and patient doses in skull, sinus, chest, abdominal, and pelvic radiography examinations. Material and Methods: 24 Finnish hospitals were asked to register pediatric examination data, including patient information and examination parameters and specifications. The total number of examinations in the study was 1916 (1426 chest, 228 sinus, 96 abdominal, 94 skull, and 72 pelvic examinations). Entrance surface dose (ESD) and dose-area products (DAP) were calculated retrospectively or DAP meters were used. Organ doses and effective doses were determined using a Monte Carlo program (PCXMC). Results: There was considerable variation in examination protocols between different hospitals, indicating large variations in patient doses. Mean effective doses of different age groups ranged from 5 muSv to 14 muSv in skull and sinus examinations, from 25 muSv to 483 muSv in abdominal examinations, and from 6 muSv to 48 muSv in chest examinations. Conclusion: In chest and sinus examinations, the amount of data was extensive, allowing national pediatric diagnostic reference levels to be defined. Parameter selection in pediatric examination protocols should be harmonized in order to reduce patient doses and improve optimization

  6. Interstitial Fe in MgO

    Mølholt, T E; Gunnlaugsson, H P; Svane, A; Masenda, H; Naidoo, D; Bharuth-Ram, K; Fanciulli, M; Gislason, H P; Johnston, K; Langouche, G; Ólafsson, S; Sielemann, R; Weyer, G


    Isolated Fe-57 atoms were studied in MgO single-crystals by emission Mossbauer spectroscopy following implantation of Mn-57 decaying to Fe-57. Four Mossbauer spectral components were found corresponding to different Fe lattice positions and/or charge states. Two components represent Fe atoms substituting Mg as Fe2+ and Fe3+, respectively; a third component is due to Fe in a strongly implantation-induced disturbed region. The fourth component, which is the focus of this paper, can be assigned to Fe at an interstitial site. Comparison of its measured isomer shift with ab initio calculations suggests that the interstitial Fe is located on, or close to, the face of the rock-salt MgO structure. To harmonize such an assignment with the measured near-zero quadrupole interaction a local motion process (cage motion) of the Fe has to be stipulated. The relation of such a local motion as a starting point for long range diffusion is discussed.

  7. Bilateral angioedema of eye with single dose of cetirizine

    Lakhan Majhee


    Full Text Available The H1-antihistamine cetirizine is considered to be one of the safest drugs with well-established safety and efficacy. Very rarely cetirizine can cause adverse drug reaction in the form of dose-dependent somnolence, dizziness, or fatigue. We report a case of 27-year-old female patient with isolated angioedema on both the eye due to the administration of single dose of cetirizine 10 mg for hemorroids with pruritus ani. The mechanism of reaction remains unclear. [Int J Basic Clin Pharmacol 2015; 4(6.000: 1296-1298

  8. Dose response problems in carcinogenesis.

    Crump, K S


    The estimation of risks from exposure to carcinogens is an important problem from the viewpoint of protection of human health. It also poses some very difficult dose-response problems. Two dose-response models may fit experimental data about equally well and yet predict responses that differ by many orders of magnitude at low doses. Mechanisms of carcinogenesis are not sufficiently understood so that the shape of the dose-response curve at low doses can be satisfactorily predicted. Mathematical theories of carcinogenesis and statistical procedures can be of use with dose-reponse problems such as this and, in addition, can lead to a better understanding of the mechanisms of carcinogenesis. In this paper, mathematical dose-response models of carcinogenesis are considered as well as various proposed dose-response procedures for estimating carcinogenic risks at low doses. Areas are suggested in which further work may be useful. These areas include experimental design problems, statistical procedures for use with time-to-occurrence data, and mathematical models that incorporate such biological features as pharmacokinetics of carcinogens, synergistic effects, DNA repair, susceptible subpopulations, and immune reactions.

  9. Suicidal Obsessions as Dose Dependent Side-Effect of Clozapine

    Aukst-Margetić, Branka; Margetić, Branimir; Boričević Maršanić, Vlatka


    Objective Although numerous reports suggest that different atypical antipsychotics can exacerbate or induce (de novo) obsessive-compulsive symptoms, there is no report of the development of ego-dystonic, suicidal obsessions during treatment with these medications. Here, the authors report the first case of clozapine-induced suicidal obsessions. Method The authors report a case of a patient diagnosed with bipolar disorder and who developed suicidal obsessions in the weeks after the dose of clozapine was increased from 150 mg/day to 300 mg/day. Results Symptoms quickly resolved after the treatment with clozapine was changed to the treatment with quetiapine and sodium valproate. Suicidal obsessions decreased promptly, within a few days, and disappeared completely when the dose of clozapine was 100 mg/day, quetiapine 600 mg/day, and sodium valproate 900 mg/day, 16 days after the initiation of changes in the medications. Conclusion The case report emphasizes the crucial need of differentiation between genuine suicidal desires and ego-dystonic suicidal obsessions. The authors suggest that in similar cases a change in antipsychotic medications to those with stronger antidopaminergic properties and lower 5HT2 receptor affinity should be considered, but also assume that the use of sodium valproate in treatment of obsessive-compulsive symptoms deserves further study. PMID:22506440

  10. Evaluation of organ doses and specific k effective dose of 64-slice CT thorax examination using an adult anthropomorphic phantom

    Hashim, S.; Karim, M. K. A.; Bakar, K. A.; Sabarudin, A.; Chin, A. W.; Saripan, M. I.; Bradley, D. A.


    The magnitude of radiation dose in computed tomography (CT) depends on the scan acquisition parameters, investigated herein using an anthropomorphic phantom (RANDO®) and thermoluminescence dosimeters (TLD). Specific interest was in the organ doses resulting from CT thorax examination, the specific k coefficient for effective dose estimation for particular protocols also being determined. For measurement of doses representing five main organs (thyroid, lung, liver, esophagus and skin), TLD-100 (LiF:Mg, Ti) were inserted into selected holes in a phantom slab. Five CT thorax protocols were investigated, one routine (R1) and four that were modified protocols (R2 to R5). Organ doses were ranked from greatest to least, found to lie in the order: thyroid>skin>lung>liver>breast. The greatest dose, for thyroid at 25 mGy, was that in use of R1 while the lowest, at 8.8 mGy, was in breast tissue using R3. Effective dose (E) was estimated using three standard methods: the International Commission on Radiological Protection (ICRP)-103 recommendation (E103), the computational phantom CT-EXPO (E(CTEXPO)) method, and the dose-length product (DLP) based approach. E103 k factors were constant for all protocols, ~8% less than that of the universal k factor. Due to inconsistency in tube potential and pitch factor the k factors from CTEXPO were found to vary between 0.015 and 0.010 for protocols R3 and R5. With considerable variation between scan acquisition parameters and organ doses, optimization of practice is necessary in order to reduce patient organ dose.

  11. Rationale for optimal obinutuzumab/GA101 dosing regimen in B-cell non-Hodgkin lymphoma.

    Cartron, Guillaume; Hourcade-Potelleret, Florence; Morschhauser, Franck; Salles, Gilles; Wenger, Michael; Truppel-Hartmann, Anna; Carlile, David J


    Obinutuzumab (GA101) is a type II, glycoengineered anti-CD20 monoclonal antibody for the treatment of hematologic malignancies. Obinutuzumab has mechanisms of action that are distinct from those of rituximab, potentially translating into improved clinical efficacy. We present the pharmacokinetic and clinical data from the phase I/II GAUGUIN and phase I GAUDI studies that were used to identify the obinutuzumab dose and regimen undergoing phase III assessment. In phase I (GAUGUIN and GAUDI), non-Hodgkin lymphoma patients received up to a maximum 9 fixed doses (obinutuzumab 50-2000 mg). In GAUGUIN phase II, patients received obinutuzumab 400/400 mg or 1600/800 mg [first dose day (D)1, D8, cycle (C) 1; second dose D1, C2-C8]. The influence of demographic factors on pharmacokinetics and drug exposure on tumor response and toxicity were analyzed using exploratory graphical analyses. Obinutuzumab serum concentrations with 1600/800 mg were compared with a 1000 mg fixed-dose regimen (D1, D8 and D15, C1; D1, C2-C8) using pharmacokinetic modeling simulations. Factors related to CD20-antigenic mass were more influential on obinutuzumab pharmacokinetics with 400/400 versus 1600/800 mg. Higher serum concentrations were observed with 1600/800 versus 400/400 mg, irrespective of CD20-antigenic mass. Tumor shrinkage was greater with 1600/800 versus 400/400 mg; there was no significant increase in adverse events. Fixed dose 1000 mg with an additional C1 infusion resulted in similar serum concentrations to 1600/800 mg in model-based analyses. The obinutuzumab 1000 mg fixed-dose regimen identified in this exploratory analysis was confirmed in a full covariate analysis of a larger dataset, and is undergoing phase III evaluation. GAUGUIN and GAUDI are registered at ( identifier:00517530 and 00825149, respectively).

  12. Comparison of hydrogen storage properties of pure Mg and milled pure Mg

    Myoung Youp Song; Young Jun Kwak; Seong Ho Lee; Hye Ryoung Park


    Hydrogen storage properties of pure Mg were studied at 593 K under 12 bar H2. In order to increase the hydriding and dehydriding rates, pure Mg was ground under hydrogen atmosphere (reactive mechanical grinding, RMG) and its hydrogen storage properties were subsequently investigated. Pure Mg absorbed hydrogen very slowly. At the number of cycles () of 1, pure Mg absorbed 0.05 wt% H for 5 min, 0.08 wt% H for 10 min and 0.29 wt% H for 60 min at 593 K under 12 bar H2. Activation was completed at the fifth cycle. At = 6, pure Mg absorbed 1.76 wt% H for 5 min, 2.17 wt% H for 10 min and 3.40 wt% H for 60 min. The activation of pure Mg after RMG was completed at the sixth cycle. At = 7, pure Mg after RMG absorbed 2.57 wt% H for 5 min, 3.21 wt% H for 10 min and 4.15 wt% H for 60 min.

  13. Midazolam 12 mg is moderately counteracted by 250 mg caffeine in man.

    Mattila, M J; Vainio, P; Nurminen, M L; Vanakoski, J; Seppälä, T


    Caffeine (Caf) counteracts various effects of benzodiazepines (BZDs). Since the effects of zolpidem, a short-acting atypical GABA(A)-BZD agonist, were not antagonized by Caf, we studied an interaction between Caf and midazolam (Mid) in healthy volunteers. In Study 1, 108 healthy students divided to 6 parallel groups were given Mid 12 mg (capsule) and Caf 125 and 250 mg (in decaffeinated coffee), alone and in combinations in the double-blind placebo-controlled manner. Objective and subjective tests were done before and at 45 and 90 min after intake. Ranked delta-values (changes from baseline) were analyzed by one-way contrast ANOVA and Scheffe's tests. In Study 2, six healthy subjects took Mid 15 mg (tablet) with and without Caf 300 mg. The dynamic effects were analyzed as in Study 1 and the plasma concentrations were assayed. In Study 1, learn effects after placebo (ad + 15%) were seen for letter cancellation and digit symbol substitution tests. Midazolam alone significantly (p 0.05). In conclusion, in a parallel group study, sedative effects of Mid 12 mg were only moderately antagonized by Caf 250 mg but not by Caf 125 mg. In a cross-over study, a weak interaction was found subjectively but not in objective measures.

  14. Evaluation of Enoxaparin Dosing as a Risk Factor for Bleeding in Lung Transplant Recipients.

    Sofjan, Amelia K; Iuppa, Jennifer A; Bain, K Bennett; Deal, Eli N; Witt, Chad A; Hachem, Ramsey R; Yusen, Roger D


    Lung transplant recipients commonly develop complications that lead to anticoagulation. Standard FDA-approved enoxaparin dosing in this population results in a high incidence of above-goal anti-Xa levels, but its association with bleeding remains unclear. To evaluate the association between enoxaparin dosing and bleeding in lung transplant recipients and assess the relationship between dosing and anti-Xa levels. We conducted a single-center retrospective cohort study of adult lung transplant recipients who received therapeutic enoxaparin between 2000 and 2012 at a tertiary academic center. We dichotomized enoxaparin dosing regimens into standard dose (FDA-approved doses with a 10% rounding margin) and reduced dose. Clinicians ordered anti-Xa levels as deemed clinically appropriate. The primary outcome was major bleeding or clinically relevant nonmajor bleeding. Of 222 patients treated with enoxaparin, 33 (14.9%) had bleeding events, of which half (17/33) were major. Bleeding occurred in 25/146 (17.1%) patients who received standard-dose enoxaparin versus 8/76 (10.5%) patients who received reduced-dose enoxaparin (P = 0.190). Multiple logistic regression demonstrated an independent association between standard-dose enoxaparin and bleeding, after adjusting for confounders (adjusted odds ratio = 3.04; 95% CI = 1.14-8.10). The median enoxaparin dose in patients with above-goal versus at-goal anti-Xa levels was 0.89 versus 0.76 mg/kg every 12 hours; P = 0.006. However, doses yielding at-goal anti-Xa levels had an interquartile range of 0.67 to 0.90 mg/kg, which overlapped with doses yielding above- and below-goal anti-Xa levels. Enoxaparin dose reduction and anti-Xa level monitoring can improve drug safety and facilitate individualized dose optimization in lung transplant recipients. © The Author(s) 2016.

  15. Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia

    Balaji Ramachandran


    Full Text Available EGCG (Epigallocatechin-3-gallate is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal] and limited [p.o (oral] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment.

  16. Dose measurements using thermoluminescent dosimeters and DoseCal software at two paediatric hospitals in Rio de Janeiro

    Mohamadain, K.E.M.; Azevedo, A.C.P.; Rosa, L.A.R. da E-mail:; Guebel, M.R.N.; Boechat, M.C.B


    A dosimetric survey in paediatric radiology is currently being carried out at the paediatric units of two large hospitals in Rio de Janeiro city: IPPMG (Instituto de Pediatria e Puericultura Martagao Gesteira, University Hospital of Federal University of Rio de Janeiro) and IFF (Instituto Fernandes Figueira, FIOCRUZ). Chest X-ray examination doses for AP, PA and LAT projections of paediatric patients have been obtained with thermoluminescent dosimeters (TLDs) and with use of a software package DoseCal. In IPPMG and IFF 100 patients have been evaluated with the use of the TLDs and another group of 100 patients with the DoseCal software. The aim of this work was to estimate the entrance skin dose (ESD) for frontal, back and lateral chest X-rays exposure of paediatric patients. For ESD evaluation, three different TL dosimeters have been used, namely LIF:Mg, Ti (TLD100), CaSO{sub 4}:Dy and LiF:Mg, Cu, P (TLD100H). The age intervals considered were 0-1, 1-5, 5-10 and 10-15 years. The results obtained with all dosimeters are similar, and it is in good agreement with the DoseCal software, especially for AP and PA projections. However, some larger discrepancies are presented for the LAT projection.

  17. Cation disorder in high-dose, neutron-irradiated spinel

    Sickafus, K.E.; Larson, A.C.; Yu, N. [Los Alamos National Lab., CA (United States)] [and others


    The objective of this effort is to determine whether MgAl{sub 2}O{sub 4} spinel is a suitable ceramic for fusion applications. The crystal structures of MgAl{sub 2}O{sub 4} spinel single crystals irradiated to high neutron fluences [>5{times}10{sup 26} n/m{sup 2} (E{sub n}>0.1 MeV)] were examined by neutron diffraction. Crystal structure refinement of the highese dose sample indicated that the average scattering strength of the tetrahedral crystal sites decreased by {approx}20% while increasing by {approx}8% on octahedral sites.