A single-aliquot OSL protocol using bracketing regenerative doses to accurately determine equivalent doses in quartz

CERN Document Server

Folz, E

1999-01-01

In most cases, sediments show inherent heterogeneity in their luminescence behaviours and bleaching histories, and identical aliquots are not available: single-aliquot determination of the equivalent dose (ED) is then the approach of choice and the advantages of using regenerative protocols are outlined. Experiments on five laboratory bleached and dosed quartz samples, following the protocol described by Murray and Roberts (1998. Measurement of the equivalent dose in quartz using a regenerative-dose single aliquot protocol. Radiation Measurements 27, 171-184), showed the hazards of using a single regeneration dose: a 10% variation in the regenerative dose yielded some equivalent dose estimates that differed from the expected value by more than 5%. A protocol is proposed that allows the use of different regenerative doses to bracket the estimated equivalent dose. The measured ED is found to be in excellent agreement with the known value when the main regeneration dose is within 10% of the true equivalent dose.

A single-aliquot OSL protocol using bracketing regenerative doses to accurately determine equivalent doses in quartz

International Nuclear Information System (INIS)

Folz, Elise; Mercier, Norbert

1999-01-01

In most cases, sediments show inherent heterogeneity in their luminescence behaviours and bleaching histories, and identical aliquots are not available: single-aliquot determination of the equivalent dose (ED) is then the approach of choice and the advantages of using regenerative protocols are outlined. Experiments on five laboratory bleached and dosed quartz samples, following the protocol described by Murray and Roberts (1998. Measurement of the equivalent dose in quartz using a regenerative-dose single aliquot protocol. Radiation Measurements 27, 171-184), showed the hazards of using a single regeneration dose: a 10% variation in the regenerative dose yielded some equivalent dose estimates that differed from the expected value by more than 5%. A protocol is proposed that allows the use of different regenerative doses to bracket the estimated equivalent dose. The measured ED is found to be in excellent agreement with the known value when the main regeneration dose is within 10% of the true equivalent dose

Single-Dose Lignocaine-Based Blood Cardioplegia in Single Valve Replacement Patients

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Jaydip Ramani

Full Text Available Abstract OBJECTIVE: Myocardial protection is the most important in cardiac surgery. We compared our modified single-dose long-acting lignocaine-based blood cardioplegia with short-acting St Thomas 1 blood cardioplegia in patients undergoing single valve replacement. METHODS: A total of 110 patients who underwent single (aortic or mitral valve replacement surgery were enrolled. Patients were divided in two groups based on the cardioplegia solution used. In group 1 (56 patients, long-acting lignocaine based-blood cardioplegia solution was administered as a single dose while in group 2 (54 patients, standard St Thomas IB (short-acting blood-based cardioplegia solution was administered and repeated every 20 minutes. All the patients were compared for preoperative baseline parameters, intraoperative and all the postoperative parameters. RESULTS: We did not find any statistically significant difference in preoperative baseline parameters. Cardiopulmonary bypass time were 73.8±16.5 and 76.4±16.9 minutes (P=0.43 and cross clamp time were 58.9±10.3 and 66.3±11.2 minutes (P=0.23 in group 1 and group 2, respectively. Mean of maximum inotrope score was 6.3±2.52 and 6.1±2.13 (P=0.65 in group 1 and group 2, respectively. We also did not find any statistically significant difference in creatine-phosphokinase-MB (CPK-MB, Troponin-I levels, lactate level and cardiac functions postoperatively. CONCLUSION: This study proves the safety and efficacy of long-acting lignocaine-based single-dose blood cardioplegia compared to the standard short-acting multi-dose blood cardioplegia in patients requiring the single valve replacement. Further studies need to be undertaken to establish this non-inferiority in situations of complex cardiac procedures especially in compromised patients.

The dose dependency of the over-dispersion of quartz OSL single grain dose distributions

DEFF Research Database (Denmark)

Thomsen, Kristina Jørkov; Murray, Andrew S.; Jain, Mayank

2012-01-01

The use of single grain quartz OSL dating has become widespread over the past decade, particularly with application to samples likely to have been incompletely bleached before burial. By reducing the aliquot size to a single grain the probability of identifying the grain population most likely...... to have been well-bleached at deposition is maximised and thus the accuracy with which the equivalent dose can be determined is – at least in principle – improved. However, analysis of single grain dose distributions requires knowledge of the dispersion of the well-bleached part of the dose distribution....... This can be estimated by measurement of a suitable analogue, e.g. a well-bleached aeolian sample, but this requires such an analogue to be available, and in addition the assumptions that the sample is in fact a) well-bleached, and b) has a similar dose rate heterogeneity to the fossil deposit. Finally...

Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid.

Science.gov (United States)

Flanagan, Shawn; Fang, Edward; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

2014-09-01

Tedizolid phosphate is a novel antibacterial under investigation for the treatment of gram-positive infections. This study was conducted to assess the pharmacokinetics, safety, and tolerability of intravenous tedizolid phosphate as well as the oral bioavailability of tedizolid phosphate. Double-blind, single-ascending dose, multiple-dose pharmacokinetics study, as well as tolerability and open-label crossover studies. Single center in the United States (Covance Clinical Research Unit, Madison, WI) between September 2009 and January 2010. Ninety healthy volunteers. Single intravenous (IV) doses of tedizolid phosphate 50 mg (lead-in) and 100-400 mg. Single oral and IV dose of tedizolid phosphate 200 mg in crossover fashion. Multiple IV doses of tedizolid phosphate 200 and 300 mg for up to 7 days. A dose-dependent increase was observed in the maximum plasma concentration (1.2-5.1 μg/ml) and the area under the concentration-time curve (17.4-58.7 μg × hr/ml) of tedizolid (the microbiologically active moiety of tedizolid phosphate) after single IV doses of tedizolid phosphate 100-400 mg. Administration of IV tedizolid phosphate 200 mg once/day for 7 days resulted in minimal (28%) tedizolid accumulation. The absolute oral bioavailability of tedizolid after a single 200-mg dose of tedizolid phosphate was 91%; pharmacokinetic parameters of tedizolid were similar with oral and IV administration. Treatment-related adverse events occurred in 41% of subjects. Most adverse events were related to infusion site and became more frequent with multiple dosing. In an additional 3-day tolerability study, IV tedizolid phosphate 200 mg and placebo were similarly tolerated, based on visual infusion phlebitis scores. These results from a population of healthy volunteers support once/day dosing of tedizolid phosphate 200 mg with both the oral and IV formulations, without the need for dose adjustment when switching administration routes. © 2014 Cubist Pharmaceuticals. Pharmacotherapy

single dose pharmacokinetics of mefloquine in healthy nigerian

African Journals Online (AJOL)

BSN

Mefloquine 500mg single dose was administered and blood samples were collected ... particle size ODS Hypersil (HETP, Macclesfield, UK) at a pressure of 55 Mpa .... dose to area under the plasma drug concentration - time curve, assuming ...

The dose dependency of the over-dispersion of quartz OSL single grain dose distributions

International Nuclear Information System (INIS)

Thomsen, Kristina J.; Murray, Andrew; Jain, Mayank

2012-01-01

The use of single grain quartz OSL dating has become widespread over the past decade, particularly with application to samples likely to have been incompletely bleached before burial. By reducing the aliquot size to a single grain the probability of identifying the grain population most likely to have been well-bleached at deposition is maximised and thus the accuracy with which the equivalent dose can be determined is – at least in principle – improved. However, analysis of single grain dose distributions requires knowledge of the dispersion of the well-bleached part of the dose distribution. This can be estimated by measurement of a suitable analogue, e.g. a well-bleached aeolian sample, but this requires such an analogue to be available, and in addition the assumptions that the sample is in fact a) well-bleached, and b) has a similar dose rate heterogeneity to the fossil deposit. Finally, it is an implicit assumption in such analysis that any over-dispersion is not significantly dose dependent. In this study we have undertaken laboratory investigations of the dose dependency of over-dispersion using a well-bleached modern sample with an average measured dose of 36 ± 3 mGy. This sample was prepared as heated (750 °C for 1 h), bleached and untreated portions which were then given uniform gamma doses ranging from 100 mGy to 208 Gy. We show that for these samples the relative laboratory over-dispersion is not constant as a function of dose and that the over-dispersion is smaller in heated samples. We also show that the dim grains in the distributions have a greater over-dispersion than the bright grains, implying that insensitive samples will have greater values of over-dispersion than sensitive samples.

Single Dose Versus 3 Doses of Intramuscular Benzathine Penicillin for Early Syphilis in HIV: A Randomized Clinical Trial.

Science.gov (United States)

Andrade, Roberto; Rodriguez-Barradas, Maria C; Yasukawa, Kosuke; Villarreal, Erick; Ross, Michael; Serpa, Jose A

2017-03-15

Patients coinfected with syphilis and human immunodeficiency virus (HIV) may have a slower decrease in rapid plasma reagin (RPR) titers. Currently a single dose of 2.4 million units of intramuscular benzathine penicillin G (BPG) is recommended for the treatment of early syphilis. Some observational studies have suggested that this regimen may lead to high failure rates in coinfected patients. We conducted an open-label randomized clinical trial to compare the efficacy of single-dose and 3-dose regimens of BPG for the treatment of early syphilis in HIV-infected individuals. RPR titers were monitored every 3 months. Treatment success was defined as a decrease in RPR titers of ≥2 dilutions (4-fold) during a 12-month follow-up period. Sixty-four patients were included. In the intention-to-treat analysis, treatment success rates were 80% (28 of 35 subjects) and 93% (27 of 29 subjects) in the single-dose and 3-dose regimens, respectively (absolute difference, 13% [95% confidence interval {CI}, -5% to 30%; P = .17). In the per-protocol analysis, success rates were 93% (27 of 29) and 100% in the single-dose and 3-dose regimens, respectively (absolute difference, 7% [95% CI, -7% to 22%]; P = .49). CD4 T-cell count, RPR titer and syphilis stage did not affect treatment results. When compared with a single dose of BPG, a 3-dose regimen did not improve syphilis serological outcomes. Our results support the Centers for Disease Control and Prevention recommendation of a single dose of BPG in HIV-infected patients with early syphilis. NCT02611765. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Efficacy of Single-Dose and Triple-Dose Albendazole and Mebendazole against Soil-Transmitted Helminths and Taenia spp.: A Randomized Controlled Trial

Science.gov (United States)

Steinmann, Peter; Utzinger, Jürg; Du, Zun-Wei; Jiang, Jin-Yong; Chen, Jia-Xu; Hattendorf, Jan; Zhou, Hui; Zhou, Xiao-Nong

2011-01-01

Background The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China. Methodology/Principal findings The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them. Conclusions/Significance Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are

Evaluation of the sterility of single-dose medications used in a multiple-dose fashion.

Science.gov (United States)

Martin, Elizabeth P; Mukherjee, Jean; Sharp, Claire R; Sinnott-Stutzman, Virginia B

2017-11-01

Bacterial proliferation was evaluated in single-dose medications used in a multi-dose fashion and when medications were intentionally inoculated with bacteria. Of 5 experimentally punctured medications, 1 of 75 vials (50% dextrose) became contaminated. When intentionally inoculated, hydroxyethyl starch and heparinized saline supported microbial growth. Based on these findings, it is recommended that hydroxyethyl starch and heparinized saline not be used in a multi-dose fashion.

Single-dose-response curves of murine gastrointestinal crypt stem cells

International Nuclear Information System (INIS)

Masuda, K.; Withers, H.R.; Mason, K.A.; Chen, K.Y.

1977-01-01

Dose-response curves for the reproductive capacity of crypt stem cells of murine colonic, jejunal, and gastric mucosae exposed in situ to multifractionated gamma ray exposures were analyzed and single-dose-survival curves of these cells were constructed. The following conclusions were drawn: (1) The single-dose-response curves bend downward over a dose range of approximately 200 to 1500 rad; (2) cell death seems to be due to nonrepairable damage at doses less than 250 rad for colon, and 220 rad for jejunum; (3) there are 21, 110, and 140 stem cells per crypt of gastric, colonic, and jejunal mucosa, respectively; and (4) jejunal stem cells are the most radiosensitive and gastric mucosal stem cells are the most resistant

Single-dose radiotherapy for painful bone metastases

International Nuclear Information System (INIS)

Kal, H.B.

1999-01-01

Background: External beam radiotherapy is frequently applied for palliative treatment of painful bone lesions with a variety of fractionation schemes. There is a continuous interest to administer only 1 or a few dose fractions for inducing pain relief. Methods: A review of the literature was made with the aim to determine whether a treatment can be deduced that is simple and effective. The linear-quadratic (L-Q) concept was applied to compare reported therapy schemes which each other for the iso-effect pain relief. Results: Single-dose and fractionated radiotherapy resulted in partial or complete pain relief in about 80% of the patients. Complete responses have been observed in about 43% of the patients. For patients responding to treatment, the duration of pain relief is at least 3 to 4 months with reported duration of up to 1 year or even longer. Conclusion: Based on this review of literature data concerning randomized trials a treatment with a single dose of 8 Gy is effective for inducing pain relief. (orig.) [de

Single point estimation of phenytoin dosing: a reappraisal.

Science.gov (United States)

Koup, J R; Gibaldi, M; Godolphin, W

1981-11-01

A previously proposed method for estimation of phenytoin dosing requirement using a single serum sample obtained 24 hours after intravenous loading dose (18 mg/Kg) has been re-evaluated. Using more realistic values for the volume of distribution of phenytoin (0.4 to 1.2 L/Kg), simulations indicate that the proposed method will fail to consistently predict dosage requirements. Additional simulations indicate that two samples obtained during the 24 hour interval following the iv loading dose could be used to more reliably predict phenytoin dose requirement. Because of the nonlinear relationship which exists between phenytoin dose administration rate (RO) and the mean steady state serum concentration (CSS), small errors in prediction of the required RO result in much larger errors in CSS.

Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

Science.gov (United States)

Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

2017-06-01

The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy and Safety of Single and Double Doses of Ivermectin versus 7-Day High Dose Albendazole for Chronic Strongyloidiasis

Science.gov (United States)

Suputtamongkol, Yupin; Premasathian, Nalinee; Bhumimuang, Kid; Waywa, Duangdao; Nilganuwong, Surasak; Karuphong, Ekkapun; Anekthananon, Thanomsak; Wanachiwanawin, Darawan; Silpasakorn, Saowaluk

2011-01-01

Background Strongyloidiasis, caused by an intestinal helminth Strongyloides stercoralis, is common throughout the tropics. It remains an important health problem due to autoinfection, which may result in hyperinfection and disseminated infection in immunosuppressed patients, especially patients receiving chemotherapy or corticosteroid treatment. Ivermectin and albendazole are effective against strongyloidiasis. However, the efficacy and the most effective dosing regimen are to be determined. Methods A prospective, randomized, open study was conducted in which a 7-day course of oral albendazole 800 mg daily was compared with a single dose (200 microgram/kilogram body weight), or double doses, given 2 weeks apart, of ivermectin in Thai patients with chronic strongyloidiasis. Patients were followed-up with 2 weeks after initiation of treatment, then 1 month, 3 months, 6 months, 9 months, and 1 year after treatment. Combination of direct microscopic examination of fecal smear, formol-ether concentration method, and modified Koga agar plate culture were used to detect strongyloides larvae in two consecutive fecal samples in each follow-up visit. The primary endpoint was clearance of strongyloides larvae from feces after treatment and at one year follow-up. Results Ninety patients were included in the analysis (30, 31 and 29 patients in albendazole, single dose, and double doses ivermectin group, respectively). All except one patient in this study had at least one concomitant disease. Diabetes mellitus, systemic lupus erythrematosus, nephrotic syndrome, hematologic malignancy, solid tumor and human immunodeficiency virus infection were common concomitant diseases in these patients. The median (range) duration of follow-up were 19 (2–76) weeks in albendazole group, 39 (2–74) weeks in single dose ivermectin group, and 26 (2–74) weeks in double doses ivermectin group. Parasitological cure rate were 63.3%, 96.8% and 93.1% in albendazole, single dose oral ivermectin

Efficacy of various single-dose regimens of ceftriaxone in ...

African Journals Online (AJOL)

The therapeutic efficacy of single intramuscular doses of ceftriaxone (Rocephin; Roche) (62,S, 125 and 250 mg), administered without probenecid, was evaluated in 167 adult males with uncomplicated acute gonococcal urethritis. Cure rates of 100% were achieved at 62,5 mg and 250 mg. In the 125 mg dose group, ...

SINGLE-DOSE VERSUS 3-DAY PROPHYLAXIS WITH CIPROFLOXACIN IN TRANSURETHRAL SURGERY - A CLINICAL-TRIAL

NARCIS (Netherlands)

BIJL, W; JANKNEGT, RA

1993-01-01

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

Single event effects and total ionizing dose effects of typical VDMOSFET devices

International Nuclear Information System (INIS)

Lou Jianshe; Cai Nan; Liu Jiaxin; Wu Qinzhi; Wang Jia

2012-01-01

In this work, single event effects and total ionizing dose effects of typical VDMOSFET irradiated by 60 Co γ-rays and 252 Cf source were studied. The single event burnout and single event gate rupture (SEB/SEGR) effects were investigated, and the relationship between drain-source breakdown voltage and ionizing dose was obtained. The results showed that the VDMOSFET devices were sensitive to SEB and SEGR, and measures to improve their resistance to SEB and SEGR should be considered seriously for their space applications. The drain-source breakdown voltage was sensitive to total ionizing dose effects as the threshold voltage. In assessing the devices' resistance to the total ionizing dose effects, both the threshold voltage and the drain-source breakdown voltage should be taken into account. (authors)

Dose optimisation in single plane interstitial brachytherapy

DEFF Research Database (Denmark)

Tanderup, Kari; Hellebust, Taran Paulsen; Honoré, Henriette Benedicte

2006-01-01

patients,       treated for recurrent rectal and cervical cancer, flexible catheters were       sutured intra-operatively to the tumour bed in areas with compromised       surgical margin. Both non-optimised, geometrically and graphically       optimised CT -based dose plans were made. The overdose index...... on the       regularity of the implant, such that the benefit of optimisation was       larger for irregular implants. OI and HI correlated strongly with target       volume limiting the usability of these parameters for comparison of dose       plans between patients. CONCLUSIONS: Dwell time optimisation significantly......BACKGROUND AND PURPOSE: Brachytherapy dose distributions can be optimised       by modulation of source dwell times. In this study dose optimisation in       single planar interstitial implants was evaluated in order to quantify the       potential benefit in patients. MATERIAL AND METHODS: In 14...

Effective dose to staff from interventional procedures: Estimations from single and double dosimetry

International Nuclear Information System (INIS)

Kuipers, G.; Velders, X. L.

2009-01-01

The exposure of 11 physicians performing interventional procedures was measured by means of two personal dosemeters. One personal dosemeter was worn outside the lead apron and an additional under the lead apron. The study was set up in order to determine the added value of a dosemeter worn under the lead apron. With the doses measured, the effective doses of the physicians were estimated using an algorithm for single dosimetry and two algorithms for double dosimetry. The effective doses calculated with the single dosimetry algorithm ranged from 0.11 to 0.85 mSv in 4 weeks. With the double dosimetry algorithms, the effective doses ranged from 0.02 mSv to 0.47 mSv. The statistical analysis revealed no significant differences in the accuracy of the effective doses calculated with single or double dosimetry algorithms. It was concluded that the effective dose cannot be considered a more accurate estimate when two dosemeters are used instead of one. (authors)

Failure Rate of Single Dose Methotrexate in Managment of Ectopic Pregnancy

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Feras Sendy

2015-01-01

Full Text Available Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67% received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225 of the patients. 28% (63/225 were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63 of failure received a second dose of methotrexate, and 37% (23/63 underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

Failure rate of single dose methotrexate in managment of ectopic pregnancy.

Science.gov (United States)

Sendy, Feras; AlShehri, Eman; AlAjmi, Amani; Bamanie, Elham; Appani, Surekha; Shams, Taghreed

2015-01-01

Background. One of the treatment modalities for ectopic pregnancy is methotrexate. The purpose of this study is to identify the failure rate of methotrexate in treating patients with ectopic pregnancy as well as the risk factors leading to treatment failure. Methods. A retrospective chart review of 225 patients who received methotrexate as a primary management option for ectopic pregnancy. Failure of single dose of methotrexate was defined as drop of BHCG level less than or equal to 14% in the seventh day after administration of methotrexate. Results. 225 patients had methotrexate. Most of the patients (151 (67%)) received methotrexate based on the following formula: f 50 mg X body surface area. Single dose of methotrexate was successful in 72% (162/225) of the patients. 28% (63/225) were labeled as failure of single dose of methotrexate because of suboptimal drop in BhCG. 63% (40/63) of failure received a second dose of methotrexate, and 37% (23/63) underwent surgical treatment. Among patient who received initial dose of methotrexate, 71% had moderate or severe pain, and 58% had ectopic mass size of more than 4 cm on ultrasound. Conclusion. Liberal use of medical treatment of ectopic pregnancy results in 71% success rate.

Correlation between the single, high dose of ingested baclofen and clinical symptoms

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Jacek Sein Anand

2017-12-01

There is a statistically significant correlation between the dose of ingested baclofen and the presence of acute respiratory failure, and duration of mechanical ventilation. Patients who have taken a single dose of baclofen of 200 mg, or higher, should be managed in centres able to provide continuous monitoring of life functions. Those with a higher level of a single dose of baclofen ingestion (>500 mg, should be hospitalized in a Toxicology Unit or Intensive Care Unit able to provide airway support and mechanical ventilation.

Protect Patients by Using Single- and Multi-Dose Vials Correctly

Centers for Disease Control (CDC) Podcasts

2014-07-10

CDC’s One & Only Campaign urges healthcare providers to recognize the differences between single-dose and multi-dose vials, and to understand appropriate use of each container type.  Created: 7/10/2014 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 7/10/2014.

Developing a single-aliquot protocol for measuring equivalent dose in biogenic carbonates

International Nuclear Information System (INIS)

Stirling, R.J.; Duller, G.A.T.; Roberts, H.M.

2012-01-01

Exploiting biogenic carbonates as thermoluminescence dosimeters requires an understanding of trap kinetics and an appropriate sequence with which to measure equivalent dose. The trap kinetics of two high temperature peaks (peaks II and III) from calcitic snail opercula have been investigated resulting in the calculation of lifetimes of 7.4 × 10 7 and 1.4 × 10 11 years for the two peaks respectively. Two measurement sequences, based upon changes in the application and measurement of a test dose, have been applied to peaks II and III, and though both methods were equally successful in dose recovery and production of a dose response curve some differences were observed. Primarily, the use of method 1 lead to dose dependant sensitivity change implying competition effects occurring during irradiation; method 2 did not experience this phenomenon. As a consequence method 2 was chosen as the most appropriate protocol for single-aliquot dating of this material. When assessing the TL behaviour of the two peaks, peak II performed poorly in dose recovery experiments recovering a dose 60–100% larger than that applied. Disproportionate growth of peak II in response to a beta dose applied prior to measurement, compared to growth following regeneration doses indicated that peak II was not suitable for use in single-aliquot protocols. However, dose recovery results for peak III were all within errors of unity of the given dose, and peak III was therefore chosen as the most appropriate peak for TL dosimetry in these single-aliquot procedures. The lifetime of charge in peak III is sufficient to date over many millions of years, and furthermore using the chosen method 2 the dose response curve has a D 0 of 3,250 ± 163 Gy allowing dating to over 3 million years.

Impact of multiple-dose versus single-dose inhaler devices on COPD patients’ persistence with long-acting β2-agonists: a dispensing database analysis

Science.gov (United States)

van Boven, Job FM; van Raaij, Joost J; van der Galiën, Ruben; Postma, Maarten J; van der Molen, Thys; Dekhuijzen, PN Richard; Vegter, Stefan

2014-01-01

Background: With a growing availability of different devices and types of medication, additional evidence is required to assist clinicians in prescribing the optimal medication in relation to chronic obstructive pulmonary disease (COPD) patients’ persistence with long-acting β2-agonists (LABAs). Aims: To assess the impact of the type of inhaler device (multiple-dose versus single-dose inhalers) on 1-year persistence and switching patterns with LABAs. Methods: A retrospective observational cohort study was performed comparing a cohort of patients initiating multiple-dose inhalers and a cohort initiating single-dose inhalers. The study population consisted of long-acting bronchodilator naive COPD patients, initiating inhalation therapy with mono-LABAs (formoterol, indacaterol or salmeterol). Analyses were performed using pharmacy dispensing data from 1994 to 2012, obtained from the IADB.nl database. Study outcomes were 1-year persistence and switching patterns. Results were adjusted for initial prescriber, initial medication, dosing regimen and relevant comorbidities. Results: In all, 575 patients initiating LABAs were included in the final study cohort. Among them, 475 (83%) initiated a multiple-dose inhaler and 100 (17%) a single-dose inhaler. Further, 269 (47%) initiated formoterol, 9 (2%) indacaterol and 297 (52%) salmeterol. There was no significant difference in persistence between users of multiple-dose or single-dose inhalers (hazard ratio: 0.98, 95% confidence interval: 0.76–1.26, P=0.99). Over 80% re-started or switched medication. Conclusions: There seems no impact of inhaler device (multiple-dose versus single-dose inhalers) on COPD patients’ persistence with LABAs. Over 80% of patients who initially seemed to discontinue LABAs, re-started their initial medication or switched inhalers or medication within 1 year. PMID:25274453

Variable dose rate single-arc IMAT delivered with a constant dose rate and variable angular spacing

International Nuclear Information System (INIS)

Tang, Grace; Earl, Matthew A; Yu, Cedric X

2009-01-01

Single-arc intensity-modulated arc therapy (IMAT) has gained worldwide interest in both research and clinical implementation due to its superior plan quality and delivery efficiency. Single-arc IMAT techniques such as the Varian RapidArc(TM) deliver conformal dose distributions to the target in one single gantry rotation, resulting in a delivery time in the order of 2 min. The segments in these techniques are evenly distributed within an arc and are allowed to have different monitor unit (MU) weightings. Therefore, a variable dose-rate (VDR) is required for delivery. Because the VDR requirement complicates the control hardware and software of the linear accelerators (linacs) and prevents most existing linacs from delivering IMAT, we propose an alternative planning approach for IMAT using constant dose-rate (CDR) delivery with variable angular spacing. We prove the equivalence by converting VDR-optimized RapidArc plans to CDR plans, where the evenly spaced beams in the VDR plan are redistributed to uneven spacing such that the segments with larger MU weighting occupy a greater angular interval. To minimize perturbation in the optimized dose distribution, the angular deviation of the segments was restricted to ≤± 5 deg. This restriction requires the treatment arc to be broken into multiple sectors such that the local MU fluctuation within each sector is reduced, thereby lowering the angular deviation of the segments during redistribution. The converted CDR plans were delivered with a single gantry sweep as in the VDR plans but each sector was delivered with a different value of CDR. For four patient cases, including two head-and-neck, one brain and one prostate, all CDR plans developed with the variable spacing scheme produced similar dose distributions to the original VDR plans. For plans with complex angular MU distributions, the number of sectors increased up to four in the CDR plans in order to maintain the original plan quality. Since each sector was

Single toxin dose-response models revisited

Energy Technology Data Exchange (ETDEWEB)

Demidenko, Eugene, E-mail: eugened@dartmouth.edu [Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH03756 (United States); Glaholt, SP, E-mail: sglaholt@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States); Kyker-Snowman, E, E-mail: ek2002@wildcats.unh.edu [Department of Natural Resources and the Environment, University of New Hampshire, Durham, NH03824 (United States); Shaw, JR, E-mail: joeshaw@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Chen, CY, E-mail: Celia.Y.Chen@dartmouth.edu [Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States)

2017-01-01

The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of the four models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 h) toxicity tests with mortality as a function of NiCl or CuSO{sub 4} toxin. - Highlights: • The paper offers a rigorous study of a sigmoid dose-response relationship. • The concentration with highest mortality rate is rigorously defined. • A table with four special points for five morality curves is presented. • Two new sigmoid dose-response models have been introduced. • The generalized linear model is advocated for estimation of sigmoid dose-response relationship.

Single-dose volume regulation algorithm for a gas-compensated intrathecal infusion pump.

Science.gov (United States)

Nam, Kyoung Won; Kim, Kwang Gi; Sung, Mun Hyun; Choi, Seong Wook; Kim, Dae Hyun; Jo, Yung Ho

2011-01-01

The internal pressures of medication reservoirs of gas-compensated intrathecal medication infusion pumps decrease when medication is discharged, and these discharge-induced pressure drops can decrease the volume of medication discharged. To prevent these reductions, the volumes discharged must be adjusted to maintain the required dosage levels. In this study, the authors developed an automatic control algorithm for an intrathecal infusion pump developed by the Korean National Cancer Center that regulates single-dose volumes. The proposed algorithm estimates the amount of medication remaining and adjusts control parameters automatically to maintain single-dose volumes at predetermined levels. Experimental results demonstrated that the proposed algorithm can regulate mean single-dose volumes with a variation of 98%. © 2010, Copyright the Authors. Artificial Organs © 2010, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine

Science.gov (United States)

Peng, Shiwen; Lyford-Pike, Sofia; Akpeng, Belinda; Wu, Annie; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.

2012-01-01

Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8+ T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8+ T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8+ T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic anti-tumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8+ T cells, which led to higher ratios of CD8+/Treg and CD8+/CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8+ T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. PMID:23011589

Low-dose ketoconazole-fluconazole combination versus fluconazole in single doses for the treatment of vaginal candidiasis

Directory of Open Access Journals (Sweden)

Jan Susilo

2011-08-01

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

Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

Science.gov (United States)

Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

2018-02-01

To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

Single-dose radiosurgical treatment for hepatic metastases - therapeutic outcome of 138 treated lesions from a single institution

International Nuclear Information System (INIS)

Habermehl, Daniel; Herfarth, Klaus K; Bermejo, Justo Lorenzo; Hof, Holger; Rieken, Stefan; Kuhn, Sabine; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E

2013-01-01

Local ablative therapies such as stereotactically guided single-dose radiotherapy or helical intensity-modulated radiotherapy (tomotherapy) with high single-doses are successfully applied in many centers in patients with liver metastasis not suitable for surgical resection. This study presents results from more than 10 years of clinical experience and evaluates long-term outcome and efficacy of this therapeutic approach. From 1997 to 2009 a total of 138 intrahepatic tumors of 90 patients were irradiated with single doses of 17 to 30 Gy (median dose 24 Gy). Median age of the patients was 64 years (range 31–89 years). Most frequent underlying tumor histologies were colorectal adenocarcinoma (70 lesions) and breast cancer (27 lesions). In 35 treatment sessions multiple targets were simultaneously irradiated (up to four lesions at once). Local progression-free (PFS) and overall survival (OS) after treatment were investigated using uni- and multiple survival regression models. Median overall survival of all patients was 24.3 months. Local PFS was 87%, 70% and 59% after 6, 12 and 18 months, respectively. Median time to local progression was 25.5 months. Patients with a single lesion and no further metastases at time of RT had a favorable median PFS of 43.1 months according to the Kaplan-Meier estimator. The type of tumor showed a statistical significant influence on local PFS, with a better prognosis for breast cancer histology than for colorectal carcinoma in uni- and multiple regression analysis (p = 0.05). Multiple regression analysis revealed no influence of planning target volume (PTV), patient age and radiation dose on local PFS. Treatment was well tolerated with no severe adverse events. This study confirms safety of SBRT in liver lesions, with 6- and 12 months local control of 87% and 70%. The dataset represents the clinical situation in a large oncology setting, with many competing treatment options and heterogeneous patient characteristics

Hypertrophic Cardiomyopathy After a Single Dose of Dexamethasone in a Preterm Infant

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Yusuf Kale

2015-08-01

Full Text Available Dexamethasone is widely used in preterm infants with severe pulmonary disease. Hypertrophic cardiomyopathy (HCM is a transient side effect observed after multiple doses of dexamethasone. We report a preterm infant with myocardial hypertrophy after a single dose of dexamethasone (0.5 mg/kg used to treat laryngeal edema secondary to prolonged intubation. A benign course was observed without left ventricular outflow tract obstruction and with recovery within 4 weeks. Myocardial effects of dexamethasone may be independent of dose and duration of treatment. The risk/benefit ratio must be carefully considered before using even a single dose of dexamethasone in preterm infants.

Coronary vasodilatory action after a single dose of nicorandil

NARCIS (Netherlands)

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

1988-01-01

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

Esophageal Toxicity From High-Dose, Single-Fraction Paraspinal Stereotactic Radiosurgery

International Nuclear Information System (INIS)

Cox, Brett W.; Jackson, Andrew; Hunt, Margie; Bilsky, Mark; Yamada, Yoshiya

2012-01-01

Purpose: To report the esophageal toxicity from single-fraction paraspinal stereotactic radiosurgery (SRS) and identify dosimetric and clinical risk factors for toxicity. Methods and Materials: A total of 204 spinal metastases abutting the esophagus (182 patients) were treated with high-dose single-fraction SRS during 2003-2010. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria for Adverse Events, version 4.0. Dose-volume histograms were combined to generate a comprehensive atlas of complication incidence that identifies risk factors for toxicity. Correlation of dose-volume factors with esophageal toxicity was assessed using Fisher’s exact test and logistic regression. Clinical factors were correlated with toxicity. Results: The median dose to the planning treatment volume was 24 Gy. Median follow-up was 12 months (range, 3-81). There were 31 (15%) acute and 24 (12%) late esophageal toxicities. The rate of grade ≥3 acute or late toxicity was 6.8% (14 patients). Fisher’s exact test resulted in significant median splits for grade ≥3 toxicity at V12 = 3.78 cm 3 (relative risk [RR] 3.7, P=.05), V15 = 1.87 cm 3 (RR 13, P=.0013), V20 = 0.11 cm 3 (RR 6, P=0.01), and V22 = 0.0 cm 3 (RR 13, P=.0013). The median split for D2.5 cm 3 (14.02 Gy) was also a significant predictor of toxicity (RR 6; P=.01). A highly significant logistic regression model was generated on the basis of D2.5 cm 3 . One hundred percent (n = 7) of grade ≥4 toxicities were associated with radiation recall reactions after doxorubicin or gemcitabine chemotherapy or iatrogenic manipulation of the irradiated esophagus. Conclusions: High-dose, single-fraction paraspinal SRS has a low rate of grade ≥3 esophageal toxicity. Severe esophageal toxicity is minimized with careful attention to esophageal doses during treatment planning. Iatrogenic manipulation of the irradiated esophagus and systemic agents classically associated with radiation recall reactions are

Single-dose and steady-state pharmacokinetics of diltiazem administered in two different tablet formulations

DEFF Research Database (Denmark)

Christrup, Lona Louring; Bonde, J; Rasmussen, S N

1992-01-01

Single-dose and steady state pharmacokinetics of diltiazem administered in two different oral formulations were assessed with particular reference to rate and extent of absorption. Following single dose administration a significant difference in tmax was observed (2.9 +/- 1.9 and 6.8 +/- 2.6 hr r...

Single-dose radiation therapy for prevention of heterotopic ossification after total hip arthroplasty

International Nuclear Information System (INIS)

Healy, W.L.; Lo, T.C.; Covall, D.J.; Pfeifer, B.A.; Wasilewski, S.A.

1990-01-01

Single-dose radiation therapy was prospectively evaluated for its efficacy in prevention of heterotopic ossification in patients at high risk after total hip arthroplasty. Thirty-one patients (34 hips) were treated between 1981 and 1988. Risk factors for inclusion in the protocol included prior evidence of heterotopic ossification, ankylosing spondylitis, and diffuse idiopathic skeletal hyperostosis. Patients with hypertrophic osteoarthritis or traumatic arthritis with osteophytes were not included. Operations on 34 hips included 19 primary total and 11 revision total hip arthroplasties and 4 excisions of heterotopic ossification. All patients received radiotherapy to the hip after operation with a single dose of 700 centigray. Radiotherapy is recommended on the first postoperative day. After this single-dose radiation treatment, no patient had clinically significant heterotopic ossification. Recurrent disease developed in two hips (6%), as seen on radiography (grades 2 and 3). This series documents a 100% clinical success rate and a 94% radiographic success rate in preventing heterotopic ossification in patients at high risk after total hip arthroplasty. Single-dose radiotherapy is as effective as other radiation protocols in preventing heterotopic ossification after total hip arthroplasty. It is less expensive and easier to administer than multidose radiotherapy

Low-Dose Sevoflurane Promotes Hippocampal Neurogenesis and Facilitates the Development of Dentate Gyrus-Dependent Learning in Neonatal Rats

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Chong Chen

2015-04-01

Full Text Available Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8% sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4–6 were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks.

Effective dose comparison between stitched and single FOV in CBCT protocols for complete dental arcade

International Nuclear Information System (INIS)

Soares, Maria Rosangela; Batista, Wilson Otto; Antonio, Patricia Lara de; Caldas, Linda V.E.; Maia, Ana F.

2015-01-01

Objective: The objective of this study was to assess and compare protocols with a single field of view and multiple stitched field of view with a similar clinical purpose by means of effective dose value. Materials and methods: Measurements of absorbed dose were performed with thermoluminescent dosemeters inserted in the position of organs/tissues of a female anthropomorphic phantom and from these values the effective dose was calculated, utilizing weighting factor tissue-ICRP 103 (2007). Results: The results obtained in this study for effective dose are within the range of 43.1 µSv and 111.5 µSv for equipment using protocols with single FOV and in the range of 44.5 µSv and 236.2 µSv for equipments that using protocols with stitched field of view. Conclusions: In terms of the value of effective dose, stitched FOV protocols do not have any advantage over the single field of view protocols. This results suggest the necessity for knowledge of the exposure parameters and effective dose values associated with each image protocol. - Highlights: • The study relies on the comparison of two protocols with similar goals of CBCT: stitched protocols and single protocols. • The stitched FOV protocol is more specific and it is good option when want imaging only of some dental units. • In relation the effective dose, single FOV protocols presents advantage over the stitched FOV protocols. • Know the exposure parameters and effective dose values associated with each image protocol is necessity for request the best CBCT tomographic image

Single-dose and multiple-dose pharmacokinetics and dose proportionality of intravenous and intramuscular HPβCD-diclofenac (Dyloject) compared with other diclofenac formulations.

Science.gov (United States)

Mermelstein, Fred; Hamilton, Douglas A; Wright, Curtis; Lacouture, Peter G; Ramaiya, Atulkumar; Carr, Daniel B

2013-10-01

To evaluate single- and repeated-dose pharmacokinetics (PK) and dose proportionality of hydroxypropyl-β-cyclodextrin (HPβCD)-diclofenac compared with Voltarol after intravenous (IV) and intramuscular (IM) administration. Study 1: Single-dose randomized four-way crossover study. Study 2: Multiple-dose randomized three-way crossover study. Clinical research center. Healthy adult volunteers. Study 1: Subjects received HPβCD-diclofenac and Voltarol, IV and IM, with a 5-day washout between treatment periods. Study 2: Subjects received two doses of IV HPβCD-diclofenac and oral Cataflam once every 6 hours for four doses with a 48-hour washout period between treatment periods. Study 1: IV HPβCD-diclofenac had a higher peak plasma concentration (Cmax ) and earlier time to reach maximum plasma concentration (Tmax ), but equivalent plasma exposure (area under the curve from time zero to t [AUC0-t ]) to IV Voltarol. The geometric mean ratio of HPβCD-diclofenac (IV) to Voltarol (IV) for AUC0-t was 106.27%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IM) for AUC0-t was 110.91%. The geometric mean ratio of HPβCD-diclofenac (IV) to HPβCD-diclofenac (IM) for AUC0-t was 101.25%. The geometric mean ratio of HPβCD-diclofenac (IM) to Voltarol (IV) for AUC0-t was 104.96%. Study 2: Cmax for diclofenac was 2904 and 6031 ng/ml after the first IV dose of 18.75 and 37.5 mg HPβCD-diclofenac, respectively, and was 3090 and 5617 ng/ml after the fourth dose, indicating no accumulation. Plasma exposures to 18.75 mg (866 ng·hour/ml) and 37.5 mg (1843 ng·hour/ml) IV HPβCD-diclofenac bracketed that of oral Cataflam 50 mg (1473 ng·hour/ml). Study 1: Bioavailability in terms of AUC after IV administration was equivalent for HPβCD-diclofenac compared with Voltarol and after IM administration of HPβCD-diclofenac and Voltarol. Bioavailability in terms of AUC after IM administration of HPβCD-diclofenac was equivalent to IV administration of HP�

Single- and multiple-dose pharmacokinetics, pharmacodynamics, and safety of apixaban in healthy Chinese subjects

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Cui Y

2013-12-01

Full Text Available Yimin Cui,1 Yan Song,2 Jessie Wang,2 Zhigang Yu,2 Alan Schuster,2 Yu Chen Barrett,2 Charles Frost2 1Peking University First Hospital, Beijing, People's Republic of China; 2Bristol-Myers Squibb, Princeton, NJ, USA Background: The pharmacokinetics (PK, pharmacodynamics (PD, and safety of apixaban were assessed in healthy Chinese subjects in this randomized, placebo-controlled, double-blind, single-sequence, single- and multiple-dose study. Subjects and methods: Eighteen subjects 18–45 years of age were randomly assigned (2:1 ratio to receive apixaban or matched placebo. Subjects received a single 10 mg dose of apixaban or placebo on day 1, followed by 10 mg apixaban or placebo twice daily for 6 days (days 4–9. The PK and PD of apixaban were assessed by collecting plasma samples for 72 hours following the dose on day 1 and the morning dose on day 9, and measuring apixaban concentration and anti-Xa activity. Safety was assessed via physical examinations, vital sign measurements, electrocardiograms, and clinical laboratory evaluations. Results: PK analysis showed similar characteristics of apixaban after single and multiple doses, including a median time to maximum concentration of ~3 hours, mean elimination half-life of ~11 hours, and renal clearance of ~1.2 L/hour. The accumulation index was 1.7, consistent with twice-daily dosing and the observed elimination half-life. Single-dose data predict multiple-dose PK, therefore apixaban PK are time-independent. The relationship between anti-Xa activity and plasma apixaban concentrations appears to be linear. Apixaban was safe and well tolerated, with no bleeding-related adverse events reported. Conclusion: Apixaban was safe and well tolerated in healthy Chinese subjects. Apixaban PK and PD were predictable and consistent with findings from previous studies in Asian and non-Asian subjects. The administration of apixaban does not require any dose modification based on race. Keywords: apixaban, oral

Management of urinary tract infections in pregnancy: a review with comments on single dose therapy.

Science.gov (United States)

Zinner, S H

1992-01-01

Most investigators agree that the adverse effects of urinary tract infections in pregnancy can be abrogated by effective early detection and treatment. However, the optimal methods for screening and treatment remain controversial. Although single-dose therapy has not been applied to pregnant women with acute pyelonephritis, most but not all studies which have compared single-dose with longer courses of beta-lactam or other antibiotics in pregnant asymptomatic bacteriuric women have shown no differences in outcome. This paper reviews recent trials of single-dose treatment of bacteriuria in pregnant women.

Marrow toxicity of fractionated vs. single dose total body irradiation is identical in a canine model

International Nuclear Information System (INIS)

Storb, R.; Raff, R.F.; Graham, T.; Appelbaum, F.R.; Deeg, H.J.; Schuening, F.G.; Shulman, H.; Pepe, M.

1993-01-01

The authors explored in dogs the marrow toxicity of single dose total body irradiation delivered from two opposing 60 Co sources at a rate of 10 cGy/min and compared results to those seen with total body irradiation administered in 100 cGy fractions with minimum interfraction intervals of 6 hr. Dogs were not given marrow transplants. They found that 200 cGy single dose total body irradiation was sublethal, with 12 of 13 dogs showing hematopoietic recovery and survival. Seven of 21 dogs given 300 cGy single dose total body irradiation survived compared to 6 of 10 dogs given 300 cGy fractionated total body irradiation. One of 28 dogs given 400 cGy single dose total body irradiation survived compared to none of six given fractionated radiation. With granulocyte colony stimulating factor (GCSF) administered from day 0-21 after 400 cGy total body irradiation, most dogs survived with hematological recovery. Because of the almost uniform success with GCSF after 400 cGy single dose total body irradiation, a study of GCSF after 400 cGy fractionated total body irradiation was deemed not to be informative and, thus, not carried out. Additional comparisons between single dose and fractionated total body irradiation were carried out with GCSF administered after 500 and 600 cGy of total body irradiation. As with lower doses of total body irradiation, no significant survival differences were seen between the two modes of total body irradiation, and only 3 of 26 dogs studied survived with complete hematological recovery. Overall, therefore, survival among dogs given single dose total body irradiation was not different from that of dogs given fractionated total body irradiation (p = .67). Similarly, the slopes of the postirradiation declines of granulocyte and platelet counts and the rates of their recovery in surviving dogs given equal total doses of single versus fractionated total body irradiation were indistinguishable. 24 refs., 3 figs., 2 tabs

Response of mouse tongue epithelium to single doses of bleomycin and radiation

International Nuclear Information System (INIS)

Dorr, W.; Hirler, E.; Honig, M.

1993-01-01

Both bleomycin (BLM) and local X-irradiation (25 kV) induce denudation in the tongue epithelium of the C3H-Neuherberg mouse in a dose-dependent manner. In the present study the effect of BLM alone and of combined single doses of drug and radiation were studied using the incidence of epithelial denudation as the end-point. In 'time-line' experiments, 8 mg/kg BLM were given before or after graded doses of X-rays. BLM treatment required a reduction of the radiation dose (ED 50 ) from 15 Gy to 5-7 Gy, independent of sequence or time interval. In contrast, the time course of the response was clearly dependent on the treatment interval. Latency decreased when the drug was injected less than 2 h before irradiation with minimum latency observed at 30 min. Isobologram analysis of experiments with varying combinations of X-rays and BLM demonstrated that small drug doses were relatively more effective than larger doses, suggesting an upward concavity of the BLM dose-effective curve in vivo, i.e. a 'negative shoulder' of the curve in the low dose region. In contrast to the response to X-rays alone, which has a constant latent time to ulcer of 10 days, the latency in combined treatment was clearly shortened with increasing drug dose and at high doses eventually approximated the epithelial turnover time of 5 days. The data suggest that BLM both as a single agent and in combination with X-rays reduced the probability of abortive divisions and through this effect shortened the latent time to epithelial denudation. (author)

Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage

DEFF Research Database (Denmark)

Holm, C; Thomsen, L L; Norgaard, A

2017-01-01

BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open-label, ran......BACKGROUND AND OBJECTIVES: To evaluate the clinical efficacy of a single-dose intravenous infusion of iron isomaltoside compared with current treatment practice with oral iron measured by physical fatigue in women after postpartum haemorrhage. MATERIALS AND METHODS: Single-centre, open...

A comparative study of single-dose treatment of chancroid using thiamphenicol versus Azithromycin.

Science.gov (United States)

Belda, Walter; Di Chiacchio, Nilton G; Di Chiacchio, Nilton; Romiti, Ricardo; Criado, Paulo R; Velho, Paulo Eduardo N Ferreira

2009-06-01

A study was conducted in São Paulo, Brazil, to compare azithromycin with thiamphenicol for the single-dose treatment of chancroid. In all, 54 men with chancroid were tested. The etiology was determined by clinical characterization and direct bacterioscopy with Gram staining. None of the patients had positive serology or dark-field examination indicating active infection with Treponema pallidum. Genital infections due to Neisseria gonorrhoeae and herpes simplex virus were excluded by polymerase chain reaction testing. For 54 patients with chancroid, cure rates with single-dose treatment were 73% with azithromycin and 89% with thiamphenicol. HIV seropositivity was found to be associated with treatment failure (p=0.001). The treatment failed in all HIV positive patients treated with azithromycin (p=0.002) and this drug should be avoided in these co-infected patients. In the view of the authors, thiamphenicol is the most indicated single-dose regimen for chancroid treatment.

A Cohort Study of Preoperative Single Dose Versus Four Doses of Antibiotics for Patients With Non-Complicated Acute Appendicitis

Directory of Open Access Journals (Sweden)

Salah H. Al Janaby

2017-02-01

Full Text Available Objective: To Test the efficacy of single preoperative dose of Cefotaxime 1gm and Metronidazole 500mg in reducing the surgical site infections (SSIs after open appendectomy in patients with non-complicated appendicitis (NCA Place and Duration of Study: Al Hilla General Teaching Hospital, Babel Governorate-Iraq, from January 2013 to January 2014. Patients & Methods: 100 patients, who underwent appendectomy for NCA and fulfilled the selection criteria, were randomized into two groups. The patients in group A received a single dose of pre-operative antibiotics (Cefotaxime sodium and metronidazole, while the group B patients received three more dose of the same antibiotics postoperatively. Patients of both groups were followed-up for 30 days to assess the postoperative infective complications. Results: Group A had 48, while group B comprised of 52 patients. The groups were comparable in the baseline characteristics. Statistically, P value in rates of SSIs between both the groups was 0.9182. None of the patients developed intra-abdominal collection. Conclusion: Single dose of pre-operative antibiotics (Cefotaxime and metronidazole was sufficient in reducing the SSIs after appendectomy for NPA. Postoperative antibiotics did not add an appreciable clinical benefit in these patients. Key words: Preoperative antibiotics, Appendectomy, Surgical site infection, Non-complicated appendicitis Abbreviations: SSI: Surgical Site Infection, NCA: non-complicated appendicitis CDC Center of Disease Control.

Single and 30 fraction tumor control doses correlate in xenografted tumor models: implications for predictive assays

International Nuclear Information System (INIS)

Gerweck, Leo E.; Dubois, Willum; Baumann, Michael; Suit, Herman D.

1995-01-01

Purpose/Objective: In a previous publication we reported that laboratory assays of tumor clonogen number, in combination with intrinsic radiosensitivity measured in-vitro, accurately predicted the rank-order of single fraction 50% tumor control doses, in six rodent and xenografted human tumors. In these studies, tumor hypoxia influenced the absolute value of the tumor control doses across tumor types, but not their rank-order. In the present study we hypothesize that determinants of the single fraction tumor control dose, may also strongly influence the fractionaled tumor control doses, and that knowledge of tumor clonogen number and their sensitivity to fractionated irradiation, may be useful for predicting the relative sensitivity of tumors treated by conventional fractionated irradiation. Methods/Materials: Five tumors of human origin were used for these studies. Special care was taken to ensure that all tumor control dose assays were performed over the same time frame, i.e., in-vitro cells of a similar passage were used to initiate tumor sources which were expanded and used in the 3rd or 4th generation. Thirty fraction tumor control doses were performed in air breathing mice, under normal blood flow conditions (two fractions/day). The results of these studies have been previously published. For studies under uniformly (clamp) hypoxic conditions, tumors arising from the same transplantation were randomized into single or fractionated dose protocols. For estimation of the fractionated TCD50 under hypoxic conditions, tumors were exposed to six 5.4 Gy fractions (∼ 2 Gy equivalent under air), followed by graded 'top-up' dose irradiation for determination of the TCD50; the time interval between doses was 6-9 hours. The single dose equivalent of the six 5.4 Gy doses was used to calculate an extrapolated 30 fraction hypoxic TCD50. Results: Fractionation substantially increased the dose required for tumor control in 4 of the 5 tumors investigated. For these 4 tumors

Efficacy of various single-dose regimens of ceftriaxone in ...

African Journals Online (AJOL)

1990-08-18

Aug 18, 1990 ... The therapeutic efficacy of single intramuscular doses of ceftriaxone (Rocephin; Roche) (62,S, 125 and 250 mg), admini- stered without probenecid, was evaluated in 167 adult males with uncomplicated acute gonococcal urethritis. Cure rates of 100% were achieved at 62,5 mg and 250 mg. In the 125 mg.

Protective effect of hypoxia in the ram testis during single and split-dose X-irradiation

International Nuclear Information System (INIS)

Vliet, J. van; Wensing, C.J.G.; Bootsma, A.L.; Peperzeel, H.A. van; Schipper, J.

1988-01-01

Spertogonial stem-cell survival in the ram was studied after single (6Gy) and split-dose X-irradiation both under normal and hypoxic conditions. Hypoxia was induced by inflation of an occluder implanted around the testicular artery. The occluders were inflated about 10 min before irradiation and deflated immediately after. Stem-cell survival was measured at 5 or 7 weeks after irradiation by determination of the Repopulation Index (RI) in histological testis sections. The RI-values after fractionated irradiation were only half those after single dose irradiation. Hypoxia had a protective effect on the stem-cell survival. After split-dose irradiation under hypoxic conditions two times more stem cells survived than under normal oxic conditions; the RI-values increased from 34% (oxic) to 68% (hypoxic). This effect of hypoxia was also found after single dose irradiation where the RI-values increased from 68% (oxic) to 84% (hypoxic). The development of the epithelium in repopulated tubules was also studied. Under hypoxia, a significantly higher fraction of tubules with complete epithelium was found after single (38 vs. 4%) as well as after split-dose irradiation (12 vs. 0%)

Single Low-Dose Ionizing Radiation Induces Genotoxicity in Adult Zebrafish and its Non-Irradiated Progeny.

Science.gov (United States)

Lemos, J; Neuparth, T; Trigo, M; Costa, P; Vieira, D; Cunha, L; Ponte, F; Costa, P S; Metello, L F; Carvalho, A P

2017-02-01

This study investigated to what extent a single exposure to low doses of ionizing radiation can induce genotoxic damage in irradiated adult zebrafish (Danio rerio) and its non-irradiated F1 progeny. Four groups of adult zebrafish were irradiated with a single dose of X-rays at 0 (control), 100, 500 and 1000 mGy, respectively, and couples of each group were allowed to reproduce following irradiation. Blood of parental fish and whole-body offspring were analysed by the comet assay for detection of DNA damage. The level of DNA damage in irradiated parental fish increased in a radiation dose-dependent manner at day 1 post-irradiation, but returned to the control level thereafter. The level of DNA damage in the progeny was directly correlated with the parental irradiation dose. Results highlight the genotoxic risk of a single exposure to low-dose ionizing radiation in irradiated individuals and also in its non-irradiated progeny.

The D1 method: career dose estimation from a combination of historical monitoring data and a single year's dose data

International Nuclear Information System (INIS)

Sont, W.N.

1995-01-01

A method is introduced to estimate career doses from a combination of historical monitoring data and a single year's dose data. This method, called D1 eliminates the bias arising from incorporating historical dose data from times when occupational doses were generally much higher than they are today. Doses calculated by this method are still conditional on the preservation of the status quo in the effectiveness of radiation protection. The method takes into account the variation of the annual dose, and of the probability of being monitored, with the time elapsed since the start of a career. It also allows for the calculation of a standard error of the projected career dose. Results from recent Canadian dose data are presented. (author)

Single dose (400 mg) versus 7 day (200 mg) daily dose itraconazole in the treatment of tinea versicolor: a randomized clinical trial.

Science.gov (United States)

Wahab, M A; Ali, M E; Rahman, M H; Chowdhury, S A; Monamie, N S; Sultana, N; Khondoker, L

2010-01-01

Tinea (pityriasis) versicolor is a superficial fungal infection and one of the most commonly found pigmentary disorders of skin caused by the yeast Malassezia. Multiple topical as well as systemic therapies are available for treatment. Systemic therapies are used for extensive disease, frequent relapse or where topical agents have failed. The aim that translates the rationale of the study was to compare the efficacy, safety, tolerability and cost effectiveness of single dose 400mg versus 7 day 200 mg daily dose of itraconazole in the treatment of tinea versicolor. A clinical study was done to compare the efficacy of single dose (400 mg) of itraconazole and 7 day 200 mg daily dose of itraconazole in the treatment of extensive tinea versicolor. Total 60 patients (aged 18-50 years) were selected for the study during the period of June 2007 to May 2008 in the department of Dermatology of three different hospitals in Bangladesh. Cases having with extensive involvement, diagnosed clinically and confirmed by wood's lamp and KOH microscopy were taken. Patients were randomly allocated into equal groups. Group A was given single dose 400 mg itraconazole and Group B was given 7 day 200 mg daily itraconazole. Fifty three (88%) male and 7(12%) female were included in the study. The mean age of group A was 32.37+/-9 years and in group B 33.23+/-8 years. The mean duration of the disease in group A was 2.63+/-2 months and 2.76+/-2 months in group B. In group A clinical responders was found cure 22(73.33%) and improvement 5(16.33%) and in group B it was found cure 24(79.99%) and improvement 4(13.33%). The measure at the End point (EP1) equals to 90% response and in-group B it was found cure 24 (79.99%) and improvement 4(13.33%). (Here the End point EP2) equals to 93.33%. The EP clinical analysis however shows 91.66% response. Both single dose and 7 day daily dose of itraconazole can be effective in the treatment of tinea versicolor with extensive involvement but single dose appears

A comparative study of single-dose treatment of chancroid using thiamphenicol versus Azithromycin

Directory of Open Access Journals (Sweden)

Walter B. Junior

Full Text Available A study was conducted in São Paulo, Brazil, to compare azithromycin with thiamphenicol for the single-dose treatment of chancroid. In all, 54 men with chancroid were tested. The etiology was determined by clinical characterization and direct bacterioscopy with Gram staining. None of the patients had positive serology or dark-field examination indicating active infection with Treponema pallidum. Genital infections due to Neisseria gonorrhoeae and herpes simplex virus were excluded by polymerase chain reaction testing. For 54 patients with chancroid, cure rates with single-dose treatment were 73% with azithromycin and 89% with thiamphenicol. HIV seropositivity was found to be associated with treatment failure (p=0.001. The treatment failed in all HIV positive patients treated with azithromycin (p=0.002 and this drug should be avoided in these co-infected patients. In the view of the authors, thiamphenicol is the most indicated single-dose regimen for chancroid treatment.

Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

International Nuclear Information System (INIS)

Moussazadeh, Nelson; Lis, Eric; Katsoulakis, Evangelia; Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily; Bilsky, Mark H.; Yamada, Yoshiya; Laufer, Ilya

2015-01-01

Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

Five-Year Outcomes of High-Dose Single-Fraction Spinal Stereotactic Radiosurgery

Energy Technology Data Exchange (ETDEWEB)

Moussazadeh, Nelson [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States); Lis, Eric [Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Katsoulakis, Evangelia [Department of Radiation Oncology, New York Methodist Hospital, Brooklyn, New York (United States); Kahn, Sweena; Svoboda, Marek; DiStefano, Natalie M.; McLaughlin, Lily [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bilsky, Mark H. [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States); Yamada, Yoshiya [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Laufer, Ilya, E-mail: lauferi@mskcc.org [Division of Neurological Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Department of Neurological Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York (United States)

2015-10-01

Purpose: To characterize local tumor control and toxicity risk in very long-term survivors (>5 years) after high-dose spinal image guided, intensity modulated radiation therapy delivered as single-dose stereotactic radiosurgery (SRS). Previously published spinal SRS outcome analyses have included a heterogeneous population of cancer patients, mostly with short survival. This is the first study reporting the long-term tumor control and toxicity profiles after high-dose single-fraction spinal SRS. Methods and Materials: The study population included all patients treated from June 2004 to July 2009 with single-fraction spinal SRS (dose 24 Gy) who had survived at least 5 years after treatment. The endpoints examined included disease progression, surgical or radiation retreatment, in-field fracture development, and radiation-associated toxicity, scored using the Radiation Therapy Oncology Group radiation morbidity scoring criteria and the Common Terminology Criteria for Adverse Events, version 4.0. Local control and fracture development were assessed using Kaplan-Meier analysis. Results: Of 278 patients, 31 (11.1%), with 36 segments treated for spinal tumors, survived at least 5 years after treatment and were followed up radiographically and clinically for a median of 6.1 years (maximum 102 months). The histopathologic findings for the 5-year survivors included radiation-resistant metastases in 58%, radiation-sensitive metastases in 22%, and primary bone tumors in 19%. In this selected cohort, 3 treatment failures occurred at a median of 48.6 months, including 2 recurrences in the radiation field and 1 patient with demonstrated progression at the treatment margins. Ten lesions (27.8%) were associated with acute grade 1 cutaneous or gastrointestinal toxicity. Delayed toxicity ≥3 months after treatment included 8 cases (22.2%) of mild neuropathy, 2 (5.6%) of gastrointestinal discomfort, 8 (22.2%) of dermatitides, and 3 (8.3%) of myalgias/myositis. Thirteen

Comparison of single-grain and small-aliquot OSL dose estimates in < 3000 years old river sediments from South India

DEFF Research Database (Denmark)

Thomas, P.J.; Jain, M.; Juyal, N.

2005-01-01

We report on OSL dose distributions derived from small-aliquot and single grains of quartz in young fluvial sediments sampled from the Penner River basin, South India. The single-grain dose distributions suggest that 13 out of 19 samples were well bleached. In many well-bleached samples, there wa......We report on OSL dose distributions derived from small-aliquot and single grains of quartz in young fluvial sediments sampled from the Penner River basin, South India. The single-grain dose distributions suggest that 13 out of 19 samples were well bleached. In many well-bleached samples......, there was an underestimation in the single-aliquot dose estimates as compared to those from the single grain-the difference between average dose estimates determined by the two methods ranged from similar to 1% to 31%. Such a dose underestimation was not detectable in poorly bleached samples. Various possible reasons...... perhaps be one of the reasons; this may occur because the stimulation wavelength affects the proportion of the medium and slow components in the initial signal. (c) 2004 Elsevier Ltd. All rights reserved....

Comparison of single-grain and small-aliquot OSL dose estimates in <3000 years old river sediments from South India

International Nuclear Information System (INIS)

Thomas, P.J.; Jain, M.; Juyal, N.; Singhvi, A.K.

2005-01-01

We report on OSL dose distributions derived from small-aliquot and single grains of quartz in young fluvial sediments sampled from the Penner River basin, South India. The single-grain dose distributions suggest that 13 out of 19 samples were well bleached. In many well-bleached samples, there was an underestimation in the single-aliquot dose estimates as compared to those from the single grain-the difference between average dose estimates determined by the two methods ranged from ∼1% to 31%. Such a dose underestimation was not detectable in poorly bleached samples. Various possible reasons for the discrepancy between single-grain and small-aliquot dose estimates are discussed. Although there is no satisfactory explanation for this discrepancy, we speculate that the difference in the stimulation wavelengths, 470+/-30nm in the case of single-aliquot and 532nm in the case of single grains, could perhaps be one of the reasons; this may occur because the stimulation wavelength affects the proportion of the medium and slow components in the initial signal

Single-dose Rituximab Therapy for Refractory Idiopathic Membranous Nephropathy: A Single-center Experience

OpenAIRE

Katsuno, Takayuki; Ozaki, Takenori; Kim, Hangsoo; Kato, Noritoshi; Suzuki, Yasuhiro; Akiyama, Shinichi; Ishimoto, Takuji; Kosugi, Tomoki; Tsuboi, Naotake; Ito, Yasuhiko; Maruyama, Shoichi

2017-01-01

To date, a recognized treatment for refractory membranous nephropathy (MN) has not been established. Recently, several reports have indicated the efficacy of rituximab as a novel treatment option. However, only a few published accounts exist of rituximab therapy for idiopathic MN (IMN) in the Asian population. We present the cases of three IMN patients who were treated with single-dose rituximab after they showed no response to conventional therapies, including corticosteroids, cyclosporine, ...

Improved long-term survival after intra-operative single high-dose ATG-Fresenius induction in renal transplantation: a single centre experience.

Science.gov (United States)

Kaden, Jürgen; May, Gottfried; Völp, Andreas; Wesslau, Claus

2009-01-01

In organ grafts donor-specific sensitization is initiated immediately after revascularization. Therefore, in 1990 we introduced the intra-operative single high-dose ATG-Fresenius (ATG-F) induction in addition to standard triple drug therapy (TDT) consisting of steroids, azathioprine and cyclosporin. A total of 778 first renal transplantations from deceased donors, performed between 1987 and 1998, were included in this evaluation. This retrospective analysis of clinic records and electronic databases presents data of all recipients of first kidney grafts who received two different ATG-F inductions (1(st) group: 9 mg/kg body weight as single high-dose intra-operatively, n=484; 2(nd) group: 3 mg/kg body weight on 7 or 8 consecutive days as multiple-dose starting also intra-operatively, n=78) and standard TDT alone (3(rd) group: TDT alone, n=216). The 10-year patient survival rates were 72.6+/-2.6% (TDT + ATG-F single high-dose), 79.5+/-5.1% (TDT + ATG-F multiple-dose) and 67.2+/-3.7%% (TDT alone; Kaplan-Meier estimates with standard errors; ATG-F vs TDT alone, p=0.001). The 10-year graft survival rates with censoring of patients that died with a functioning graft were 73.8+/-2.4%, 57.7+/-5.8% and 58.4+/-3.6% (Kaplan-Meier estimates with standard errors; 1(st) vs 2(nd )and 3(rd) group, respectively, p<0.001) and the 10-year graft survival rates with patient death counted as graft failure were 58.3+/-2.7%, 55.7+/-5.8% and 48.2+/-3.5% (Kaplan-Meier estimates with standard errors; ATG-F single high-dose vs TDT, p=0.023). In pre-sensitized recipients there were also significant differences in favour of ATG-F, more notably in the single high-dose ATG-F induction. A total of 69% of the patients in the two cohorts receiving ATG-F did not experience any transplant rejections compared to 56% in patients undergoing TDT alone (p=0.018). The incidence of infectious complications was comparable across all groups. According to evidence obtained from the routine documentation of 778

Single-fraction stereotactic radiotherapy: a dose-response analysis of arteriovenous malformation obliteration

International Nuclear Information System (INIS)

Touboul, Emmanuel; Al Halabi, Assem; Buffat, Laurent; Merienne, Louis; Huart, Judith; Schlienger, Michel; Lefkopoulos, Dimitrios; Mammar, Hamid; Missir, Odile; Meder, Jean-Francois; Laurent, Alex; Housset, Martin

1998-01-01

Purpose: Stereotactic radiotherapy delivered in a high-dose single fraction is an effective technique to obliterate intracranial arteriovenous malformations (AVM). To attempt to analyze the relationships between dose, volume, and obliteration rates, we studied a group of patients treated using single-isocenter treatment plans. Methods and Materials: From May 1986 to December 1989, 100 consecutive patients with angiographically proven AVM had stereotactic radiotherapy delivered as a high-dose single fraction using a single-isocenter technique. Distribution according to Spetzler-Martin grade was as follows: 79 grade 1-3, three grade 4, 0 grade 5, and 18 grade 6. The target volume was spheroid in 74 cases, ellipsoid in 11, and large and irregular in 15. The targeted volume of the nidus was estimated using two-dimensional stereotactic angiographic data and, calculated as an ovoid-shaped lesion, was 1900 ± 230 mm 3 (median 968 mm 3 ; range 62-11, 250 mm 3 ). The mean minimum target dose (D min ) was 19 ± 0.6 Gy (median 20 Gy; range: 3-31.5). The mean volume within the isodose which corresponded to the minimum target dose was 2500 ± 300 mm 3 (median 1200 mm 3 ; range 75-14 900 mm 3 ). The mean maximum dose (D max ) was 34.5 ± 0.5 Gy (median 35 Gy; range 15-45). The mean angiographic follow-up was 42 ± 2.3 months (median 37.5; range 7-117). Results: The absolute obliteration rate was 51%. The 5-year actuarial obliteration rate was 62.5 ± 7%. After univariate analysis, AVM obliteration was influenced by previous surgery (p = 0.0007), D min by steps of 5 Gy (p = 0.005), targeted volume of the nidus (≤968 mm 3 vs. >968 mm 3 ; p = 0.015), and grade according to Spetzler-Martin (grade 1-3 vs. grade 4-6; p = 0.011). After multivariate analysis, the independent factors influencing AVM obliteration were the D min [relative risk (RR) 1.9; 95% confidence interval (CI) 1.4-2.5; p min but does not seem to be influenced by D max and the targeted volume of the nidus

Application of the luminescence single-aliquot technique for dose estimation in the Marmara Sea

International Nuclear Information System (INIS)

Tanir, Guenes; Sencan, Emine; Boeluekdemir, M. Hicabi; Tuerkoez, M. Burak; Tel, Eyuep

2005-01-01

The aim of this study is to obtain the equivalent dose, which is the important quantity for all the studies related to the use of luminescence in dating sediments. Recent advances in luminescence dating have led to increasing application of the technique to sediment from the depositional environmental samples. The sample used in this study is the active main fault sample that was collected from the Sea of Marmara in NW Turkey. Equivalent dose was measured using both the multiple-aliquots and the single-aliquot techniques. In this study single aliquot regeneration on additive dose (SARA) procedure was also used. The result obtained was not in agreement with the results evaluated from the multiple-aliquots procedure. So a simple modification was suggested for SARA procedure. In our modified procedure the calculated dose (D) values were obtained by using the additive dose protocol instead of regeneration protocol

Effect of Low-Dose (Single-Dose Magnesium Sulfate on Postoperative Analgesia in Hysterectomy Patients Receiving Balanced General Anesthesia

Directory of Open Access Journals (Sweden)

Arman Taheri

2015-01-01

Full Text Available Background and Aim. Aparallel, randomized, double blinded, placebo-controlled trial study was designed to assess the efficacy of single low dose of intravenous magnesium sulfate on post-total abdominal hysterectomy (TAH pain relief under balanced general anesthesia. Subject and Methods. Forty women undergoing TAH surgery were assigned to two magnesium sulfate (N=20 and normal saline (N=20 groups randomly. The magnesium group received magnesium sulfate 50 mg·kg−1 in 100 mL of normal saline solution i.v as single-dose, just 15 minutes before induction of anesthesia whereas patients in control group received 100 mL of 0.9% sodium chloride solution at the same time. The same balanced general anesthesia was induced for two groups. Pethidine consumption was recorded over 24 hours precisely as postoperative analgesic. Pain score was evaluated with Numeric Rating Scale (NRS at 0, 6, 12, and 24 hours after the surgeries. Results. Postoperative pain score was lower in magnesium group at 6, 12, and 24 hours after the operations significantly (P<0.05. Pethidine requirement was significantly lower in magnesium group throughout 24 hours after the surgeries (P=0.0001. Conclusion. Single dose of magnesium sulfate during balanced general anesthesia could be considered as effective and safe method to reduce postoperative pain and opioid consumption after TAH.

Evaluation of the Pharmacokinetics of Single- and Multiple-dose Buprenorphine Buccal Film in Healthy Volunteers.

Science.gov (United States)

Bai, Stephen A; Xiang, Qinfang; Finn, Andrew

2016-02-01

Buprenorphine, a partial μ-receptor agonist, is approved for the management of moderate to severe pain, but it has low oral bioavailability. Two open-label studies were performed to determine the pharmacokinetic profile of buprenorphine from buccal film formulations of buprenorphine. Both studies enrolled healthy volunteers, aged 18 to 55 years, who received concurrent oral naltrexone to reduce adverse events (AEs); subjects with a history or evidence of substance abuse or current use of any product affecting cytochrome P450 3A4 activity were excluded. The first study (n = 25) was a 5-period crossover trial with 4 single doses (75 and 300 and 300 and 1200 μg) of 2 formulations (F14 and F24) of buccal buprenorphine (BBUP) and a 300-μg intravenous dose of buprenorphine with a 7-day washout between periods. In the second study, each subject (n = 10) received 6 doses of 4 BBUP strengths (60, 120, 180, and 240 μg BID) in a dose-escalation design. Plasma concentrations of buprenorphine and norbuprenorphine were assayed, and pharmacokinetics were summarized with descriptive statistics and analyzed by using a linear mixed effects model (single-dose study). AEs were recorded. In the single-dose study, the 2 formulations exhibited comparable bioavailability of 46% to 51% that was independent of dose, with a single buprenorphine peak concentration from each BBUP dose occurring at 2.5 to 3 hours. The mean buprenorphine Cmax across the doses ranged from 0.17 ng/mL for the 75-µg dose to 1.43 ng/mL for the 1200-µg dose. AUC0-∞, AUC0-last, and Cmax were proportional to the dose of BBUP administered. Cmax of norbuprenorphine after BBUP administration was approximately one tenth that of buprenorphine Cmax. In the multiple-dose study, steady state was reached within 3 days of BID dosing. There was a linear increase in exposure across the dose range from 60 to 240 μg BID. Treatment-emergent AEs in both studies were consistent with those reported with opiate administration to

Low-dose sevoflurane promotes hippocampal neurogenesis and facilitates the development of dentate gyrus-dependent learning in neonatal rats.

Science.gov (United States)

Chen, Chong; Shen, Feng-Yan; Zhao, Xuan; Zhou, Tao; Xu, Dao-Jie; Wang, Zhi-Ru; Wang, Ying-Wei

2015-01-01

Huge body of evidences demonstrated that volatile anesthetics affect the hippocampal neurogenesis and neurocognitive functions, and most of them showed impairment at anesthetic dose. Here, we investigated the effect of low dose (1.8%) sevoflurane on hippocampal neurogenesis and dentate gyrus-dependent learning. Neonatal rats at postnatal day 4 to 6 (P4-6) were treated with 1.8% sevoflurane for 6 hours. Neurogenesis was quantified by bromodeoxyuridine labeling and electrophysiology recording. Four and seven weeks after treatment, the Morris water maze and contextual-fear discrimination learning tests were performed to determine the influence on spatial learning and pattern separation. A 6-hour treatment with 1.8% sevoflurane promoted hippocampal neurogenesis and increased the survival of newborn cells and the proportion of immature granular cells in the dentate gyrus of neonatal rats. Sevoflurane-treated rats performed better during the training days of the Morris water maze test and in contextual-fear discrimination learning test. These results suggest that a subanesthetic dose of sevoflurane promotes hippocampal neurogenesis in neonatal rats and facilitates their performance in dentate gyrus-dependent learning tasks. © The Author(s) 2015.

Is a single dose of meningococcal serogroup C conjugate vaccine sufficient for protection? experience from the Netherlands

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Kaaijk Patricia

2012-02-01

Full Text Available Abstract Background The first meningococcal serogroup C (MenC conjugate vaccine was licensed in 1999 and introduced in the United Kingdom. Countries that have implemented the MenC vaccine since then in their national immunisation programmes use different schedules. Nevertheless, all involved countries seem to experience substantial declines in the incidence of MenC disease. Discussion Since 2001, the MenC conjugate vaccine has been implemented in the Netherlands by offering a single dose to all children aged 14 months. Prior to the introduction of the vaccine into the national immunisation programme, a catch-up vaccination campaign was initiated in which a single dose of the MenC conjugate vaccine was offered to all children aged from 14 months up to and including 18 years. Since then, there has been no report of any case of MenC disease among immunocompetent vaccinees. Administration of a single dose of MenC conjugate vaccine after infancy could be beneficial considering the already complex immunisation schedules with large numbers of vaccinations in the first year of life. The present paper deals with the advantages and critical aspects of a single dose of the MenC conjugate vaccine. Summary A single dose of MenC conjugate vaccine at the age of 14 months in combination with a catch up vaccine campaign appeared to be a successful strategy to prevent MenC disease in the Netherlands, thereby confirming that a single dose of the vaccine could sufficiently protect against disease. Nevertheless, this approach can only be justified in countries with a relatively low incidence of serogroup C meningococcal disease in the first year of life. Furthermore, a good surveillance programme is recommended for timely detection of vaccine breakthroughs and outbreaks among non-vaccinees, since long-term protection after a single dose in the second year of life cannot currently be guaranteed.

Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET)

NARCIS (Netherlands)

Vollenweider, FX; Leenders, KL; Oye, [No Value; Hell, D; Angst, J

Until recently, racemic ketamine (S-ketamine/R-ketamine=50:50) has been used to study NMDA receptor hypofunction in relation to pathophysiological models of schizophrenia. Ketamine given to normal humans in subanesthetic doses produces a model psychosis including both positive and negative symptoms

Bile duct evaluation of potential living liver donors with Gd-EOB-DTPA enhanced MR cholangiography: Single-dose, double dose or half-dose contrast enhanced imaging

Energy Technology Data Exchange (ETDEWEB)

Kinner, Sonja, E-mail: Sonja.Kinner@uni-due.de [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Steinweg, Verena [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Maderwald, Stefan [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany); Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); Radtke, Arnold; Sotiropoulos, Georgios [Department of General Surgery, University Hospital Essen (Germany); Forsting, Michael; Schroeder, Tobias [Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen (Germany)

2014-05-15

Introduction: Detailed knowledge of the biliary anatomy is essential to avoid complications in living donor liver transplantation. The aim of this study was to determine the optimal dosage of Gd-EOB-DTPA for contrast-enhanced magnetic resonance cholangiography (ce-MRC) with reference to contrast-enhanced CT cholangiography (ce-CTC). Materials and methods: 30 potential living liver donors (PLLD) underwent both ce-CTC and ce-MRC. Ten candidates each received single, double or half-dose Gd-EOB-DTPA. Ce-MRC images with and without inversion recovery pulses (T1w ± IR) were acquired 20–30 min after intravenous contrast injection. Image data was quantitatively and qualitatively reviewed by two radiologists based on a on a 5-point scale. Data sets were compared using a Mann–Whitney-U-test or Wilcoxon-rank-sum-test. Kappa values were also calculated. Results: All image series provided sufficient diagnostic information both showing normal biliary anatomy and variant bile ducts. Ce-CTC showed statistically significant better results compared to all ce-MRC data sets. T1w MRC with single dose Gd-EOB-DTPA proved to be superior to half and double dose in subjective and objective evaluation without a statistically significant difference. Conclusions: Ce-MRC is at any dosage inferior to ce-CTC. As far as preoperative planning of bile duct surgery is focused on the central biliary anatomy, ce-MRC can replace harmful ce-CTC strategies, anyway. Best results were seen with single dose GD-EOB-DTPA on T1w MRC+IR.

Single dose toxicity and biodistribution studies of [18F] fluorocholine

International Nuclear Information System (INIS)

Campos, Danielle C.; Santos, Priscilla F.; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D.

2013-01-01

[ 18 F]Fluorocholine ( 18 FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of 18 FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of 18 FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

Science.gov (United States)

Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

2011-05-01

The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

Single and Multiple Ascending-dose Studies of Oral Delafloxacin: Effects of Food, Sex, and Age.

Science.gov (United States)

Hoover, Randall; Hunt, Thomas; Benedict, Michael; Paulson, Susan K; Lawrence, Laura; Cammarata, Sue; Sun, Eugene

2016-01-01

The objective of this report is describe the results of 2 studies that examined the pharmacokinetic parameters, safety profile, and tolerability of single and multiple ascending doses of oral delafloxacin and the effects of food, sex, and age on oral delafloxacin pharmacokinetic parameters, safety profile, and tolerability. The first study contained 3 parts and used unformulated delafloxacin in a capsule. Part 1 was a randomized, double-blind, placebo-controlled, single (50, 100, 200, 400, 800, 1200, and 1600 mg) ascending-dose study of oral delafloxacin in healthy men. Part 2 was a single-dose crossover study in which 20 men received 250 mg delafloxacin with or without food. Part 2 also included a parallel group, double-blind, placebo-controlled study in 16 women and 16 elderly men and women who were randomized (3:1) to receive 250 mg delafloxacin or placebo. Part 3 was a randomized, double-blind, placebo-controlled, multiple (100, 200, 400, 800, 1200 mg once daily for 5 days) ascending-dose study of oral delafloxacin in healthy men. The second study was a single-dose, randomized, 3-period crossover study in which participants received 900 mg delafloxacin (2 × 450-mg tablets) under fasted conditions, with a high-fat meal, or fasted with a high-fat meal 2 hours after dosing. Serial blood samples were collected, and plasma pharmacokinetic parameters of delafloxacin were determined. Delafloxacin Cmax and AUC0-∞ increased with increasing oral dose over the dose range of 50 to 1600 mg. The increases in delafloxacin AUC0-∞ were dose proportional at doses of ≥200 mg. Steady state was reached by day 3 of dosing with minimal accumulation of delafloxacin. The Cmax of delafloxacin was decreased slightly in the presence of food. No sex difference in delafloxacin pharmacokinetic parameters was observed. In the elderly men and women, mean delafloxacin Cmax and AUC0-∞ were 35% higher than observed for young adults, which could be partially explained by a decrease in

Study on children patient dose in single-detector and multi-detector row helical computed tomography

International Nuclear Information System (INIS)

Lu Heqing; Zhu Guoying; Zhuo Weihai; Liu Haikuan; Guo Changyi

2008-01-01

Objective: To study and evaluate the radiation dose of children patient in single-detector and multi-detector row helical CT scan. Methods: The head and body CT dose index of 21 CT scanners were tested. Then the values of CTDI w , CTDI vol and DLP were calculated combining with the parameters of routine head and chest scan for children of 0-1 year old group, 5 years old group, 10 years old group and adults. The effective doses of children of every age group and adults in routine head and chest scan were subsequently estimated from effective dose per DLP by age and the calculated values of DLP. Results: CTDI per mAs is greater in the head than that in the body. In head routine scan, the effective doses of 0-1 year old group,5 years old group and 10 year old group were 2.2, 1.3 and 1.1 mSv, respectively. In chest routine scan, the effective doses of 0-1 year old group,5 years old group and 10 years old group were 5.3, 3.1 and 3.4 mSv, respectively. Effective doses to children per mAs are equally 1.8 times higher than corresponding values for adults. The CTDI vol , DLP and effective dose to children in head routine scan for MDCT were greater those that for single-detector CT and dual- detector CT. The CTDI vol , DLP and effective dose to children in chest routine scan for MDCT and dual-detector row CT were smaller than that for single-detector row CT. Conclusions: Children me more radiation risk in CT examination as compared with adults. So we should strictly abide by justification of children CT examination, and optimize the parameters of CT scan rationally in order to reduce the radiation dose to children patient as much as possible. (authors)

Acoustic neuromas: single dose vs fractionated therapy

Energy Technology Data Exchange (ETDEWEB)

Fuss, M; Debus, J; Lohr, F; Engenhart-Cabillic, R; Wannenmacher, M

1997-07-01

Purpose: Radiosurgical treatment (RS) of acoustic neuromas is a well established treatment. However, few data are available concerning conformal fractionated radiotherapy (FT) of this tumor entity. We evaluated treatment outcome and toxicity for both treatment modalities in 41 patients treated at our institution between 1984 and 1997. Material and Methods: All treatments were performed using a specially adapted linear accelerator and circular collimators for convergent beam RS or multi-leaf collimators (leaf thickness 1 or 3mm) for multi-field RS or fractionated treatment. 22 patients (7 male, 15 female, median age 60 years, range 20-83 years) were treated radiosurgically with single doses between 7 and 28 Gray (median 15 Gy) prescribed to the 80% isodose line. Tumor volumes ranged from 0.7 to 10.5 ccm with a median volume of 3.4 ccm. The median number of isocenters was 2 (1-4 isocenters). One patient was treated by a multi-field technique (14 isocentric irregularly shaped noncoplanar fields). 19 patients (5 male, 14 female, median age 55 years, range 20-81 years) were treated with stereotactic conformal radiotherapy. Median dose was 60 Gray with a median daily fraction size of 2 Gy and a median of 3 (1-4) irregularly shaped isocentric fields. Tumor volumes ranged from 0.7 to 32.4 ccm (median 15 ccm). Median follow-up was 30 months (7-149 months) for radiosurgical and 30 months (2-88 months) for fractionated treatment. Seven patients who underwent fractionated treatment had previously undergone neurosurgical resection on the contralateral side. One had undergone radiosurgery on the opposite side before. Results: All tumors were locally controlled. A volume reduction of more than 20% was seen in 16% after RS and 18% following FT. Typical posttherapeutic central reduction of contrast media enhancement was found in 73% following RS after a median of 8 (3-12) months and in 63% following FT after a median of 6 (1-12) months. Temporary brainstem edema was diagnosed in 4

Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults.

Science.gov (United States)

Barden, Jodie; Derry, Sheena; McQuay, Henry J; Moore, R Andrew

2009-10-07

Ketoprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. To assess efficacy, duration of action, and associated adverse events of single dose oral ketoprofen and dexketoprofen in acute postoperative pain in adults. We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to August 2009. Randomised, double blind, placebo-controlled trials of single dose orally administered ketoprofen and dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number-needed-to-treat-to-benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals was collected. Fourteen studies compared ketoprofen (968 participants) at mainly 25 mg and 50 mg with placebo (520 participants). Seven studies compared dexketoprofen (681 participants) at mainly 10 mg to 25 mg with placebo (289 participants). Studies were of adequate reporting quality, and participants had pain following dental, orthopaedic, obstetric, gynaecological and general surgery. There was considerable clinical heterogeneity between studies in dental and other types of surgery, particularly bunionectomy, which limited analysis.Ketoprofen at doses between 12.5 mg and 100 mg produced NNTs for at least 50% pain relief over 4 to 6

Effect of propranolol in head tremor: quantitative study following single-dose and sustained drug administration.

Science.gov (United States)

Calzetti, S; Sasso, E; Negrotti, A; Baratti, M; Fava, R

1992-12-01

The effect of the beta-adrenoceptor antagonist propranolol has been investigated in nine patients suffering from isolated (six patients) or prominent (three patients) essential tremor of the head. In a double-blind, placebo-controlled study the tremorolytic efficacy of propranolol has been assessed by a quantitative accelerometric method after a single oral dose (120 mg) and following 2 weeks of sustained treatment with two different dosage regimens of the drug (120 and 240 mg daily). As compared with placebo, a significant reduction in tremor magnitude was found following a single oral dose but not on sustained administration of the beta-blocker at either dosage. The results suggest that the efficacy of sustained propranolol on isolated or prominent essential head tremor is less predictable and satisfactory than expected on the basis of the single-dose response, as compared with hand tremor.

Mouse single oral dose toxicity test of bupleuri radix aqueous extracts.

Science.gov (United States)

Kim, Kyung-Hu; Gam, Cheol-Ou; Choi, Seong-Hun; Ku, Sae-Kwang

2012-03-01

The aim of this study was to evaluate the single oral dose toxicity of Bupleuri Radix (BR) aqueous extracts, it has been traditionally used as anti-inflammatory agent, in male and female mice. BR extracts (yield = 16.52%) was administered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 14 principal organs were examined. As the results, no BR extracts treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principal organs were detected up to 2,000 mg/kg in both female and male mice, except for soft feces and related body weight decrease detected in male mice treated with 2,000 mg/kg. Therefore, LD50 (50% lethal dose) and approximate LD of BR aqueous extracts after single oral treatment in female and male mice were considered over 2000 mg/kg, respectively. Although it was also observed that the possibilities of digestive disorders, like soft feces when administered over 2,000 mg/kg of BR extracts in the present study, these possibilities of digestive disorders can be disregard in clinical use because they are transient in the highest dosages male only.

Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [F-18]fluorodeoxyglucose (FDG)

NARCIS (Netherlands)

Vollenweider, FX; Leenders, KL; Scharfetter, C; Antonini, A; Maguire, P; Missimer, J; Angst, J

To date, the ketamine/PCP model of psychosis has been proposed to be one of the best pharmacological models to mimic schizophrenic psychosis in healthy volunteers, since ketamine can induce both positive and negative symptoms of schizophrenia. At subanesthetic doses, ketamine has been reported to

Pharmacokinetics of lansoprazole and its main metabolites after single and multiple intravenous doses in healthy Chinese subjects.

Science.gov (United States)

Zhang, Dan; Zhang, Yanan; Liu, Man; Wang, Xiaolin; Yang, Man; Han, Jing; Liu, Huichen

2013-09-01

The aim of the study was to evaluate and compare the pharmacokinetics of lansoprazole (LPZ) and its main metabolites, 5'-hydroxy lansoprazole (HLPZ) and lansoprazole sulfone (LPZS), after single and multiple intravenous (i.v.) doses of LPZ in healthy Chinese subjects. Twelve subjects (six males and six females) were given a single dose of LPZ by i.v. infusion on day 1, and multiple doses from day 2 to day 6. Blood samples were collected at designated time points for analysis of plasma concentrations of LPZ, HLPZ and LPZS by an LC-MS/MS method. LPZ was generally well tolerated in healthy Chinese subjects. After single and multiple i.v. doses of 30 mg LPZ, the C max values of LPZ, HLPZ and LPZS were 1490 ± 290 and 1450 ± 280, 175 ± 71 and 154 ± 56, and 51.3 ± 82.9 and 74.1 ± 158.7 ng/mL, with the AUC0-t values 3280 ± 2550 and 4260 ± 3880, 381 ± 128 and 389 ± 111, and 389 ± 1204 and 700 ± 2255 ng h/mL, respectively. The t 1/2 and CL values of LPZ after single and multiple i.v. doses were 1.48 ± 1.03 and 2.19 ± 1.03 h, and 11.67 ± 4.49 and 9.56 ± 4.08 L/h, respectively. Compared with the pharmacokinetics of LPZ after a single dose, t 1/2 increased markedly, CL decreased significantly and AUC increased by over 20 % after multiple doses. The results indicated that there was drug accumulation of LPZ after multiple i.v. doses, and there was no gender-related difference in pharmacokinetics of LPZ and its two metabolites.

A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles.

Science.gov (United States)

Kurosawa, Yuko; Nirengi, Shinsuke; Homma, Toshiyuki; Esaki, Kazuki; Ohta, Mitsuhiro; Clark, Joseph F; Hamaoka, Takafumi

2015-06-25

Our aim was to determine the quantitative effects of a single-dose of Nattokinase (NK) administration on coagulation/fibrinolysis parameters comprehensively in healthy male subjects. A double-blind, placebo-controlled cross-over NK intervention study was carried out in 12 healthy young males. Following the baseline blood draw, each subject was randomized to receive either a single-dose of 2,000 FU NK (NSK-SD, Japan Bio Science Laboratory Co., Ltd) or placebo with subsequent cross-over of the groups. Subjects donated blood samples at 2, 4, 6 and 8 hours following administration for analysis of coagulation/fibrinolysis parameters. As a result, D-dimer concentrations at 6, and 8 hours, and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively). Factor VIII activity declined at 4 and 6 hours (p < 0.05, respectively), blood antithrombin concentration was higher at 2 and 4 hours (p < 0.05, respectively), and the activated partial thromboplastin time prolonged significantly at 2 and 4 hours following NK administration (p < 0.05 and p < 0.01, respectively). All the changes, however, were within the normal range. In conclusion, thus, a single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.

Comparative pharmacokinetics of oxytetracycline in blunt-snout bream (Megalobrama amblycephala) with single and multiple-dose oral administration.

Science.gov (United States)

Li, Ru-Qin; Ren, Yu-Wei; Li, Jing; Huang, Can; Shao, Jun-Hui; Chen, Xiao-Xuan; Wu, Zhi-Xin

2015-06-01

Research into the pharmacokinetics and residue elimination of oxytetracycline (OTC) is important both to determine the optimal dosage regimens and to establish a safe withdrawal time in fish. A depletion study is presented here for OTC in Megalobrama amblycephala with a single-dose (100 mg/kg) and multiple-dose (100 mg/kg for five consecutive days) oral administration. The study was conducted at 25 °C. As a result, a one-compartment model was developed. For the single dose, the absorption half-life was 5.79, 9.40, 6.96, and 8.06 h in the plasma, liver, kidney, and muscle, respectively. However, the absorption half-life was 3.62, 7.33, 4.59, and 6.02 h with multiple-dose oral administration. The elimination half-time in the plasma, liver, kidney, and muscle was 58.63, 126.43, 65.1, and 58.85 h when M. amblycephala was treated with a single dose. However, the elimination half-time changed to 91.75, 214.87, 126.22, and 135.84 h with multiple-dose oral administration.

Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

Energy Technology Data Exchange (ETDEWEB)

Hong, Linda X.; Garg, Madhur; Lasala, Patrick; Kim, Mimi; Mah, Dennis; Chen, Chin-Cheng; Yaparpalvi, Ravindra; Mynampati, Dinesh; Kuo, Hsiang-Chi; Guha, Chandan; Kalnicki, Shalom [Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Neurosurgery, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Epidemiology and Population Health, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States)

2011-03-15

Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems, Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group

Incorporating single-side sparing in models for predicting parotid dose sparing in head and neck IMRT

International Nuclear Information System (INIS)

Yuan, Lulin; Wu, Q. Jackie; Yin, Fang-Fang; Yoo, David; Jiang, Yuliang; Ge, Yaorong

2014-01-01

Purpose: Sparing of single-side parotid gland is a common practice in head-and-neck (HN) intensity modulated radiation therapy (IMRT) planning. It is a special case of dose sparing tradeoff between different organs-at-risk. The authors describe an improved mathematical model for predicting achievable dose sparing in parotid glands in HN IMRT planning that incorporates single-side sparing considerations based on patient anatomy and learning from prior plan data. Methods: Among 68 HN cases analyzed retrospectively, 35 cases had physician prescribed single-side parotid sparing preferences. The single-side sparing model was trained with cases which had single-side sparing preferences, while the standard model was trained with the remainder of cases. A receiver operating characteristics (ROC) analysis was performed to determine the best criterion that separates the two case groups using the physician's single-side sparing prescription as ground truth. The final predictive model (combined model) takes into account the single-side sparing by switching between the standard and single-side sparing models according to the single-side sparing criterion. The models were tested with 20 additional cases. The significance of the improvement of prediction accuracy by the combined model over the standard model was evaluated using the Wilcoxon rank-sum test. Results: Using the ROC analysis, the best single-side sparing criterion is (1) the predicted median dose of one parotid is higher than 24 Gy; and (2) that of the other is higher than 7 Gy. This criterion gives a true positive rate of 0.82 and a false positive rate of 0.19, respectively. For the bilateral sparing cases, the combined and the standard models performed equally well, with the median of the prediction errors for parotid median dose being 0.34 Gy by both models (p = 0.81). For the single-side sparing cases, the standard model overestimates the median dose by 7.8 Gy on average, while the predictions by the combined

Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses.

Science.gov (United States)

Wach, Achim; Dembowsky, Klaus; Dale, Glenn E

2018-04-01

Murepavadin is the first in class of the outer membrane protein-targeting antibiotics (OMPTA) and a pathogen-specific peptidomimetic antibacterial with a novel, nonlytic mechanism of action targeting Pseudomonas aeruginosa Murepavadin is being developed for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The pharmacokinetics (PK) and safety of single and multiple doses of murepavadin were investigated in healthy male subjects. Part A of the study was a double-blind, randomized, placebo-controlled, single-ascending-dose investigation in 10 sequential cohorts where each cohort comprised 6 healthy male subjects; 4 subjects were randomized to murepavadin, and 2 subjects were randomized to placebo. Part B was a double-blind, randomized, placebo-controlled, multiple-ascending-dose investigation in 3 sequential cohorts. After a single dose of murepavadin, the geometric mean half-life (2.52 to 5.30 h), the total clearance (80.1 to 114 ml/h/kg), and the volume of distribution (415 to 724 ml/kg) were consistent across dose levels. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Murepavadin was well tolerated, adverse events were transient and generally mild, and no dose-limiting toxicity was identified. Copyright © 2018 American Society for Microbiology.

Determination of burial dose in incompletely bleached fluvial samples using single grains of quartz

DEFF Research Database (Denmark)

Thomsen, Kristina Jørkov; Murray, A.S.; Bøtter-Jensen, Lars

2007-01-01

We determine the burial dose in three known-age incompletely bleached fluvial samples using single grains of quartz. Estimation of burial dose in incompletely bleached samples requires that the characteristics of the well-bleached part of the distribution are known in order to distinguish between...... well-bleached and poorly bleached grains. It is especially important to investigate if the uncertainties assigned to individual estimates of dose adequately describe the observed variability in well-bleached dose distributions. We investigate this by quantifying the overdispersion in laboratory-bleached...

Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Sanchez-Migallon Guzman, David; Flammer, Keven; Papich, Mark G; Grooters, Amy M; Shaw, Shannon; Applegate, Jeff; Tully, Thomas N

2010-04-01

To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). 15 clinically normal adult Hispaniolan Amazon parrots. Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

Single dose planning for radioiodine-131 therapy of Graves' disease

International Nuclear Information System (INIS)

Kita, Tamotsu; Yokoyama, Kunihiko; Kinuya, Seigo; Taki, Junichi; Michigishi, Takatoshi; Tonami, Norihisa

2004-01-01

Patients with Graves' disease were studied one year after radioiodine-131 therapy to assess the relationship between the effectiveness of the therapy and the radioiodine doses used. Patients were classified into three groups according to thyroid function as hyperthyroidism, euthyroidism and hypothyroidism at one year after I-131 therapy. In these groups we compared the mean values of dose, dose per thyroid weight calculated with I-123 uptake before the therapy (pre D/W), dose per thyroid weight calculated with therapeutic I-131 uptake (post D/W), and absorbed dose. No significant differences were found between the three groups in terms of dose or pre D/W. The mean values of post D/W and absorbed dose in the non-hyperthyroid (euthyroid and hypothyroid) group were significantly greater than those in the hyperthyroid group. Post D/W of 6.3 MBq/g was a threshold separating the non-hyperthyroid group from the hyperthyroid group. There was no correlation between pre D/W and post D/W; however, the mean post D/W was significantly greater than the mean pre D/W. All patients with pre D/W above 6.3 MBq/g showed non-hyperthyroidism at one year after the radioiodine treatment. No indicators before the radioiodine therapy had significant relationships with the effectiveness of the therapy at one year after the treatment. However, the single therapy planned for setting the pre D/W above 6.3 MBq/g will certainly make the patients non-hyperthyroid. As this proposal of dose planning is based on a small number of patients, further study is needed. (author)

Absorption, Distribution, and Excretion of 14C-APX001 after Single-Dose Administration to Rats and Monkeys

OpenAIRE

Mansbach, Robert; Shaw, Karen J; Hodges, Michael R; Coleman, Samantha; Fitzsimmons, Michael E

2017-01-01

Abstract Background APX001 is a small-molecule therapeutic agent in clinical development for the treatment of invasive fungal infections (IFI). Methods The absorption, distribution and excretion profiles of [14C]APX001-derived radioactivity were determined in rats (albino and pigmented) and monkeys. Rats (some implanted with bile duct cannulae) were administered a single 100 mg/kg oral dose or a 30 mg/kg intravenous (IV) dose. Monkeys were administered a single 6 mg/kg IV dose. Samples of blo...

Improved metabolic control in tetrahydrobiopterin (BH4), responsive phenylketonuria with sapropterin administered in two divided doses vs. a single daily dose.

Science.gov (United States)

Kör, Deniz; Yılmaz, Berna Şeker; Bulut, Fatma Derya; Ceylaner, Serdar; Mungan, Neslihan Önenli

2017-07-26

Phenylketonuria (PKU) often requires a lifelong phenylalanine (Phe)-restricted diet. Introduction of 6R-tetrahydrobiopterin (BH4) has made a huge difference in the diets of patients with PKU. BH4 is the co-factor of the enzyme phenylalanine hydroxylase (PAH) and improves PAH activity and, thus, Phe tolerance in the diet. A limited number of published studies suggest a pharmacodynamic profile of BH4 more suitable to be administered in divided daily doses. After a 72-h BH4 loading test, sapropterin was initiated in 50 responsive patients. This case-control study was conducted by administering the same daily dose of sapropterin in group 1 (n=24) as a customary single dose or in two divided doses in group 2 (n=26) over 1 year. Mean daily consumption of Phe increased significantly after the first year of BH4 treatment in group 2 compared to group 1 (p<0.05). At the end of the first year of treatment with BH4, another dramatic difference observed between the two groups was the ability to transition to a Phe-free diet. Eight patients from group 2 and two from group 1 could quit dietary restriction. When given in two divided daily doses, BH4 was more efficacious than a single daily dose in increasing daily Phe consumption, Phe tolerance and the ability to transition to a Phe-unrestricted diet at the end of the first year of treatment.

Single dose of fluoxetine increases muscle activation in chronic stroke patients.

NARCIS (Netherlands)

van Genderen, Hanneke Irene; Nijlant, Juliette M.M.; van Putten, Michel Johannes Antonius Maria; Movig, Kris L.L.; IJzerman, Maarten Joost

2009-01-01

Objectives: This pilot study explores the influence of a single dose of fluoxetine (20 mg) on the muscle activation patterns and functional ability of the muscles in the lower part of the arm in chronic stroke patients. Methods: A crossover, placebo-controlled clinical trial was conducted in 10

A single 2 g oral dose of extended-release azithromycin for treatment of gonococcal urethritis.

Science.gov (United States)

Yasuda, Mitsuru; Ito, Shin; Kido, Akira; Hamano, Kiminari; Uchijima, Yutaka; Uwatoko, Noriyasu; Kusuyama, Hiroyuki; Watanabe, Akiko; Miyamura, Ryuzou; Miyata, Kazutoyo; Deguchi, Takashi

2014-11-01

We treated gonococcal urethritis in men with a single 2 g dose of azithromycin extended-release formulation (azithromycin-SR) to determine its microbiological outcomes and tolerability. We enrolled 189 Japanese men with gonococcal urethritis between April 2009 and December 2013. The patients were given a single 2 g dose of azithromycin-SR. Microbiological efficacy was evaluated by the results of the post-treatment molecular testing of Neisseria gonorrhoeae. MIC testing was performed only for pretreatment isolates of N. gonorrhoeae collected from the patients. We evaluated 130 patients for microbiological outcomes. Of these patients, 122 (93.8%) were judged to be microbiologically cured on the basis of negative test results. All isolates for which the azithromycin MICs were ≤0.25 mg/L were eradicated, whereas 5 of 12 isolates for which the MICs were 1 mg/L persisted after the treatment. Forty-six adverse events occurred in 41 patients. However, all adverse events were classified as mild. The eradication rate of N. gonorrhoeae was 93.8% in men with gonococcal urethritis treated with a single 2 g dose of azithromycin-SR. The breakpoint MIC of a 2 g dose of azithromycin-SR for gonococcal urethritis associated with clinical treatment failures appeared to be 1 mg/L. With regard to side effects of higher doses of azithromycin, the 2 g dose of azithromycin-SR appeared to improve tolerability. However, the widespread use of a high-dose regimen of azithromycin might lead to the development of further resistance to azithromycin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Single dose oral piroxicam for acute postoperative pain

Science.gov (United States)

Moore, R Andrew; Edwards, Jayne; Loke, Yoon; Derry, Sheena; McQuay, Henry J

2014-01-01

Background This is an updated version of the original Cochrane review published in Issue 2, 2000. Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations. Objectives To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics. Search methods Published studies were identified from systematic searching of MEDLINE, Biological Abstracts, EMBASE, CENTRAL and the Oxford Pain Relief Database in December 2007. Additional studies were identified from the reference lists of retrieved reports. Selection criteria The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult participants, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam. Data collection and analysis Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of participants obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat-to-benefit (NNT) for one participant to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-treat-to-harm (NNH) were calculated. Main results In this update no further studies were found. The original search identified three studies (141 participants) which compared oral piroxicam 20 mg with placebo and

Compendium of Single Event Effects, Total Ionizing Dose, and Displacement Damage for Candidate Spacecraft Electronics for NASA

Science.gov (United States)

LaBel, Kenneth A.; OBryan, Martha V.; Chen, Dakai; Campola, Michael J.; Casey, Megan C.; Pellish, Jonathan A.; Lauenstein, Jean-Marie; Wilcox, Edward P.; Topper, Alyson D.; Ladbury, Raymond L.;

Regional cerebral energy metabolism during intravenous anesthesia with etomidate, ketamine or thiopental

International Nuclear Information System (INIS)

Davis, D.W.

1987-01-01

Regional brain glucose utilization (rCMRglc) was measured in rats during steady-state levels of intravenous anesthesia to determine if alterations in brain function due to anesthesia could provide information on the mechanisms of anesthesia. Intravenous anesthetics from three different chemical classes were studied: etomidate, ketamine and thiopental. All rCMRglc experiments were conducted in freely moving rats in isolation chambers, with the use of [6- 14 C] glucose and guantitative autoradiography. Etomidate caused a rostral-to-caudal gradient of depression of rCMRglc. The four doses of etomidate did not differ in their effects on energy metabolism. Sub-anesthetic (5 mg kg -1 ) and anesthetic (30 mg kg -1 ) doses of ketamine produced markedly different patterns of behavior. Brain energy metabolism during the sub-anesthetic dose was stimulated in most regions, while the anesthetic dose selectively stimulated the hippocampus, leaving most brain regions unaffected. Thiopental produced a dose-dependent reduction of rCMRglc in all gray matter regions. No brain region was selectively affected. Comparison of the drug-specific alterations of cerebral energy metabolism suggests these anesthetics do not act through a common mechanism. The hypothesis that each acts by binding to specific cell membrane receptors is consistent with these observations

Single fixed-dose oral dexketoprofen plus tramadol for acute postoperative pain in adults.

Science.gov (United States)

Derry, Sheena; Cooper, Tess E; Phillips, Tudor

2016-09-22

Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. A new combination of dexketoprofen (a nonsteroidal anti-inflammatory drug) plus tramadol (an opioid) has been tested in acute postoperative pain conditions. It is not yet licensed for use. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions. To assess the analgesic efficacy and adverse effects of a single fixed-dose of oral dexketoprofen plus tramadol, compared with placebo, for moderate to severe postoperative pain in adults, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. A secondary objective was to compare the combination with the individual analgesics alone. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via CRSO, MEDLINE via Ovid, and Embase via Ovid from inception to 31 May 2016. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. Randomised, double-blind trials of oral dexketoprofen plus tramadol administered as a single oral dose, for the relief of acute postoperative pain in adults, and compared to placebo. Two review authors independently considered trials for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) for dexketoprofen plus tramadol, compared with placebo with 95% confidence intervals (CI). We collected information on the number of participants with at least 50% of

The effects of peritoneal dialysis on the single dose and steady state pharmacokinetics of valproic acid in a uremic epileptic child.

Science.gov (United States)

Orr, J M; Farrell, K; Abbott, F S; Ferguson, S; Godolphin, W J

1983-01-01

The pharmacokinetics of valproic acid (VPA) have been studied during peritoneal dialysis in a uremic male epileptic child following a single 500 mg dose and after multiple doses over 5 months (700 mg daily) of valproic acid as the syrup. Serum level decline was biphasic in both instances with a terminal half-life of 27.2 after the single dose and 10.2 h at steady-state. Total serum clearance was 0.0236 l/h/kg after the single dose and increased to 0.0408 l/h/kg after 5 months. Free (intrinsic) serum clearances were 0.1489 and 0.1518 l/h/kg and serum free fractions were 0.224 and 0.272 respectively for the single dose and steady-state studies. Peritoneal dialysis for periods of 12 or 24 h removed an average of 4.5% of the VPA dose.

A Systematic Review on Effect of Single-Dose Preoperative Antibiotics at Surgical Osteotomy Extraction of Lower Third Molars

DEFF Research Database (Denmark)

Marcussen, Karoline Brørup; Laulund, Anne Sofie; Jørgensen, Henrik L

2016-01-01

PURPOSE: We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effectiveness of a single dose of preoperative antibiotic administered perorally, intravenously, intramuscularly, or topically for preventing infection and alveolar osteitis in lower third molar...... that penicillin V was effective in reducing the incidence of alveolar osteitis (OR = 0.1; 95% CI, 0.03 to 0.30; P ≤ .0001). CONCLUSIONS: A single oral dose of 2 g of amoxicillin before lower third molar osteotomy surgical extraction significantly decreased the incidence of SSI. A single dose of 0.8 g...... of penicillin V before lower third molar osteotomy surgical extraction significantly decreased the incidence of alveolar osteitis....

Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge

CSIR Research Space (South Africa)

Mallajosyula, JK

2014-03-01

Full Text Available 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H 1 N 1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large...

Sources of variability in OSL dose measurements using single grains of quartz

DEFF Research Database (Denmark)

Thomsen, Kristina Jørkov; Murray, A.S.; Bøtter-Jensen, L.

2005-01-01

spread. In this preliminary study, dose distributions have been studied using single grains of heated and laboratory irradiated quartz. By heating the sample, the contribution from incomplete zeroing was excluded and at the same time the sample was sensitised. The laboratory gamma irradiation...

Effects of a preovulatory single low dose of mifepristone on ovarian function

NARCIS (Netherlands)

van der Stege, Jolande G.; Pahl-van Beest, Elske H.; Beerthuizen, Rob J. C. M.; van Lunsen, Rik H. W.; Scholten, Piet C.; Bogchelman, Dick H.

Objectives To investigate the effect of a single low dose of mifepristone on ovarian function, when administered in the preovulatory period. Methods Healthy women with regular menstrual cycles were studied during two consecutive menstrual cycles. Either mifepristone or placebo was given in a

Optimizing a single fixed dose of Iodine-131 in Graves' Disease (An Experience)

International Nuclear Information System (INIS)

Khan, S.H.

2007-01-01

Full text: Kashmir is a Himalayan mountain state of India enclosed by high snow capped ridges of Pir Panjal Mountains at an average height of 4000-5000 meters above the sea level. For most of the 4 million inhabitants in this land locked valley, agriculture horticulture and handcrafts are the main source of income. Due to long and severe winters the terraced farming on the mountain slopes yield just a single crop of rice which is barely sufficient to meet the local needs of this staple diet. People are relatively poor with low annual per capita income. Goiter is endemic in the Valley of Kashmir. In a published report the overall prevalence of goiter among the school going children in Kashmir between the ages of 5 years is 45.2% (+ SEM) with urinary iodine excretion of 49 + 3.55 μg per gram of creatinine. The extremely shy people of Kashmir are casual towards the aesthetic aspects of their goiters but nevertheless seek medical advice when associated with physical symptoms. In a published study of 203 patients of thyrotoxicosis from Kashmir, Graves' disease was the commonest cause, accounting for 63% of patients. One hundred and twentyone patients of Graves' disease were prospectively studied for their response to a single fixed dose of I-131. Patients were randomly treated with two different fixed doses of I- 131. Sixty four patients belonging to Group-I received a fixed dose of 185 MBq (Low Dose) and 57 patients belonging to Group -2 received 370 MBq (High Dose) of I- 131. Following therapy all patients were evaluated at 3 months. Patients with normal or reduced thyroid hormone levels were termed as responders and those with persistently elevated levels of thyroid hormone were termed as non responders. The response rates among the two groups were analyzed for their statistical significance. Patients treated with the high fixed dose of 370 MBq revealed good response to therapy achieving a rate of 91.22%, while the response rate in the group of patients treated with

Functional and morphological changes in pig skin after single or fractionated doses in x rays

International Nuclear Information System (INIS)

Young, C.M.A.; Hopewell, J.W.

1982-01-01

The flank skin of pigs has been treated with either single or fractionated doses of x-irradiation. A single dose (2070 cGy) was compared with treatment given as 6 fractions in 18 days (6f/18 days; 3780 cGy) or 30 fractions in 39 days (30f/39 days; 8000 cGy). The doses were selected on the basis that similar levels of late tissue damage would result. Radiation induced changes in the skin were assessed by observing the skin reactions and by the measurement of isotope clearance (functional study), relative field contraction, dermal and epidermal thickness and dermal vascular density (morphological studies). In the three treatment groups the early radiation reaction varied considerably. In the first wave reaction (3 to 6 weeks after treatment) bright red erythema was recorded in many fields but moist desquamation developed only in the 30f/39 days treatment group. The second wave (10-16 weeks) was characterized by an ischemic mauve/dusky reaction. Dermal necrosis developed in 50% of the single dose fields. In the 30f/39 days regimen persistent moist desquamation progressed to dermal necrosis. Neither desquamation nor necrosis developed after 6f/18 days. Different levels of vascular damage in the dermis were assessed using an isotope clearance technique; for example in the early reaction significant changes were recorded in the papillary dermis (faster clearance) prior to the development of moist desquamation (30f/39 days) and in the reticular dermis (slower clearance) before necrosis (single dose). Changes in clearance rates have been correlated with changes in the vascular density and thickness of the dermis. Between 26 and 52 weeks (the late reaction) relative field contraction was slightly greater in the 30f/39 days group than in the other treatment groups

Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

International Nuclear Information System (INIS)

Leith, J.L.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Walton, R.E.; Woodruff, K.H.; Howard, J.

1980-01-01

The response of rat spinal cord to irradiation with accelerated heavy ions, in particular carbon and neon ions has been studied. Two different ionization regions in the modified Bragg curve for each ion have been studied for both single and fractionated exposures. We have defined the paralytic response as a function of dose and dose per fraction, and we have determined RBE and repair values. The response of rat spinal cord is both dose and LET dependent, which allows the derivation of RBE and repair values

Cell kinetic changes in the follicular epithelium of pig skin after irradiation with single and fractionated doses of X rays

International Nuclear Information System (INIS)

Morris, G.M.; Hopewell, J.W.

1989-01-01

Changes in cell kinetics of the follicular epithelium of the pig were studied after x-irradiation with single and fractionated doses (30 fractions/39 days) and compared with previous epidermal data. In the follicular epithelium there was an initial degenerative phase, when the rate of cell depletion was independent of radiation dose and mode of administration. Repopulation was seen between the 14th and 18th days after single doses (15 or 20 Gy) and by the 28th day after the start of irradiation with fractionated doses (52.3-80.0 Gy). The degree of cell depletion and subsequent rate of repopulation were independent of dose. The regenerative phase was characterized by an increased cell proliferation. Islands of cells with appearance similar to cells in the normal follicular epithelium, were seen 18 days after a single dose of 20 Gy and 42 days after the start of fractionated irradiation. Compared with the epidermis, the follicular epithelium exhibited considerably less evidence of damage after both single and fractionated doses. There was a lower incidence of degenerate cells and reduced levels of cell depletion in the follicular epithelium. (author)

Sources of variability in OSL dose measurements using single grains of quartz

International Nuclear Information System (INIS)

Thomsen, K.J.; Murray, A.S.; Boetter-Jensen, L.

2005-01-01

In luminescence-based measurements of dose distributions in unheated mineral samples, the observed spread in dose values is usually attributed to four main factors: fluctuations in the number of photons counted, incomplete zeroing of any prior trapped charge (including signals arising from thermal transfer), heterogeneity in dosimetry, and instrument reproducibility. For correct interpretation of measured dose distributions in retrospective dosimetry, it is important to understand the relative importance of these components, and to establish whether other factors also contribute to the observed spread. In this preliminary study, dose distributions have been studied using single grains of heated and laboratory irradiated quartz. By heating the sample, the contribution from incomplete zeroing was excluded and at the same time the sample was sensitised. The laboratory gamma irradiation was designed to deliver a uniform dose to the sample. Thus it was anticipated that statistical fluctuations in the number of photons counted and instrument reproducibility, both quantifiable entities, should be able to account for all the observed variance in the measured dose distributions. We examine this assumption in detail, and discuss the origins and importance of the residual variance in our data

Evaluation of sphingolipids in Wistar rats treated to prolonged and single oral doses of fumonisin b₁.

Science.gov (United States)

Direito, Glória M; Almeida, Adriana P; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

2009-01-01

The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B(1) (FB(1)). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB(1). Prolonged exposure to FB(1) caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB(1). Animals receiving a single dose of FB(1) presented variations in Sa and So levels and in the Sa/So ratio.

Single dose toxicity and biodistribution studies of [{sup 18}F] fluorocholine

Energy Technology Data Exchange (ETDEWEB)

Campos, Danielle C.; Santos, Priscilla F., E-mail: dcc@cdtn.br [Universidade Federal de Minas Gereais (INCT-MM/UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina. Instituto Nacional de Ciencia e Tecnologia de Medicina Molecular; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da, E-mail: radiofarmacoscdtn@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D., E-mail: cassalig@icb.ufmg.br [Universidade Federal de Minas Gerais (LPC/UFMG), Belo Horizonte, MG (Brazil). Lab. de Patologia Comparada

2013-07-01

[{sup 18}F]Fluorocholine ({sup 18}FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of {sup 18}FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of {sup 18}FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

Concentrations of amoxicillin and clindamycin in teeth following a single dose of oral medication.

Science.gov (United States)

Schüssl, Yvonne; Pelz, Klaus; Kempf, Jürgen; Otten, Jörg-Elard

2014-01-01

The main purpose of this study is the detection of amoxicillin and clindamycin concentrations in teeth. Eleven patients received 2 g of amoxicillin, and 11 patients received 600 mg of clindamycin in a single dose of oral medication at least 60 min prior to tooth extraction due to systemic diseases. The concentrations were determined in crowns and roots separately using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Amoxicillin (13 samples) and clindamycin (12 samples) were detected in the samples of the root and crown preparations of the extracted teeth. The mean concentration of amoxicillin was 0.502 μg/g in the roots and 0.171 μg/g in the crowns. The mean concentration of clindamycin was 0.270 μg/g in the roots and 0.064 μg/g in the crowns. A single dose of oral amoxicillin and clindamycin leads to concentrations of both antibiotics in teeth which exceed the minimal inhibition concentration of some oral bacteria. The proof of antibacterial activity in dental hard tissue after oral single-dose application is new. The antimicrobial effect of amoxicillin and clindamycin concentrations in roots of teeth may be of clinical relevance to bacterial reinfection from dentinal tubules.

Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

Science.gov (United States)

Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

2016-01-01

Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a

Single-shot, high-dose rabbit ATG for rejection prophylaxis after kidney transplantation

NARCIS (Netherlands)

R. Zietse (Bob); E.P.M. van Steenberge (E. P M); C.J. Hesse (Cees); L.B. Vaessen (L.); J.N.M. IJzermans (Jan); W. Weimar (Willem)

1993-01-01

textabstractWe studied the effects of a single intravenous injection of rabbit ATG (RIVM, Bilthoven, The Netherlands) in a dose of 8 mg/kg body weight administered 6 h after kidney transplantation on graft survival, rejection incidence, T-cell subsets, and cost-effectiveness. A total of 58 (37

Single and 2-week repeated intravenous dose toxicity studies of disodium mercaptoundecahydro-closo-dodecaborate in rats

Energy Technology Data Exchange (ETDEWEB)

Itoh, Fumio; Yabuuchi, Kazuya; Ohno, Kouji; Muraoka, Yoshihiro [Shionogi and Co. Ltd., Toyonaka, Osaka (Japan). Developmental Research Lab.; Ikeuchi, Isao

1998-10-01

Disodium mercaptoundecahydro-closo-dodecaborate (BSH) is a boron compound used in Boron Neutron Capture Therapy for malignant brain tumors. Intravenous single and 2-week repeated dose toxicity studies of BSH were performed in Sprague-Dawley rats. In the single-dose study, BSH was administered at doses of 100, 300 or 600 mg/kg. Death occurred within 10 min (acute type) or from 5 hr to 2 days (delayed type) after dosing in the 600 mg/kg group. No differences in mortality by sex and dosing speed were observed. Major causes of death were considered to be circulatory disorder in acute death and renal injury in delayed death. The renal injury was observed in the 300 and 600 mg/kg groups. In the 2-week repeated dose study, BSH was administered at doses of 30, 100 or 300 mg/kg/day for 14 days. Body weight gain was suppressed in the 100 and 300 mg/kg groups. One male in the 300 mg/kg group died due to renal and pulmonary lesions at day 8. Slight anemia was observed in the 300 mg/kg group. Pathologically, the kidney showed tubular regeneration with increase of weight in the 300 mg/kg. From these results, the NOAEL of BSH is 30 mg/kg/day. (author)

Radiotherapy for calcaneodynia. Results of a single center prospective randomized dose optimization trial

Energy Technology Data Exchange (ETDEWEB)

Ott, O.J.; Jeremias, C.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R. [University Hospital Erlangen (Germany). Dept. of Radiation Oncology

2013-04-15

The aim of this work was to compare the efficacy of two different dose fractionation schedules for radiotherapy of patients with calcaneodynia. Between February 2006 and April 2010, 457 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy using the orthovoltage technique. One radiotherapy series consisted of 6 single fractions/3 weeks. In case of insufficient remission of pain after 6 weeks a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. Endpoint was pain reduction. Pain was measured before, immediately after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS). The overall response rate for all patients was 87 % directly after and 88 % 6 weeks after radiotherapy. The mean VAS values before, immediately after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 65.5 {+-} 22.1 and 64.0 {+-} 20.5 (p = 0.188), 34.8 {+-} 24.7 and 39.0 {+-} 26.3 (p = 0.122), and 25.1 {+-} 26.8 and 28.9 {+-} 26.8 (p = 0.156), respectively. The mean CPS before, immediately after, and 6 weeks after treatment was 10.1 {+-} 2.7 and 10.0 {+-} 3.0 (p = 0.783), 5.6 {+-} 3.7 and 6.0 {+-} 3.9 (p = 0.336), 4.0 {+-} 4.1 and 4.3 {+-} 3.6 (p = 0.257), respectively. No statistically significant differences between the two single dose trial arms for early (p = 0.216) and delayed response (p = 0.080) were found. Radiotherapy is an effective treatment option for the management of calcaneodynia. For radiation protection reasons, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy. (orig.)

Controlled single-blind clinical evaluation of low-dose mammographic screen: film systems

International Nuclear Information System (INIS)

Sickles, E.A.; Genant, H.K.

1979-01-01

The ability of five low-dose mammographic screen-film systems to portray normal and abnormal breast structures was evaluated in parallel with a study of physical image properties. Single-blind evaluations of the visibility of normal breast architecture, mass lesions, and calcifications were made on the mammograms of 100 patients radiographed with each of the systems. There was increased noise and slightly poorer resolution of the faster recording systems, but there was no difference in final diagnostic impressions among the five systems. These results suggest that the faster systems will result in substantial dose reduction without sacrificing diagnostic accuracy

Single versus double dose praziquantel comparison on efficacy and Schistosoma mansoni re-infection in preschool-age children in Uganda

DEFF Research Database (Denmark)

Nalugwa, Allen; Nuwaha, Fred; Tukahebwa, Edridah Muheki

2015-01-01

BACKGROUND: Schistosoma mansoni infection is proven to be a major health problem of preschool-age children in sub-Saharan Africa, yet this age category is not part of the schistosomiasis control program. The objective of this study was to compare the impact of single and double dose praziquantel...... (PZQ) treatment on cure rates (CRs), egg reduction rates (ERRs) and re-infection rates 8 months later, in children aged 1-5 years living along Lake Victoria, Uganda. METHODOLOGY/PRINCIPAL FINDINGS: Infected children (n= 1017) were randomized to receive either a single or double dose of PZQ. Initially...... all children were treated with a single standard oral dose 40 mg/kg body weight of PZQ. Two weeks later a second dose was administered to children in the double dose treatment arm. Side effects were monitored at 30 minutes to 24 hours after each treatment. Efficacy in terms of CRs and ERRs for the two...

Bronchodilator Efficacy of Single Doses of Indacaterol in Japanese Patients with COPD: A Randomised, Double-Blind, Placebo-Controlled Trial

Directory of Open Access Journals (Sweden)

Motokazu Kato

Full Text Available ABSTRACT: Background: Indacaterol is an investigational, novel, inhaled once-daily ultra-long-acting beta-2 agonist for the treatment of chronic obstructive pulmonary disease (COPD. This study evaluated the 24-h bronchodilatory efficacy and safety of indacaterol in Japanese patients with COPD. Methods: This Phase-II, randomised, placebo-controlled, crossover study comprised four double-blind, single-dose treatment periods (washout between periods: 14-28 days. Japanese patients aged 40-75 years with moderate-to-severe COPD were randomised to receive single doses of indacaterol (150, 300, or 600 μg or placebo via a single-dose dry-powder inhaler. Efficacy (primary endpoint: standardised FEV1AUC22-24h and safety were assessed for 24 h post-dose in each treatment period. Results: Of the 50 patients randomised (92% male; mean age, 67.2 years, 45 completed the study. Standardised FEV1AUC22-24h was significantly higher for all indacaterol doses as compared with placebo, with clinically relevant differences of 130, 160, and 170 mL for 150, 300, and 600 μg, respectively (P < 0.001. The improvement in FEV1 was seen as early as 5 min post-dose with indacaterol and sustained for 24 h (P < 0.001 vs placebo at all time points. All indacaterol doses were well tolerated and showed no clinically meaningful effect on pulse rate, blood pressure, QTc interval, and laboratory parameters when compared with placebo. Conclusions: In the Japanese COPD population studied, single doses of indacaterol (150, 300, and 600 μg provided sustained 24-h bronchodilation, with onset of action within 5 min post-dose. All doses were well tolerated. These results are consistent with data from Caucasian populations. KEY WORDS: beta2-agonists, bronchodilator, COPD, efficacy, indacaterol

Increased apoptotic potential and dose-enhancing effect of gold nanoparticles in combination with single-dose clinical electron beams on tumor-bearing mice

International Nuclear Information System (INIS)

Chang Mengya; Chen Yuhung; Chang Chihjui; Chen Helen H-W; Wu Chaoliang; Shiau Aili

2008-01-01

High atomic number material, such as gold, may be used in conjunction with radiation to provide dose enhancement in tumors. In the current study, we investigated the dose-enhancing effect and apoptotic potential of gold nanoparticles in combination with single-dose clinical electron beams on B16F10 melanoma tumor-bearing mice. We revealed that the accumulation of gold nanoparticles was detected inside B16F10 culture cells after 18 h of incubation, and moreover, the gold nanoparticles were shown to be colocalized with endoplasmic reticulum and Golgi apparatus in cells. Furthermore, gold nanoparticles radiosensitized melanoma cells in the colony formation assay (P=0.02). Using a B16F10 tumor-bearing mouse model, we further demonstrated that gold nanoparticles in conjunction with ionizing radiation significantly retarded tumor growth and prolonged survival compared to the radiation alone controls (P<0.05). Importantly, an increase of apoptotic signals was detected inside tumors in the combined treatment group (P<0.05). Knowing that radiation-induced apoptosis has been considered a determinant of tumor responses to radiation therapy, and the length of tumor regrowth delay correlated with the extent of apoptosis after single-dose radiotherapy, these results may suggest the clinical potential of gold nanoparticles in improving the outcome of melanoma radiotherapy. (author)

Efficacy of prophylactic single-dose therapy using fluoroquinolone for prostate brachytherapy

International Nuclear Information System (INIS)

Nomura, Takeo; Hirai, Kenichi; Yamasaki, Mutsushi; Inoue, Toru; Takahashi, Mika; Kawashima, Takayuki; Sato, Fuminori; Mimata, Hiromitsu

2012-01-01

There is little definitive evidence to guide the use of prophylactic antibiotics for prostate brachytherapy. The purpose of this study is to evaluate the incidence of postimplant infections in patients who receive antimicrobial prophylaxis with pazufloxacin (PZFX). A total of 84 patients who underwent prostate brachytherapy received a single intravenous dose of PZFX at 500 mg perioperatively for 1 day. No postimplant antibiotic medication was prescribed. Urinalysis, plasma white blood cell (WBC) count, and C reactive protein (CRP) levels were evaluated before the implantation, on the day after implantation, and on the 7th and 28th days after brachytherapy. None of the 84 patients (0.0%) developed a symptomatic urinary tract infection or had febrile infectious complications after brachytherapy. There were statistically significant elevations in the levels of erythrocytes, leukocytes, bacteria in urine, plasma WBC and CRP postoperatively, but these values did not exceed the normal range or were only slightly elevated on the day after brachytherapy (day 1) and on day 7. All laboratory examinations had returned to the normal range on day 28. Single-dose therapy with fluoroquinolone helps to prevent infections after prostate brachytherapy. (author)

Effect of single lithium doses on haemopoiesis regeneration after radiation exposure in mice

International Nuclear Information System (INIS)

Krajewski, K.

1988-01-01

The reported experiment failed to demonstrate any effect of single doses of lithium carbonate on haemopoiesis regeneration in experimental haematological syndrome of acute radiation sickness. The effects of gamma radiation on blood formation are shown. 3 figs., 6 refs. (author)

Mechanistic and single-dose in vivo therapeutic studies of Cry5B anthelmintic action against hookworms.

Directory of Open Access Journals (Sweden)

Yan Hu

Full Text Available Hookworm infections are one of the most important parasitic infections of humans worldwide, considered by some second only to malaria in associated disease burden. Single-dose mass drug administration for soil-transmitted helminths, including hookworms, relies primarily on albendazole, which has variable efficacy. New and better hookworm therapies are urgently needed. Bacillus thuringiensis crystal protein Cry5B has potential as a novel anthelmintic and has been extensively studied in the roundworm Caenorhabditis elegans. Here, we ask whether single-dose Cry5B can provide therapy against a hookworm infection and whether C. elegans mechanism-of-action studies are relevant to hookworms.To test whether the C. elegans invertebrate-specific glycolipid receptor for Cry5B is relevant in hookworms, we fed Ancylostoma ceylanicum hookworm adults Cry5B with and without galactose, an inhibitor of Cry5B-C. elegans glycolipid interactions. As with C. elegans, galactose inhibits Cry5B toxicity in A. ceylanicum. Furthermore, p38 mitogen-activated protein kinase (MAPK, which controls one of the most important Cry5B signal transduction responses in C. elegans, is functionally operational in hookworms. A. ceylanicum hookworms treated with Cry5B up-regulate p38 MAPK and knock down of p38 MAPK activity in hookworms results in hypersensitivity of A. ceylanicum adults to Cry5B attack. Single-dose Cry5B is able to reduce by >90% A. ceylanicum hookworm burdens from infected hamsters, in the process eliminating hookworm egg shedding in feces and protecting infected hamsters from blood loss. Anthelmintic activity is increased about 3-fold, eliminating >97% of the parasites with a single 3 mg dose (∼30 mg/kg, by incorporating a simple formulation to help prevent digestion in the acidic stomach of the host mammal.These studies advance the development of Cry5B protein as a potent, safe single-dose anthelmintic for hookworm therapy and make available the information of how

Low-Dose Ketamine Infusion for Adjunct Management during Vaso-occlusive Episodes in Adults with Sickle Cell Disease: A Case Series.

Science.gov (United States)

Palm, Nicole; Floroff, Catherine; Hassig, Tanna B; Boylan, Alice; Kanter, Julie

2018-05-23

The optimal management of recurrent painful episodes in individuals living with sickle cell disease (SCD) remains unclear. Currently, the primary treatment for these episodes remains supportive, using fluids and intravenous opioid and anti-inflammatory medications. Few reports have described the use of adjunct subanesthetic doses of ketamine to opioids for treatment of refractory pain in SCD. This article reports a retrospective case series of five patients admitted to the intensive care unit (ICU) with prolonged vaso-occlusive episodes (VOEs). Patients were treated with a continuous-infusion of low-dose ketamine (up to 5 µg/kg/min) after insufficient pain control with opioid analgesic therapy. Outcomes studied included impact on opioid analgesic use, a description of ketamine dosing strategy, and an analysis of adverse events due to opioid or ketamine analgesia. Descriptive statistics are provided. During ketamine infusion, patients experienced a lower reported pain score (mean numeric rating scale [NRS] score 7.2 vs. 6.4), reduced opioid-induced adverse effects, and decreased opioid dosing requirements (median reduction of 90 mg morphine equivalents per patient). The average duration of severe pain during admission prior to ketamine therapy was 8 days. Only one of five patients reported an adverse effect (vivid dreams) secondary to ketamine infusion. The Richmond Agitation Sedation Scale (RASS) was assessed throughout therapy, with only one patient experiencing light drowsiness. Low-dose ketamine infusion may be considered as an adjunct analgesic agent in patients with vaso-occlusive episodes who report continued severe pain despite high-dose opioid therapy, particularly those experiencing opioid-induced adverse effects.

The Effect of Nicotine Administration on Physical and Psychological Signs of Withdrawal Syndrome Induced by Single or Frequent Doses of Morphine in Rats

OpenAIRE

Mohammad Allahtavakoli; Fatemeh Amin; Elham Hakimizadeh; Ali Roohbakhsh; Sayed Ali Haeri Rohani; Ahmad Taghavi Rafsanjani; Abbas Haghparast; Ali Shamsizadeh

2012-01-01

Introduction. Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Materials and methods. Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later t...

Radiation hardening at 77 K in Zn and Cu single crystals at low doses

International Nuclear Information System (INIS)

Gonzalez, H.C.; Bisogni, E.A.

1980-01-01

There is controversy about radiation hardening phenomenon and its additivity with other hardening mechanisms. The purpose of this work is to contribute to the understanding of this subject, through measurements made in Zn and Cu single crystals. Post-irradiation measurements of yield stress of Zn, made on different single crystals, show a direct proportionality to the 0.5 power of the dose. It is determined that for a dose greater than 3.7 x 10 16 neutrons cm -2 s -1 there is always cleavage. The maximum critical resolved shear stress measured is about 8.82 MPa. In order to study additivity it is necessary to lower experimental errors. A micro tensile machine is designed to operate in the CNEA facility RA1 in a bath of liquid N 2 . Experimental measurements of yield stress with dose are carried out in-situ on the same single crystals. Experimental results on Cu and Zn show that radiation induced yield stress increases with a 0.5 power law. It must be taken into account that the definition of radiation induced yield stress stands for radiation created obstacles operating alone. The radiation induced yield stress adds algebraically to the athermal component of the initial yield stress but is not exactly additive to the other thermally activated mechanisms. A gradual transition from one to the other type of obstacles is observed. (author)

Pharmacokinetics of a telmisartan/rosuvastatin fixed-dose combination: a single-dose, randomized, open-label, 2-period crossover study in healthy Korean subjects.

Science.gov (United States)

Chae, Dong Woo; Son, Mijeong; Kim, Yukyung; Son, Hankil; Jang, Seong Bok; Seo, Jeong Min; Nam, Su Youn; Park, Kyungsoo

2015-10-01

As hypertension and dyslipidemia are frequent comorbidities, antihypertensive drugs and lipid-lowering agents are often prescribed together for their treatment. Telmisartan and rosuvastatin are widely used together to treat hypertension and dyslipidemia. A combination formulation of these two drugs would improve patient compliance due to ease of dosing. The purpose of this study was to assess bioequivalence of single-dose administration of a newly-developed fixed-dose combination (FDC) tablet containing telmisartan/rosuvastatin 80/20 mg (test treatment) and coadministration of a telmisartan 80-mg tablet and a rosuvastatin 20-mg tablet (reference treatment) in healthy Korean male volunteers. This was a single-dose, randomized, open-label, 2-period crossover study enrolling healthy males aged 20 - 50 years with BMI between 18.5 and 25 kg/m2. Each subject received a single dose of the reference and test treatments with a 14-day washout period. Blood sampling was performed at prespecified intervals for up to 72 hours after dosing. Primary pharmacokinetic parameters were Cmax, AUClast, and AUC0-∞ of telmisartan, rosuvastatin, and N-desmethyl rosuvastatin. Bioequivalence was assessed by determining whether the 90% confidence intervals (CIs) of the geometric mean ratios (test treatment/reference treatment) of these parameters were within the standard range of 80% to 125%. Adverse events were monitored via regular interviews with the subjects and by physical examinations. 60 subjects were enrolled and 55 completed the study. The 90% CIs of the geometric mean ratios of Cmax, AUClast, and AUC00-∞ were 0.9262-1.1498, 0.9294-1.0313, and 0.9312-1.0320 for telmisartan, 0.9041-1.0428, 0.9262-1.0085, and 0.9307-1.0094 for rosuvastatin, and 0.8718-1.0022, 0.8901-0.9904, and 0.8872-0.9767 for N-desmethyl rosuvastatin, respectively. There was no statistical difference in the incidence of adverse events (AEs) (all of which were mild or moderate) between the reference and test

Pharmacokinetics of [14C]teicoplanin in male rats after single intravenous dose

International Nuclear Information System (INIS)

Bernareggi, A.; Cavenaghi, L.; Assandri, A.

1986-01-01

The pharmacokinetic profile of [ 14 C]teicoplanin was studied in male Sprague-Dawley rats given a single 10,000-U/kg intravenous dose. The disposition of the antimicrobial activity in the body was estimated by a three-compartment open model. Plasma concentration data were fitted to a three-exponent equation. The profile of total 14 C in plasma was similar to that of the microbiological activity. The cumulative recovery of total 14 C 5 days after drug administration averaged 76.3% of the administered dose in the urine and 8.7% in the feces. The residual dose remaining in the animal carcasses was 11.1%. Teicoplanin was widely distributed in the body. In almost all organs, the maximum concentration of [ 14 C]teicoplanin was already reached at the first time of killing, which was 0.25 h after the administration of drug. The liver, kidneys, skin, and fat contained most of the residual dose found in the animal carcasses 120 h after administration and behaved as a deep compartment with the adrenal glands and spleen

Misonidazole cytotoxicity in vivo: a comparison of large single doses with smaller doses and extended contact of the drug with tumor cells

International Nuclear Information System (INIS)

Conroy, P.J.; Sutherland, R.M.; Passalacqua, W.

1980-01-01

Experiments were performed to determine the kinetics and magnitude of misonidazole cytotoxicity in EMT6/Ro tumors using an in vivo-in vitro clonogenicity assay. A comparison was made between the cytotoxic effects of large single doses with smaller doses of misonidazole administered ip and those produced on extended contact of the drug with tumor cells using a continuous iv drug infusion system. After a single ip dose of 1 mg/g, cytotoxicity was maximum at 18 to 24 h; by 72 h the clonogenic cells per tumor had returned to control levels. The maximum cytotoxicity was greater (a decrease of 10 times) if the animals were kept at 37 0 C compared with ambient conditions (a decrease of 4.5 times) where the body temperature would decrease due to the drug. A dose-response curve performed with the animals at 37 0 C showed no significant cytotoxicity at 18 h after single ip doses of 0.5 mg/g or less. Other experiments were carried out at 37 0 C using a drug continuous infusion system. Two profiles were studied: (a) continuous constant rate infusion over 3 days of constant serum and tumor levels of both 100 and 200 μg/ml and (b) continuous variable rate infusion where the maximum serum levels reached 80 or 200 μg/ml after 2 to 4 h and decayed with a half-life of 12 h as in humans. Significant cytotoxicity was obtained under both of these conditions. Maximum cytotoxicity occurred at about 24 h in both types of experiments and amounted to decreases of clonogenic tumor cells of 4.5 and 7 times for 100 and 200 μg/ml, respectively, after constant rate infusion and 2 to 4 times for 80 and 200 μg/ml, respectively, after variable rate infusion. Because of the relatively rapid recovery in the number of clonogenic tumor cells by 72 h, the cytotoxic effects were not reflected as changes in tumor size even when the animals were maintained at 37 0 C

Dual-sided reading versus single-sided reading: comparison of image quality and radiation dose between the two computed radiography system

International Nuclear Information System (INIS)

Song Shaojuan; Qi Hengtao; Zhao Yongxia; Jiao Fanglian

2007-01-01

Objective: To assess and compare the difference in image quality and exposure dose between single-sided reading image plate (IP) and dual-sided reading IP. Methods: A contrast-detail phantom CDRAD 2.0 was exposed by single-sided and dual-sided reading IP with different mAs sets. The entrance surface doses were recorded for all images. Images were then presented to two radiologists on a high resolution monitor of diagnosis workstation. The image quality figure (IQF) was measured for each image. Statistical analysis was performed using Spearman's correlation test and Wilcoxon signed-rank test to compare the difference in image quality and exposure dose between single-sided IP and dual-sided reading IP. Results: With different tube current dosage of 5.6, 12.0, 20.0, 25.0, and 40.0 mAs, IQF values of single-sided reading IP were 47.95, 37.68, 34.31, 28.61, and 24.65, respectively, while those of dual- sided reading IP were 38.83, 29.81, 29.65, 25.16, and 21.43, respectively. The IQF difference between them showed statistical significance (P<0.05). Conclusion: Image quality of dual-sided reading IP has been proved to be far superior to that of single-sided reading IP, in particular for low contrast detail. The image quality of single-sided reading IP is similar to that of dual-sided reading IP only at high dose levels. The clinical application of dual-sided reading IP will reduce the exposure dose by about 25% compared with single-sided reading IP. (authors)

Single oral dose toxicity test of platycodin d, a saponin from platycodin radix in mice.

Science.gov (United States)

Lee, Won-Ho; Gam, Cheol-Ou; Ku, Sae-Kwang; Choi, Seong-Hun

2011-12-01

The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively.

Accelerated repopulation of mouse tongue epithelium during fractionated irradiations or following single doses

International Nuclear Information System (INIS)

Doerr, W.; Kummermehr, J.

1990-01-01

Mouse tongue mucosa was established as an animal model to study repopulation after large single doses or during continuous irradiation. A top-up irradiation technique was used employing priming doses or fractionated treatment to the whole snout (300 kV X-rays) followed by local test doses (25 kV X-rays) to elicit denudation in a confined field of the inferior tongue surface. Clearcut quantal dose-response curves of ulcer incidence were obtained to all protocols; animal morbidity, i.e. body weight loss was minimal. Repopulation following priming doses of 10 and 13 Gy started with a delay of at least 3 days and then progressed rapidly to nearly restore original tissue tolerance by day 11. During continuous fractionation over 1 to 3 weeks with 5 fractions/week and doses per fraction of 2.5, 3 and 3.5 Gy, repopulation was small in week one but subsequently increased to fully compensate the weekly dose at all dose levels. Additional measurements of cell density during a 4 weeks course of 5 x 3 Gy or 5 x 4 Gy per week showed only moderate depletion to 67% of the control figures. The fact that rapid repopulation is achieved at relatively moderate damage levels should be taken into account when the timing of a treatment split is considered. (author). 18 refs.; 7 figs.; 1 tab

Using the OSL single-aliquot regenerative-dose protocol with quartz extracted from building materials in retrospective dosimetry

DEFF Research Database (Denmark)

Bøtter-Jensen, L.; Solongo, S.; Murray, A.S.

2000-01-01

We report on the application of the single-aliquot regenerative-dose (SAR) protocol to the optically stimulated luminescence signal from quartz extracted from fired bricks acid unfired mortar in retrospective dosimetry. The samples came from a radioactive materials storage facility, with ambient...... dose rates of about 0.1 mGy/h. A detailed dose-depth profile was analysed from one brick, and compared with dose records from area TL dosemeters. Small-aliquot dose-distributions were analysed from the mortar samples; one associated with the exposed brick, and one from a remote site exposed only...

Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

International Nuclear Information System (INIS)

Leith, J.T.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Howard, J.

1982-01-01

The thoraco-lumbar (T12-L1) region of the spinal cord of rats was exposed to either single or fractionated (four daily exposures) doses of X rays (230 kVp) or heavy ions. The heavy ions used were carbon and neon, and the relative biological effectiveness (RBE) of both the plateau ionization region and the midpeak region of 4-cm spread-out Bragg peaks of each heavy ion were investigated. For single doses of carbon and neon ions in the plateau ionization region, RBE values of 1.45 +/- 0.25 (propagated 95% confidence limits) and 1.46 +/- 0.33, respectively, were obtained. In the spread peak regions for carbon and neon ions, the RBE values were 1.48 +/- 0.18 and 1.86 +/- 0.42, respectively. These values were obtained using the dose needed to produce 50% paralysis in a group of irradiated rats as the isoeffect comparison dose (ED 50 dose). Similarly, in groups of rats receiving four daily exposures, the RBE values for carbon and neon ions in the plateau ionization region were 1.31 +/- 0.27 and 1.80 +/- 0.24, respectively. In the spread peak regions of ionization for carbon and neon ions, the RBE values were 1.95 +/- 0.19 and 2.18 +/- 0.23, respectively. Similar values for RBE were obtained using changes in the activity of enzymes in spinal cord tissue (cyclic nucleotide phosphohydrolase and γ-glutamyl transpeptidase). Also, it was estimated that, for X irradiation, the fractional amount of dose repaired (at the ED 50 dose) was 0.64 +/- 0.10 (95% confidence limits). For carbon and neon ions in the plateau ionization region, the values for the fractional amount of dose repaired were 0.70 +/- 0.27 and 0.48 +/- 0.20, and for carbon and neon ions in the spread peak region of ionization, the fractional repair values were 0.40 +/- 0.10 and 0.52 +/- 0.17. Spinal cord tissue therefore shows a high capacity for subeffective damage repair

Pharmacokinetics of pregabalin controlled-release in healthy volunteers: effect of food in five single-dose, randomized, clinical pharmacology studies.

Science.gov (United States)

Chew, Marci L; Plotka, Anna; Alvey, Christine W; Pitman, Verne W; Alebic-Kolbah, Tanja; Scavone, Joseph M; Bockbrader, Howard N

2014-09-01

The pharmacokinetic properties of the immediate-release (IR) and the recently developed controlled-release (CR) formulation of pregabalin are dose proportional. Pregabalin IR can be taken with or without food. This analysis characterizes the effect of food on pregabalin CR. The objectives of this analysis were: (1) to evaluate the effect of administration time and fat or caloric content of an accompanying meal on the pharmacokinetic properties of a single dose of pregabalin CR (330 mg) relative to a single dose of pregabalin IR (300 mg); (2) to evaluate the pharmacokinetic properties of a single dose of pregabalin CR administered fasted relative to a single dose of pregabalin CR administered immediately after food; and (3) to determine the safety and tolerability of single-dose administration of pregabalin CR and IR with and without food. The effect of food on the pharmacokinetic properties of pregabalin CR was determined in five phase I, open-label, single-dose, crossover studies (24-28 participants/study). Caloric and fat content of meals were varied and treatments were administered in the morning, at midday, or in the evening. Blood samples were collected up to 48 h post-dose. Pharmacokinetic parameters were estimated from plasma concentration-time data using standard noncompartmental methods. Adverse events were monitored throughout all studies. One hundred and twenty-eight healthy participants (19-54 years of age) received pregabalin. Peak plasma concentrations (C max) were lower for CR than the respective pregabalin IR doses, and time to C max occurred later. When pregabalin CR was administered with food at midday or in the evening, total exposures [area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC∞)] were equivalent for pregabalin CR and IR formulations regardless of fat or caloric content. When pregabalin CR was administered with an 800-1,000 calorie medium-fat breakfast, AUC∞ was equivalent for

Single dose oral flurbiprofen for acute postoperative pain in adults

Science.gov (United States)

Sultan, Asquad; McQuay, Henry J; Moore, R Andrew; Derry, Sheena

2014-01-01

Background Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug (NSAID), related to ibuprofen and naproxen, used to treat acute and chronic painful conditions. There is no systematic review of its use in acute postoperative pain. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults. Search methods We searched Cochrane CENTRAL, MEDLINE, EMBASE and the Oxford Pain Relief Database for studies to January 2009. Selection criteria Randomised, double blind, placebo-controlled trials of single dose orally administered flurbiprofen in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk (RR) and number needed to treat to benefit (NNT) were calculated. Numbers of participants using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Information on adverse events and withdrawals were collected. Main results Eleven studies compared flurbiprofen (699 participants) with placebo (362 participants) in studies lasting 6 to 12 hours. Studies were of adequate reporting quality, and most participants had pain following dental extractions. The dose of flurbiprofen used was 25 mg to 100 mg, with most information for 50 mg and 100 mg. The NNT for at least 50% pain relief over 4 to 6 hours for flurbiprofen 50 mg compared with placebo (692 participants) was 2.7 (2.3 to 3.3) and for 100 mg (416 participants) it was 2.5 (2.0 to 3.1). With flurbiprofen 50 mg and 100 mg 65% to 70% of participants experienced at least 50% pain relief, compared with 25% to 30% with placebo. Rescue medication was used by 25

Monte Carlo uncertainty analysis of dose estimates in radiochromic film dosimetry with single-channel and multichannel algorithms.

Science.gov (United States)

Vera-Sánchez, Juan Antonio; Ruiz-Morales, Carmen; González-López, Antonio

2018-03-01

To provide a multi-stage model to calculate uncertainty in radiochromic film dosimetry with Monte-Carlo techniques. This new approach is applied to single-channel and multichannel algorithms. Two lots of Gafchromic EBT3 are exposed in two different Varian linacs. They are read with an EPSON V800 flatbed scanner. The Monte-Carlo techniques in uncertainty analysis provide a numerical representation of the probability density functions of the output magnitudes. From this numerical representation, traditional parameters of uncertainty analysis as the standard deviations and bias are calculated. Moreover, these numerical representations are used to investigate the shape of the probability density functions of the output magnitudes. Also, another calibration film is read in four EPSON scanners (two V800 and two 10000XL) and the uncertainty analysis is carried out with the four images. The dose estimates of single-channel and multichannel algorithms show a Gaussian behavior and low bias. The multichannel algorithms lead to less uncertainty in the final dose estimates when the EPSON V800 is employed as reading device. In the case of the EPSON 10000XL, the single-channel algorithms provide less uncertainty in the dose estimates for doses higher than four Gy. A multi-stage model has been presented. With the aid of this model and the use of the Monte-Carlo techniques, the uncertainty of dose estimates for single-channel and multichannel algorithms are estimated. The application of the model together with Monte-Carlo techniques leads to a complete characterization of the uncertainties in radiochromic film dosimetry. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Nitrous Oxide Induces Prominent Cell Proliferation in Adult Rat Hippocampal Dentate Gyrus

Directory of Open Access Journals (Sweden)

Farah Chamaa

2018-05-01

Full Text Available The identification of distinct and more efficacious antidepressant treatments is highly needed. Nitrous oxide (N2O is an N-methyl-D-aspartic acid (NMDA antagonist that has been reported to exhibit antidepressant effects in treatment-resistant depression (TRD patients. Yet, no studies have investigated the effects of sub-anesthetic dosages of N2O on hippocampal cell proliferation and neurogenesis in adult brain rats. In our study, adult male Sprague-Dawley rats were exposed to single or multiple exposures to mixtures of 70% N2O and 30% oxygen (O2. Sham groups were exposed to 30% O2 and the control groups to atmospheric air. Hippocampal cell proliferation was assessed by bromodeoxyuridine (BrdU incorporation, and BrdU-positive cells were counted in the dentate gyrus (DG using confocal microscopy. Results showed that while the rates of hippocampal cell proliferation were comparable between the N2O and sham groups at day 1, levels increased by 1.4 folds at day 7 after one session exposure to N2O. Multiple N2O exposures significantly increased the rate of hippocampal cell proliferation to two folds. Therefore, sub-anesthetic doses of N2O, similar to ketamine, increase hippocampal cell proliferation, suggesting that there will ultimately be an increase in neurogenesis. Future studies should investigate added N2O exposures and their antidepressant behavioral correlates.

Evaluation of Sphingolipids in Wistar Rats Treated to Prolonged and Single Oral Doses of Fumonisin B1

Science.gov (United States)

Direito, Glória M.; Almeida, Adriana P.; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

2009-01-01

The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B1 (FB1). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB1. Prolonged exposure to FB1 caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB1. Animals receiving a single dose of FB1 presented variations in Sa and So levels and in the Sa/So ratio. PMID:19333435

A simulation study on the dose distribution for a single beam of the gamma knife

International Nuclear Information System (INIS)

Chen, Chin-cheng; Jiang, Shiang-Huei; Lee, Chung-chi; Shiau, Cheng-Ying

2000-01-01

The purpose of this study is to evaluate the impact of the tissue heterogeneity on the dose distribution for a single beam of the gamma knife. The EGS4 Monte Carlo code was used to simulate both depth and radial profiles of the radiation dose in homogeneous and heterogeneous phantoms, respectively. The results are compared with the dose distribution calculated using the mathematical model of Gamma Plan, the treatment planning system of the gamma knife. The skull and sinus heterogeneity were simulated by a Teflon shell and an air shell, respectively. It was found that the tissue heterogeneity caused significant perturbation on the absolute depth dose at the focus as well as on the depth-dose distribution near the phantom surface and/or at the interface but little effect on the radial dose distribution. The effect of the beam aperture on the depth-dose distribution was also investigated in this study. (author)

An explanation for the multiplicative and the additive dose-effect relationship with the single-hit model

International Nuclear Information System (INIS)

Kottbauer, M.M.; Fleck, C.M.; Schoellnberger, H.

1997-01-01

For solid tumors and for leukemia the excess cancer rate after a single radiation dose D is different. The multiplicative model describes the excess solid tumor probability rate which is proportional to the background rate of cancer and dependent on dose D. The additive model describes the excess probability rate for leukaemia which is proportional to the dose D but unrelated to the spontaneous rate of cancer. A second great difference between the two models is the duration of the increased cancer probability rate. The multiplicative mode predicts that the additional cancer risk persist the whole lifetime after exposure and the additive model predicts excess risk over a period of time. With the Single-hit model (SHM) which is a multistage cancer model both dose-response relationships can be described. It will be shown that only small differences in the derivation will lead to the different relationships. We then analyze the incidence data of leukemia (1950-1987) and of all solid tumors (1958-1987) of the atomic bomb survivors. (author)

Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

Science.gov (United States)

Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula

2018-01-20

The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.

The effect of single and double doses of gamma radiation on pre-rigor mortis filleted saithe

International Nuclear Information System (INIS)

Underdahl, B.; Lunde, G.

1973-01-01

Saithe, caught off the western coast of Norway, were filleted immediately after killing, packed in plastic bags and irradiated using a cobalt-60 source at the Institutt for Atomenergi, Kjeller. The doses were 50, 100, 150, 50+50 and 50+100 krad. All samples were analysed for their total bacterial count, proteolytic activity, ammonia, total volatile acids, trimethylamine oxide, tri- and dimethylamine and formaldehyde. The organoleptic quality was evaluated by a panel of tasters. Double doses were more effective in reducing the total bacterial count than an equivalent single dose. A close relation was found between the bacterial count and the proteolytic activity. The trimethylamine oxide concentration was found to vary between 33 and 44 mg/100 g muscle, decreasing rapidly in non-irradiated fillets to 3 mg/100 g. In non-irradiated fillets trimethylamine oxide was mainly reduced to trimethylamine and in irradiated fillets to dimethylamine and formaldehyde. A split dose of 50+50 krad may have a favourable effect on the total bacterial number, but the analyses of proteolytic activity, the volatile acids and the trimethylamine indicate that a higher proportion of spoilage bacteria survive. The low proteolytic activity and the high content of DMA/FA prove that the split doses of 50+100 krad as compared with a single dose of 150 krad are particularly favourable in the case of saithe. (Auth.)

Vaginal bleeding following the use of a single dose of 1.5mg ...

African Journals Online (AJOL)

Introduction: Recent studies have shown that a single dose of 1.5 mg levonorgestrel is an effective and safe emergency contraceptive but detailed information on its menstrual side effects is lacking. This study assessed the vaginal bleeding patterns in healthy women who used the medication for emergency contraception.

Quantitative assessment of changes in the dermal fibroblast population of pig skin after single doses of X-rays

Energy Technology Data Exchange (ETDEWEB)

Hamlet, R.; Hopewell, J.W.

1988-10-01

Changes in the density of fibroblast nuclei in reticular dermis of pigs was studied from 6 to 104 weeks after a single dose of 15.4 Gy of X-rays. The largest decrease in fibroblasts occurred between 12 and 26 weeks after irradiation; after this there was only a slight fall in fibroblast number until 104 weeks when observations ceased. At 26 weeks and later times after irradiation reduction in the density of fibroblast nuclei in the reticular dermis was dose-dependent for single doses in the range 8.0-20.7 Gy. The dose-response curve had an initial shoulder, after which the fall in the fibroblast nuclear density was linearly related to dose. Data obtained between 26 weeks and 104 weeks after irradiation, could be fitted by the same dose-response curve. The fall in the counts of fibroblast nuclei was compared with earlier studies. The loss of fibroblasts occurred after an initial reduction in blood flow in the pig skin but was concomitant with general reduction in dermal thickness.

Can a single dose of human papillomavirus (HPV) vaccine prevent cervical cancer? Early findings from an Indian study.

Science.gov (United States)

Sankaranarayanan, Rengaswamy; Joshi, Smita; Muwonge, Richard; Esmy, Pulikottil Okkuru; Basu, Partha; Prabhu, Priya; Bhatla, Neerja; Nene, Bhagwan M; Shaw, Janmesh; Poli, Usha Rani Reddy; Verma, Yogesh; Zomawia, Eric; Pimple, Sharmila; Tommasino, Massimo; Pawlita, Michael; Gheit, Tarik; Waterboer, Tim; Sehr, Peter; Pillai, Madhavan Radhakrishna

2018-03-15

Human papillomavirus (HPV) vaccination is a major strategy for preventing cervical and other ano-genital cancers. Worldwide HPV vaccination introduction and coverage will be facilitated if a single dose of vaccine is as effective as two or three doses or demonstrates significant protective effect compared to 'no vaccination'. In a multi-centre cluster randomized trial of two vs three doses of quadrivalent HPV vaccination (Gardasil™) in India, suspension of the vaccination due to events unrelated to the study led to per protocol and partial vaccination of unmarried 10-18 year old girls leading to four study groups, two by design and two by default. They were followed up for the primary outcomes of immunogenicity in terms of L1 genotype-specific binding antibody titres, neutralising antibody titres, and antibody avidity for the vaccine-targeted HPV types and HPV infections. Analysis was per actual number of vaccine doses received. This study is registered with ISRCTN, number ISRCTN98283094; and with ClinicalTrials.gov, number NCT00923702. Of the 17,729 vaccinated girls, 4348 (25%) received three doses on days 1, 60, 180 or later, 4979 (28%) received two doses on days 1 and 180 or later, 3452 (19%) received two doses on days 1 and 60, and 4950 (28%) received one dose. One dose recipients demonstrated a robust and sustained immune response against HPV 16 and 18, albeit inferior to that of 3- or 2-doses and the antibody levels were stable over a 4 year period. The frequencies of cumulative incident and persistent HPV 16 and 18 infections up to 7 years of follow-up were similar and uniformly low in all the vaccinated study groups; the frequency of HPV 16 and 18 infections were significantly higher in unvaccinated age-matched control women than among vaccine recipients. The frequency of vaccine non-targeted HPV types was similar in the vaccinated groups but higher in the unvaccinated control women. Our results indicate that a single dose of quadrivalent HPV

Comparison of scatter doses from a multislice and a single slice CT scanner

International Nuclear Information System (INIS)

Burrage, J. W.; Causer, D. A.

2006-01-01

During shielding calculations for a new multislice CT (MSCT) scanner it was found that the manufacturer's data indicated significantly higher external scatter doses than would be generated for a single slice CT (SSCT). Even allowing for increased beam width, the manufacturer's data indicated that the scatter dose per scan was higher by a factor of about 3 to 4. The magnitude of the discrepancy was contrary to expectations and also contrary to a statement by the UK ImPACT group, which indicated that when beam width is taken into account, the scatter doses should be similar. The matter was investigated by comparing scatter doses from an SSCT and an MSCT. Scatter measurements were performed at three points using a standard perspex CTDI phantom, and CT dose indices were also measured to compare scanner output. MSCT measurements were performed with a 40 mm wide beam, SSCT measurements with a 10 mm wide beam. A film badge survey was also performed after the installation of the MSCT scanner to assess the adequacy of lead shielding in the room. It was found that the scatter doses from the MSCT were lower than indicated by the manufacturer's data. MSCT scatter doses were approximately 4 times higher than those from the SSCT, consistent with expectations due to beam width differences. The CT dose indices were similar, and the film badge survey indicated that the existing shielding, which had been adequate for the SSCT, was also adequate for the MSCT

Single dose oral ketoprofen or dexketoprofen for acute postoperative pain in adults.

Science.gov (United States)

Gaskell, Helen; Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

2017-05-25

This review is an update of "Single dose oral ketoprofen and dexketoprofen for acute postoperative pain in adults" last updated in Issue 4, 2009. Ketoprofen is a non-selective nonsteroidal anti-inflammatory drug (NSAID) used to treat acute and chronic painful conditions. Dexketoprofen is the (S)-enantiomer, which is believed to confer analgesia. Theoretically dexketoprofen is expected to provide equivalent analgesia to ketoprofen at half the dose, with a consequent reduction in gastrointestinal adverse events. This review is one of a series on oral analgesics for acute postoperative pain. Individual reviews have been brought together in two overviews to provide information about the relative efficacy and harm of the different interventions. To assess the efficacy and safety of single dose oral ketoprofen and oral dexketoprofen compared with placebo for acute postoperative pain, using methods that permit comparison with other analgesics evaluated in the same way, and criteria of efficacy recommended by an in-depth study at the individual patient level. For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase from 2009 to 28 March 2017. We also searched the reference lists of retrieved studies and reviews, and two online clinical trial registries. Randomised, double-blind, placebo-controlled trials of single dose orally administered ketoprofen or dexketoprofen in adults with moderate to severe acute postoperative pain. Two review authors independently considered studies for inclusion in the review, examined issues of study quality and potential bias, and extracted data. For dichotomous outcomes, we calculated risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or harmful outcome (NNH) with 95% confidence intervals (CI) for ketoprofen and dexketoprofen, compared with placebo, where there were sufficient data. We collected information on the number of participants with at least 50

Attention benefits after a single dose of metadoxine extended release in adults with predominantly inattentive ADHD.

Science.gov (United States)

Manor, Iris; Rubin, Jonathan; Daniely, Yaron; Adler, Lenard A

2014-09-01

To assess the first-dose effectiveness and tolerability of metadoxine extended release (MDX) in adults with predominantly inattentive attention-deficit/hyperactivity disorder (ADHD-PI). In this double-blind, placebo-controlled, crossover study, adults with ADHD-PI were randomized 1:1:1 to receive a single dose of MDX 1400 mg, MDX 700 mg, and placebo (ClinicalTrials.gov identifier: NCT01685281). The primary efficacy end point was the mean change in the Test of Variables of Attention (TOVA) ADHD score from baseline to 3 to 5 hours after drug administration. Secondary assessments included TOVA subscores, TOVA response rates (defined as an increase of 0.8 points in the TOVA ADHD score), and the Cambridge Neuropsychological Automated Test Battery. Safety assessments included adverse events and vital signs. The intention-to-treat population included 36 patients (52.8% men; mean age, 32 years). The efficacy of MDX 1400 mg was demonstrated by a statistically significant difference in the mean (± SD) change in the TOVA ADHD score at baseline to 3 to 5 hours after drug administration compared with placebo (2.0 [4.2]; P = 0.009). The TOVA response time variability subscore was significantly different between MDX 1400 mg and placebo (mean difference, 7.9 [19.2] points; P = 0.022). Significantly more adults responded to single-dose MDX 1400 mg versus placebo (97.1% vs 71.4%, P = 0.006). There were no statistically significant differences between MDX 700 mg and placebo on any measures. Exploratory analyses of the Cambridge Neuropsychological Automated Test Battery did not yield significant findings. Fatigue and headache were the 2 most frequently reported adverse events. There were no clinically significant abnormalities in laboratory values, vital signs measurements, Columbia-Suicide Severity Rating Scale scores, or electrocardiographic parameters. Single-dose MDX 1400 mg significantly improved sustained and selective attention in adults with ADHD-PI as measured by the TOVA

Single Intramuscular-dose Toxicity of Water soluble Carthmi-Flos herbal acupuncture (WCF in Sprague-Dawley Rats

Directory of Open Access Journals (Sweden)

Lee Hyung-geol

2014-03-01

Full Text Available Objectives: This experiment was conducted to examine the toxicity of WCF (Water soluble Carthmi-Flos herbal acupuncture by administering a single intramuscular dose of WCF in 6-week-old, male and female Sprague-Dawley rats and to find the lethality dose for WCF. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices under a request by the Korean Pharmacopuncture Institute. This experiment was performed based on the testing standards of “Toxicity Test Standards for Drugs” by the Ministry of Food and Drug Safety. Subjects were divided into 4 groups: 1 control group in which normal saline was administered and 3 test groups in which 0.1, 0.5 or 1.0 mL of WCF was administered; a single intramuscular dose was injected into 5 males and 5 females in each group. General symptoms and body weights were observed/measured for 14 days after injection. At the end of the observation period, hematological and clinical chemistry tests were performed, followed by necropsy and histopathological examinations of the injected sections. Results: No mortalities were observed in any group. Also, symptoms, body weight, hematology, clinical chemistry and necropsy were not affected. However, histopathological examination of the injected part in one female in the 1.0-mL group showed infiltration of mononuclear cells and a multi-nucleated giant cell around eosinophilic material. Conclusion: Administration of single intramuscular doses of WCF in 3 groups of rats showed that the approximate lethal dose of WCF for all rats was in excess of 1.0 mL, as no mortalities were observed for injections up to and including 1.0 mL.

Dose-response curve for translocation frequency with single pair of painted chromosome. A comparison with dicentric and micronuclei frequency

Energy Technology Data Exchange (ETDEWEB)

Venkatachalam, P.; Paul, S.F.D.; Mohankumar, M.N.; Prabhu, B.K.; Gajendiran, N.; Jeevanram, R.K

2000-07-01

A translocation dose-response curve using a single pair of painted chromosomes was constructed. The translocation frequencies observed at different doses were compared to those obtained for dicentrics (DC) and micronuclei (MN). The translocation and DC frequency followed the Poisson distribution and MN showed over-dispersion. The translocation and DC frequencies were nearly the same for each dose point. Micronuclei showed a comparatively lower frequency. The alpha/beta ratio for translocations (0.916) and DC (0.974) were comparable, whereas the value for MN (1.526) was much higher. The equal frequencies of translocations and DC observed for a given dose indicated that genomic translocation frequency estimated using a single pair of painted chromosomes provides a reliable and easy method to measure translocation frequency. (autho000.

Dose-response curve for translocation frequency with single pair of painted chromosome. A comparison with dicentric and micronuclei frequency

International Nuclear Information System (INIS)

Venkatachalam, P.; Paul, S.F.D.; Mohankumar, M.N.; Prabhu, B.K.; Gajendiran, N.; Jeevanram, R.K.

2000-01-01

A translocation dose-response curve using a single pair of painted chromosomes was constructed. The translocation frequencies observed at different doses were compared to those obtained for dicentrics (DC) and micronuclei (MN). The translocation and DC frequency followed the Poisson distribution and MN showed over-dispersion. The translocation and DC frequencies were nearly the same for each dose point. Micronuclei showed a comparatively lower frequency. The alpha/beta ratio for translocations (0.916) and DC (0.974) were comparable, whereas the value for MN (1.526) was much higher. The equal frequencies of translocations and DC observed for a given dose indicated that genomic translocation frequency estimated using a single pair of painted chromosomes provides a reliable and easy method to measure translocation frequency. (author)

Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.

Science.gov (United States)

Derry, Christopher J; Derry, Sheena; Moore, R Andrew

2013-06-24

Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations. To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543

Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study.

Science.gov (United States)

Huttner, Angela; Agnandji, Selidji Todagbe; Combescure, Christophe; Fernandes, José F; Bache, Emmanuel Bache; Kabwende, Lumeka; Ndungu, Francis Maina; Brosnahan, Jessica; Monath, Thomas P; Lemaître, Barbara; Grillet, Stéphane; Botto, Miriam; Engler, Olivier; Portmann, Jasmine; Siegrist, Denise; Bejon, Philip; Silvera, Peter; Kremsner, Peter; Siegrist, Claire-Anne

2018-04-04

The recombinant vesicular stomatitis virus (rVSV) vaccine expressing the Zaire Ebola virus (ZEBOV) glycoprotein is efficacious in the weeks following single-dose injection, but duration of immunity is unknown. We aimed to assess antibody persistence at 1 and 2 years in volunteers who received single-dose rVSV-ZEBOV in three previous trials. In this observational cohort study, we prospectively followed-up participants from the African and European phase 1 rVSV-ZEBOV trials, who were vaccinated once in 2014-15 with 300 000 (low dose) or 10-50 million (high dose) plaque-forming units (pfu) of rVSV-ZEBOV vaccine to assess ZEBOV glycoprotein (IgG) antibody persistence. The primary outcome was ZEBOV glycoprotein-specific IgG geometric mean concentrations (GMCs) measured yearly by ELISA compared with 1 month (ie, 28 days) after immunisation. We report GMCs up to 2 years (Geneva, Switzerland, including neutralising antibodies up to 6 months) and 1 year (Lambaréné, Gabon; Kilifi, Kenya) after vaccination and factors associated with higher antibody persistence beyond 6 months, according to multivariable analyses. Trials and the observational study were registered at ClinicalTrials.gov (Geneva: NCT02287480 and NCT02933931; Kilifi: NCT02296983) and the Pan-African Clinical Trials Registry (Lambaréné PACTR201411000919191). Of 217 vaccinees from the original studies (102 from the Geneva study, 75 from the Lambaréné study, and 40 from the Kilifi study), 197 returned and provided samples at 1 year (95 from the Geneva study, 63 from the Lambaréné, and 39 from the Kilifi study) and 90 at 2 years (all from the Geneva study). In the Geneva group, 44 (100%) of 44 participants who had been given a high dose (ie, 10-50 million pfu) of vaccine and who were seropositive at day 28 remained seropositive at 2 years, whereas 33 (89%) of 37 who had been given the low dose (ie, 300 000 pfu) remained seropositive for 2 years (p=0·042). In participants who had received a high dose

Single-dose Toxicity of ShinYangHur Herbal Acupuncture

Directory of Open Access Journals (Sweden)

Eunhye Cha

2015-06-01

Full Text Available Objectives: This study was carried out to analyze the single-dose toxicity of ShinYangHur (SYH herbal acupuncture injected into the muscles of Sprague-Dawley (SD rats. Methods: The SYH herbal acupuncture was made in a clean room at the Korean Pharmacopuncture Institute (KPI, Korea-Good Manufacturing Practice, K-GMP. After the mixing process with sterile distilled water, the pH was controlled to between 7.0 and 7.5. Then, NaCl was added to make a 0.9% isotonic solution by using sterilized equipment. All experiments were conducted at Biotoxtech, an institution authorized to perform non clinical studies under the regulations of Good Laboratory Practice (GLP. SD rats were chosen for the pilot study. Doses of SYH herbal acupuncture, 0.25, 0.5, and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy was used to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion: The above outcomes suggest that treatment with SYH herbal acupuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

Single and repeated dose pharmacokinetics of dexketoprofen trometamol in patients with impaired liver function.

Science.gov (United States)

Valles, J; Artigas, R; Bertolotti, M; Crea, A; Muller, F; Paredes, I; Capriati, A

2006-06-01

Dexketoprofen trometamol, a high water-soluble salt of the active enantiomer of rac-ketoprofen, is a nonsteroidal antiinflammatory drug (NSAID) used for pain relief. This study compared the pharmacokinetics of dexketoprofen in patients with impaired liver function and normal subjects following single and repeated oral dosing. Subjects with normal liver function (n = 6) and with Child-Pugh A (n = 7) or Child-Pugh B (n = 5) hepatic impairment scores completed this open-label and parallel study. They received 25 mg dexketoprofen (equivalent to 37 mg of its tromethamine salt) as a single (day 1) and a 3-day repeated dose (1 dose every 8 hours for a total of 10 doses). Dexketoprofen concentrations were determined in plasma and urine by reverse-phase high performance liquid chromatography (HPLC). Model-independent pharmacokinetic parameters were obtained. All subjects completed the study. No serious adverse events were recorded. Following the single dose, mean (+/- SEM) Cmax were 3027.7 +/- 429.3 ng/ml (healthy subjects), 2856.3 +/- 340.3 ng/ml (Child-Pugh A) and 1937.2 +/- 328.0 ng/ml (Child-Pugh B). Median tmax were 0.49 h (0.33-0.68) h, 0.50 h (0.33-0.67) h and 0.67 h (0.33-1.50) h. AUC0-x averaged 3778.0 +/- 439.0 ng.h/ml, 4890.4 +/- 539.1 ng.h/ml and 3985.0 +/- 712.0 ng.h/ml. Mean CL/F were 101.1 +/- 11.3 ml/h/kg, 73.3 +/- 9.9 ml/h/kg and 88.8 +/- 15.5 ml/h/kg and V/F averaged 0.192 +/- 0.018 l/kg, 0.162 +/- 0.006 l/kg and 0.214 +/- 0.044 l/kg. Following the repeated administration, similar results were obtained showing no drug accumulation. As related to the administered dose, median excretions of unchanged and conjugated dexketoprofen in urine were 2.1% and 67.1% in healthy subjects, 2.8% and 60.9% in Child-Pugh A subjects and 4.4% and 47.7% in Child-Pugh B volunteers. A trend towards a reduced urinary excretion of conjugated dexketoprofen in hepatic patients, more evident in the Child-Pugh B than in the Child-Pugh A groups, was observed when compared with healthy

Pharmacokinetics of colistin methanesulfonate (CMS) in healthy Chinese subjects after single and multiple intravenous doses.

Science.gov (United States)

Zhao, Miao; Wu, Xiao-Jie; Fan, Ya-Xin; Zhang, Ying-Yuan; Guo, Bei-Ning; Yu, Ji-Cheng; Cao, Guo-Ying; Chen, Yuan-Cheng; Wu, Ju-Fang; Shi, Yao-Guo; Li, Jian; Zhang, Jing

2018-05-01

The high prevalence of extensively drug-resistant Gram-negative pathogens has forced clinicians to use colistin as a last-line therapy. Knowledge on the pharmacokinetics of colistin methanesulfonate (CMS), an inactive prodrug, and colistin has increased substantially; however, the pharmacokinetics in the Chinese population is still unknown due to lack of a CMS product in China. This study aimed to evaluate the pharmacokinetics of a new CMS product developed in China in order to optimise dosing regimens. A total of 24 healthy subjects (12 female, 12 male) were enrolled in single- and multiple-dose pharmacokinetic (PK) studies. Concentrations of CMS and formed colistin in plasma and urine were measured, and PK analysis was conducted using a non-compartmental approach. Following a single CMS dose [2.36 mg colistin base activity (CBA) per kg, 1 h infusion], peak concentrations (C max ) of CMS and formed colistin were 18.0 mg/L and 0.661 mg/L, respectively. The estimated half-life (t 1/2 ) of CMS and colistin were 1.38 h and 4.49 h, respectively. Approximately 62.5% of the CMS dose was excreted via urine within 24 h after dosing, whilst only 1.28% was present in the form of colistin. Following multiple CMS doses, colistin reached steady-state within 24 h; there was no accumulation of CMS, but colistin accumulated slightly (R AUC  = 1.33). This study provides the first PK data in the Chinese population and is essential for designing CMS dosing regimens for use in Chinese hospitals. The urinary PK data strongly support the use of intravenous CMS for serious urinary tract infections. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

Evaluation of preclinical single and multiple dose toxicity and efficacy of 213 Bi-labeled plasminogen activator inhibitor 2 for breast and prostate cancer

International Nuclear Information System (INIS)

Rizvi, S.; Li, Y.; Allen, B.; Littlejohn, T.; Ranson, M.; Links, M.; Irving, D.; Andrews, J.

2003-01-01

The aim of the study was to evaluate the single and multiple dose toxicity (maximum tolerated dose or MTD) regimes for 213 Bi-labeled PAI2. Dose range of 2-8 mCi/kg was used for the single dose toxicity studies. It was found that end point (20% weight loss and/or distressed behaviour) was not reached for the highest dose either with single or multiple dose injections. For multiple dose toxicity studies, the dose levels ranged between 0.4 - 2 mCi/kg, and were administered daily for 5 days. The highest level tested (2mCi/kg/day x 5) was the maximum tolerated dose as 3/6 mice succumbed to the endpoints. However, histological examination of major organs showed no adverse morphological changes. From these toxicity studies, we concluded that either a dose of 1.6mCi/kg of 213 Bi-PAI2 per day for 5 days or a single injection of 8 mCi/kg can be administered without reaching the endpoints. These dose levels were used for efficacy trials. The efficacy studies were conducted to examine if the 1.6mCi/kgday x 5 multiple dose schedule (sub-maximum tolerated dose) showed efficacy against established and early stage human breast and prostate tumours in mice. Statistical analyses of the data indicate a significant tumour growth rate delay and increased time to reach tumour size endpoint for alpha-PAI2 treatment compared to control tumours, in both pre-tumour stage and established tumour models

A luminescence imaging system for the routine measurement of single-grain OSL dose distributions

DEFF Research Database (Denmark)

Kook, Myung Ho; Lapp, Torben; Murray, Andrew

2015-01-01

the potential of an electron multiplying charge-coupled device (EMCCD), providing extremely low level light detection. We characterize the performance of the device by discussing reproducibility and evaluating uncertainties in OSL signals. Finally we derive a typical single grain natural dose distribution...

Remifentanil dose for laryngeal mask airway insertion with a single standard dose of propofol during emergency airway management in elderly patients.

Science.gov (United States)

Ryu, Junghee; Oh, Ah Young; Baek, Ji-Seok; Kim, Jin-Hee; Park, Sang-Heon; Noh, Jae-Mun

2014-04-01

This study determined the dose of remifentanil to use during insertion of a Classic™ laryngeal mask airway (LMA, The Laryngeal Mask Co., Nicosia, Cyprus) in elderly patients during emergency airway management when combined with a single dose of propofol. Patients aged 65-80 years were enrolled. Anesthesia was induced with propofol 1 mg/kg, and then a blinded dose of remifentanil was infused over 30 s after confirming the patient's loss of consciousness. The dose of remifentanil was determined using Dixon's up-and-down method, starting at 0.5 µg/kg (a step size of 0.1 µg/kg). Insertion of the LMA was attempted 60 s after loss of consciousness. In total, 23 patients were recruited and the mean age ± standard deviation was 72 ± 3 years. The effective dose for successful LMA insertion in 50% of the patients (ED50) was 0.20 ± 0.05 µg/kg. No patient needed more than 0.3 µg/kg. Remifentanil 0.20 ± 0.05 µg/kg with propofol 1 mg/kg resulted in excellent LMA insertion in 50% of elderly patients without significant hemodynamic changes during emergency airway management.

Spatial resolution of 2D ionization chamber arrays for IMRT dose verification: single-detector size and sampling step width

International Nuclear Information System (INIS)

Poppe, Bjoern; Djouguela, Armand; Blechschmidt, Arne; Willborn, Kay; Ruehmann, Antje; Harder, Dietrich

2007-01-01

The spatial resolution of 2D detector arrays equipped with ionization chambers or diodes, used for the dose verification of IMRT treatment plans, is limited by the size of the single detector and the centre-to-centre distance between the detectors. Optimization criteria with regard to these parameters have been developed by combining concepts of dosimetry and pattern analysis. The 2D-ARRAY Type 10024 (PTW-Freiburg, Germany), single-chamber cross section 5 x 5 mm 2 , centre-to-centre distance between chambers in each row and column 10 mm, served as an example. Additional frames of given dose distributions can be taken by shifting the whole array parallel or perpendicular to the MLC leaves by, e.g., 5 mm. The size of the single detector is characterized by its lateral response function, a trapezoid with 5 mm top width and 9 mm base width. Therefore, values measured with the 2D array are regarded as sample values from the convolution product of the accelerator generated dose distribution and this lateral response function. Consequently, the dose verification, e.g., by means of the gamma index, is performed by comparing the measured values of the 2D array with the values of the convolution product of the treatment planning system (TPS) calculated dose distribution and the single-detector lateral response function. Sufficiently small misalignments of the measured dose distributions in comparison with the calculated ones can be detected since the lateral response function is symmetric with respect to the centre of the chamber, and the change of dose gradients due to the convolution is sufficiently small. The sampling step width of the 2D array should provide a set of sample values representative of the sampled distribution, which is achieved if the highest spatial frequency contained in this function does not exceed the 'Nyquist frequency', one half of the sampling frequency. Since the convolution products of IMRT-typical dose distributions and the single

Single-dose and steady-state pharmacokinetics of tenofovir disoproxil fumarate in human immunodeficiency virus-infected children.

Science.gov (United States)

Hazra, Rohan; Balis, Frank M; Tullio, Antonella N; DeCarlo, Ellen; Worrell, Carol J; Steinberg, Seth M; Flaherty, John F; Yale, Kitty; Poblenz, Marianne; Kearney, Brian P; Zhong, Lijie; Coakley, Dion F; Blanche, Stephane; Bresson, Jean Louis; Zuckerman, Judith A; Zeichner, Steven L

2004-01-01

Tenofovir disoproxil fumarate (DF) is a potent nucleotide analog reverse transcriptase inhibitor approved for the treatment of human immunodeficiency virus (HIV)-infected adults. The single-dose and steady-state pharmacokinetics of tenofovir were evaluated following administration of tenofovir DF in treatment-experienced HIV-infected children requiring a change in antiretroviral therapy. Using increments of tenofovir DF 75-mg tablets, the target dose was 175 mg/m(2); the median administered dose was 208 mg/m(2). Single-dose pharmacokinetics were evaluated in 18 subjects, and the geometric mean area under the concentration-time curve from 0 h to infinity (AUC(0- infinity )) was 2,150 ng. h/ml and the geometric mean maximum concentration (C(max)) was 266 ng/ml. Subsequently, other antiretrovirals were added to each patient's regimen based upon treatment history and baseline viral resistance results. Steady-state pharmacokinetics were evaluated in 16 subjects at week 4. The steady-state, geometric mean AUC for the 24-h dosing interval was 2,920 ng. h/ml and was significantly higher than the AUC(0- infinity ) after the first dose (P = 0.0004). The geometric mean C(max) at steady state was 302 ng/ml. Tenofovir DF was generally very well tolerated. Steady-state tenofovir exposures in children receiving tenofovir DF-containing combination antiretroviral therapy approached values seen in HIV-infected adults (AUC, approximately 3,000 ng. h/ml; C(max), approximately 300 ng/ml) treated with tenofovir DF at 300 mg.

PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS).

Science.gov (United States)

Barbosa, Lorraine; Johnson, Shawn P; Papich, Mark G; Gulland, Frances

2015-06-01

Ciprofloxacin is commonly selected for clinical use due to its broad-spectrum efficacy and is a frequently administered antibiotic at The Marine Mammal Center, a marine mammal rehabilitation facility. Ciprofloxacin is used for treatment of California sea lions ( Zalophus californianus ) suffering from a variety of bacterial infections at doses extrapolated from other mammalian species. However, as oral absorption is variable both within and across species, a more accurate determination of appropriate dosage is needed to ensure effective treatment and avoid emergence of drug-resistant bacterial strains. A pharmacokinetic study was performed to assess plasma concentrations of ciprofloxacin in California sea lions after a single oral dose. Twenty healthy California sea lions received a single 10-mg/kg oral dose of ciprofloxacin administered in a herring fish. Blood was then collected at two of the following times from each individual: 0.5, 0.75, 1, 2, 4, 8, 10, 12, 18, and 24 hr postingestion. Plasma ciprofloxacin concentration was assessed via high-performance liquid chromatography. A population pharmacokinetics model demonstrated that an oral ciprofloxacin dose of 10 mg/kg achieved an area under the concentration vs. time curve of 6.01 μg hr/ml. Absorption was rapid, with ciprofloxacin detectable in plasma 0.54 hr after drug administration; absorption half-life was 0.09 hr. A maximum plasma concentration of 1.21 μg/ml was observed at 1.01 hr, with an elimination half-life of 3.09 hr. Ciprofloxacin administered orally at 10 mg/kg produced therapeutic antibacterial exposure for only some of the most susceptible bacterial organisms commonly isolated from California sea lions.

Pharmacokinetic Effects of Antidrug Antibodies Occurring in Healthy Subjects After a Single Dose of Intravenous Infliximab.

Science.gov (United States)

Ehrenpreis, Eli D

2017-12-01

Infliximab pharmacokinetic studies have been performed in patients receiving chronic infliximab therapy. In these patients, infliximab antidrug antibodies (ADAs) increase infliximab clearance and decrease serum levels and drug efficacy. This study analyzed the pharmacokinetic effect of infliximab ADAs in healthy subjects receiving a single dose of intravenous infliximab. Data were obtained from a single-blind, parallel-group, single-dose study of healthy subjects receiving 5 mg/kg of intravenous SB2 (infliximab biosimilar), EU-sourced Remicade (EU-IFX) or US-sourced Remicade (US-IFX). Serum infliximab was measured at 1, 2, 3, 6, 12, 24, 48, and 72 h and at 5, 7, 14, 21, 28, 42, 56, and 70 days after administration. ADAs were measured pre-dose and at 29 and 71 days. Data from the first ten subjects randomized to each treatment arm were utilized for this study. A two-compartment model of the serum infliximab vs. time curve was developed using nonlinear regression. At 10 weeks, 11 subjects (37%) developed ADAs. ADAs were detected in four subjects after SB2, one subject after EU-IFX, and six subjects after US-IFX infusion. Of these, neutralizing antibodies occurred in one subject after SB2, in no subjects after EU-IFX, and in three subjects after US-IFX infusion. Infliximab clearance was increased in subjects with ADAs vs. those without ADAs (12.89 ± 2.69 vs. 9.90 ± 1.74 ml/h; p ADAs (282.4 ± 56.4 vs. 343.3 ± 61.9 h; p ADAs are common in healthy subjects after a single intravenous dose of infliximab and result in faster infliximab clearance, shorter elimination time, and lower serum infliximab levels. These data confirm that ADAs are common with biologic therapy and significantly impact the efficacy of these drugs.

Population Pharmacokinetic Modelling of FE 999049, a Recombinant Human Follicle-Stimulating Hormone, in Healthy Women After Single Ascending Doses

DEFF Research Database (Denmark)

Rose, Trine Høyer; Röshammar, Daniel; Erichsen, Lars

2016-01-01

reproductive technologies. Methods: Serum FSH levels were measured following a single subcutaneous FE 999049 injection of 37.5, 75, 150, 225 or 450 IU in 27 pituitary-suppressed healthy female subjects participating in this first-in-human single ascending dose trial. Data was analysed by nonlinear mixed...... volume of distribution (V/F) estimates were found to increase with body weight. Body weight was included as an allometrically scaled covariate with a power exponent of 0.75 for CL/F and 1 for V/F. Conclusions: The single-dose pharmacokinetics of FE 999049 were adequately described by a population...

Effects of single and split doses of cobalt-60 gamma rays and 14 MeV neutrons on mouse stem cell spermatogonia.

Science.gov (United States)

Hacker-Klom, U B; Köhnlein, W; Göhde, W

2000-12-01

The long-term effects of ionizing radiation on male gonads may be the result of damage to spermatogonial stem cells. Doses of 10 cGy to 15 Gy (60)Co gamma rays or 10 cGy to 7 Gy 14 MeV neutrons were given to NMRI mice as single or split doses separated by a 24-h interval. The ratios of haploid spermatids/2c cells and the coefficients of variation of DNA histogram peaks as measures of both the cytocidal and the clastogenic actions of radiation were analyzed by DNA flow cytometry after DAPI staining. The coefficient of variation is not only a statistical examination of the data but is also used here as a measure of residual damage to DNA (i.e. a biological dosimeter). Testicular histology was examined in parallel. At 70 days after irradiation, the relative biological effectiveness for neutrons at 50% survival of spermatogonial stem cells was 3.6 for single doses and 2.8 for split doses. The average coefficient of variation of unirradiated controls of elongated spermatids was doubled when stem cells were irradiated with single doses of approximately 14 Gy (60)Co gamma rays or 3 Gy neutrons and observed 70 days later. Split doses of (60)Co gamma rays were more effective than single doses, doubling DNA dispersion at 7 Gy. No fractionation effect was found with neutrons with coefficients of variation.

Using the OSL single-aliquot regenerative-dose protocol with quartz extracted from building materials in retrospective dosimetry

International Nuclear Information System (INIS)

Boetter-Jensen, L.; Solongo, S.; Murray, A.S.; Banerjee, D.; Jungner, H.

2000-01-01

We report on the application of the single-aliquot regenerative-dose (SAR) protocol to the optically stimulated luminescence signal from quartz extracted from fired bricks and unfired mortar in retrospective dosimetry. The samples came from a radioactive materials storage facility, with ambient dose rates of about 0.1 mGy/h. A detailed dose-depth profile was analysed from one brick, and compared with dose records from area TL dosemeters. Small-aliquot dose-distributions were analysed from the mortar samples; one associated with the exposed brick, and one from a remote site exposed only to background radiation. We conclude that unfired materials have considerable potential in retrospective dosimetry

8 Gy single-dose radiotherapy is effective in metastatic spinal cord compression: Results of a phase III randomized multicentre Italian trial

International Nuclear Information System (INIS)

Maranzano, Ernesto; Trippa, Fabio; Casale, Michelina; Costantini, Sara; Lupattelli, Marco; Bellavita, Rita; Marafioti, Luigi; Pergolizzi, Stefano; Santacaterina, Anna; Mignogna, Marcello; Silvano, Giovanni; Fusco, Vincenzo

2009-01-01

Background and purpose: In a previous randomized trial we showed that the short-course radiotherapy (RT) regimen of 8 Gy x 2 was feasible in patients with metastatic spinal cord compression (MSCC) and short life expectancy. This phase III trial was planned to determine whether in the same category of patients 8 Gy single-dose is as effective as 8 Gy x 2. Materials and methods: Three hundred and twenty-seven patients with MSCC and short life expectancy were randomly assigned to a short-course of 8 Gy x 2 or to 8 Gy single-dose RT. Median follow-up was 31 months (range, 4-58). Results: A total of 303 (93%) patients are assessable, 150 treated with the short-course and 153 with the single-dose RT. No difference in response was found between the two RT schedules adopted. Median duration of response was 5 and 4.5 months for short-course and single-dose RT (p = 0.4), respectively. The median overall survival was 4 months for all cases. Light acute toxicity was registered in a minority of cases. Late toxicity was never recorded. Conclusions: Both RT schedules adopted were effective. As already shown in several trials evaluating RT regimens in uncomplicated painful bone metastases, also MSCC patients may achieve palliation with minimal toxicity and inconvenience with a single-dose of 8 Gy.

The Effect of Nicotine Administration on Physical and Psychological Signs of Withdrawal Syndrome Induced by Single or Frequent Doses of Morphine in Rats

Directory of Open Access Journals (Sweden)

Mohammad Allahtavakoli

2012-07-01

Full Text Available Introduction. Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Materials and methods. Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose (the 8th day were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat′s behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p<0.05 was considered as significant difference. Findings. Results showed that the injection of frequent and single doses of morphine lead to morphine dependency. In single dose protocol, nicotine consumption attenuated the signs of withdrawal syndrome, especially weight of excrement and total withdrawal score. In frequent dose protocol, in addition to these effects, nicotine induced weight loss and place aversion. Conclusion. The inhibitory effects of nicotine on signs of withdrawal syndrome may involve a dopaminergic portion of the central nervous system and is mediated by central nicotinic receptors. There is also a cross-dependence between nicotine and morphine.

A Single-Dose, Single-Period Pharmacokinetic Assessment of an Extended-Release Orally Disintegrating Tablet of Methylphenidate in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder.

Science.gov (United States)

Childress, Ann; Newcorn, Jeffrey; Stark, Jeffrey G; McMahen, Russ; Tengler, Mark; Sikes, Carolyn

2016-08-01

To determine the pharmacokinetic (PK) profile of a proprietary formulation of methylphenidate (MPH) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) in a phase 1 study. Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) combine two technologies in a single-tablet formulation-an extended-release profile that was designed for once-daily dosing in an ODT that does not require water or chewing for ingestion. This was a single-dose, open-label, single-period, single-treatment study, in which 32 children with ADHD who were receiving MPH in doses of 40 or 60 mg before beginning the study each received a 60-mg dose (2 × 30 mg) of MPH XR-ODT. The following plasma PK parameters of MPH were determined for participants grouped by age (6-7, 8-9, 10-12, and 13-17 years old): maximum concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (T½), area under the curve from 0 hours to infinity (AUCinf), oral clearance (CL/F), and volume of distribution in the terminal phase (Vz/F). Safety and tolerability were also assessed. A total of 32 participants received the study drug. For all participants, plasma concentration-time profiles of MPH exhibited a broad peak after administration of MPH XR-ODT through ∼8 hours, indicating extended release from the formulation, followed by an apparent first-order elimination phase. As age increased, MPH exposure decreased and mean estimates of CL/F increased; however, weight-normalized CL/F values were comparable across age groups. Similarly, mean estimates of Vz/F increased with age, but weight-normalization decreased differences across age groups, with the exception of the youngest age group, which had higher values. All adverse events (AEs) were mild. This XR-ODT formulation of MPH demonstrated weight-normalized clearance rates that were consistent across all age groups, a PK profile consistent with once-daily dosing, and an AE profile consistent with

Disposition and metabolism of codeine after single and chronic doses in one poor and seven extensive metabolisers.

Science.gov (United States)

Chen, Z R; Somogyi, A A; Reynolds, G; Bochner, F

1991-04-01

1. The pharmacokinetics, metabolism and partial clearances of codeine to morphine, norcodeine and codeine-6-glucuronide after single (30 mg) and chronic (30 mg 8 h for seven doses) administration of codeine were studied in eight subjects (seven extensive and one poor metaboliser of dextromethorphan). Codeine, codeine-6-glucuronide, morphine and norcodeine were measured by high performance liquid chromatographic assays. 2. After the single dose, the time to achieve maximum plasma codeine concentrations was 0.97 +/- 0.31 h (mean +/- s.d.) and for codeine-6-glucuronide it was 1.28 +/- 0.49 h. The plasma AUC of codeine-6-glucuronide was 15.8 +/- 4.5 times higher than that of codeine. The AUC of codeine in saliva was 3.4 +/- 1.1 times higher than that in plasma. The elimination half-life of codeine was 3.2 +/- 0.3 h and that of codeine-6-glucuronide was 3.2 +/- 0.9 h. 3. The renal clearance of codeine was 183 +/- 59 ml min-1 and was inversely correlated with urine pH (r = 0.81). These data suggest that codeine undergoes filtration at the glomerulus, tubular secretion and passive reabsorption. The renal clearance of codeine-6-glucuronide was 55 +/- 21 ml min-1, and was not correlated with urine pH. Its binding to human plasma was less than 10%. These data suggest that codeine-6-glucuronide undergoes filtration at the glomerulus and tubular reabsorption. This latter process is unlikely to be passive. 4. After chronic dosing, the pharmacokinetics of codeine and codeine-6-glucuronide were not significantly different from the single dose pharmacokinetics. 5. After the single dose, 86.1 +/- 11.4% of the dose was recovered in urine, of which 59.8 +/- 10.3% was codeine-6-glucuronide, 7.1 +/- 1.1% was total morphine, 6.9 +/- 2.1% was total norcodeine and 11.8 +/- 3.9% was unchanged codeine. These recoveries were not significantly different (P greater than 0.05) after chronic administration. 6. After the single dose, the partial clearance to morphine was 137 +/- 31 ml min-1 in

Palonosetron-A Single-Dose Antiemetic Adjunct for Hepatic Artery Radioembolization: A Feasibility Study

International Nuclear Information System (INIS)

Siddiqi, Nasir H.; Khan, Atif J.; Devlin, Phillip M.

2009-01-01

Nausea and vomiting may occur in a significant minority of patients following hepatic artery embolization with yttrium-90 spheres (K. T. Sato et al. Radiology 247:507-515, 2008). This encumbers human and economic resources and undercuts the assertion that it is as a well-tolerated outpatient treatment. A single intravenous dose of palonosetron HCl was administered before hepatic artery embolization with yttrium-90 spheres to ameliorate posttreatment nausea and vomiting, in 23 consecutive patients. The patients were discharged the day of procedure on oral antiemetics, steroids, and blockers of gastric acid release. All patients had clinical and laboratory evaluation at 2 weeks after the procedure. The data were gathered and reviewed retrospectively. At 2-week follow-up, none reported significant nausea, vomiting, additional antiemetic use, need for parenteral therapy, hospital readmission, or palonosetron-related side effects. All patients recovered from postembolization symptoms within a week after treatment. In conclusion, this retrospective study suggests that single-dose palonosetron is feasible, safe, and effective for acute and delayed nausea and vomiting in this group of patients. The added cost may be offset by benefits.

Effects of local single and fractionated X-ray doses on rat bone marrow blood flow and red blood cell volume

International Nuclear Information System (INIS)

Pitkaenen, M.A.; Hopewell, J.W.

1985-01-01

Time and dose dependent changes in blood flow and red blood cell volume were studied in the locally irradiated bone marrow of the rat femur after single and fractionated doses of X-rays. With the single dose of 10 Gy the bone marrow blood flow although initially reduced returned to the control levels by seven months after irradiation. With doses >=15 Gy the blood flow was still significantly reduced at seven months. The total dose levels predicted by the nominal standard dose equation for treatments in three, six or nine fractions produced approximately the same degree of reduction in the bone marrow blood flow seven months after the irradiation. However, the fall in the red blood cell volume was from 23 to 37% greater in the three fractions groups compared with that in the nine fractions groups. Using the red blood cell volume as a parameter the nominal standard dose formula underestimated the severity of radiation damage in rat bone marrow at seven months for irradiation with small numbers of large dose fractions. (orig.) [de

Study on dose-effect relationship of radiation-induced DNA damage using single cell gel electrophoresis

International Nuclear Information System (INIS)

Liu Qiang; Jiang Enhai; Li Jin; Tang Weisheng; Wang Zhiquan; Zhao Yongcheng; Fan Feiyue

2006-01-01

Objective: To explore a new, simple and quick radiation biodosimeter, which can be applied to estimate biological dose in case of radiation accident. Methods: DNA double-strand break were detected using neutral single cell gel electrophoresis (SCGE), and all the indexes of comet assay including HDNA%, TDNA%, CL, TL, TM, and OTM were analyzed by CASP (Comet Assay Software Project). The curve of dose-effect was fitted using SPSS 12.0 software. Results: Statistically significant dose-effect relationships were observed in all the indexes of comet assay, OTM was superior to other indexes. Conclusions: Application of neutral comet assay combined with CASP analysis could serve as a new radiation biodosimeter. (authors)

Regulatory T Cell Responses in Participants with Type 1 Diabetes after a Single Dose of Interleukin-2: A Non-Randomised, Open Label, Adaptive Dose-Finding Trial

Science.gov (United States)

Todd, John A.; Porter, Linsey; Smyth, Deborah J.; Rainbow, Daniel B.; Ferreira, Ricardo C.; Yang, Jennie H.; Bell, Charles J. M.; Schuilenburg, Helen; Challis, Ben; Clarke, Pamela; Coleman, Gillian; Dawson, Sarah; Goymer, Donna; Kennet, Jane; Brown, Judy; Greatorex, Jane; Goodfellow, Ian; Evans, Mark; Mander, Adrian P.; Bond, Simon; Wicker, Linda S.

2016-01-01

Background Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. Methods and Findings To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = −0

Pharmacokinetics of diclofenac in pigs after intramuscular administration of a single dose

OpenAIRE

Pejčić Zorica; Pokrajac Milena; Jezdimirović Milanka

2006-01-01

The pharmacokinetics of diclofenac was studied in 10 clinically normal male Yorkshire pigs, following intramuscular (i.m) administration of a single dose of diclofenac-sodium (2.5 mg/kg body weight). Diclofenac serum concentrations were determined by high pressure- liquid-chromatography (HPLC), with UV detection (226 nm). Following i.m. administration all individual diclofenac serum levels best fitted the one-compartment open model for extravascular administration. The maximal diclofenac seru...

A quantitative assessment of changes in the dermal fibroblast population of pig skin after single doses of X-rays

International Nuclear Information System (INIS)

Hamlet, R.; Hopewell, J.W.

1988-01-01

Changes in the density of fibroblast nuclei in reticular dermis of pigs was studied from 6 to 104 weeks after a single dose of 15.4 Gy of X-rays. The largest decrease in fibroblasts occurred between 12 and 26 weeks after irradiation; after this there was only a slight fall in fibroblast number until 104 weeks when observations ceased. At 26 weeks and later times after irradiation reduction in the density of fibroblast nuclei in the reticular dermis was dose-dependent for single doses in the range 8.0-20.7 Gy. The dose-response curve had an initial shoulder, after which the fall in the fibroblast nuclear density was linearly related to dose. Data obtained between 26 weeks and 104 weeks after irradiation, could be fitted by the same dose-response curve. The fall in the counts of fibroblast nuclei was compared with earlier studies. The loss of fibroblasts occurred after an initial reduction in blood flow in the pig skin but was concomitant with general reduction in dermal thickness. (author)

Treatment of chronic spontaneous urticaria with a single dose of omalizumab: A study of four cases

Directory of Open Access Journals (Sweden)

Radhakrishnan Subramaniyan

2016-01-01

Full Text Available Background: Chronic spontaneous urticaria (CSU has a detrimental effect on patients′ emotional and physical quality of life. Omalizumab, an anti-immunoglobulin E humanized monoclonal antibody, has been shown to be very effective in the treatment of refractory chronic urticaria patients but may not be an economically viable option for all CSU patients. However, we present a case series where a single dose of omalizumab gave sustained relief of symptoms in patients with CSU, which may be an economical option. Aims: The aim of this study is to assess the efficacy of a single dose of omalizumab in the treatment of CSU. Materials and Methods: Four patients of CSU whose disease was not controlled with four times the licensed dose of tablet fexofenadine 180 mg were exhibited one subcutaneous injection of omalizumab and were followed up at 4 weekly intervals for 24 weeks for Weekly Urticaria Activity Score 7 (UAS7 and Dermatology Life Quality Index (DLQI. Results: A sharp decline in UAS7 and DLQI was documented in 7-10 days. The decline was maintained up to 16 weeks in one case and 20 weeks in the other three cases. Both the scores at the end of the follow-up period of 24 weeks were better than the pre-omalizumab scores. Conclusion: The results of this case series indicate the efficacy of a single-dose omalizumab in treating moderate to severe refractory CSU. Further studies are required to identify the minimum frequency of administering omalizumab to effectively control CSU. This would greatly reduce the cost of this novel therapy.

Effect of a single dose of dextromethorphan on psychomotor performance and working memory capacity.

Science.gov (United States)

Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Ashor, Ammar Waham

2012-04-01

Previous studies show that the prolonged use of dextromethorphan produces cognitive deterioration in humans. The aim of this study was to investigate the effect of a single dose of dextroemthrophan on psychomotor performance and working memory capacity. This is a randomized, double-blind, controlled, and prospective study. Thirty-six (17 women, 19 men) medical students enrolled in the study; half of them (7 women, 11 men) were given placebo, while the other half (10 women, 8 men) received dextromethorphan. The choice reaction time, critical flicker fusion threshold, and N-back working memory task were measured before and after 2 h of taking the drugs. Dextromethorphan showed a significant deterioration in the 3-back working memory task (P0.05). On the other hand, placebo showed no significant changes as regards the choice reaction time, critical flicker fusion threshold, and N-back working memory task (P>0.05). A single dose of dextromethorphan has no effect on attention and arousal but may significantly impair the working memory capacity.

Distribution of 99Tcm-rh-Annexin vin tumor and expression relationship of bcl-2, bax after a single dose of chemotherapy

International Nuclear Information System (INIS)

Zhang Xin; Li Yaming; Zhang Yanjun; Tao Li; Zhu Yi; Yang Chun; Ji Xiaopeng; Zhao Ming; Tian Aijuan; Zhang Jianying; Zhao Zhenzhen

2007-01-01

The expression of bcl-2 and bax after the single dose of chemotherapy with 99 Tc m -rh-Annexin V as the tracer of tumor apoptosis imaging is studied. tumor cell apoptosis is examined by TUNEL methods, and the expression of bcl-2 and bax in tumor are determined by immunohistochemical methods. Single dose of chemotherapy significantly increased the tumor uptake of 99 Tc m -rh-annexin V and the positive number of TUNEL, as well as the expression of bax (P 99 Tc m -rh-annexin V in tumor reflectes not only the degree of apoptosis of tumor cells, but also the change of bax expression after the single dose of chemotherapy. (authors)

Effects of single dose X-irradiation on the guinea-pig spinal cord

Energy Technology Data Exchange (ETDEWEB)

Knowles, J F [Medical Research Council, Harwell (UK). Radiobiological Research Unit

1981-09-01

Lumbar or cervical regions of the guinea-pig spinal cord were irradiated with a single dose of 250 kV X-rays. The latency for paralysis, whether of hind- or fore-limbs, and the histopathology of the radiation-induced cord lesions depended critically on the radiation dose. There were definite but only minor differences between the reactions of lumbar and cervical cord to the same radiation dose. After 30 or 40 Gy there was white matter necrosis but after 20 Gy widespread demyelination associated with vacuolar spaces occurred. After irradiation of the lumbar cord with 30-40 Gy, the lesions in the guinea-pig differed from those reported in the rat. White-matter necrosis in the guinea-pig cord was only occasionally associated with spinal nerve root necrosis, whereas in the rat, nerve-root necrosis with sparing of the white matter was the main lesion. After 20 Gy to the cervical or lumbar cord the guinea-pig showed widespread demyelination and vacuolation whereas in rats vascular lesions were the main result.

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

International Nuclear Information System (INIS)

Lee, Eun-Jung; Kim, Jun Won; Yoo, Hyun; Kwak, Woori; Choi, Won Hoon; Cho, Seoae; Choi, Yu Jeong; Lee, Yoon-Jin; Cho, Jaeho

2015-01-01

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm 2 fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL-33

Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33 secreted from impaired vessels in the skin compared to fractionated irradiation

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Lee, Eun-Jung, E-mail: forejs2@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kim, Jun Won, E-mail: JUNWON@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Yoo, Hyun, E-mail: gochunghee@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Kwak, Woori, E-mail: asleo02@snu.ac.kr [Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul 151-747 (Korea, Republic of); Choi, Won Hoon, E-mail: wonhoon@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Cho, Seoae, E-mail: seoae@cnkgenomics.com [C& K Genomics, Seoul National University Mt.4-2, Main Bldg. #514, SNU Research Park, NakSeoungDae, Gwanakgu, Seoul 151-919 (Korea, Republic of); Choi, Yu Jeong, E-mail: yunk9275@daum.net [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of); Lee, Yoon-Jin, E-mail: yjlee8@kirams.re.kr [Division of Radiation Effects, Research Center for Radiotherapy, Korea Institute of Radiological & Medical Sciences, Seoul 139-760 (Korea, Republic of); Cho, Jaeho, E-mail: jjhmd@yuhs.ac [Department of Radiation Oncology, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

2015-08-14

We have revealed in a porcine skin injury model that eosinophil recruitment was dose-dependently enhanced by a single high-dose irradiation. In this study, we investigated the underlying mechanism of eosinophil-associated skin fibrosis and the effect of high-dose-per-fraction radiation. The dorsal skin of a mini-pig was divided into two sections containing 4-cm{sup 2} fields that were irradiated with 30 Gy in a single fraction or 5 fractions and biopsied regularly over 14 weeks. Eosinophil-related Th2 cytokines such as interleukin (IL)-4, IL-5, and C–C motif chemokine-11 (CCL11/eotaxin) were evaluated by quantitative real-time PCR. RNA-sequencing using 30 Gy-irradiated mouse skin and functional assays in a co-culture system of THP-1 and irradiated-human umbilical vein endothelial cells (HUVECs) were performed to investigate the mechanism of eosinophil-mediated radiation fibrosis. Single high-dose-per-fraction irradiation caused pronounced eosinophil accumulation, increased profibrotic factors collagen and transforming growth factor-β, enhanced production of eosinophil-related cytokines including IL-4, IL-5, CCL11, IL-13, and IL-33, and reduced vessels compared with 5-fraction irradiation. IL-33 notably increased in pig and mouse skin vessels after single high-dose irradiation of 30 Gy, as well as in irradiated HUVECs following 12 Gy. Blocking IL-33 suppressed the migration ability of THP-1 cells and cytokine secretion in a co-culture system of THP-1 cells and irradiated HUVECs. Hence, high-dose-per-fraction irradiation appears to enhance eosinophil-mediated fibrotic responses, and IL-33 may be a key molecule operating in eosinophil-mediated fibrosis in high-dose-per fraction irradiated skin. - Highlights: • Single high-dose irradiation aggravates eosinophil-mediated fibrosis through IL-33. • Vascular endothelial cells damaged by high-dose radiation secrete IL-33. • Blocking IL-33 suppressed migration of inflammatory cells and cytokine secretion. • IL

Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis

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Oliveira João

2010-09-01

Full Text Available Abstract Background The effects of gonadotrophin-releasing hormone agonist (GnRH-a administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes. Methods The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures. Results All cycles presented statistically significantly higher rates of implantation (P Conclusions These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

Fluralaner as a single dose oral treatment for Caparinia tripilis in a pygmy African hedgehog.

Science.gov (United States)

Romero, Camilo; Sheinberg Waisburd, Galia; Pineda, Jocelyn; Heredia, Rafael; Yarto, Enrique; Cordero, Alberto M

2017-12-01

African pygmy hedgehogs (Atelerix albiventris) are popular pets belonging to the Erinaceidae family of spined mammals. Amongst the most common skin diseases occurring in this species is infestation caused by the mite Caparinia spp. Due to their skin anatomy and spiny coat, detection of skin lesions in these hedgehogs can be difficult. This may result in delays in seeking medical care, which may lead to secondary bacterial infection and self-inflicted trauma. Multiple therapies have been used in the treatment of this skin condition including ivermectin, amitraz, fipronil and selamectin. A drug which could be administered as a single oral dose would be advantageous to these pets and their owners. To evaluate the effect of a single oral dose (15 mg/kg) of fluralaner on Caparinia tripilis infestation in the African pygmy hedgehog. A 10-month-old African pygmy hedgehog weighing 184 g. Response to treatment was monitored by dermatological examination and superficial skin scrapings repeated at 7, 14, 21, 30, 60, 90 and 120 days following fluralaner administration. On Day 7 after treatment, adult mites were observed exhibiting normal movement. On Day 14, only dead mites were observed. No life stages of the mites were found after Day 21. A single oral dose at 15 mg/kg of fluralaner was effective within 21 days after treatment for capariniasis in this case. Further studies are required to evaluate the drug's safety and toxicology in hedgehogs, and to confirm efficacy. © 2017 ESVD and ACVD.

Frequency of wound infection in non-perforated appendicitis with use of single dose perforative antibiotics

International Nuclear Information System (INIS)

Ali, K.; Latif, H.; Ahmad, S.

2015-01-01

Antibiotics are used both pre and post-operatively in acute appendicitis for preventing wound infection. It has been observed that the routine use of post-operative antibiotics is not necessary in cases of non-perforated appendicitis as only prophylactic antibiotics are sufficient to prevent wound infection. The aim of this study was to see the frequency of wound infection in non-perforated appendicitis with single dose preoperative antibiotics only. Method: This observational study was conducted at the Department of Surgery, Ayub Medical College, Abbottabad from May to November 2014. A total of 121 patients with non-perforated appendicitis were included in the study. Only single dose preoperative antibiotics were used. The patients were followed for wound infection till 8th post-operative day. Results: 121 patients, 56(46.28%) male and 65(53.72%) female were included in the study. The mean age of patients was 27.41 ± 7.12 years with an age range of 18 to 45 years. In the entire series, 7(5.78%) patients developed wound infection. The infection was minor which settled with conservative therapy. Prophylactic antibiotics were found efficacious in 114(94.21%) patients. There was no significant association between wound infection and age and gender. Conclusion: Single dose preoperative antibiotics were found effective in controlling post-operative wound infection without the need of extending the antibiotics to post-operative period in cases of non-perforated appendicitis. (author)

Effect of single oral dose of tramadol on gastric secretions pH

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Khan Mueen Ullah

2015-01-01

Full Text Available Background: Tramadol is an atypical analgesic agent. It has been shown that intramuscular or intravenous injection tramadol is able to inhibit M3 muscarinic receptors. Tramadol is able to mediate smooth muscles contraction and glandular secretions. We have evaluated the effects of single oral dose of tramadol given preoperatively on gastric juices pH in patients electively scheduled for laparoscopic cholecystectomy. Materials and Methods: Sixty adult, American Society of Anesthesiologist I and II patients scheduled for laparoscopic cholecystectomy were included in the study. Patients were randomly assigned to receive either placebo (n = 30 or oral tramadol 50 mg (n = 30. General anesthesia was induced using propofol, fentanyl and cisatracurium. After induction of anesthesia 5 ml of gastric fluid was aspirated through orogastric tube. The gastric fluid pH was measured using pH meter. Result: There was no significant difference in the pH between the groups. Gastric pH of the placebo and tramadol groups was 1.97 versus 1.98 (P = 0.092 respectively. Conclusion: Preoperatively single oral dose of tramadol was unable to elevate the desired level of gastric acid secretions pH (>2.5. This may be due to pharmacokinetic disparity between the analgesic and pH elevating properties of tramadol.

Serum tocopherol levels in very preterm infants after a single dose of vitamin E at birth.

Science.gov (United States)

Bell, Edward F; Hansen, Nellie I; Brion, Luc P; Ehrenkranz, Richard A; Kennedy, Kathleen A; Walsh, Michele C; Shankaran, Seetha; Acarregui, Michael J; Johnson, Karen J; Hale, Ellen C; Messina, Lynn A; Crawford, Margaret M; Laptook, Abbot R; Goldberg, Ronald N; Van Meurs, Krisa P; Carlo, Waldemar A; Poindexter, Brenda B; Faix, Roger G; Carlton, David P; Watterberg, Kristi L; Ellsbury, Dan L; Das, Abhik; Higgins, Rosemary D

2013-12-01

Our aim was to examine the impact of a single enteral dose of vitamin E on serum tocopherol levels. The study was undertaken to see whether a single dose of vitamin E soon after birth can rapidly increase the low α-tocopherol levels seen in very preterm infants. If so, this intervention could be tested as a means of reducing the risk of intracranial hemorrhage. Ninety-three infants vitamin E or placebo by gastric tube within 4 hours of birth. The vitamin E group received 50 IU/kg of vitamin E as dl-α-tocopheryl acetate (Aquasol E). The placebo group received sterile water. Blood samples were taken for measurement of serum tocopherol levels by high-performance liquid chromatography before dosing and 24 hours and 7 days after dosing. Eighty-eight infants received the study drug and were included in the analyses. The α-tocopherol levels were similar between the groups at baseline but higher in the vitamin E group at 24 hours (median 0.63 mg/dL vs. 0.42 mg/dL, P = .003) and 7 days (2.21 mg/dL vs 1.86 mg/dL, P = .04). There were no differences between groups in γ-tocopherol levels. At 24 hours, 30% of vitamin E infants and 62% of placebo infants had α-tocopherol levels vitamin E raised serum α-tocopherol levels, but to consistently achieve α-tocopherol levels >0.5 mg/dL, a higher dose or several doses of vitamin E may be needed.

Effect of single-dose radiation on cell survival and growth hormone secretion by rat anterior pituitary cells

International Nuclear Information System (INIS)

Hochberg, Z.; Kuten, A.; Hertz, P.; Tatcher, M.; Kedar, A.; Benderly, A.

1983-01-01

Cranial irradiation has been shown to impair growth hormone secretion in children. In this study a cell culture of dispersed rat anterior pituitary cells was exposed to single doses of radiation in the range of 100 to 1500 rad. Survival curves were obtained for the different anterior pituitary cell lines, and growth hormone secretion was measured in the tissue culture medium. Both survival and growth hormone secretion curves showed an initial shoulder in the range of 0 to 300 rad, followed by a decline between 300 to 750 rad. It is concluded that growth hormone secreting acidophilic pituicytes are sensitive to radiation at single doses greater than 300 rad

Single-dose and fractionated irradiation of four human lung cancer cell lines in vitro

International Nuclear Information System (INIS)

Brodin, O.; Lennartsson, L.; Nilsson, S.

1991-01-01

Four established human lung cancer cell lines were exposed to single-dose irradiation. The survival curves of 2 small cell lung carcinomas (SCLC) were characterized by a limited capacity for repair with small and moderate shoulders with extrapolation numbers (n) of 1.05 and 1.60 respectively. Two non-small cell lung carcinoma (NSCLC) cell lines, one squamous cell (SQCLC) and one large cell (LCLC) had large shoulders with n-values of 73 and 15 respectively. The radiosensitivity when measured as D 0 did not, however, differ as much from cell line to cell line, with values from 1.22 to 1.65. The surviving fraction after 2 Gy (SF2) was 0.24 and 0.42 respectively in the SCLC cell lines and 0.90 and 0.88 respectively in the NSCLC cell lines. Fractionated irradiation delivered according to 3 different schedules was also investigated. All the schedules delivered a total dose of 10 Gy in 5 days and were applied in 1, 2 and 5 Gy dose fractions respectively. Survival followed the pattern found after single-dose irradiation; it was lowest in the SCLC cell line with the lowest SF and highest in the two NSCLC cell lines. In the SCLC cell lines all schedules were approximately equally efficient. In the LCLC and in the SQCLC cell lines, the 5 Gy schedule killed more cells than the 1 and 2 Gy schedules. The results indicate that the size of the shoulder of the survival curve is essential when choosing the most tumoricidal fractionation schedule. (orig.)

Study of single dose toxic test of Sweet Bee Venom in Beagle Dogs

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Hye-Chul, Yoon

2010-12-01

Full Text Available Objectives : This study was performed to analyse single dose toxicity of Sweet Bee Venom(Sweet BV extracted from the bee venom in Beagle dogs. Methods : All experiments were conducted under the regulations of Good Laboratory Practice (GLP at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of single dose toxicity of Sweet BV which was administered at the level of 9.0 ㎎/㎏ body weight which is 1300 times higher than the clinical application dosage as the high dosage, followed by 3.0 and 1.0 ㎎/㎏ as midium and low dosage, respectively. Equal amount of excipient(normal saline to the Sweet BV experiment groups was administered as the control group. Results : 1. No mortality was witnessed in all of the experiment groups. 2. Hyperemia and movement disorder were observed around the area of administration in all the experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, brain, liver, lung, kidney, and spinal cords were removed and histologocal observation using H-E staining was conducted. In the histologocal observation of thigh muscle, cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes depend on the dose of Sweet BV. But the other organs did not showed in any abnormality. 5. The maximum dose of Sweet BV in Beagle dogs were over 9 ㎎/㎏ in this study. Conclusions : The above findings of this study suggest that Sweet BV is a relatively safe treatment medium. Further studies on the toxicity of Sweet BV should be conducted to yield more concrete evidences.

A comparison in young and elderly subjects of the pharmacokinetics and pharmacodynamics of single and multiple doses of benazepril.

Science.gov (United States)

Macdonald, N J; Elliott, H L; Hughes, D M; Reid, J L

1993-01-01

1. The pharmacokinetics and pharmacodynamics of single and multiple oral doses of the ACE inhibitor benazepril were investigated in young and elderly normotensive subjects. 2. Following multiple doses the trough concentrations were significantly higher in the elderly and the areas under the plasma concentration-time curves (AUC0-24) were significantly greater, by approximately 23%. 3. The fall in blood pressure tended to be greater in the elderly subjects but this is likely to be attributable to their higher initial blood pressures, although it may reflect the small differences in pharmacokinetics. 4. The age related differences in kinetics and dynamics following multiple dosing are quantitatively similar to those obtained with single doses. However, there appears to be a quantitative difference between benazepril and other ACE inhibitors in that the age related increases were of a relatively smaller magnitude. PMID:9114904

X-γ dose rate continuous monitor with wide range based on single-chip microcomputer

International Nuclear Information System (INIS)

Wu Debo; Ling Qiu; Guo Lanying; Yang Binhua

2007-01-01

This paper describes a concept about circuit designing of X-γ dose rate continuous monitor with wide range based on single-chip microcomputer, and also presents the design procedure of hardware and software, and gives several methods for solving the design procedure of hardware and software with emphasis. (authors)

Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE

DEFF Research Database (Denmark)

Grunberg, Steven; Chua, Daniel; Maru, Anish

2011-01-01

multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous...

Time and dose-related changes in the thickness of pig skin after irradiation with single doses of 90Sr/90Y β-rays

International Nuclear Information System (INIS)

Rezvani, M.; Hamlet, R.; Hopewell, J.W.; Sieber, V.K.

1994-01-01

Time-related changes in pig skin thickness have been evaluated using a non-invasive ultrasound technique after exposure to a range of single doses of 90 Sr/ 90 Yr β-rays. The reduction in relative skin thickness developed in two distinct phases: the first was between 12 and 20 weeks postirradiation. No further changes were then seen until 52 weeks postirradiation when a second phase of skin thinning was observed. This was complete after 76 weeks and no further changes in relative skin thickness were seen in the maximum follow up period of 129 weeks. The timings of these phases of damage were independent of the radiation dose, however, the severity of both phases of radiation-induced skin thinning were dose related. (Author)

Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS)

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Pauls, Mathilde M H; Clarke, Natasha; Trippier, Sarah

2017-01-01

vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. METHODS/DESIGN: Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double......-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. SAMPLE SIZE: 54 participants are required to detect a 15% increase in cerebral blood...

Study on relations between heavy ions single event upset cross sections and γ accumulated doses

International Nuclear Information System (INIS)

He Chaohui; Geng Bin; Wang Yanping; Peng Honglun; Yang Hailiang; Chen Xiaohua; Li Guozheng

2002-01-01

Experiments were done under 252 Cf and 60 Co γ source to study the relation between heavy ion Single Event Upset (SEU) cross sections and γ accumulated doses. There was no obvious rule and little influence of γ accumulated doses on SEU cross sections when Static Random Access Memories were in power off mode and static power on mode. In active measuring mode, the SEU cross section increased as the accumulated doses increasing when same data were written in memory cells. If reverse data, such as '55' and 'AA', were written in memory cells during the experiment, the SEU cross sections decreased to the level when memories were not irradiated under 60 Co γ source, even more small. It implied that the influence of γ accumulated doses on SEU cross sections can be set off by this method

Efficacy of single and double doses of albendazole and mebendazole alone and in combination in the treatment of Trichuris trichiura in school-age children in Uganda

DEFF Research Database (Denmark)

Namwanje, Harriet; Kabatereine, Narcis B.; Olsen, Annette

2011-01-01

A randomised clinical trial was conducted in Kabale District, southwestern Uganda, to compare the efficacies of single and double doses of a combination of 400mg albendazole (ALB) and 500mg mebendazole (MBZ) with those of single and double doses of each drug given alone in the treatment of Trichu......A randomised clinical trial was conducted in Kabale District, southwestern Uganda, to compare the efficacies of single and double doses of a combination of 400mg albendazole (ALB) and 500mg mebendazole (MBZ) with those of single and double doses of each drug given alone in the treatment...

Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

Science.gov (United States)

Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

2013-06-01

To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

Ocular Pharmacokinetics of Dorzolamide and Brinzolamide After Single and Multiple Topical Dosing: Implications for Effects on Ocular Blood FlowS⃞

Science.gov (United States)

Kadam, Rajendra S.; Jadhav, Gajanan; Ogidigben, Miller

2011-01-01

Ophthalmic carbonic anhydrase inhibitors have been shown to improve retinal and optic nerve blood flow. However, the relative tissue distributions of commercially available carbonic anhydrase inhibitors to the optic nerve are not known. The objective of this study was to compare the ocular pharmacokinetics and tissue distribution profiles of dorzolamide and brinzolamide after single and multiple topical applications. Pigmented rabbits were treated with single or multiple topical administrations of 30 μl of Trusopt (dorzolamide hydrochloride ophthalmic solution, 2%) to one eye and 30 μl of Azopt (brinzolamide ophthalmic suspension, 1%) to the other eye. Rabbits were euthanized at 10 predetermined time intervals over a period of 24 h, and ocular tissues and plasma samples were collected. For multiple dosing, rabbits were dosed twice per day with an 8-h interval between two doses, groups of rabbits were euthanized at 7, 14, and 21 days at 1 h after the last dose, and ocular tissues and plasma samples were collected. Drug levels in tissue samples were measured using liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters (Cmax, Tmax, and AUC0–24) were estimated by noncompartmental analysis. After a single dose, dorzolamide delivery (AUC0–24) to the aqueous humor, anterior sclera, posterior sclera, anterior retina, posterior retina, anterior vitreous, and optic nerve was 2-, 7-, 2.6-, 1.4-, 1.9-, 1.2-, and 9-fold higher than those of brinzolamide. Cmax was 2- to 5-fold higher for dorzolamide than that of brinzolamide in all of the ocular tissue. After multiple dosing, dorzolamide levels in the aqueous humor, sclera, retina, vitreous humor, and optic nerve were higher than those of brinzolamide, but statistical significance was achieved only with aqueous humor, vitreous humor, and optic nerve. Dorzolamide levels in the aqueous humor, anterior vitreous, posterior vitreous, and optic nerve were 1.4- to 3.2-, 2.4- to 2.7-, 2.2- to 4.5-, and 2.4- to

In vivo assessment of the gastric mucosal tolerance dose after single fraction, small volume irradiation of liver malignancies by computed tomography-guided, high-dose-rate brachytherapy

International Nuclear Information System (INIS)

Streitparth, Florian; Pech, Maciej; Boehmig, Michael; Ruehl, Ricarda; Peters, Nils; Wieners, Gero; Steinberg, Johannes; Lopez-Haenninen, Enrique; Felix, Roland; Wust, Peter; Ricke, Jens

2006-01-01

Purpose: The aim of this study was to assess the tolerance dose of gastric mucosa for single-fraction computed tomography (CT)-guided, high-dose-rate (HDR) brachytherapy of liver malignancies. Methods and Materials: A total of 33 patients treated by CT-guided HDR brachytherapy of liver malignancies in segments II and/or III were included. Dose planning was performed upon a three-dimensional CT data set acquired after percutaneous applicator positioning. All patients received gastric protection post-treatment. For further analysis, the contours of the gastric wall were defined in every CT slice using Brachyvision Software. Dose-volume histograms were calculated for each treatment and correlated with clinical data derived from questionnaires assessing Common Toxicity Criteria (CTC). All patients presenting symptoms of upper GI toxicity were examined endoscopically. Results: Summarizing all patients the minimum dose applied to 1 ml of the gastric wall (D 1ml ) ranged from 6.3 to 34.2 Gy; median, 14.3 Gy. Toxicity was present in 18 patients (55%). We found nausea in 16 (69%), emesis in 9 (27%), cramping in 13 (39%), weight loss in 12 (36%), gastritis in 4 (12%), and ulceration in 5 patients (15%). We found a threshold dose D 1ml of 11 Gy for general gastric toxicity and 15.5 Gy for gastric ulceration verified by an univariate analysis (p = 0.01). Conclusions: For a single fraction, small volume irradiation we found in the upper abdomen a threshold dose D 1ml of 15.5 Gy for the clinical endpoint ulceration of the gastric mucosa. This in vivo assessment is in accordance with previously published tolerance data

A single dose of dark chocolate increases parasympathetic modulation and heart rate variability in healthy subjects

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Ana Amélia Machado DUARTE

Full Text Available ABSTRACT Objective: The aim of this study was to investigate the acute effect of a single dose of dark chocolate (70% cocoa on blood pressure and heart rate variability. Methods: Thirty-one healthy subjects (aged 18-25 years; both sexes were divided into two groups: 10 subjects in the white chocolate (7.4 g group and 21 in the dark chocolate (10 g group; measurements were performed at the university's physiology lab. An electrocardiogram measured the sympathovagal balance by spectral and symbolic analysis. Results: A single dose of dark chocolate significantly reduced systolic blood pressure and heart rate. After consuming 10 g of dark chocolate, significant increases were observed for heart rate variability, standard deviation of RR intervals standard deviation of all NN intervals, square root of the mean squared differences between adjacent normal RR intervals root mean square of successive differences, and an increase in the high frequency component in absolute values, representing the parasympathetic modulation. Conclusion: In conclusion the importance of our results lies in the magnitude of the response provoked by a single dose of cocoa. Just 10 g of cocoa triggered a significant increase in parasympathetic modulation and heart rate variability. These combined effects can potentially increase life expectancy because a reduction in heart rate variability is associated with several cardiovascular diseases and higher mortality.

The origin of dose distributions in fluvial sediments, and the prospect of dating single grains from fluvial deposits using optically stimulated luminescence

International Nuclear Information System (INIS)

Olley, J.M.; Caitcheon, G.G.; Roberts, R.G.

1999-01-01

We examine the causes of the asymmetric distributions of dose observed from measurements of the optically stimulated luminescence emitted by small aliquots of fluvial quartz, and deduce that the asymmetry arises as a result of samples being composed of a mix of mainly well bleached grains with grains that were effectively unbleached at the time of deposition. We demonstrate that the shapes of the dose distributions can be used to assess the likelihood that aliquots consist only of grains that were well-bleached at the time of deposition. The more asymmetric the distribution, the greater the probability that the aliquots with the lowest dose most closely represent the true burial dose. Single grains with differing doses are present in each of the samples examined, and the population with the lowest dose gives an optical age consistent with the expected burial age. This result implies that the beta-dose heterogeneity in these deposits is small, and that the effects of micro-dosimetric variations on optical dating of individual grains are not significant for these samples. We demonstrate that single-grain dating of fluvial material is possible and practicable using standard Risoe optical dating equipment, and we conclude that application of a new regenerative-dose protocol to single grains of quartz, using the lowest dose population to estimate the burial dose, is the best available means of obtaining reliable luminescence ages for heterogeneously bleached fluvial sediments

‌‌The effect of nicotine administration on physical and psychological signs of withdrawal syndrome induced by single or frequent doses of morphine in rats

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Ali Shamsizadeh

2012-07-01

Full Text Available Introduction: Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Methods: Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose (the 8th day were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat′s behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p<0.05 was considered as significant difference. Results: Results showed that the injection of frequent and single doses of morphine lead to morphine dependency. In single dose protocol, nicotine consumption attenuated the signs of withdrawal syndrome, especially weight of excrement and total withdrawal score. In frequent dose protocol, in addition to these effects, nicotine induced weight loss and place aversion. Discussion: The inhibitory effects of nicotine on signs of withdrawal syndrome may involve a dopaminergic portion of the central nervous system and is mediated by central nicotinic receptors. There is also a cross-dependence between nicotine and morphine.

Hematological changes after single large dose half-body irradiation

International Nuclear Information System (INIS)

Herrmann, T.; Friedrich, S.; Jochem, I.; Eberhardt, H.J.; Koch, R.; Knorr, A.

1981-01-01

The determination of different peripheral blood parameters aimed at the study of side effects on the hematological cellular system following a 5 - 8 Gy single large dose half-body irradiation in 20 patients. Compared to the initial values the leukocytes between the 6. and 14., the thrombocytes between the 14. and 21. postirradiation day as well as the lymphocytes between 3 hours and 4 weeks postirradiation were significantly decreased without exhibiting complications such as hemorrhages or infections. The hemoglobin, hematocrit and reticulocyte values revealed but a slight decrease normalized within a 28 days postirradiation period. Transfusions were necessary when a tumor-caused anemia was present prior to irradiation. Changes in serum activity of aminotransferases and lactate dehydrogenase occured during the first hours after irradiation and were due to enzyme release from destroyed tumor cells

Efficacy of praziquantel against Schistosoma mekongi and Opisthorchis viverrini: a randomized, single-blinded dose-comparison trial.

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Leonore Lovis

Full Text Available BACKGROUND: Schistosomiasis and opisthorchiasis are of public health importance in Southeast Asia. Praziquantel (PZQ is the drug of choice for morbidity control but few dose comparisons have been made. METHODOLOGY: Ninety-three schoolchildren were enrolled in an area of Lao PDR where Schistosoma mekongi and Opisthorchis viverrini coexist for a PZQ dose-comparison trial. Prevalence and intensity of infections were determined by a rigorous diagnostic effort (3 stool specimens, each examined with triplicate Kato-Katz before and 28-30 days after treatment. Ninety children with full baseline data were randomized to receive PZQ: the 40 mg/kg standard single dose (n = 45 or a 75 mg/kg total dose (50 mg/kg+25 mg/kg, 4 hours apart; n = 45. Adverse events were assessed at 3 and 24 hours posttreatment. PRINCIPAL FINDINGS: Baseline infection prevalence of S. mekongi and O. viverrini were 87.8% and 98.9%, respectively. S. mekongi cure rates were 75.0% (95% confidence interval (CI: 56.6-88.5% and 80.8% (95% CI: 60.6-93.4% for 40 mg/kg and 75 mg/kg PZQ, respectively (P = 0.60. O. viverrini cure rates were significantly different at 71.4% (95% CI: 53.4-84.4% and 96.6% (95% CI: not defined, respectively (P = 0.009. Egg reduction rates (ERRs against O. viverrini were very high for both doses (>99%, but slightly lower for S. mekongi at 40 mg/kg (96.4% vs. 98.1% and not influenced by increasing diagnostic effort. O. viverrini cure rates would have been overestimated and no statistical difference between doses found if efficacy was based on a minimum sampling effort (single Kato-Katz before and after treatment. Adverse events were common (96%, mainly mild with no significant differences between the two treatment groups. CONCLUSIONS/SIGNIFICANCE: Cure rate from the 75 mg/kg PZQ dose was more efficacious than 40 mg/kg against O. viverrini but not against S. mekongi infections, while ERRs were similar for both doses. TRIAL REGISTRATION: Controlled

Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh).

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Flammer, Keven; Nettifee Osborne, Julie A; Webb, Donna J; Foster, Laura E; Dillard, Stacy L; Davis, Jennifer L

2008-01-01

To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots. 20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh). In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments). Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group. In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.

Safety, tolerability, and pharmacokinetics of single oral doses of tofacitinib, a Janus kinase inhibitor, in healthy volunteers.

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Krishnaswami, Sriram; Boy, Mary; Chow, Vincent; Chan, Gary

2015-03-01

Tofacitinib is an oral Janus kinase inhibitor. This randomized, double-blind, parallel-group, placebo-controlled study was the first evaluation of tofacitinib in humans. The objectives were to characterize the safety and tolerability, pharmacokinetics (PK), and pharmacodynamics of escalating single tofacitinib doses in healthy subjects. Tofacitinib (0.1, 0.3, 1, 3, 10, 30, 60, and 100 mg) or placebo was administered as oral powder for constitution. For each dose, 7-9 subjects were randomized to tofacitinib and 3-5 subjects to placebo. Ninety-five males and females (age range 19-45) completed the study. Forty-nine treatment-emergent all-causality adverse events (AEs) were observed; nausea and headache were the most frequently reported. Tofacitinib PK was characterized by rapid absorption (time to peak serum concentration [Tmax ] 0.5-1 hour), rapid elimination (mean terminal half-lives 2.3-3.1 hours), and dose-proportional systemic exposures (peak serum concentration [Cmax ] and area under the serum concentration-time curve from time zero to infinity [AUC0-∞ ]). No appreciable correlation was observed between tofacitinib dose and lymphocyte subset counts. Single-dose tofacitinib up to 100 mg in healthy subjects had a safety profile of mostly mild AEs, and no deaths, serious AEs, severe AEs or discontinuations due to AEs. © 2014, The American College of Clinical Pharmacology.

A quality improvement project to reduce the intraoperative use of single-dose fentanyl vials across multiple patients in a pediatric institution.

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Buck, David; Subramanyam, Rajeev; Varughese, Anna

2016-01-01

The use of a single-dose vial across multiple patients presents a risk to sterility and is against CDC guidelines. We initiated a quality improvement (QI) project to reduce the intraoperative use of single-dose vials of fentanyl across multiple patients at Cincinnati Children's Hospital Medical Center (CCHMC). The initial step of the improvement project was the development of a Key Driver Diagram. The diagram has the SMART aim of the project, key drivers inherent to the process we are trying to improve, and specific interventions targeting the key drivers. The number of patients each week receiving an IV dose of fentanyl, from a vial previously accessed for another patient was tracked in a high turnover operating room (OR). The improvement model used was based on the concept of building Plan-Do-Study-Act (PDSA) cycles. Tests of change included provider education, provision of an increased number of fentanyl vials, alternate wasting processes, and provision of single-use fentanyl syringes by the pharmacy. Prior to initiation of this project, it was common for a single fentanyl vial to be accessed for multiple patients. Our data showed an average percentage of failures of just over 50%. During the end of the project, after 7 months, the mean percentage failures had dropped to 5%. Preparation of 20 mcg single-use fentanyl syringes by pharmacy, combined with education of providers on appropriate use, was successful in reducing failures to below our goal of 25%. Appropriately sized fentanyl syringes prepared by pharmacy, education on correct use of single-dose vials, and reminders in the OR, reduced the percentage of patients receiving a dose of fentanyl from a vial previously accessed for another patient in a high-volume otolaryngology room. © 2015 John Wiley & Sons Ltd.

Safety and pharmacokinetics of single and multiple intravenous bolus doses of diclofenac sodium compared with oral diclofenac potassium 50 mg: A randomized, parallel-group, single-center study in healthy subjects.

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Munjal, Sagar; Gautam, Anirudh; Okumu, Franklin; McDowell, James; Allenby, Kent

2016-01-01

In a randomized, parallel-group, single-center study in 42 healthy adults, the safety and pharmacokinetic parameters of an intravenous formulation of 18.75 and 37.5 mg diclofenac sodium (DFP-08) following single- and multiple-dose bolus administration were compared with diclofenac potassium 50 mg oral tablets. Mean AUC0-inf values for a 50-mg oral tablet and an 18.75-mg intravenous formulation were similar (1308.9 [393.0]) vs 1232.4 [147.6]). As measured by the AUC, DFP-08 18.75 mg and 37.5 mg demonstrated dose proportionality for extent of exposure. One subject in each of the placebo and DFP-08 18.75-mg groups and 2 subjects in the DFP-08 37.5-mg group reported adverse events that were considered by the investigator to be related to the study drug. All were mild in intensity and did not require treatment. Two subjects in the placebo group and 1 subject in the DFP-08 18.75-mg group reported grade 1 thrombophlebitis; no subjects reported higher than grade 1 thrombophlebitis after receiving a single intravenous dose. The 18.75- and 37.5-mg doses of intravenous diclofenac (single and multiple) were well tolerated for 7 days. Additional efficacy and safety studies are required to fully characterize the product. © 2015, The American College of Clinical Pharmacology.

Single daily dosing of antibiotics: importance of in vitro killing rate, serum half-life, and protein binding.

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Potel, G; Chau, N P; Pangon, B; Fantin, B; Vallois, J M; Faurisson, F; Carbon, C

1991-10-01

The relative importance of pharmacokinetic and pharmacodynamic parameters for the feasibility of a single daily dose (SDD) of antibiotics remains to be established. Therefore, we studied the relationship between in vitro bacteriological parameters (MIC, MBC, and killing rate [KR], defined as the reduction in the inoculum within 3 h), pharmacokinetic parameters (t1/2 and protein binding [PB], and in vivo antibacterial effect of a single antibiotic dose in an experimental rabbit model of Escherichia coli endocarditis. Nine antibiotics were investigated: two aminoglycosides, two quinolones, and five beta-lactams. For each drug, the minimal effective dose (MED) (in milligrams per kilogram) was defined as the lowest dose able to achieve a significant difference (P less than 0.05) of CFU in the vegetations in comparison with controls 24 h after a single intravenous injection. Aminoglycosides and quinolones had the lowest MEDs, followed by beta-lactams. Univariate regression analysis showed that KR was the major determinant of MED. A stepwise regression analysis showed that t1/2 significantly improved the predictive value of KR, while PB, MIC, and MBC did not. The final equation was MED = 1,586-238 KR-297 t1/2 (r = 0.90, P = 0.01). We concluded that the pharmacodynamic parameters (especially the high KR) of aminoglycosides and quinolones explained their low MEDs and might allow SDD. In contrast, the low KR of beta-lactams emphasized the critical importance of a long t1/2, as for ceftriaxone, allowing the use of this beta-lactam alone in SDD.

Effect of treatment with single total-dose intravenous iron versus daily oral iron(III-hydroxide polymaltose on moderate puerperal iron-deficiency anemia

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Iyoke CA

2017-05-01

Full Text Available Chukwuemeka Anthony Iyoke,1 Fausta Chioma Emegoakor,1 Euzebus Chinonye Ezugwu,1 Lucky Osaheni Lawani,2 Leonard Ogbonna Ajah,1 Jude Anazoeze Madu,3 Hyginus Uzo Ezegwui,1 Frank Okechukwu Ezugwu4 1Department of Obstetrics and Gynaecology, University of Nigeria, Enugu Campus, 2Department of Obstetrics and Gynaecology, Federal Teaching Hospital, Abakaliki, 3Department of Haematology, University of Nigeria, Nsukka, 4Department of Obstetrics and Gynaecology, College of Medicine, Enugu State University, Enugu, Nigeria Background: Iron-deficiency anemia is the most common nutritional cause of anemia in pregnancy and is often responsible for puerperal anemia. Puerperal anemia can impair postpartum maternal and neonatal well-being. Objective: To determine the effect of treatment of moderate puerperal iron-deficiency anemia using a single intravenous total-dose iron dextran versus daily single dose oral iron(III-hydroxide polymaltose. Methodology: A randomized controlled study in which postpartum women with moderate iron-deficiency anemia were randomized into treatment with either a single total-dose intravenous iron dextran or with daily single doses of oral iron(III-hydroxide polymaltose tablets for 6 weeks. Effects on hemoglobin concentration using either method were compared at 6 weeks postpartum. Analysis was per protocol using SPSS version 17 for windows. P-values ≤0.05 were considered significant. Results: Two hundred eighty-four women were recruited for the study: 142 women received single total dose intravenous infusion of iron dextran while 142 received daily oral iron(III-hydroxide polymaltose tablets. Approximately 84.0% (237/282 completed the study and were analyzed including 81% (115/142 of those randomized to injectable iron therapy compared to 85.9% (122/142 of those randomized to oral treatment. The proportions of women who had attained hemoglobin concentration of at least 10 g/dL by the 6 weeks postpartum visit did not differ

Single dose pharmacokinetics of fenspiride hydrochloride: phase I clinical trial.

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Montes, B; Catalan, M; Roces, A; Jeanniot, J P; Honorato, J M

1993-01-01

The absolute bioavailability of fenspiride has been studied in twelve healthy volunteers. It was administered IV and orally in single doses of 80 mg fenspiride hydrochloride according to a randomised crossover pattern. Following IV administration, the plasma clearance of fenspiride was about 184 ml.min-1, and its apparent volume of distribution was moderately large (215 l). When given orally as a tablet, fenspiride exhibited fairly slow ab- sorption; the maximum plasma concentration (206 ng.ml-1) was achieved 6 h after administration. The absolute bioavailability was almost complete (90%). The tablet had slow release characteristics. The elimination half-life obtained from the plasma data was 14 to 16 h independent of the route of administration.

A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage.

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Shan, Chao; Muruato, Antonio E; Jagger, Brett W; Richner, Justin; Nunes, Bruno T D; Medeiros, Daniele B A; Xie, Xuping; Nunes, Jannyce G C; Morabito, Kaitlyn M; Kong, Wing-Pui; Pierson, Theodore C; Barrett, Alan D; Weaver, Scott C; Rossi, Shannan L; Vasconcelos, Pedro F C; Graham, Barney S; Diamond, Michael S; Shi, Pei-Yong

2017-09-22

Zika virus infection during pregnancy can cause congenital abnormities or fetal demise. The persistence of Zika virus in the male reproductive system poses a risk of sexual transmission. Here we demonstrate that live-attenuated Zika virus vaccine candidates containing deletions in the 3' untranslated region of the Zika virus genome (ZIKV-3'UTR-LAV) prevent viral transmission during pregnancy and testis damage in mice, as well as infection of nonhuman primates. After a single-dose vaccination, pregnant mice challenged with Zika virus at embryonic day 6 and evaluated at embryonic day 13 show markedly diminished levels of viral RNA in maternal, placental, and fetal tissues. Vaccinated male mice challenged with Zika virus were protected against testis infection, injury, and oligospermia. A single immunization of rhesus macaques elicited a rapid and robust antibody response, conferring complete protection upon challenge. Furthermore, the ZIKV-3'UTR-LAV vaccine candidates have a desirable safety profile. These results suggest that further development of ZIKV-3'UTR-LAV is warranted for humans.Zika virus infection can result in congenital disorders and cause disease in adults, and there is currently no approved vaccine. Here Shan et al. show that a single dose of a live-attenuated Zika vaccine prevents infection, testis damage and transmission to the fetus during pregnancy in different animal models.

The Efficacy of Single-Dose versus Double-Dose Praziquantel Treatments on Schistosoma mansoni Infections: Its Implication on Undernutrition and Anaemia among Primary Schoolchildren in Two On-Shore Communities, Northwestern Tanzania

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Buza, Joram; Mpolya, Emmanuel A.; Angelo, Teckla; Kinung'hi, Safari M.

2017-01-01

Administering more than one treatment may increase Praziquantel cure and egg reduction rates, thereby hastening achievement of schistosomiasis transmission control. A total of 431 S. mansoni-infected schoolchildren were randomized to receive either a single or repeated 40 mg/kg Praziquantel dose. Heights, weights, and haemoglobin levels were determined using a stadiometer, weighing scale, and HemoCue, respectively. At 8 weeks, cure rate was higher on repeated dose (93.10%) compared to single dose (68.68%) (p 0.05) and 8 (p > 0.05) months with no difference in reinfection rate. No difference in the prevalence of stunting was observed between the two treatment regimens (p > 0.05) at 8 months, but there was an increase in the prevalence of wasting among those on repeated dose (p 0.05). To achieve reduction of transmission intensity and disease control in highly endemic areas, repeated treatments alone may not be sufficient. This trial was registered with PACTR201601001416338. PMID:29094048

A comparison of a single-dose and a seven-day treatment with Amoxicillin in asymptomatic bacteriuria in pregnancy

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Niro Manesh S

1994-05-01

Full Text Available In this study, 1600 pregnant women who had referred to two prenatal clinics (Imam Khomeini and Mirza Kochek-Khan were investigated. Ninety cases of asymptomatic bacteriuria were observed; 77 of those cooperated with us until the end of our study. The subjects, who were within the 14-36 weeks of gestational age, were randomly divided into two groups: Group A received the medicine (Amoxicillin in a single-dose (3gr.; and, group B received it within seven days (1gr. TDS. The rate of recovery (65% in group A and 56.8% in group B, based on chi-squared test, showed no significant difference (P=0.747%. According to the results of this study, we can conclude that single-dose treatment has the same value as a seven-day treatment and the advantages such as decreased total dose, lower cost, and a better patient compliance.

Efficiency of early, single-dose probiotic administration methods on performance, small intestinal morphology, blood biochemistry, and immune response of Japanese quail.

Science.gov (United States)

Seifi, Kazem; Karimi Torshizi, Mohammad Amir; Rahimi, Shaban; Kazemifard, Mohammad

2017-07-01

The aim of the present study was to investigate the efficacy of early probiotics (single dose) administered in different ways, on quails' performance, small intestine morphology, blood biochemistry, and immune response. In total, 192 day-old chicks were used in one of the following experimental groups before being transferred to a raising room: 1) Control (no probiotic administered), 2) oral gavage, 3) spray, and 4) vent lip. Four replicates of 12 chicks per cage were considered for each treatment and birds were raised up to 35 d in the same conditions. Probiotic treated birds had higher d 1 to 35 feed intake than the control group (P birds had a higher body weight gain as compared to the control (P birds compared to control (P  0.01). None of the immune-related parameters were affected by the probiotic (P > 0.05). Single dose usage of probiotics exerts its beneficial effects on quails' body weight gain, feed intake and mortality in 1 to 35 d period, regardless of the route of administration. This work generally supports the efficacy of single-dose usage of probiotics and suggests the spray of probiotics as an early, single-dose administration method. © 2017 Poultry Science Association Inc.

Iron concentration in breast milk normalised within one week of a single high-dose infusion of iron isomaltoside in randomised controlled trial

DEFF Research Database (Denmark)

Holm, Charlotte; Thomsen, Lars Lykke; Nørgaard, Astrid

2017-01-01

AIM: We compared the iron concentration in breast milk after a single high-dose of intravenous iron isomaltoside or daily oral iron for postpartum haemorrhage. METHODS: In this randomised controlled trial, the women were allocated a single dose of intravenous 1,200mg iron isomaltoside or oral iron...... deviation) iron concentration in breast milk in the intravenous and oral groups were 0.72 ± 0.27 mg/L and 0.40 ± 0.18 mg/L at three days (p birth. CONCLUSION: A single high...

Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance

NARCIS (Netherlands)

Lamers, CTJ; Ramaekers, JG; Muntjewerff, ND; Sikkema, KL; Samyn, N; Read, NL; Brookhuis, KA; Riedel, WJ

2003-01-01

Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition,

Pharmacokinetics, Safety and Tolerability of Sacubitril/Valsartan (LCZ696) After Single-Dose Administration in Healthy Chinese Subjects.

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Han, Yi; Ayalasomayajula, Surya; Pan, Wei; Yang, Fan; Yuan, Yaozong; Langenickel, Thomas; Hinder, Markus; Kalluri, Sampath; Pal, Parasar; Sunkara, Gangadhar

2017-02-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) and has been recently approved in several countries for the treatment of patients with heart failure and reduced ejection fraction. This was the first study conducted to characterise the pharmacokinetics of LCZ696 analytes (pro-drug sacubitril, active neprilysin inhibitor LBQ657 and valsartan) after single-dose administration of LCZ696 in healthy Chinese subjects. In this open-label, randomised, parallel-group study, following screening and baseline evaluation, eligible healthy subjects received single oral doses of LCZ696 50, 100, 200 or 400 mg. The pharmacokinetics, safety and tolerability of LCZ696 were assessed up to 72 h after dosing. A total of 40 healthy male subjects were enrolled, and all completed the study. Following oral administration, LCZ696 delivered systemic exposure to sacubitril, LBQ657 and valsartan with a median time to reach maximum plasma concentration (T max ) ranging from 0.50 to 1.25, 2.00 to 3.00 and 1.50 to 2.50 h, respectively, over the investigated dose range. The mean terminal elimination half-life (T 1/2 ) ranged from 0.89 to 1.35, 8.57 to 9.24 and 5.33 to 7.91 h for sacubitril, LBQ657 and valsartan, respectively. The area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUC 0-last ), and maximum plasma concentration (C max ) for LBQ657 increased dose proportionally over the entire dose range. Dose linear increase in the exposure was observed across the dose range for sacubitril and valsartan. LCZ696 was safe and well tolerated at all doses in this study. Adverse events of only mild intensity, which required no treatment, were reported in 6 (15 %) subjects. The pharmacokinetic profiles of LCZ696 analytes in Chinese subjects are similar to those reported previously in Caucasian subjects.

A single daily dose enhances the adherence to immunosuppressive treatment in kidney transplant recipients: a cross-sectional study.

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Obi, Yoshitsugu; Ichimaru, Naotsugu; Kato, Taigo; Kaimori, Jun-Ya; Okumi, Masayoshi; Yazawa, Koji; Rakugi, Hiromi; Nonomura, Norio; Isaka, Yoshitaka; Takahara, Shiro

2013-04-01

Nonadherence to treatment regimens for immunosuppressive agents is one of the major risk factors for allograft failure in kidney transplant recipients. The aim of this study was to estimate the relative effect of daily dosing on treatment adherence, not to identify how patients are non-adherent, in long-term kidney transplant recipients. In January 2009, a cross-sectional, anonymous, and voluntary questionnaire survey was given to kidney transplant recipients who regularly visited Inoue Hospital. A self-reporting questionnaire underestimates nonadherence, but we reasoned that the effect of the dosing regimen should be estimated with relative accuracy by using the generalized ordered logit/partial proportional hazard odds model given that the distribution patterns in the degree of nonadherence have been shown to be similar with other measures. Of 336 eligible patients, 312 (92.9 %) participated in this study. Two hundred seventy-four patients (87.8 %) were more than 3 years post-transplant. Univariate analysis revealed that a single daily dose was significantly associated with better adherence. After controlling for age, sex, time since transplantation, and the number of prescribed drugs, the effect of a single daily dose still remained significant [odds ratio, 0.40 (95 % confidence interval, 0.19-0.81); p = 0.011]. Several sensitivity analyses yielded similar results. To our knowledge, this is the first report that, in long-term kidney transplant recipients, a single daily regimen-one of few modifiable factors-might improve treatment adherence and allograft survival.

Dose performance and image quality: Dual source CT versus single source CT in cardiac CT angiography

International Nuclear Information System (INIS)

Wang Min; Qi Hengtao; Wang Ximing; Wang Tao; Chen, Jiu-Hong; Liu Cheng

2009-01-01

Objective: To evaluate dose performance and image quality of 64-slice dual source CT (DSCT) in comparison to 64-slice single source CT (SSCT) in cardiac CT angiography (CTA). Methods: 100 patients examined by DSCT and 60 patients scanned by SSCT were included in this study. Objective indices such as image noise, contrast-to-noise ratio and signal-to-noise ratio were analyzed. Subjective image quality was assessed by two cardiovascular radiologists in consensus using a four-point scale (1 = excellent to 4 = not acceptable). Estimation of effective dose was performed on the basis of dose length product (DLP). Results: At low heart rates ( 0.05), but, at high heart rates (>70 bpm), DSCT provided robust image quality (P 70 bpm), DSCT is able to provide robust diagnostic image quality at doses far below that of SSCT.

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

International Nuclear Information System (INIS)

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

2010-01-01

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.

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

Science.gov (United States)

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

2010-09-01

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.

Cost-effectiveness of a chemoprophylactic intervention with single dose rifampicin in contacts of new leprosy patients.

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Willemijn J Idema

Full Text Available BACKGROUND: With 249,007 new leprosy patients detected globally in 2008, it remains necessary to develop new and effective interventions to interrupt the transmission of M. leprae. We assessed the economic benefits of single dose rifampicin (SDR for contacts as chemoprophylactic intervention in the control of leprosy. METHODS: We conducted a single centre, double blind, cluster randomised, placebo controlled trial in northwest Bangladesh between 2002 and 2007, including 21,711 close contacts of 1,037 patients with newly diagnosed leprosy. We gave a single dose of rifampicin or placebo to close contacts, with follow-up for four years. The main outcome measure was the development of clinical leprosy. We assessed the cost effectiveness by calculating the incremental cost effectiveness ratio (ICER between the standard multidrug therapy (MDT program with the additional chemoprophylaxis intervention versus the standard MDT program only. The ICER was expressed in US dollars per prevented leprosy case. FINDINGS: Chemoprophylaxis with SDR for preventing leprosy among contacts of leprosy patients is cost-effective at all contact levels and thereby a cost-effective prevention strategy. In total, $6,009 incremental cost was invested and 38 incremental leprosy cases were prevented, resulting in an ICER of $158 per one additional prevented leprosy case. It was the most cost-effective in neighbours of neighbours and social contacts (ICER $214, slightly less cost-effective in next door neighbours (ICER $497 and least cost-effective among household contacts (ICER $856. CONCLUSION: Chemoprophylaxis with single dose rifampicin given to contacts of newly diagnosed leprosy patients is a cost-effective intervention strategy. Implementation studies are necessary to establish whether this intervention is acceptable and feasible in other leprosy endemic areas of the world.

Randomized, controlled, assessor-blind clinical trial to assess the efficacy of single- versus repeated-dose albendazole to treat ascaris lumbricoides, trichuris trichiura, and hookworm infection.

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Adegnika, Ayola A; Zinsou, Jeannot F; Issifou, Saadou; Ateba-Ngoa, Ulysse; Kassa, Roland F; Feugap, Eliane N; Honkpehedji, Yabo J; Dejon Agobe, Jean-Claude; Kenguele, Hilaire M; Massinga-Loembe, Marguerite; Agnandji, Selidji T; Mordmüller, Benjamin; Ramharter, Michael; Yazdanbakhsh, Maria; Kremsner, Peter G; Lell, Bertrand

2014-05-01

In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.).

Comparison of single-dose nalbuphine versus tramadol for postoperative pain management in children: a randomized, controlled trial.

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Liaqat, Naeem; Dar, Sajid Hameed

2017-04-01

Acute postoperative pain control in children is an essential component of postoperative care, particularly in daycare procedures. Giving patients continuous narcotic analgesics can be risky; however, a single dose may be sufficient. This study used a prospective, randomized controlled design and was conducted at the Pediatric Surgery Unit, Services Hospital, Lahore. In total, 150 patients who underwent inguinal herniotomy (age range: 1-12 years) were randomly assigned to two groups: group A (nalbuphine) and group B (tramadol). Patients were given a single dose of either nalbuphine (0.2 mg/kg) or tramadol (2 mg/kg) immediately after surgery and pain was measured at 0, 1, 2, 4, and 8 h. The demographic characteristics were similar between the two groups. The mean pain score was lower in group A than in group B at 0 and 1 h (P pain scores in group A were still lower, but not significantly. In all, 9 patients (12.0%) required rescue analgesics in group A compared to 16 patients (21.3%) in group B (P = 0.051). The mean time for requirement of rescue analgesics was 6.5 ± 0.5 h in group A and 5.3 ± 1.7 h in group B (P = 0.06). A single dose of nalbuphine is sufficient, and superior to tramadol, for postoperative pain management in children who have undergone daycare procedures.

Effect of single dose, fractionated, and hyperfractionated trunk irradiation on weight gain, respiration frequency, and survival in rats

International Nuclear Information System (INIS)

Kimler, B.F.; Giri, P.G.S.; Giri, U.P.; Cox, G.G.

1986-01-01

It is concluded that, in this rat trunk irradiation model, fractionation of a single dose into two equal doses separated by 4-6 h produced a sparing effect of approx. 5Gy as measured by delay in weight gain; approx. 4Gy as measured by increased respiration frequency; and approx. 6Gy as measured by survival. Fractionation into daily doses or hyperfractionation into twice-daily doses permitted an approximate doubling of the dose required for the same suppression of weight gain. For the respiration rates and survival endpoints, fractionation or hyperfractionation produced an even greater sparing effect since there was no increase in the respiration frequency at twice the doses that would produce changes if delivered within a few hours; and since essentially no lethality was observed at twice the doses that would kill 70%-100% of animals if delivered in one day. (UK)

Single high dose intraoperative electrons for advanced stage pancreatic cancer: Phase I pilot study

International Nuclear Information System (INIS)

Goldson, A.L.; Ashaveri, E.; Espinoza, M.C.

1981-01-01

Phase I toxicity studies with intraoperative radiotherapy proved to be a feasible adjunct to surgery for unresectable malignancies of the pancreas at Howard University Hospital. There have been minimal side effects or complications related to the combination of limited surgical decompression and intraoperative radiotherapy alone. The toxic effects of intraoperative radiotherapy on normal tissues is being assessed on a dose volume basis. Doses of 2000 to 2500 rad in a single exposure to include the pancreas, regional nodes and duodenum are acceptable if the total treatment volume is less than or equal to 100 cm. The tumoricidal effects on the cancer are demonstratable when one reviews the pathological specimens that illustrate massive tumor necrosis and fibros replacement, but in all cases reviewed, viable cancer was noted. Intraoperative radiotherapy, therefore, represents a significant boost dose for resectable, partially resectable or non-resectable tumors when added to conventional external beam irradiation and/or chemotherapy. Preliminary clinical data and minimal toxicity justifies further investigation

Radiobiological restrictions and tolerance doses of repeated single-fraction hdr-irradiation of intersecting small liver volumes for recurrent hepatic metastases

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Wust Peter

2010-05-01

Full Text Available Abstract Background To assess radiobiological restrictions and tolerance doses as well as other toxic effects derived from repeated applications of single-fraction high dose rate irradiation of small liver volumes in clinical practice. Methods Twenty patients with liver metastases were treated repeatedly (2 - 4 times at identical or intersecting locations by CT-guided interstitial brachytherapy with varying time intervals. Magnetic resonance imaging using the hepatocyte selective contrast media Gd-BOPTA was performed before and after treatment to determine the volume of hepatocyte function loss (called pseudolesion, and the last acquired MRI data set was merged with the dose distributions of all administered brachytherapies. We calculated the BED (biologically equivalent dose for a single dose d = 2 Gy for different α/β values (2, 3, 10, 20, 100 based on the linear-quadratic model and estimated the tolerance dose for liver parenchyma D90 as the BED exposing 90% of the pseudolesion in MRI. Results The tolerance doses D90 after repeated brachytherapy sessions were found between 22 - 24 Gy and proved only slightly dependent on α/β in the clinically relevant range of α/β = 2 - 10 Gy. Variance analysis showed a significant dependency of D90 with respect to the intervals between the first irradiation and the MRI control (p 90 and the pseudolesion's volume. No symptoms of liver dysfunction or other toxic effects such as abscess formation occurred during the follow-up time, neither acute nor on the long-term. Conclusions Inactivation of liver parenchyma occurs at a BED of approx. 22 - 24 Gy corresponding to a single dose of ~10 Gy (α/β ~ 5 Gy. This tolerance dose is consistent with the large potential to treat oligotopic and/or recurrent liver metastases by CT-guided HDR brachytherapy without radiation-induced liver disease (RILD. Repeated small volume irradiation may be applied safely within the limits of this study.

A Randomised Trial Evaluating the Safety and Immunogenicity of the Novel Single Oral Dose Typhoid Vaccine M01ZH09 in Healthy Vietnamese Children

NARCIS (Netherlands)

Tran, T.H.; Nguyen, T.D.; Nguyen, T.T.; Ninh, T.T.V.; Tran, N.B.C.; Nguyen, V.M.H.; Tran, T.T.N.; Cao, T.T.; Pham, V.M.; Nguyen, T.C.B.; Tran, T.D.H.; Pham, V.T.; To, S.D.; Campbell, J.I.; Stockwell, E.; Schultsz, C.; Simmons, C.P.; Glover, C.; Lam, W.; Marques, F.; May, J.P.; Upton, A.; Budhram, R.; Dougan, G.; Farrar, J.; Nguyen, V.V.C.; Dolecek, C.

2010-01-01

Background: The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)

Single exposure simultaneous acquisition of digital and conventional radiographs utilizing unaltered dose

International Nuclear Information System (INIS)

Oestmann, J.W.; Greene, R.

1988-01-01

We describe the simultaneous acquisition of digital and conventional radiographs with a single standard radiographic exposure. A digitizable storage phosphor (ST Imaging Plate, Fuji) is sandwiched into a radiographic cassette (X-Omatic, Kodak) behind a conventional radiographic film-screen combination (Lanex medium screens, OC film, Kodak). The barium fluorohalide storage phosphor is digitized with a helium-neon laser scanner (TCR 201, Toshiba), and the conventional radiograph is processed in the standard fashion (M7B, Kodak). The storage phosphor is exposed by the 'wasted' radiation normally exiting the back of the film-screen combination (32% of the cassette entrance dose at 141 kVp). At a standard exposure (6.3 mAs), the conventional radiograph is of unaltered quality, and the digital image appears to have an adequate signal-to-noise ratio for chest studies despite the lower exposure dose. This technique produces twin images of identical spatial and temporal registration and avoids the added radiation exposure normally required to carry out comparative studies. (orig.)

Time and dose-related changes in the thickness of pig skin after irradiation with single doses of [sup 90]Sr/[sup 90]Y [beta]-rays

Energy Technology Data Exchange (ETDEWEB)

Rezvani, M.; Hamlet, R.; Hopewell, J.W.; Sieber, V.K. (Churchill Hospital, Oxford (United Kingdom))

1994-04-01

Time-related changes in pig skin thickness have been evaluated using a non-invasive ultrasound technique after exposure to a range of single doses of [sup 90]Sr/[sup 90]Yr [beta]-rays. The reduction in relative skin thickness developed in two distinct phases: the first was between 12 and 20 weeks postirradiation. No further changes were then seen until 52 weeks postirradiation when a second phase of skin thinning was observed. This was complete after 76 weeks and no further changes in relative skin thickness were seen in the maximum follow up period of 129 weeks. The timings of these phases of damage were independent of the radiation dose, however, the severity of both phases of radiation-induced skin thinning were dose related. (Author).

Contrast Dose and Radiation Dose Reduction in Abdominal Enhanced Computerized Tomography Scans with Single-phase Dual-energy Spectral Computerized Tomography Mode for Children with Solid Tumors.

Science.gov (United States)

Yu, Tong; Gao, Jun; Liu, Zhi-Min; Zhang, Qi-Feng; Liu, Yong; Jiang, Ling; Peng, Yun

2017-04-05

Contrast dose and radiation dose reduction in computerized tomography (CT) scan for adult has been explored successfully, but there have been few studies on the application of low-concentration contrast in pediatric abdominal CT examinations. This was a feasibility study on the use of dual-energy spectral imaging and adaptive statistical iterative reconstruction (ASiR) for the reduction of radiation dose and iodine contrast dose in pediatric abdominal CT patients with solid tumors. Forty-five patients with solid tumors who had initial CT (Group B) and follow-up CT (Group A) after chemotherapy were enrolled. The initial diagnostic CT scan (Group B) was performed using the standard two-phase enhanced CT with 320 mgI/ml concentration contrast, and the follow-up scan (Group A) was performed using a single-phase enhanced CT at 45 s after the beginning of the 270 mgI/ml contrast injection using spectral mode. Forty percent ASiR was used for the images in Group B and monochromatic images with energy levels ≥60 keV in Group A. In addition, filtered back-projection (FBP) reconstruction was used for monochromatic images hounsfield unit (HU). The abdominal organs of Groups A and B had similar degrees of absolute and relative enhancement (t = 0.36 and -1.716 for liver, -0.153 and -1.546 for pancreas, and 2.427 and 0.866 for renal cortex, all P> 0.05). Signal-to-noise ratio of the abdominal organs was significantly lower in Group A than in Group B (t = -8.11 for liver, -7.83 for pancreas, and -5.38 for renal cortex, all P 3, indicating clinically acceptable image quality. Single-phase, dual-energy spectral CT used for children with solid abdominal tumors can reduce contrast dose and radiation dose and can also maintain clinically acceptable image quality.

Effect of a single gemfibrozil dose on the pharmacokinetics of rosuvastatin in bile and plasma in healthy volunteers.

Science.gov (United States)

Bergman, Ebba; Matsson, Elin M; Hedeland, Mikael; Bondesson, Ulf; Knutson, Lars; Lennernäs, Hans

2010-09-01

The effect of a single intrajejunal dose of gemfibrozil (600 mg) on the plasma pharmacokinetics and biliary excretion of a single intrajejunal dose of rosuvastatin (20 mg) was investigated by using a multichannel catheter positioned in the distal duodenum-proximal jejunum in 8 healthy volunteers. Bile and plasma samples were collected every 20 minutes for 200 minutes, with additional plasma samples being drawn for up to 48 hours. Gemfibrozil did not affect the bioavailability of rosuvastatin, although it increased the apparent absorption phase during the initial 200 minutes (AUC(plasma,200min)) by 1.56-fold (95% confidence interval, 1.14-2.15). The interaction was less pronounced in this single-dose study than in a previous report when gemfibrozil was administered repeatedly; nevertheless, the interaction coincided with the highest exposure to gemfibrozil. The plausible reason why the interaction in this investigation was only minor is the low exposure to gemfibrozil (and its metabolites), suggesting that the total plasma concentration of gemfibrozil needs to be above 20 µM to affect the disposition of rosuvastatin. This study demonstrates the value of monitoring the plasma pharmacokinetics of the inhibitor, and not only the drug under investigation, to improve the mechanistic interpretation.

Effects of single doses of X-rays on renal function in the pig after the irradiation of both kidneys

International Nuclear Information System (INIS)

Robbins, M.E.C.; Hopewell, J.W.

1988-01-01

Irradiation of a single kidney in the pig with relatively low doses of X-rays, in the order of 8 Gy, produces a pronounced reduction in both glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). This apparent high radiosensitivity may be due, in part, to the compensatory hypertrophy displayed by the contralateral unirradiated kidney. This could suppress any potential for recovery by the irradiated kidney. To test this hypothesis, both kidneys of 14-week-old Large White pigs were sequentially irradiated with single doses of 250 kV X-rays, in the range 8.8 to 12.6 Gy. Two weeks after irradiation, GFR and ERPF increased markedly in all irradiated kidneys; levels then declined in a dose-dependent manner. Following a dose of 8.8 Gy renal haemodynamics returned to control values within 4 weeks of irradiation. After higher doses, GFR and ERPF decreased markedly and remained below control values up to 24 weeks after irradiation. At all doses the mean functional status of irradiated kidneys in animals in which both kidneys were irradiated was significantly greater than that previously observed in the irradiated kidney of pigs in which only one kidney was irradiated. The findings support the above hypothesis, and indicate that individual kidneys in the same animal may differ in their response to a similar nephrotoxic insult. 35 refs.; 6 figs.; 2 tabs

Absorbed dose in CT. Comparison by CT dose index

International Nuclear Information System (INIS)

Yamamoto, Kenji; Akazawa, Hiroshi; Andou, Takashi

2002-01-01

Few reports have discussed the absorbed dose on CT units with increased scanning capacity even with the current widespread adoption of multi-slice CT units. To compare and investigate the dose indexes among CT units, we measured the absorbed dose on CT units operating in Nagano Prefecture Japan. The measurements showed proportionality between phantom absorbed dose and the exposured mAs values in conventional scanning operation. Further, the measurements showed that the absorbed dose in the center of the phantom differed by about 2.1-fold between the highest and lowest levels on individual CT units. Within a single company, multi-slice CT units of the same company gave absorbed doses of about 1.3 to 1.5 times those of conventional single-slice CT units under the same exposured conditions of conventional scanning. When the scanning pitch was reduced in helical scanning, the absorbed dose at the center of the phantom increased. (author)

beta-Carotene in breast milk and serum is increased after a single beta-carotene dose.

Science.gov (United States)

Canfield, L M; Giuliano, A R; Neilson, E M; Yap, H H; Graver, E J; Cui, H A; Blashill, B M

1997-07-01

Normal lactating mothers were administered a single dose of 60 or 210 mg beta-carotene and changes in serum and milk retinol, alpha-tocopherol, and carotenoids were monitored for 8 d. Average serum beta-carotene concentrations increased 4.1- and 4.0-fold after the 60- and 210-mg doses, respectively. Milk beta-carotene concentrations increased 4.1- and 3.0-fold after the 60- and 210-mg doses, respectively. Maximum serum concentrations were reached 24 h after both supplements, although concentrations of milk beta-carotene continued to rise for 2-3 d. After 8 d, both serum and milk beta-carotene continued to rise for 2-3 d. After 8 d, both serum and milk beta-carotene concentrations remained about twofold higher than baseline concentrations. Increases in serum or milk beta-carotene concentrations were not dose-dependent. Initial serum and milk concentrations of beta-carotene predicted increases after supplementation, and increases in serum beta-carotene concentrations predicted those in milk. Concentrations of milk carotenoids were less than one-tenth their respective concentrations in serum. Lutein, beta-cryptoxanthin, lycopene, alpha-carotene, retinol, and alpha-tocopherol concentrations in serum or milk did not change significantly after beta-carotene supplementation. Retinol esters account for most of the retinol equivalents in the milk of well-nourished mothers. Initial and maximum concentrations of beta-carotene in serum and milk were strongly correlated for individual mothers. Collectively, the data showed that a single 60-mg supplement of beta-carotene sustained elevated beta-carotene concentrations in serum and milk for > 1 wk in normal mothers but did not affect concentrations of other major carotenoids, retinol, or alpha-tocopherol.

Efficacy of Single-dose and 2-dose Intravenous Administration of Ramosetron in Preventing Postoperative Nausea and Vomiting After Laparoscopic Gynecologic Operation: A Randomized, Double-blind, Placebo-controlled, Phase 2 Trial.

Science.gov (United States)

Lee, Banghyun; Kim, Kidong; Suh, Dong Hoon; Shin, Hyun-Jung; No, Jae Hong; Lee, Jung Ryeol; Jee, Byung Chul; Hwang, Jung Won; Do, Sang Hwan; Kim, Yong Beom

2017-06-01

This randomized trial investigated whether a 2-dose administration of intravenous ramosetron (5-hydroxytryptamine type 3 receptor antagonist) is more effective than a single-dose administration in preventing postoperative nausea and vomiting (PONV) in 89 patients who were scheduled to undergo laparoscopic operation for benign gynecologic diseases and to receive intravenous patient-controlled analgesia for relief of postoperative pain. After assignment at a ratio of 1:1, intravenous ramosetron (0.3 mg) was initially administered at the end of skin closure in all patients. Thereafter, ramosetron (0.3 mg) and placebo were administered to the study and control groups, respectively, at 4 hours after the operation. The baseline and operative characteristics were similar between the groups. The incidence of PONV during the 24-hour period after operation which was assessed as the primary endpoint did not differ between the groups. No serious adverse events occurred in either group. A 2-dose administration of intravenous ramosetron may not be superior to a single-dose administration in preventing PONV in patients undergoing laparoscopic operation for benign gynecologic diseases.

Feasibility of optimizing the dose distribution in lung tumors using fluorine-18-fluorodeoxyglucose positron emission tomography and single photon emission computed tomography guided dose prescriptions

International Nuclear Information System (INIS)

Das, S.K.; Miften, M.M.; Zhou, S.; Bell, M.; Munley, M.T.; Whiddon, C.S.; Craciunescu, O.; Baydush, A.H.; Wong, T.; Rosenman, J.G.; Dewhirst, M.W.; Marks, L.B.

2004-01-01

The information provided by functional images may be used to guide radiotherapy planning by identifying regions that require higher radiation dose. In this work we investigate the dosimetric feasibility of delivering dose to lung tumors in proportion to the fluorine-18-fluorodeoxyglucose activity distribution from positron emission tomography (FDG-PET). The rationale for delivering dose in proportion to the tumor FDG-PET activity distribution is based on studies showing that FDG uptake is correlated to tumor cell proliferation rate, which is shown to imply that this dose delivery strategy is theoretically capable of providing the same duration of local control at all voxels in tumor. Target dose delivery was constrained by single photon emission computed tomography (SPECT) maps of normal lung perfusion, which restricted irradiation of highly perfused lung and imposed dose-function constraints. Dose-volume constraints were imposed on all other critical structures. All dose-volume/function constraints were considered to be soft, i.e., critical structure doses corresponding to volume/function constraint levels were minimized while satisfying the target prescription, thus permitting critical structure doses to minimally exceed dose constraint levels. An intensity modulation optimization methodology was developed to deliver this radiation, and applied to two lung cancer patients. Dosimetric feasibility was assessed by comparing spatially normalized dose-volume histograms from the nonuniform dose prescription (FDG-PET proportional) to those from a uniform dose prescription with equivalent tumor integral dose. In both patients, the optimization was capable of delivering the nonuniform target prescription with the same ease as the uniform target prescription, despite SPECT restrictions that effectively diverted dose from high to low perfused normal lung. In one patient, both prescriptions incurred similar critical structure dosages, below dose-volume/function limits

Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects.

Science.gov (United States)

Anderson, Matt S; Gilmartin, Jocelyn; Cilissen, Caroline; De Lepeleire, Inge; Van Bortel, Luc; Dockendorf, Marissa F; Tetteh, Ernestina; Ancona, June K; Liu, Rachael; Guo, Ying; Wagner, John A; Butterton, Joan R

2015-01-01

Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). Doravirine has low potential to cause drug-drug interactions since it is primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes. The pharmacokinetics and safety of doravirine were investigated in two double-blind, dose-escalation studies in healthy males. Thirty-two subjects received single doses of doravirine (6-1,200 mg) or matching placebo tablets; 40 subjects received doravirine (30-750 mg) or matching placebo tablets once daily for 10 days. In addition, the effect of doravirine (120 mg for 14 days) on single-dose pharmacokinetics of the CYP3A substrate midazolam was evaluated (10 subjects). The maximum plasma concentration (Cmax) of doravirine was achieved within 1-5 h with an apparent terminal half-life of 12-21 h. Consistent with single-dose pharmacokinetics, steady state was achieved after approximately 7 days of once daily administration, with accumulation ratios (day 10/day 1) of 1.1-1.5 in the area under the plasma concentration-time curve during the dosing interval (AUC0-24 h), Cmax and trough plasma concentration (C24 h). All dose levels produced C24 h>19 nM. Administration of 50 mg doravirine with a high-fat meal was associated with slight elevations in AUC time zero to infinity (AUC0-∞) and C24 h with no change in Cmax. Midazolam AUC0-∞ was slightly reduced by coadministration of doravirine (geometric mean ratio 0.82, 90% CI 0.70, 0.97). There was no apparent relationship between adverse event frequency or intensity and doravirine dose. No rash or significant central nervous system events other than headache were reported. Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once

Pharmacokinetics and safety of fentanyl sublingual spray and fentanyl citrate intravenous: a single ascending dose study in opioid-naïve healthy volunteers.

Science.gov (United States)

Rauck, Richard; Oh, D Alexander; Parikh, Neha; Koch, Christian; Singla, Neil; Yu, Jin; Nalamachu, Srinivas; Vetticaden, Santosh

2017-11-01

Fentanyl sublingual spray offers rapid pain relief in opioid-tolerant cancer patients, and may be useful in acute or post-operative pain. Both opioid-naïve and non-tolerant patients are likely to receive opioids in these settings. Understanding the relationship between systemic exposure of fentanyl sublingual spray and effects on respiratory function in opioid-naïve or non-tolerant populations is important to ensure patient safety. This study evaluated single-dose fentanyl sublingual spray in opioid-naïve participants. Participants were randomized to receive single-dose fentanyl sublingual spray (100, 200, 400, 600, 800 mcg) or fentanyl citrate IV in one of five cohorts. Dosing occurred following a 10-h fast, with fasting continuing for 4 h post-dose. Dose proportionality was assessed using analysis of variance and linear regression techniques. PK assessments and safety monitoring were performed through 24 h post-dose. Safety assessments, including adverse event (AE) monitoring, occurred from dosing through Day 7. Fifty participants (19-53 years) received fentanyl sublingual spray or fentanyl citrate IV. Mean maximum plasma concentrations were reached between 0.27-0.60 h post-dose for fentanyl sublingual spray. Peak (C max ) and total (AUC 0- t , AUC 0-∞ ) fentanyl exposures increased in a linear, but more than dose-proportional manner, with higher doses. The most common AEs were somnolence, nausea, and vomiting. All AEs were mild or moderate in severity. Doses at 400, 600, and 800 mcg were associated with nausea and vomiting, requiring pharmacologic intervention. Hypoxia episodes requiring nasal cannula oxygenation were observed with 600mcg and 800mcg doses. Overall, single-dose fentanyl sublingual spray (100-800 mcg) was generally well tolerated, with greater incidences of AEs (e.g. nausea, vomiting, hypoxia) at higher doses. Doses up to 200 mcg may be safely administered to healthy opioid-naïve individuals with routine monitoring; doses

Pharmacokinetic interaction of enrofloxacin/trimethoprim combination following single-dose intraperitoneal and oral administration in rats.

Science.gov (United States)

Choi, Myung-Jin; Yohannes, Sileshi Belew; Lee, Seung-Jin; Damte, Dereje; Kim, Jong-Choon; Suh, Joo-Won; Park, Seung-Chun

2014-03-01

The pharmacokinetic interaction of enrofloxacin and trimethoprim was evaluated after single-dose intraperitoneal or oral co-administration in rats. Plasma concentrations of the two drugs were determined by high-performance liquid chromatography. Following intraperitoneal combination, a significant (P trimethoprim, respectively. There was a significant (P trimethoprim. Further study is recommended in other species of animals.

A randomised trial evaluating the safety and immunogenicity of the novel single oral dose typhoid vaccine M01ZH09 in healthy Vietnamese children

NARCIS (Netherlands)

Tran, Tinh Hien; Nguyen, Thi Dung; Nguyen, Thanh Truong; Ninh, Thi Thanh Van; Tran, Nguyen Bich Chau; Nguyen, Van Minh Hoang; Tran, Thi Thu Nga; Cao, Thu Thuy; Pham, Van Minh; Nguyen, Thi Cam Binh; Tran, Thi Diem Ha; Pham, Van Toi; To, Song Diep; Campbell, James I.; Stockwell, Elaine; Schultsz, Constance; Simmons, Cameron P.; Glover, Clare; Lam, Winnie; Marques, Filipe; May, James P.; Upton, Anthony; Budhram, Ronald; Dougan, Gordon; Farrar, Jeremy; Nguyen, Van Vinh Chau; Dolecek, Christiane

2010-01-01

The emergence of drug resistant typhoid fever is a major public health problem, especially in Asia. An oral single dose typhoid vaccine would have major advantages. M01ZH09 is a live oral single dose candidate typhoid vaccine containing Salmonella enterica serovar Typhi (Ty2 aroC(-)ssaV(-)) ZH9 with

Distribution of 14C-lindane in the rat after a single dose intraperitoneal and intravenous injection

International Nuclear Information System (INIS)

Lievremont, Maurice; Le Flohic, J.-F.; Pascaud, Marc

1981-01-01

14 C-Lindane retentions in rat tissues were studied until 24 hrs after a single dose pesticide administration. Each organ shows particular kinetics. Adipose tissue is the most active in pesticide fixation but the lungs retain momentarily a large fraction of Lindane after intravenous injection [fr

Residual toxicity in hematopoietic cells following a single dose of methylnitrosourea

Energy Technology Data Exchange (ETDEWEB)

Inoue, T.; Cronkite, E.P.; Commerford, S.L.; Carsten, A.L.

1984-01-01

The residual injury to the proliferation capability of hemopoietic stem cells (CFU-S) which results from their exposure to leukemogenic agents was evaluated in mice given a single leukemogenic dose of methol nitrosourea. Bone marrow cellularity, splenic weight, number of CFU-S and the proportion of cycling to noncycling CFU-S were measured in an effort to detect acute and residual injury to the CFU-S from mice given MNU 21 and 3 days earlier. Marrow cells were also transferred into lethally irradiated mice to observe the self-renewal capability of the CFU-S in the recipient spleen and bone marrow. The results of these measurements show that the CFU-S in marrow from mice given 50 mg/kg of MNU 21 days earlier still have a defective ability for self-renewal, although the total cellularity, number of CFU-S and proportion of cycling and noncycling CFU-S in the donor have returned to the normal range. The relationship of this self-renewal defect to the development of leukemia after this leukemogenic dose of MNU is not known. 21 references, 9 figures, 3 tables.

Maternal methadone dosing schedule and fetal neurobehavior

Science.gov (United States)

Jansson, Lauren M.; DiPietro, Janet A.; Velez, Martha; Elko, Andrea; Knauer, Heather; Kivlighan, Katie T.

2008-01-01

Objective Daily methadone maintenance is the standard of care for opiate dependency during pregnancy. Previous research has indicated that single-dose maternal methadone administration significantly suppresses fetal neurobehaviors. The purpose of this study was to determine if split-dosing would have less impact on fetal neurobehavior than single-dose administration. Methods Forty methadone-maintained women were evaluated at peak and trough maternal methadone levels on single- and split-dosing schedules. Monitoring sessions occurred at 36 and 37 weeks gestation in a counterbalanced study design. Fetal measures included heart rate, variability, accelerations, motor activity and fetal movement-heart rate coupling (FM-FHR). Maternal measures included heart period, variability, skin conductance, respiration and vagal tone. Repeated measure analysis of variance was used to evaluate within-subject changes between split- and single-dosing regimens. Results All fetal neurobehavioral parameters were suppressed by maternal methadone administration, regardless of dosing regimen. Fetal parameters at peak were significantly lower during single vs. split methadone administration. FM-FHR coupling was less suppressed from trough to peak during split-dosing vs. single-dosing. Maternal physiologic parameters were generally unaffected by dosing condition. Conclusion Split- dosed fetuses displayed less neurobehavioral suppression from trough to peak maternal methadone levels as compared to single-dosed fetuses. Split-dosing may be beneficial for methadone-maintained pregnant women. PMID:19085624

Is single-dose fosfomycin trometamol a good alternative for asymptomatic bacteriuria in the second trimesterof pregnancy?

Science.gov (United States)

Bayrak, Omer; Cimentepe, Ersin; Inegöl, Ilknur; Atmaca, Ali Fuat; Duvan, Candan Iltemir; Koç, Akif; Turhan, Nilgün Oztürk

2007-05-01

Untreated asymptomatic bacteriuria has been associated with acute pyelonephritis, which may have a role in many maternal and fetal complications. Acute pyelonephritis in pregnancy is related to anemia, septicemia, transient renal dysfunction, and pulmonary insufficiency. A randomized study was conducted to assess the clinical and microbiological efficacy of a single dose of fosfomycin trometamol for the treatment of asymptomatic bacteriuria in the second trimester of pregnancy compared with a 5-day regimen of cefuroxime axetyl. Forty-four women received fosfomycin trometamol and 40 women received cefuroxime axetyl. There were no statistically significant differences between both groups regarding the mean age and mean duration of pregnancy. Therapeutic success was achieved in 93.2% of the patients treated with fosfomycin trometamol vs 95% of those treated with cefuroxime axetyl. A single dose of fosfomycin trometamol is a safe and effective alternative in the treatment of asymptomatic urinary tract infections in the second trimester of pregnancy.

Benign painful shoulder syndrome. Initial results of a single-center prospective randomized radiotherapy dose-optimization trial

International Nuclear Information System (INIS)

Ott, O.J.; Hertel, S.; Gaipl, U.S.; Frey, B.; Schmidt, M.; Fietkau, R.

2012-01-01

Background and purpose: To compare the efficacy of two different dose-fractionation schedules for radiotherapy of patients with benign painful shoulder syndrome. Patients and methods: Between February 2006 and February 2010, 312 consecutive evaluable patients were recruited for this prospective randomized trial. All patients received radiotherapy with an orthovoltage technique. One radiotherapy course consisted of 6 single fractions in 3 weeks. In case of insufficient remission of pain after 6 weeks, a second radiation series was performed. Patients were randomly assigned to receive either single doses of 0.5 or 1.0 Gy. The endpoint was pain reduction. Pain was measured before, right after, and 6 weeks after radiotherapy using a visual analogue scale (VAS) and a comprehensive pain score (CPS). Results: The overall response rate for all patients was 83% directly after and 85% 6 weeks after radiotherapy. The mean VAS values before, directly after, and 6 weeks after treatment for the 0.5 and 1.0 Gy groups were 56.8 ± 23.7 and 53.2 ± 21.8 (p = 0.158), 38.2 ± 26.1 and 34.0 ± 24.5 (p = 0.189), and 33.0 ± 27.2 and 23.7 ± 22.7 (p = 0.044), respectively. The mean CPS before, directly after, and 6 weeks after treatment was 9.7 ± 3.0 and 9.5 ± 2.7 (p = 0.309), 6.1 ± 3.6 and 5.4 ± 3.6 (p = 0.096), 5.3 ± 3.7 and 4.1 ± 3.7 (p = 0.052), respectively. Despite a slight advantage in the VAS analysis for the 1.0 Gy group for delayed response, the CPS analysis revealed no statistically significant differences between the two single-dose trial arms for early (p = 0.652) and delayed response quality (p = 0.380). Conclusion: Radiotherapy is an effective treatment option for the management of benign painful shoulder syndrome. Concerning radiation protection, the dose for a radiotherapy series is recommended not to exceed 3-6 Gy. (orig.)

Dose rate-dependent marrow toxicity of TBI in dogs and marrow sparing effect at high dose rate by dose fractionation.

Science.gov (United States)

Storb, R; Raff, R F; Graham, T; Appelbaum, F R; Deeg, H J; Schuening, F G; Sale, G; Seidel, K

1999-01-01

We evaluated the marrow toxicity of 200 and 300 cGy total-body irradiation (TBI) delivered at 10 and 60 cGy/min, respectively, in dogs not rescued by marrow transplant. Additionally, we compared toxicities after 300 cGy fractionated TBI (100 cGy fractions) to that after single-dose TBI at 10 and 60 cGy/min. Marrow toxicities were assessed on the basis of peripheral blood cell count changes and mortality from radiation-induced pancytopenia. TBI doses studied were just below the dose at which all dogs die despite optimal support. Specifically, 18 dogs were given single doses of 200 cGy TBI, delivered at either 10 (n=13) or 60 (n=5) cGy/min. Thirty-one dogs received 300 cGy TBI at 10 cGy/min, delivered as either single doses (n=21) or three fractions of 100 cGy each (n=10). Seventeen dogs were given 300 cGy TBI at 60 cGy/min, administered either as single doses (n=5) or three fractions of 100 cGy each (n=10). Within the limitations of the experimental design, three conclusions were drawn: 1) with 200 and 300 cGy single-dose TBI, an increase of dose rate from 10 to 60 cGy/min, respectively, caused significant increases in marrow toxicity; 2) at 60 cGy/min, dose fractionation resulted in a significant decrease in marrow toxicities, whereas such a protective effect was not seen at 10 cGy/min; and 3) with fractionated TBI, no significant differences in marrow toxicity were seen between dogs irradiated at 60 and 10 cGy/min. The reduced effectiveness of TBI when a dose of 300 cGy was divided into three fractions of 100 cGy or when dose rate was reduced from 60 cGy/min to 10 cGy/min was consistent with models of radiation toxicity that allow for repair of sublethal injury in DNA.

Intravenous iron isomaltoside 1000 administered by high single-dose infusions or standard medical care for the treatment of fatigue in women after postpartum haemorrhage

DEFF Research Database (Denmark)

Holm, Charlotte; Thomsen, Lars Lykke; Norgaard, Astrid

2015-01-01

1000 with standard medical care on physical fatigue in women with postpartum haemorrhage. METHODS/DESIGN: In a single centre, open-labelled, randomised trial, women with postpartum haemorrhage exceeding 700 mL will be allocated to either a single dose of 1,200 mg of iron isomaltoside 1000 or standard...... Inventory. The primary objective will be considered to have been met if an intravenous high single dose of iron isomaltoside 1000 is shown to be superior to standard medical care in women after postpartum haemorrhage regarding physical fatigue.For claiming superiority, we set the minimal clinically relevant...... randomised controlled studies have compared the clinical efficacy and safety of standard medical care with intravenous administration of iron supplementation after postpartum haemorrhage.The primary objective of this study is to compare the efficacy of an intravenous high single-dose of iron isomaltoside...

Accuracy in radiosurgery: The influence of collimator diameters and arc weights on the dose distribution for single target

Energy Technology Data Exchange (ETDEWEB)

Plazas, M S [National Univ. of Colombia (Colombia); Lefkopoulus, D; Schlienger, M [Service de Radiotherapie, Hopital Tenon, Paris (France). Unite de Radiophysique; Merienne, L [Hopital Sainte Anne, Paris (France). Service de Neurochirurgie

1996-08-01

The dosimetric characteristics of mini-beams and dose distributions in beams used for radio surgery defer substantially from beams used in common radiotherapy. The aim of radio surgery is to deliver a high dose to the lesion in one single fraction, while minimizing the dose delivered to the surrounding normal brain tissue. This type of irradiation is performed with a number of continuous arcs located in various corneal (patient sitting) or sagittal (patient in a supine position) inclined planes using a linear accelerator. A treatment planning system should take into account a large number of irradiation parameters such as the collimator diameter, number of arcs, their angular positions, length and weight of the arcs. We analysed the influence of collimator diameters in the range of 6 to 20 mm using 15 MV X-rays and stereo-tactic irradiation of ellipsoidal inclined arterio venous malformations (AVMs) with a single isocenter. Special arc weights were used to obtain an optimized dose distribution with 13 arcs distributed over an angular sector of 120 deg. x 13 deg. In the two studies made we used 3 dimensional dosimetric calculations. The results were used for the treatment of patients and enabled the choice of the optimal irradiation configuration for each patient. (author). 10 refs, 9 figs.

Single Low Dose Primaquine (0.25 mg/kg Does Not Cause Clinically Significant Haemolysis in G6PD Deficient Subjects.

Directory of Open Access Journals (Sweden)

Germana Bancone

Full Text Available Primaquine is the only drug consistently effective against mature gametocytes of Plasmodium falciparum. The transmission blocking dose of primaquine previously recommended was 0.75 mg/kg (adult dose 45 mg but its deployment was limited because of concerns over haemolytic effects in patients with glucose-6-phosphate dehydrogenase (G6PD deficiency. G6PD deficiency is an inherited X-linked enzymatic defect that affects an estimated 400 million people around the world with high frequencies (15-20% in populations living in malarious areas. To reduce transmission in low transmission settings and facilitate elimination of P. falciparum, the World Health Organization now recommends adding a single dose of 0.25 mg/kg (adult dose 15 mg to Artemisinin-based Combination Therapies (ACTs without G6PD testing. Direct evidence of the safety of this low dose is lacking. Adverse events and haemoglobin variations after this treatment were assessed in both G6PD normal and deficient subjects in the context of targeted malaria elimination in a malaria endemic area on the North-Western Myanmar-Thailand border where prevalence of G6PD deficiency (Mahidol variant approximates 15%.The tolerability and safety of primaquine (single dose 0.25 mg base/kg combined with dihydroartemisinin-piperaquine (DHA-PPQ given three times at monthly intervals was assessed in 819 subjects. Haemoglobin concentrations were estimated over the six months preceding the ACT + primaquine rounds of mass drug administration. G6PD deficiency was assessed with a phenotypic test and genotyping was performed in male subjects with deficient phenotypes and in all females. Fractional haemoglobin changes in relation to G6PD phenotype and genotype and primaquine round were assessed using linear mixed-effects models. No adverse events related to primaquine were reported during the trial. Mean fractional haemoglobin changes after each primaquine treatment in G6PD deficient subjects (-5.0%, -4.2% and -4

Placental and milk transfer, disposition and elimination of a single oral dose of [14C acetyl] acephate in Sprague Dawley rats

International Nuclear Information System (INIS)

Bakry, N.M.; Salama, A.K.; Abou-Donia, M.B.

1991-01-01

A single oral dose of 40 mg/kg (6.4 μCi/kg) of [ 14 C acetyl]acephate was administered on day 18 of gestation to pregnant Sprague Dawley rats. Eight groups of three rats were killed after 10 min and 0.5, 1, 3, 6, 12, 24, and 48 hr. At the end of the 48 hr experimental period, a total of 22.38% of the dose was exhaled as carbon dioxide, while only 1.25% and 0.60% of the dose were eliminated in the urine and feces, respectively. Trace amount (0.03% of the dose) was recovered in expired air as volatile materials. Radioactive acephate was rapidly absorbed and distributed in the tissues, with levels in most tissues reaching a peak concentration within 1 to 3 hr. The highest concentration of radioactivity was present in the maternal stomach followed by the liver. A total of 0.72% of the dose was recovered in the fetus. In another study, a single oral dose of 40 mg/kg [ 14 C acetyl]acephate was administered to the dams right after delivery. Nursing and suckling groups were killed at intervals of 1, 3, 6, 12, 24, 36, and 48 hr after dosing. Generally, the highest concentrations of radioactivity were present in the stomach, small intestine, liver, lung, and kidneys. A total of 0.96% of the dose was recovered in the sucklings

Economic and microbiologic evaluation of single-dose vial extension for hazardous drugs.

Science.gov (United States)

Rowe, Erinn C; Savage, Scott W; Rutala, William A; Weber, David J; Gergen-Teague, Maria; Eckel, Stephen F

2012-07-01

The update of US Pharmacopeia Chapter in 2008 included guidelines stating that single-dose vials (SDVs) opened and maintained in an International Organization for Standardization Class 5 environment can be used for up to 6 hours after initial puncture. A study was conducted to evaluate the cost of discarding vials after 6 hours and to further test sterility of vials beyond this time point, subsequently defined as the beyond-use date (BUD). Financial determination of SDV waste included 2 months of retrospective review of all doses prescribed. Additionally, actual waste log data were collected. Active and control vials (prepared using sterilized trypticase soy broth) were recovered, instead of discarded, at the defined 6-hour BUD. The institution-specific waste of 19 selected SDV medications discarded at 6 hours was calculated at $766,000 annually, and tracking waste logs for these same medications was recorded at $770,000 annually. Microbiologic testing of vial extension beyond 6 hours showed that 11 (1.86%) of 592 samples had one colony-forming unit on one of two plates. Positive plates were negative at subsequent time points, and all positives were single isolates most likely introduced during the plating process. The cost of discarding vials at 6 hours was significant for hazardous medications in a large academic medical center. On the basis of microbiologic data, vial BUD extension demonstrated a contamination frequency of 1.86%, which likely represented exogenous contamination; vial BUD extension for the tested drugs showed no growth at subsequent time points and could provide an annual cost savings of more than $600,000.

Single therapeutic and supratherapeutic doses of sacubitril/valsartan (LCZ696) do not affect cardiac repolarization.

Science.gov (United States)

Langenickel, Thomas H; Jordaan, Pierre; Petruck, Jesika; Kode, Kiran; Pal, Parasar; Vaidya, Soniya; Chandra, Priya; Rajman, Iris

2016-08-01

Sacubitril/valsartan (LCZ696) is a first-in-class angiotensin receptor neprilysin inhibitor (ARNI) indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA class II-IV) and reduced ejection fraction. This study was aimed to evaluate the effect of single oral therapeutic (400 mg) and supratherapeutic (1200 mg) doses of LCZ696 on cardiac repolarization. This randomized double-blind crossover study in healthy male subjects compared the effect of therapeutic and supratherapeutic doses of LCZ696 with placebo and moxifloxacin 400 mg (open-label treatment) as positive control. The primary assessment was mean baseline- and placebo-corrected QTcF (∆∆QTcF; Fridericia correction). Additional assessments included the ∆∆QTcB (Bazett's correction), PR interval, QRS duration, heart rate (HR), LCZ696 pharmacokinetics, pharmacokinetic/pharmacodynamic relationships, and safety. Of the 84 subjects enrolled, 81 completed the study. The maximum upper bound of the two-sided 90 % confidence interval for ∆∆QTcF for LCZ696 400 mg and 1200 mg were <10 ms, and assay sensitivity was confirmed with moxifloxacin. No relevant treatment-emergent changes were observed in any of the ECG-derived parameters with LCZ696 or placebo, and the incidence of adverse events was comparable among the treatment groups. Single therapeutic and supratherapeutic doses of LCZ696 did not affect cardiac repolarization as defined by the E14 ICH guidelines.

Hardening of single crystals of magnesium by low neutron doses at 77 K

International Nuclear Information System (INIS)

Gonzalez, H.C.

1984-01-01

Radiation hardening in Mg single crystals at 77 K is studied with a microtensile machine operating in-situ in the CNEA reactor facility RA1. Experimental results show that the dose dependence of the yield stress is similar to that previously observed in irradiated Cu and Zn. The radiation-induced yield stress, due to the presence of radiation obstacles operating alone, increases according to a 0.5 power law. It adds algebraically to the athermal component of the initial yield stress, but is not exactly additive to the other thermally activated mechanisms. For doses higher than 4.5 x 10 16 neutrons/cm 2 , a strong instability in the deformation is observed. Post irradiation experiments in tensile tests performed with a hard machine show a continuous stress drop. This effect is attributed to the dislocation channeling phenomenon which takes place during the tensile test. (author)

Evaluation of fleroxacin (RO 23-6240) as single-oral-dose therapy of culture-proven chancroid in Nairobi, Kenya.

Science.gov (United States)

MacDonald, K S; Cameron, D W; D'Costa, L; Ndinya-Achola, J O; Plummer, F A; Ronald, A R

1989-01-01

Chancroid is gaining importance as a sexually transmitted disease because of its association with transmission of human immunodeficiency virus type 1 (HIV-1). Effective, simply administered therapy for chancroid is necessary. Fleroxacin is effective against Haemophilus ducreyi in vitro. We performed an initial randomized clinical trial to assess the efficacy of fleroxacin for treatment of chancroid in Nairobi, Kenya. Fifty-three men with culture-positive chancroid were randomly assigned to receive either 200 mg (group 1) or 400 mg (group 2) of fleroxacin as a single oral dose. Groups 1 and 2 were similar with regard to severity of disease, bubo formation, and HIV-1 status. A satisfactory clinical response to therapy was noted in 23 of 26 patients (88%) in group 1 and 18 of 23 patients (78%) in group 2. Bacteriological failure occurred in 1 of 26 evaluable patients (4%) in group 1 and 4 of 23 evaluable patients (17%) in group 2. Two of 37 HIV-1-seronegative men (5%) and 3 of 11 HIV-1-infected men (27%) were bacteriological failures. Fleroxacin, 200 or 400 mg as a single oral dose, is efficacious therapy for microbiologically proven chancroid in patients who do not have concurrent HIV-1 infection. Among HIV-1-infected men, a single dose of 200 or 400 mg of fleroxacin is inadequate therapy for chancroid. PMID:2502065

Dose proportionality and pharmacokinetics of carvedilol sustained-release formulation: a single dose-ascending 10-sequence incomplete block study

Directory of Open Access Journals (Sweden)

Kim YH

2015-06-01

Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Yook-Hwan Noh,1 Shi Hyang Lee,1 Hyeong-Seok Lim,1 Chin Kim,2 Kyun-Seop Bae11Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, 2Chong Kun Dang Clinical Research and Clinical Epidemiology and Medical Information, CKD Pharmaceuticals, Seoul, Republic of KoreaBackground: Carvedilol is a third-generation β-blocker indicated for congestive heart failure and high blood pressure. The aim of this study was to investigate the dose proportionality of the carvedilol sustained-release (SR formulation in healthy male subjects.Methods: An open-label, single dose-ascending, 10-sequence, 3-period balanced incomplete block study was performed using healthy male subjects. In varying sequences, each subject received three of five carvedilol SR formulations (8, 16, 32, 64, or 128 mg once. The treatment periods were separated by a washout period of 7 days. Serial blood samples were collected up to 48 h after dosing. The plasma concentrations of carvedilol were determined by using validated liquid chromatography–tandem mass spectrometry. Pharmacokinetic parameters including the area under the plasma concentration–time curve (AUC from time 0 to the last measurable time (AUClast, AUC extrapolated to infinity (AUCinf, and the measured peak plasma concentration (Cmax were obtained by noncompartmental analysis. Dose proportionality was evaluated if the ln–ln plots of AUClast, AUCinf, and Cmax versus dose were linear and the 90% confidence intervals (CIs of the slopes were within 0.9195 and 1.0805. Tolerability was assessed by vital signs, electrocardiogram, clinical laboratory tests, and monitoring of adverse events (AEs throughout the study.Results: A total of 31 subjects were enrolled, and 30 completed the study. The assessment of dose proportionality meets the statistical criteria; the point estimates of slope were 1.0104 (90% CI: 0.9849–1.0359 for AUClast, 1

Synergistic effects of total ionizing dose on single event upset sensitivity in static random access memory under proton irradiation

International Nuclear Information System (INIS)

Xiao Yao; Guo Hong-Xia; Zhang Feng-Qi; Zhao Wen; Wang Yan-Ping; Zhang Ke-Ying; Ding Li-Li; Luo Yin-Hong; Wang Yuan-Ming; Fan Xue

2014-01-01

Synergistic effects of the total ionizing dose (TID) on the single event upset (SEU) sensitivity in static random access memories (SRAMs) were studied by using protons. The total dose was cumulated with high flux protons during the TID exposure, and the SEU cross section was tested with low flux protons at several cumulated dose steps. Because of the radiation-induced off-state leakage current increase of the CMOS transistors, the noise margin became asymmetric and the memory imprint effect was observed. (interdisciplinary physics and related areas of science and technology)

Effectiveness of single dose rifampicin in preventing leprosy in close contacts of patients with newly diagnosed leprosy: cluster randomised controlled trial

NARCIS (Netherlands)

Moet, F. Johannes; Pahan, David; Oskam, Linda; Richardus, Jan H.; van Brakel, Wim H.; Klatser, Paul R.; Saunderson, Paul R.; Smith, W. Cairns S.; Withington, Steve G.; Richardus, Jan Hendrik; Schuring, Ron P.; Faber, Roel; Borsboom, Gerard J. J. M.

2008-01-01

OBJECTIVE: To determine the effectiveness of chemoprophylaxis using a single dose of rifampicin to prevent leprosy in close contacts. DESIGN: Single centre, double blind, cluster randomised, placebo controlled trial. SETTING: Leprosy control programme in two districts of northwest Bangladesh with a

A single-dose antihelminthic treatment does not influence immunogenicity of a meningococcal and a cholera vaccine in Gabonese school children.

Science.gov (United States)

Brückner, Sina; Agnandji, Selidji Todagbe; Elias, Johannes; Berberich, Stefan; Bache, Emmanuel; Fernandes, José; Loembe, Marguerite Massinga; Hass, Johanna; Lell, Bertrand; Mordmüller, Benjamin; Adegnika, Ayola Akim; Kremsner, Peter; Esen, Meral

2016-10-17

We recently described the effect of a single-dose antihelminthic treatment on vaccine immunogenicity to a seasonal influenza vaccine. Here we report the effect of antihelminthics on the immunogenicity of a meningococcal vaccine and a cholera vaccine in primary school children living in Lambaréné, Gabon. Since infection with helminths remains a major public health problem and the influence on cognitive and physical development as well as the immunomodulatory effects are well established, we investigated if a single-dose antihelminthic treatment prior to immunization positively influences antibody titers and vaccine-specific memory B-cells. In this placebo-controlled, double-blind trial the effect of a single-dose antihelminthic treatment prior to immunization with a meningococcal as well as with a cholera vaccine was investigated. Anti-meningococcal antibodies were assessed by serum bactericidal assay, cholera vaccine-specific antibody titers by Enzyme-linked Immunosorbent Assay (ELISA) at baseline (Day 0; vaccination), four weeks (Day 28) and 12weeks (Day 84) following vaccination. Meningococcal and cholera vaccine-specific memory B-cells were measured at Day 0 and 84 by vaccine-specific Enzyme-linked Immunospot (ELISpot) assay. The helminth burden of the participants was assessed four weeks before vaccination (Day -28) and at Day 84 by the Merthiolate-Iodine-Formaldehyde technique. Out of 280 screened school children, 96 received a meningococcal vaccine and 89 a cholera vaccine following allocation to either the single-dose antihelminthic treatment group or the placebo group. Bactericidal antibody titers increased following immunization with the meningococcal vaccine at Day 28 and Day 84 in 68 participants for serogroup A, and in 80 participants for serogroup C. The cholera vaccine titers increased in all participants with a peak at Day 28. The number of memory B-cells increased following vaccination compared to baseline. There was no statistically significant

Comparative Assessment of a Single Dose and a 2-dose Vaccination Series of a Quadrivalent Meningococcal CRM-conjugate Vaccine (MenACWY-CRM) in Children 2-10 Years of Age.

Science.gov (United States)

Johnston, William; Essink, Brandon; Kirstein, Judith; Forleo-Neto, Eduardo; Percell, Sandra; Han, Linda; Keshavan, Pavitra; Smolenov, Igor

2016-01-01

We compared the immunogenicity, safety and 1-year antibody persistence of a single-dose and a 2-dose series of a licensed meningococcal ACWY-CRM conjugate vaccine (MenACWY-CRM) in 2- to 10-year-old children. In this phase III, multicenter, observer-blind study, children aged 2-5 years (n = 359) and 6-10 years (n = 356) were randomized 1:1 to receive 2 doses of MenACWY-CRM (ACWY2) or 1 dose of placebo followed by 1 dose of MenACWY-CRM (ACWY1), 2 months apart. Immunogenicity was measured using serum bactericidal activity with human complement (hSBA). Primary outcomes were to assess the immunologic noninferiority and superiority of ACWY2 versus ACWY1. One-month after the second dose, the hSBA seroresponse in ACWY2 was noninferior to ACWY1 for all 4 serogroups, in both age cohorts, and was superior for serogroups C and Y in the 2- to 5-year-old age cohort and for serogroup Y in the 6- to 10-year-old age cohort. Overall, 90%-99% of subjects in ACWY2 and 65%-96% in ACWY1 had hSBA titers ≥ 8; geometric mean titers were 1.8- to 6.4-fold higher in ACWY2 than ACWY1 across serogroups. At 1 year postvaccination, geometric mean titers declined, and the differences between ACWY2 and ACWY1 remained significant for serogroups A and C in the 2- to 5-year-old age cohort and for serogroups C and Y in the 6- to 10-year-old age cohort. The safety profile of MenACWY-CRM was similar in both groups. The single dose and 2-dose MenACWY-CRM series were immunogenic and well tolerated. Although antibody responses were greater after 2 doses, especially in the 2- to 5-year-old age cohort, this difference was less pronounced at 1 year postvaccination.

Development of a synthetic single crystal diamond dosimeter for dose measurement of clinical proton beams

Science.gov (United States)

Moignier, Cyril; Tromson, Dominique; de Marzi, Ludovic; Marsolat, Fanny; García Hernández, Juan Carlos; Agelou, Mathieu; Pomorski, Michal; Woo, Romuald; Bourbotte, Jean-Michel; Moignau, Fabien; Lazaro, Delphine; Mazal, Alejandro

2017-07-01

The scope of this work was to develop a synthetic single crystal diamond dosimeter (SCDD-Pro) for accurate relative dose measurements of clinical proton beams in water. Monte Carlo simulations were carried out based on the MCNPX code in order to investigate and reduce the dose curve perturbation caused by the SCDD-Pro. In particular, various diamond thicknesses were simulated to evaluate the influence of the active volume thickness (e AV) as well as the influence of the addition of a front silver resin (250 µm in thickness in front of the diamond crystal) on depth-dose curves. The simulations indicated that the diamond crystal alone, with a small e AV of just 5 µm, already affects the dose at Bragg peak position (Bragg peak dose) by more than 2% with respect to the Bragg peak dose deposited in water. The optimal design that resulted from the Monte Carlo simulations consists of a diamond crystal of 1 mm in width and 150 µm in thickness with the front silver resin, enclosed by a water-equivalent packaging. This design leads to a deviation between the Bragg peak dose from the full detector modeling and the Bragg peak dose deposited in water of less than 1.2%. Based on those optimizations, an SCDD-Pro prototype was built and evaluated in broad passive scattering proton beams. The experimental evaluation led to probed SCDD-Pro repeatability, dose rate dependence and linearity, that were better than 0.2%, 0.4% (in the 1.0-5.5 Gy min-1 range) and 0.4% (for dose higher than 0.05 Gy), respectively. The depth-dose curves in the 90-160 MeV energy range, measured with the SCDD-Pro without applying any correction, were in good agreement with those measured using a commercial IBA PPC05 plane-parallel ionization chamber, differing by less than 1.6%. The experimental results confirmed that this SCDD-Pro is suitable for measurements with standard electrometers and that the depth-dose curve perturbation is negligible, with no energy dependence and no significant dose rate

Measured Neutron Spectra and Dose Equivalents From a Mevion Single-Room, Passively Scattered Proton System Used for Craniospinal Irradiation

Energy Technology Data Exchange (ETDEWEB)

Howell, Rebecca M., E-mail: rhowell@mdanderson.org [Department of Radiation Physics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States); Burgett, Eric A.; Isaacs, Daniel [Department of Nuclear Engineering, Idaho State University, Pocatello, Idaho (United States); Price Hedrick, Samantha G.; Reilly, Michael P.; Rankine, Leith J.; Grantham, Kevin K.; Perkins, Stephanie; Klein, Eric E. [Department of Radiation Oncology, Washington University, St. Louis, Missouri (United States)

2016-05-01

Purpose: To measure, in the setting of typical passively scattered proton craniospinal irradiation (CSI) treatment, the secondary neutron spectra, and use these spectra to calculate dose equivalents for both internal and external neutrons delivered via a Mevion single-room compact proton system. Methods and Materials: Secondary neutron spectra were measured using extended-range Bonner spheres for whole brain, upper spine, and lower spine proton fields. The detector used can discriminate neutrons over the entire range of the energy spectrum encountered in proton therapy. To separately assess internally and externally generated neutrons, each of the fields was delivered with and without a phantom. Average neutron energy, total neutron fluence, and ambient dose equivalent [H* (10)] were calculated for each spectrum. Neutron dose equivalents as a function of depth were estimated by applying published neutron depth–dose data to in-air H* (10) values. Results: For CSI fields, neutron spectra were similar, with a high-energy direct neutron peak, an evaporation peak, a thermal peak, and an intermediate continuum between the evaporation and thermal peaks. Neutrons in the evaporation peak made the largest contribution to dose equivalent. Internal neutrons had a very low to negligible contribution to dose equivalent compared with external neutrons, largely attributed to the measurement location being far outside the primary proton beam. Average energies ranged from 8.6 to 14.5 MeV, whereas fluences ranged from 6.91 × 10{sup 6} to 1.04 × 10{sup 7} n/cm{sup 2}/Gy, and H* (10) ranged from 2.27 to 3.92 mSv/Gy. Conclusions: For CSI treatments delivered with a Mevion single-gantry proton therapy system, we found measured neutron dose was consistent with dose equivalents reported for CSI with other proton beamlines.

Acoustic neuromas: single dose vs fractionated therapy

International Nuclear Information System (INIS)

Fuss, M.; Debus, J.; Lohr, F.; Engenhart-Cabillic, R.; Wannenmacher, M.

1997-01-01

Purpose: Radiosurgical treatment (RS) of acoustic neuromas is a well established treatment. However, few data are available concerning conformal fractionated radiotherapy (FT) of this tumor entity. We evaluated treatment outcome and toxicity for both treatment modalities in 41 patients treated at our institution between 1984 and 1997. Material and Methods: All treatments were performed using a specially adapted linear accelerator and circular collimators for convergent beam RS or multi-leaf collimators (leaf thickness 1 or 3mm) for multi-field RS or fractionated treatment. 22 patients (7 male, 15 female, median age 60 years, range 20-83 years) were treated radiosurgically with single doses between 7 and 28 Gray (median 15 Gy) prescribed to the 80% isodose line. Tumor volumes ranged from 0.7 to 10.5 ccm with a median volume of 3.4 ccm. The median number of isocenters was 2 (1-4 isocenters). One patient was treated by a multi-field technique (14 isocentric irregularly shaped noncoplanar fields). 19 patients (5 male, 14 female, median age 55 years, range 20-81 years) were treated with stereotactic conformal radiotherapy. Median dose was 60 Gray with a median daily fraction size of 2 Gy and a median of 3 (1-4) irregularly shaped isocentric fields. Tumor volumes ranged from 0.7 to 32.4 ccm (median 15 ccm). Median follow-up was 30 months (7-149 months) for radiosurgical and 30 months (2-88 months) for fractionated treatment. Seven patients who underwent fractionated treatment had previously undergone neurosurgical resection on the contralateral side. One had undergone radiosurgery on the opposite side before. Results: All tumors were locally controlled. A volume reduction of more than 20% was seen in 16% after RS and 18% following FT. Typical posttherapeutic central reduction of contrast media enhancement was found in 73% following RS after a median of 8 (3-12) months and in 63% following FT after a median of 6 (1-12) months. Temporary brainstem edema was diagnosed in 4

Effects of food intake on the pharmacokinetics of diclofenac potassium soft gelatin capsules: a single-dose, randomized, two-way crossover study.

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Scallion, Ralph; Moore, Keith A

2009-10-01

Diclofenac potassium liquid-filled soft gelatin capsule (DPSGC) is an investigational formulation that uses dispersing agents designed to facilitate rapid and consistent absorption of this NSAID. The aim of this study was to characterize the effects of food intake on the pharmacokinetic (PK) profile of oral DPSGC at doses of 25 and 50 mg. In this open-label, randomized, single-dose (2 distinct doses), 2-way crossover bioavailability study, healthy adult volunteers were randomly assigned to receive a single dose of DPSGC 25 or 50 mg after an overnight fast (fasted condition) or high-fat breakfast (fed condition) (period 1). After 7 days, the participants received the same dose under the opposite fed/fasted condition (period 2). Serial blood samples were obtained before and through 6 hours after study drug administration. Concentrations of diclofenac in plasma were determined using HPLC, and PK profiles were studied using ANCOVA. Adverse events (AEs) were monitored and recorded on each in-clinic day. Of 47 participants included in the study, 24 received the 25-mg dose of DPSGC and 23 received the 50-mg dose. The majority of participants were male (80.9%), and the mean age was 28.6 years. The mean (SD) AUC values for the fasted and fed states were 691 (195) and 680 (184) ng x h/mL, respectively, with the 25-mg dose, and 1521 (377) and 1416 (366) ng . h/mL, respectively, with the 50-mg dose, suggesting that the extent of absorption was similar with both dietary conditions at each dose. Food intake was associated with decreases in C(max) by nearly half in the 25-mg group (fasted vs fed, 1156 [482] vs 686 [411] ng/mL, respectively; P < 0.05) and the 50-mg group (2365 [1034] vs 1154 [592 ng/mL; P < 0.05) and delayed T(max) in the 25-mg group (0.49 [0.16] vs 1.02 [0.55] hours; P < 0.05) and 50-mg group (0.51 [0.19] vs 1.28 [0.71] hours; P < 0.05). Two mild AEs (nasal congestion and light-headedness) were reported in 2 participants who received 25 mg under fed conditions

Single- and multiple-dose pharmacokinetics of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155 compared with immediate-release hydrocodone bitartrate/ibuprofen and immediate-release tramadol HCl/acetaminophen

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Devarakonda K

2015-09-01

Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young41Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, 2Mallinckrodt Pharmaceuticals, 3Research and Development, Mallinckrodt Pharmaceuticals, 4Department of Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USAObjective: To characterize the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (IR/ER HB/APAP, IR HB/ibuprofen, and IR tramadol HCl/APAP.Methods: In this single-center, open-label, randomized, four-period crossover study, healthy participants received four treatments under fasted conditions: 1 a single dose of two IR/ER HB/APAP 7.5/325 mg tablets (15/650 mg total dose on day 1, followed by two tablets every 12 hours (q12h beginning on day 3; 2 a single dose of IR HB/ibuprofen 15/400 mg (divided as one 7.5/200 mg tablet at hour 0 and 6, followed by one tablet every 6 hours (q6h beginning on day 3; 3 a single dose of IR tramadol HCl/APAP 75/650 mg (divided as one 37.5/325 mg tablet at hour 0 and 6, followed by one tablet q6h beginning on day 3; and 4 a single dose of three IR/ER HB/APAP 7.5/325 mg tablets (22.5/975 mg total dose on day 1, a three-tablet initial dose at 48 hours followed by two-tablet doses q12h beginning on day 3. Hydrocodone and APAP single-dose and steady-state PK were assessed. Adverse events were monitored.Results: The PK analysis was carried out on 29 of 48 enrolled participants who completed all treatment periods. Single-dose hydrocodone exposure was similar for IR/ER HB/APAP 22.5/975 mg and IR HB/ibuprofen 15/400 mg; time to maximum observed plasma concentration was shorter and half-life was longer for IR/ER HB/APAP (22.5/975 mg and 15/650 mg vs IR HB/ibuprofen. Single-dose APAP exposure was similar for IR/ER HB/APAP 15/650 mg and IR tramadol HCl/APAP 75/650 mg. Steady-state hydrocodone and APAP exposures

Pharmacokinetics After Single Ascending Dose, Food Effect, and Safety of Sacubitril/Valsartan (LCZ696), an Angiotensin Receptor and Neprilysin Inhibitor, in Healthy Japanese Subjects.

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Akahori, Mizuki; Ayalasomayajula, Surya; Langenickel, Thomas; Pal, Parasar; Zhou, Wei; Sunkara, Gangadhar

2017-06-01

LCZ696 (sacubitril/valsartan) is a novel angiotensin receptor neprilysin inhibitor (ARNI) that has been developed for treatment of heart failure patients with reduced ejection fraction and approved in the US, Europe, and many other countries. This randomized, placebo-controlled study was conducted in healthy Japanese male subjects (N = 50) to assess the pharmacokinetics and safety of single ascending oral doses (20-600 mg) of LCZ696. Food effect was also evaluated following administration of 200 mg dose. Plasma and urine samples from 40 subjects receiving LCZ696 were collected to assess pharmacokinetics of LCZ696 analytes (sacubitril, sacubitrilat, and valsartan). Following single oral dose administration of LCZ696, sacubitril and valsartan rapidly appeared in systemic circulation with a dose-linear increase in the exposure to the LCZ696 analytes. Of the administered dose, approximately 0.85 %, 54.0 %, and 8.19 % of sacubitril, sacubitrilat, and valsartan, respectively, were recovered in urine. Food reduced AUC of sacubitril, sacubitrilat, and valsartan by 21, 8, and 40 %, respectively, and C max by 72, 27, and 51 %, respectively. Single oral doses of up to 600 mg of LCZ696 were safe and generally well tolerated in healthy Japanese male subjects.

Radioprotective effects in mice by a single dose of subcutaneous administration of cobaltous chloride post γ-rays irradiation with a sublethal dose

International Nuclear Information System (INIS)

Izumo, Yoshiro; Ogata, Hiromitsu

1993-01-01

Radioprotective effects were investigated in mice which received subcutaneously a single dose of each inorganic metal: Co, Cu, Rb, Sr, Mo and W 24 hours post irradiation of 60 Co γ-rays with a sublethal dose. The effects were observed in mice injected with Co at an optimum dosage of 20 mg/kg·body weight. Then to elucidate mechanisms of the effects, mice were injected with Co containing the radioactive tracer ( 60 Co) following the radiation exposure, measured elimination of the radioactivity for 7 days, then sacrificed and divided to some tissues and organs. The radioactivity in whole body during this period resulted in a markedly higher retention than that for mice injected with [ 60 Co] alone, as well as liver in the organs. These higher retentions appeared to be related to the radioprotective effects. (author)

Exploratory pilot study assessing the risk of cognitive impairment or sedation in the elderly following single doses of solifenacin 10 mg.

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Wesnes, Keith A; Edgar, Chris; Tretter, Reiner N; Bolodeoku, John

2009-11-01

To assess the cognitive effects of single doses of solifenacin 10 mg compared with placebo (primary objective) and oxybutynin immediate release (IR) 10 mg (secondary objective) in elderly subjects. Single-centre, randomised, double-blind, placebo-controlled study in 12 healthy elderly volunteers, with three crossover periods separated by two 14-day washout periods. Each sequence consisted of a single dose of solifenacin 10 mg in one period, oxybutynin IR 10 mg in another and placebo in another. Aspects of attention, information processing, working memory, episodic memory and self-rated mood and alertness were tested using the validated Cognitive Drug Research computerised assessment system. There was no evidence from absolute mean values or changes from baseline to suggest that solifenacin 10 mg impaired cognition or self-ratings of mood and alertness versus placebo. Post-hoc ANCOVA showed no statistically significant cognitive deterioration with solifenacin versus placebo, when measured at a time point closest to the probable C(max) of solifenacin. Oxybutynin was associated with statistically significant impairments in several measures of cognitive function at a time point corresponding with its probable C(max). In this pilot study, single 10 mg doses of solifenacin did not show any clear propensity to impair cognitive function in a healthy elderly population.

Single Oral Dose Toxicity Test of Blue Honeysuckle Concentrate in Mice

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Park, Sang-In; Choi, Seung-Hoon; Song, Chang-Hyun; Park, Soo-Jin; Shin, Yong-Kook; Han, Chang-Hyun; Lee, Young Joon; Ku, Sae-Kwang

2015-01-01

The objective of this study was to obtain single oral dose toxicity information for concentrated and lyophilized powder of blue honeysuckle (Lonicera caerulea L., Caprifoliaceae; BHcL) in female and male ICR mice to aid in the process of developing natural origin medicinal ingredients or foods following proximate analysis and phytochemical profile measurement. The proximate analysis revealed that BHcL had an energy value of 3.80 kcal/g and contained 0.93 g/g of carbohydrate, 0.41 g/g of sugar, 0.02 g/g of protein, and 0.20 mg/g of sodium. BHcL did not contain lipids, including saturated lipids, trans fats, or cholesterols. Further, BHcL contained 4.54% of betaine, 210.63 mg/g of total phenols, 159.30 mg/g of total flavonoids, and 133.57 mg/g of total anthocyanins. Following administration of a single oral BHcL treatment, there were no treatment-related mortalities, changes in body weight (bw) or organ weight, clinical signs, necropsy or histopathological findings up to 2,000 mg/kg bw, the limited dosage for rodents of both sexes. We concluded that BHcL is a practically non-toxic material in toxicity potency. PMID:25874034

Investigation of radial dose effect on single event upset cross-section due to heavy ions using GEANT4

International Nuclear Information System (INIS)

Boorboor, S.; Feghhi, S.A.H.; Jafari, H.

2015-01-01

The heavy ions are the main cause to produce single event upset (SEU) damage on electronic devices since they are high LET radiations. The dimension of electronic components in new technology, arise a challenge in radiation effect estimations. Accurate investigations require fully considering the ion track in energy deposition as a radial dose distribution. In this work, the distribution of delta rays as well as LET have been calculated to determine ionization structure around ion track by a Monte Carlo code, GEANT4. The radial dose of several heavy ions with different energy in silicon was investigated and compared with the works by other authors in this field. The results showed that heavy ions with identical LET can have different SEU cross-section in silicon transistors. As a demonstrative example, according to our results, the error probability for 4.8 GeV iron was 8 times greater than that for 15 MeV carbon ions, in transistors with new process technology which have small dimension and low critical charges. Our results show that considering radial dose distribution considerably improves the accuracy of the SEU cross-section estimation in electronic devices especially for new technologies. - Highlights: • The single event upset is produced by heavy ions interaction on electronic devices. • The radial dose of several heavy ions in silicon was calculated by GEANT4. • Heavy ions with identical LET had different SEU cross-section in silicon transistors. • Low dimension and critical charge devices were more sensitive to radial dose effect

Dose-effect relationship for cataract induction after single-dose total body irradiation and bone marrow transplantation for acute leukemia

International Nuclear Information System (INIS)

Kempen-Harteveld, M. Loes van; Belkacemi, Yazid; Kal, Henk B.; Labopin, Myriam; Frassoni, Francesco

2002-01-01

Purpose: To determine a dose-effect relationship for cataract induction, the tissue-specific parameter, α/β, and the rate of repair of sublethal damage, μ value, in the linear-quadratic formula have to be known. To obtain these parameters for the human eye lens, a large series of patients treated with different doses and dose rates is required. The data of patients with acute leukemia treated with single-dose total body irradiation (STBI) and bone marrow transplantation (BMT) collected by the European Group for Blood and Marrow Transplantation were analyzed. Methods and Materials: The data of 495 patients who underwent BMT for acute leukemia, who had STBI as part of their conditioning regimen, were analyzed using the linear-quadratic concept. The end point was the incidence of cataract formation after BMT. Of the analyzed patients, 175 were registered as having cataracts. Biologic effective doses (BEDs) for different sets of values for α/β and μ were calculated for each patient. With Cox regression analysis, using the overall chi-square test as the parameter evaluating the goodness of fit, α/β and μ values were found. Risk factors for cataract induction were the BED of the applied TBI regimen, allogeneic BMT, steroid therapy for >14 weeks, and heparin administration. To avoid the influence of steroid therapy and heparin on cataract induction, patients who received steroid or heparin treatment were excluded, leaving only the BED as a risk factor. Next, the most likely set of α/β and μ values was obtained. With this set, the cataract-free survival rates were calculated for specific BED intervals, according to the Kaplan-Meier method. From these calculations, cataract incidences were obtained as function of the BED at 120 months after STBI. Results: The use of BED instead of the TBI dose enabled the incidence of cataract formation to be predicted in a reasonably consistent way. With Cox regression analysis for all STBI data, a maximal chi-square value was

Single-Dose Azithromycin for the Treatment of Haemophilus ducreyi Skin Ulcers in Papua New Guinea.

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González-Beiras, Camila; Kapa, August; Vall-Mayans, Marti; Paru, Raymond; Gavilán, Sergi; Houinei, Wendy; Bieb, Sibauk; Sanz, Sergi; Martins, Rosario; Mitjà, Oriol

2017-11-29

Haemophilus ducreyi (HD) and Treponema pallidum subspecies pertenue (TP) are major causative agents of cutaneous ulcer (CU) in the tropics. Azithromycin is recommended to treat sexually transmitted HD infections and has good in vitro activity against HD strains from both genital and skin ulcers. We investigated the efficacy of oral single-dose azithromycin on HD-CU. We conducted a community-based cohort study in Lihir Island, Papua New Guinea, from October 2014 through May 2016. Consenting patients with skin ulcers >1 cm in diameter were eligible for this study and had collected a lesional swab for polymerase chain reaction (PCR). All participants were treated with single-dose azithromycin (30 mg/kg) and were followed up for assessment of clinical resolution. We retrospectively classified patients according to PCR results into HD, TP, and PCR-negative groups. The primary endpoint was healing rates of HD-CU at 14 days after treatment. We obtained full outcome data from 246 patients; 131 (53.3%) were HD PCR positive, 37 (15.0%) were TP positive, and 78 (31.7%) were negative for all tests. Healing rates were 88.5% (95% confidence interval [CI], .82-.93) in the HD group, 78.4% [95% CI, .63-.89] in the TP group, and 74.4% (95% CI, .64-.83) in the PCR-negative group. If we included the participants with improved ulcers, the healing rates increased to 94.7%, 97.3%, and 89.7% respectively. HD cases classified as not healed all converted to HD-negative PCR. Based upon clinical resolution and PCR conversion to HD negative, a single oral dose of azithromycin is efficacious for the treatment of HD-CU. These results have implications for the treatment of individual patients and for the use of antibiotics in public health strategies to control CU in the tropics. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Optimal timing and frequency of bone marrow soup therapy for functional restoration of salivary glands injured by single-dose or fractionated irradiation.

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Fang, Dongdong; Shang, Sixia; Liu, Younan; Bakkar, Mohammed; Sumita, Yoshinori; Seuntjens, Jan; Tran, Simon D

2018-02-01

Injections of bone marrow (BM) cell extract, known as 'BM soup', were previously reported to mitigate ionizing radiation (IR) injury to salivary glands (SGs). However, the optimal starting time and frequency to maintain BM soup therapeutic efficacy remains unknown. This study tested the optimal starting time and frequency of BM soup injections in mice radiated with either a single dose or a fractionated dose. First, BM soup treatment was started at 1, 3 or 7 weeks post-IR; positive (non-IR) and negative (IR) control mice received injections of saline (vehicle control). Second, BM soup-treated mice received injections at different frequencies (1, 2, 3 and 5 weekly injections). Third, a 'fractionated-dose radiation' model to injure mouse SGs was developed (5 Gy × 5 days) and compared with the single high dose radiation model. All mice (n = 65) were followed for 16 weeks post-IR. The results showed that starting injections of BM soup between 1 and 3 weeks mitigated the effect of IR-induced injury to SGs and improved the restoration of salivary function. Although the therapeutic effect of BM soup lessens after 8 weeks, it can be sustained by increasing the frequency of weekly injections. Moreover, both single-dose and fractionated-dose radiation models are efficient and comparable in inducing SG injury and BM soup treatments are effective in restoring salivary function in both radiation models. In conclusion, starting injections of BM soup within 3 weeks post-radiation, with 5 weekly injections, maintains 90-100% of saliva flow in radiated mice. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of a Single Dose of Dextromethorphan on Psychomotor Performance and Working Memory Capacity

OpenAIRE

Al-Kuraishy, Hayder M.; Al-Gareeb, Ali I.; Ashor, Ammar Waham

2012-01-01

Background: Previous studies show that the prolonged use of dextromethorphan produces cognitive deterioration in humans. Aim: The aim of this study was to investigate the effect of a single dose of dextroemthrophan on psychomotor performance and working memory capacity. Materials and Methods: This is a randomized, double-blind, controlled, and prospective study. Thirty-six (17 women, 19 men) medical students enrolled in the study; half of them (7 women, 11 men) were given placebo, while the o...

Liposomal bupivacaine as a single-injection peripheral nerve block: a dose-response study.

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Ilfeld, Brian M; Malhotra, Nisha; Furnish, Timothy J; Donohue, Michael C; Madison, Sarah J

2013-11-01

Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration of fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. There were statistically significant dose responses in MVIC (0.09%/mg, SE = 0.03, 95% confidence interval [CI], 0.04-0.14, P = 0.002) and tolerance to cutaneous current (-0.03 mA/mg, SE = 0.01, 95% CI, -0.04 to -0.02, P 40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 hours in 100% of subjects (95% CI, 56%-100%). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI, 54%-100%). Motor block duration was not correlated with bupivacaine dose (0.06 hour/mg, SE = 0.14, 95% CI, -0.27 to 0.39, P = 0.707). The results of this investigation suggest that deposition of a liposomal bupivacaine formulation adjacent to the femoral nerve results in a partial sensory and motor block of >24 hours for the highest doses examined. However, the high variability of block magnitude among subjects and inverse relationship of dose and response magnitude attests to the need for a phase 3 study with a far larger sample size, and that these results should be viewed as suggestive, requiring confirmation in a future trial.

Single dose silodosin prior to voiding cystourethrogram: a pharmacological adjunct to enhance visualization of posterior urethra.

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Nagathan, Deepak Sharanappa; Dalela, Divakar; Sankhwar, Satyanarayan; Goel, Apul; Dwivedi, Amod Kumar; Yadav, Rahul

2014-03-04

Voiding cystourethrogram (VCUG) is needed to ascertain the upper end of urethral stricture. Occasionally, a patient is unable to open the bladder neck with resultant failure of the test. Realizing the strong and prompt alpha antagonistic action of silodosin, we evaluated single 8 mg dose as a pharmacological adjunct prior to VCUG to overcome this problem.

Cyclosporine promotes the induction of thymic lymphomas in C57BL/6 mice initiated by a single dose of γ-radiation

International Nuclear Information System (INIS)

Yabu, Koji; Warty, V.S.; Gorelik, E.; Shinozuka, Hisashi

1991-01-01

We previously demonstrated that a single dose of γ-radiation (350 rads) was able to induce thymic lymphomas in C57BL mice when followed by promoting treatment with oral cyclosporine (CsA), a non-genotoxic immunosuppressant. We have now tested the efficacy of various doses of γ-radiation as an initiator of CsA promotion of the induction of thymic lymphomas in male C57BL mice. The effects of oral CsA on the splenic natural killer (NK) cell activity of non-irradiated and irradiated (400 rads, 1X) mice were tested by the standard 51 Cr release assays against YAC-1 cells. The cumulative incidence of thymic lymphomas induced by a single dose of γ-radiation at 100, 200, 400 and 600 rads were 10, 25, 63 and 75% respectively, after 42 weeks of CsA promotion. The splenic NK cell activity in non-irradiated mice given CsA for 4 weeks was twice as high as that in the control mice. CsA inhibited poly I:C-induced augmentation of the splenic NK cell activity. In mice given a single dose (400 rads) of γ-radiation and CsA for 4 weeks, a similar but reduced enhancement of the splenic NK cell activity as seen in non-irradiated mice was observed. These results indicate that the efficacy of CsA promotion in the induction of thymic lymphomas is dependent on the initiating doses of γ-radiation, and that CsA enhances host splenic NK cell activity during the early stage of tumor promotion. (author)

Assessment of coverage levels of single dose measles vaccine

International Nuclear Information System (INIS)

Tariq, P.

2003-01-01

Objective: To study the consequences of low coverage levels of a single dose of measles vaccine. Results: mean age observed in measles cases was 2 years and 8 months with a range from 3 months to 8 years. Maximum number of cases reported were <1 year of age (n=22,32%). Fifty percent of cases were seen among vaccinated children. Seventy-five percent (n=51) had history of contact with a measles case. Pneumonia was the commonest complication followed by acute gastroenteritis, encephalitis, febrile convulsions, oral ulcers, oral thrush, eye changes of vitamin-A deficiency and pulmonary tuberculosis (T.B.) in descending order of frequency. Fifty four cases were successfully treated for complications of measles and discharged. Nine cases left against medical advice. Five patients died all of them had encephalitis either alone (n=1) or in combination with pneumonia and acute gastroenteritis (n=4). Conclusion: There is a dire need to increase the immunization coverage to reduce the rate of vaccine failure and achieve effective control of measles.(author)

Multifaceted empathy of healthy volunteers after single doses of MDMA: A pooled sample of placebo-controlled studies.

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Kuypers, Kim Pc; Dolder, Patrick C; Ramaekers, Johannes G; Liechti, Matthias E

2017-05-01

Previous placebo-controlled experimental studies have shown that a single dose of MDMA can increase emotional empathy in the multifaceted empathy test (MET) without affecting cognitive empathy. Although sufficiently powered to detect main effects of MDMA, these studies were generally underpowered to also validly assess contributions of additional parameters, such as sex, drug use history, trait empathy and MDMA or oxytocin plasma concentrations. The present study examined the robustness of the MDMA effect on empathy and investigated the moderating role of these additional parameters. Participants ( n = 118) from six placebo-controlled within-subject studies and two laboratories were included in the present pooled analysis. Empathy (MET), MDMA and oxytocin plasma concentrations were assessed after oral administration of MDMA (single dose, 75 or 125 mg). Trait empathy was assessed using the interpersonal reactivity index. We confirmed that MDMA increased emotional empathy at both doses without affecting cognitive empathy. This MDMA-related increase in empathy was most pronounced during presentation of positive emotions as compared with negative emotions. MDMA-induced empathy enhancement was positively related to MDMA blood concentrations measured before the test, but independent of sex, drug use history and trait empathy. Oxytocin concentrations increased after MDMA administration but were not associated with behavioral effects. The MDMA effects on emotional empathy were stable across laboratories and doses. Sex did not play a moderating role in this effect, and oxytocin levels, trait empathy and drug use history were also unrelated. Acute drug exposure was of significant relevance in the MDMA-induced emotional empathy elevation.

Ketamine as an Adjunct to Postoperative Pain Management in Opioid Tolerant Patients After Spinal Fusions: A Prospective Randomized Trial

OpenAIRE

Urban, Michael K.; Ya Deau, Jacques T.; Wukovits, Barbara; Lipnitsky, Jane Y.

2007-01-01

Management of acute postoperative pain is challenging, particularly in patients with preexisting narcotic dependency. Ketamine has been used at subanesthetic doses as a N-methyl d-aspartate (NMDA) receptor antagonist to block the processing of nociceptive input in chronic pain syndromes. This prospective randomized study was designed to assess the use of ketamine as an adjunct to acute pain management in narcotic tolerant patients after spinal fusions. Twenty-six patients for 1–2 level poster...

Safe and Effective Use of the Once Weekly Dulaglutide Single-Dose Pen in Injection-Naïve Patients With Type 2 Diabetes.

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Matfin, Glenn; Van Brunt, Kate; Zimmermann, Alan G; Threlkeld, Rebecca; Ignaut, Debra A

2015-04-21

This 4-week, phase 3b, multicenter, open-label, single-arm, outpatient study demonstrated the safe and effective use of the dulaglutide single-dose pen containing 0.5 mL of placebo for subcutaneous injection in injection-naïve adult patients with type 2 diabetes (T2D), with A1C ≤ 8.5% (69 mmol/mol), BMI ≥ 23 kg/m2 and ≤ 45 kg/m(2). Patients completed a modified self-injecting subscale of the Diabetes Fear of Injecting and Self-Testing Questionnaire (mD-FISQ) and were trained to self-inject with the single-dose pen. Patients completed the initial self-injection at the site, injected at home for 2 subsequent weeks, and returned to the site for the final injection. The initial and final self-injections were evaluated for success; the final (initial) self-injection success rate was the primary (secondary) outcome measure, and the primary (secondary) objective was to demonstrate this success rate as being significantly greater than 80%. Patients recorded their level of pain after each injection. After the final injection, patients completed the mD-FISQ and the Medication Delivery Device Assessment Battery (MDDAB) to assess their perceptions of the single-dose pen, including ease of use and experience with the device. Among 211 patients (mean age: 61 years), the primary objective was met, with a final injection success rate of 99.1% (95% CI: 96.6% to 99.7%). Among 214 patients, the initial injection success rate was 97.2% (95% CI: 94.0% to 98.7%), meeting the key secondary objective. Overall, most patients (>96%) found the device easy to use, were satisfied with the device, and would be willing to continue to use the single-dose pen after the study. There was a significant reduction (P injecting, as measured by the mD-FISQ. The dulaglutide single-dose pen was found to be a safe and effective device for use by patients with T2D who were injection-naïve. A positive injection experience is an important factor for patients and providers when initiating injectable

Single dose systemic acetaminophen to improve patient reported quality of recovery after ambulatory segmental mastectomy: A prospective, randomized, double-blinded, placebo controlled, clinical trial.

Science.gov (United States)

De Oliveira, Gildasio S; Rodes, Meghan E; Bialek, Jane; Kendall, Mark C; McCarthy, Robert J

2017-11-15

Few systemic drug interventions are efficacious to improve patient reported quality of recovery after ambulatory surgery. We aimed to evaluate whether a single dose systemic acetaminophen improve quality of recovery in female patients undergoing ambulatory breast surgery. We hypothesized that patients receiving a single dose systemic acetaminophen at the end of the surgical procedure would have a better global quality of postsurgical recovery compared to the ones receiving saline. The study was a prospective randomized double blinded, placebo controlled, clinical trial. Healthy female subjects were randomized to receive 1 g single dose systemic acetaminophen at the end of the surgery or the same volume of saline. The primary outcome was the Quality of Recovery 40 (QOR-40) questionnaire at 24 hours after surgery. Other data collected included opioid consumption and pain scores. Data were analyzed using group t tests and the Wilcoxon exact test. The association between opioid consumption and quality of recovery was evaluated using Spearman rho. P quality of recovery, P = .007. A single dose of systemic acetaminophen improves patient reported quality of recovery after ambulatory breast surgery. The use of systemic acetaminophen is an efficacious strategy to improve patient perceived quality of postsurgical recovery and analgesic outcomes after hospital discharge for ambulatory breast surgery. © 2017 Wiley Periodicals, Inc.

Synthetic CT: Simulating low dose single and dual energy protocols from a dual energy scan

International Nuclear Information System (INIS)

Wang, Adam S.; Pelc, Norbert J.

2011-01-01

Purpose: The choice of CT protocol can greatly impact patient dose and image quality. Since acquiring multiple scans at different techniques on a given patient is undesirable, the ability to predict image quality changes starting from a high quality exam can be quite useful. While existing methods allow one to generate simulated images of lower exposure (mAs) from an acquired CT exam, the authors present and validate a new method called synthetic CT that can generate realistic images of a patient at arbitrary low dose protocols (kVp, mAs, and filtration) for both single and dual energy scans. Methods: The synthetic CT algorithm is derived by carefully ensuring that the expected signal and noise are accurate for the simulated protocol. The method relies on the observation that the material decomposition from a dual energy CT scan allows the transmission of an arbitrary spectrum to be predicted. It requires an initial dual energy scan of the patient to either synthesize raw projections of a single energy scan or synthesize the material decompositions of a dual energy scan. The initial dual energy scan contributes inherent noise to the synthesized projections that must be accounted for before adding more noise to simulate low dose protocols. Therefore, synthetic CT is subject to the constraint that the synthesized data have noise greater than the inherent noise. The authors experimentally validated the synthetic CT algorithm across a range of protocols using a dual energy scan of an acrylic phantom with solutions of different iodine concentrations. An initial 80/140 kVp dual energy scan of the phantom provided the material decomposition necessary to synthesize images at 100 kVp and at 120 kVp, across a range of mAs values. They compared these synthesized single energy scans of the phantom to actual scans at the same protocols. Furthermore, material decompositions of a 100/120 kVp dual energy scan are synthesized by adding correlated noise to the initial material

A Pilot Study on Single-dose Toxicity Testing of Scolopendrid Pharmacopuncture in Sprague-Dawley Rats

Directory of Open Access Journals (Sweden)

Ilhong Son

2014-06-01

Full Text Available Objectives:This study was performed to analyze single dose toxicity and the lethal dose of Scolopendrid Pharmacopuncture in rats. Methods:All experiments were conducted at the Korea Testing & Research Institute (KTR, an institution authorized to perform non-clinical studies, under the regulations of Good Laboratory Practice (GLP. Sprague-Dawley rats were chosen for the pilot study. Doses of Scolopendrid pharmacopuncture, 0.1, 0.5, and 1.0 mL, were administered to the experimental group, and 1.0 mL doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethic Committee. Results:No deaths or abnormalities occurred in any of the groups. No significant changes in the weight, hematological parameters or clinical chemistry were noted between the control group and the experimental group. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion:The above findings suggest Scolopendrid Pharmacopuncture is a relatively safe to use for treatment. Further studies on the subject should be conducted to yield more concrete evidence.

Antimalarial iron chelator, FBS0701, shows asexual and gametocyte Plasmodium falciparum activity and single oral dose cure in a murine malaria model.

Directory of Open Access Journals (Sweden)

Patricia Ferrer

Full Text Available Iron chelators for the treatment of malaria have proven therapeutic activity in vitro and in vivo in both humans and mice, but their clinical use is limited by the unsuitable absorption and pharmacokinetic properties of the few available iron chelators. FBS0701, (S3"-(HO-desazadesferrithiocin-polyether [DADFT-PE], is an oral iron chelator currently in Phase 2 human studies for the treatment of transfusional iron overload. The drug has very favorable absorption and pharmacokinetic properties allowing for once-daily use to deplete circulating free iron with human plasma concentrations in the high µM range. Here we show that FBS0701 has inhibition concentration 50% (IC(50 of 6 µM for Plasmodium falciparum in contrast to the IC(50 for deferiprone and deferoxamine at 15 and 30 µM respectively. In combination, FBS0701 interfered with artemisinin parasite inhibition and was additive with chloroquine or quinine parasite inhibition. FBS0701 killed early stage P. falciparum gametocytes. In the P. berghei Thompson suppression test, a single dose of 100 mg/kg reduced day three parasitemia and prolonged survival, but did not cure mice. Treatment with a single oral dose of 100 mg/kg one day after infection with 10 million lethal P. yoelii 17XL cured all the mice. Pretreatment of mice with a single oral dose of FBS0701 seven days or one day before resulted in the cure of some mice. Plasma exposures and other pharmacokinetics parameters in mice of the 100 mg/kg dose are similar to a 3 mg/kg dose in humans. In conclusion, FBS0701 demonstrates a single oral dose cure of the lethal P. yoelii model. Significantly, this effect persists after the chelator has cleared from plasma. FBS0701 was demonstrated to remove labile iron from erythrocytes as well as enter erythrocytes to chelate iron. FBS0701 may find clinically utility as monotherapy, a malarial prophylactic or, more likely, in combination with other antimalarials.

Universal Survival Curve and Single Fraction Equivalent Dose: Useful Tools in Understanding Potency of Ablative Radiotherapy

International Nuclear Information System (INIS)

Park, Clint; Papiez, Lech; Zhang Shichuan; Story, Michael; Timmerman, Robert D.

2008-01-01

Purpose: Overprediction of the potency and toxicity of high-dose ablative radiotherapy such as stereotactic body radiotherapy (SBRT) by the linear quadratic (LQ) model led to many clinicians' hesitating to adopt this efficacious and well-tolerated therapeutic option. The aim of this study was to offer an alternative method of analyzing the effect of SBRT by constructing a universal survival curve (USC) that provides superior approximation of the experimentally measured survival curves in the ablative, high-dose range without losing the strengths of the LQ model around the shoulder. Methods and Materials: The USC was constructed by hybridizing two classic radiobiologic models: the LQ model and the multitarget model. We have assumed that the LQ model gives a good description for conventionally fractionated radiotherapy (CFRT) for the dose to the shoulder. For ablative doses beyond the shoulder, the survival curve is better described as a straight line as predicted by the multitarget model. The USC smoothly interpolates from a parabola predicted by the LQ model to the terminal asymptote of the multitarget model in the high-dose region. From the USC, we derived two equivalence functions, the biologically effective dose and the single fraction equivalent dose for both CFRT and SBRT. Results: The validity of the USC was tested by using previously published parameters of the LQ and multitarget models for non-small-cell lung cancer cell lines. A comparison of the goodness-of-fit of the LQ and USC models was made to a high-dose survival curve of the H460 non-small-cell lung cancer cell line. Conclusion: The USC can be used to compare the dose fractionation schemes of both CFRT and SBRT. The USC provides an empirically and a clinically well-justified rationale for SBRT while preserving the strengths of the LQ model for CFRT

Efficacy and safety of a single oral 150 mg dose of fluconazole for the treatment of vulvovaginal candidiasis in Japan.

Science.gov (United States)

Mikamo, Hiroshige; Matsumizu, Miyako; Nakazuru, Yoshiomi; Okayama, Akifumi; Nagashima, Masahito

2015-07-01

Vulvovaginal candidiasis is the second most common cause of vaginal infections following bacterial vaginosis. For the treatment of vulvovaginal candidiasis, antifungal agents are used either as topical (vaginal tablets and cream) or oral formulations. A single oral 150 mg dose of fluconazole has been recommended as the standard therapy for uncomplicated, acute vulvovaginal candidiasis in global guidelines; however, in Japan oral fluconazole therapy has not been approved. We conducted a phase 3 study to evaluate the efficacy and safety of a single oral 150 mg dose of fluconazole in Japanese subjects with vulvovaginal candidiasis for regulatory submission. A total of 157 subjects received a single oral 150 mg dose of fluconazole. Candida species (104 strains) were identified by fungal culture from 102 subjects at baseline, including Candida albicans (100 strains). The efficacy rate for the therapeutic outcome (assessed based on a comprehensive evaluation of the clinical and mycological efficacy in each subject) was 74.7% (74/99) on Day 28 in the modified Intent-To-Treat (m-ITT) population. Concerning the clinical and mycological efficacy on Day 28 in the m-ITT population, the cure, cure or improvement, and eradication rates were 81.6%, 95.9%, and 85.9%, respectively. The most common treatment-related adverse events were diarrhea and nausea (1.9% for each). No clinically significant safety issues were reported. A single oral 150 mg dose of fluconazole demonstrated excellent therapeutic efficacy and was well tolerated in Japanese subjects with vulvovaginal candidiasis. NCT01806623. Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Absorption, Distribution, and Excretion of 14C-APX001 after Single-Dose Administration to Rats and Monkeys

Science.gov (United States)

Mansbach, Robert; Shaw, Karen J; Hodges, Michael R; Coleman, Samantha; Fitzsimmons, Michael E

2017-01-01

Abstract Background APX001 is a small-molecule therapeutic agent in clinical development for the treatment of invasive fungal infections (IFI). Methods The absorption, distribution and excretion profiles of [14C]APX001-derived radioactivity were determined in rats (albino and pigmented) and monkeys. Rats (some implanted with bile duct cannulae) were administered a single 100 mg/kg oral dose or a 30 mg/kg intravenous (IV) dose. Monkeys were administered a single 6 mg/kg IV dose. Samples of blood, urine, feces and bile, as well as carcasses, were collected through 168 hours after dosing. Samples were analyzed for total radioactivity content by liquid scintillation counting, and carcasses were analyzed by quantitative whole-body autoradiography. Results [14C]APX001-derived radioactivity was rapidly and extensively absorbed and extensively distributed to most tissues for both routes of administration in both species. In rats, tissues with the highest radioactivity Cmax values included bile, abdominal fat, reproductive fat, subcutaneous fat, and liver, but radioactivity was also detected in tissues associated with IFI, including lung, brain and eye. In monkeys, the highest Cmax values were in bile, urine, uveal tract, bone marrow, abdominal fat, liver, and kidney cortex. Liver and kidney were the tissues with highest radioactivity, but as in the rat, radioactivity was also detected in lung, brain and eye tissues. In pigmented rats, radiocarbon was densely distributed into pigmented tissue and more slowly cleared than from other tissues. Mean recovery of radioactivity in rats was approximately 95–100%. In bile duct-intact rats, >90% of radioactivity was recovered in feces. In cannulated rats, biliary excretion of radioactivity was the major route of elimination and accounted for 88.8% of the dose, whereas urinary and fecal excretion of radioactivity was minor and accounted for 2.56% and 5.42% of the dose, respectively. In monkeys, the overall recovery of radioactivity

Hepatitis A vaccine. A new convenient single-dose schedule with booster when long-term immunization is warranted

DEFF Research Database (Denmark)

Victor, J; Knudsen, J D; Nielsen, L P

1994-01-01

A total of 162 anti-HAV-negative healthy adults were immunized with a single high dose (1440 ELISA units = 1 ml) of inactivated hepatitis A vaccine and a booster was given at month 6. Antibodies were measured after modification of a commercial ELISA kit, enabling quantification of titres down to 6...

Dose-to-dose variations with single packages of counterfeit medicines and adulterated dietary supplements as a potential source of false negatives and inaccurate health risk assessments.

Science.gov (United States)

Venhuis, B J; Zwaagstra, M E; Keizers, P H J; de Kaste, D

2014-02-01

In this report, we show three examples of how the variability in dose units in single packages of counterfeit medicines and adulterated dietary supplements may contribute to a false negative screening result and inaccurate health risk assessments. We describe a counterfeit Viagra 100mg blister pack and a box of an instant coffee both containing dose units with and without an active pharmaceutical ingredient (API). We also describe a purportedly herbal slimming product with capsules that mutually differed in API and impurities. The adulterated dietary supplements contained sibutramine, benzyl-sibutramine, N-desmethyl-sibutramine (DMS), N,N-didesmethyl-sibutramine (DDMS) and several other related impurities. Counterfeit medicines and adulterated dietary supplements are a health risk because their quality is unreliable. Health risks are even greater when such unreliability extends to fundamental differences between dose units in one package. Because dose-to-dose variability for these products is unpredictable, the confidence interval of a sample size is unknown. Consequently, the analyses of a selection of dose units may not be representative for the package. In the worst case, counterfeit or unauthorised medicines are not recognised as such or a health risk is not identified. In order to reduce erroneous results particular care should be taken when analysing a composite of dose units, when finding no API in a dietary supplement and when finding conformity in a suspect counterfeit medicine. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of a single high dose of 55Fe in mice

International Nuclear Information System (INIS)

Laissue, J.A.; Burlington, H.; Cronkite, E.P.; Heldman, B.; Reincke, U.

1979-01-01

High doses of 55 Fe induced cytocide in maturing erythroid cells, due to the short-range deposition of decay energy. Organ damage at the time of death was evaluated in a group of 45 female mice of the C 57 BL/6 J strain given a single i.v. injection of 2,800 μCi, 1,400 μCi or 700 μCi of 55 FeCl 3 when 10 to 14 weeks old. A corresponding amount of cold iron was given to control animals by the same route. Radioiron-treated mice died spontaneously, or were killed when moribund. Mice given 2,800 μCi died after a median survival time of 27 days with severe depletion of hemopoietic cells in bone marrow and spleen, marked atrophy of lymphoid tissues and mild liver damage. After 1,400 μCi or 700 μCi, the median survival time was 117 and 439, respectively. In contrast, median survival was 847 days in control animals allowed to survive. In the two lower 55 Fe-dose groups, there was a dose-dependent pancytopenia. Atrophy of lymphoid tissues was moderate, and signs of liver damage slight. The degree of organ hemosiderosis in experimental and control animals was slight to moderate. Organ damage associated with deposition of cold iron was not apparent in tissue sections. Morphological signs of damage to non-hemopoietic organs such as the liver were not conspicuous. Direct radiation damage, primarily to the erythroid series, and competition for stem cells between the heavily depleted erythroid and the other hemopoietic cell lines must be considered among the possible factors leading to pancytopenia. Out of 14 55 Fe-treated mice who survived longer than 300 days developed tumors of hemopoietic and lymphoid tissues, or osteosarcomas. (orig./MG) [de

Single-dose brachytherapy versus metal stent placement for the palliation of dysphagia from oesophageal cancer: multicentre randomised trial

NARCIS (Netherlands)

Homs, Marjolein Y. V.; Steyerberg, Ewout W.; Eijkenboom, Wilhelmina M. H.; Tilanus, Hugo W.; Stalpers, Lukas J. A.; Bartelsman, Joep F. W. M.; van Lanschot, Jan J. B.; Wijrdeman, Harm K.; Mulder, Chris J. J.; Reinders, Janny G.; Boot, Henk; Aleman, Berthe M. P.; Kuipers, Ernst J.; Siersema, Peter D.

2004-01-01

Background Both single-dose brachytherapy and self-expanding metal stent placement are commonly used for palliation of oesophageal obstruction due to inoperable cancer, but their relative merits are unknown. We under-took a randomised trial to compare the outcomes of brachytherapy and stent

Single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone after arthroscopic knee surgery: a meta-analysis of randomized controlled trials.

Science.gov (United States)

Yang, Ye; Zeng, Chao; Wei, Jie; Li, Hui; Yang, Tuo; Deng, Zhen-Han; Li, Yu-Sheng; Yang, Tu-Bao; Lei, Guang-Hua

2017-03-01

The purpose of this meta-analysis was to compare the efficacy and safety of single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone for pain management following arthroscopic knee surgery. A comprehensive literature search was conducted to identify randomized controlled trials that used single-dose intra-articular bupivacaine plus morphine and bupivacaine alone for post-operative pain, using MEDLINE (1966-2014), Cochrane Library and EMBASE databases. The weighted mean difference (WMD), relative risk (RR) and their corresponding 95 % confidence intervals (CIs) were calculated using RevMan statistical software. A total of twenty-nine trials (n = 1167) were included. The post-operative visual analog scale (VAS) pain score of the bupivacaine plus morphine group compared with the bupivacaine alone group was significantly lower (WMD -1.15, 95 % CI -1.67 to -0.63, p bupivacaine plus morphine was shown to be significantly better than bupivacaine alone at relieving post-operative pain after arthroscopic knee surgery without increasing the short-term side effects. Routine use of single-dose intra-articular bupivacaine plus morphine is an effective way for pain management after arthroscopic knee surgery. II.

Randomized trial of single dose versus fractionated palliative radiotherapy of bone metastases

International Nuclear Information System (INIS)

Nielsen, O.S.; Bentzen, S.M.; Sandberg, E.; Gadeberg, C.C.; Timothy, A.R.

1998-01-01

Purpose: Data in the literature suggest that for painful bone metastases a single dose is as effective as fractionated radiotherapy. In the present multicentre prospective trial, the effects of 8 Gy x1 and 5 Gy x4 were compared. Patients and methods: A total of 241 patients were randomized to 8 Gy (122 patients) or 20 Gy (119 patients). The primary tumour was in the breast in 39% of patients, in the prostate in 34% of patients, in the lung in 13% of patients and in other locations in 14% of patients. Outcome measures were pain relief as measured by VAS and in half of the patients also by a five-point categorical pain scale, global quality of life (QoL) and analgesic consumption. Evaluation was performed before and 4, 8, 12 and 20 weeks after treatment. Results: A total of 239 patients were evaluable for response. The two groups did not differ with respect to age, sex, primary tumour, metastasis localization, analgesic consumption (type and dose), performance status, prior systemic treatment, degree of pain and QoL. The treatment was completed as planned in 98% of patients. The degree of pain relief did not differ between the two treatment groups. At 4 weeks the difference in pain relief was 6% (95% CI 7, 20%) and at 8 weeks the difference was 13% (95% CI 3, 28%). Neither was there any significant difference in the duration of pain relief, the number of new painful sites and the need for reirradiation and toxicity was minor. Conclusion: The present randomized study showed that a single fraction of 8 Gy was as effective as 5 Gy x4 in relieving pain from bone metastasis. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Macroscopic, pathologic and immunologic investigations of ten patients with carcinoma of oral cavity treated by a single large dose irradiation

International Nuclear Information System (INIS)

Mikuriya, Shuichi; Saito, Tsutomu; Konoeda, Koichi; Igarashi, Seishi; Hirohashi, Hitoshi

1979-01-01

The immunosuppressive effect of radiation has been emphasized. Although the irradiated cancer cells die gradually during the treatment, it is understood that they keep cancer specific antigenecity in that process. Another words, we assume that the immunologic capacity participates in the dying process of cancer cells by radiotherapy. We have been preferring to treat carcinoma by a single large dose irradiation method because this method does not impair the patient's immunologic capacity. On this time, we treated ten patients with carcinoma of oral cavity by this method and could obtain favorable results. 1) Ten patients with carcinoma of oral cavity classified in T1N0M0-T3N0M0 were irradiated by 4 - 10 MeV betatron electron. In seven patients, 2,500 - 3,000 rads were given at once and other three patients were irradiated with fractionated dose of 1,000 rads three times within two weeks (total 3,000 rads per two weeks). 2) Effects of a single large dose irradiation were remarkable and almost all cancer cells in these patients disappeared both macroscopically and pathologically. 3) According to the results of cellular immunity tests, numbers of peripheral lymphocytes, absolute numbers of fractionated T and B cells, and blastoid formation rate of lymphocytes stimulated by PHA in vitro were all increased and values obtained by four kinds of skin tests were also elevated after the radiations. These results indicate that the single large dose irradiation for these patients does not impair the immunologic capacity of the patients. (author)

A randomized treatment trial: single versus 7-day dose of metronidazole for the treatment of Trichomonas vaginalis among HIV-infected women.

Science.gov (United States)

Kissinger, Patricia; Mena, Leandro; Levison, Judy; Clark, Rebecca A; Gatski, Megan; Henderson, Harold; Schmidt, Norine; Rosenthal, Susan L; Myers, Leann; Martin, David H

2010-12-15

To determine if the metronidazole (MTZ) 2-gm single dose (recommended) is as effective as the 7-day 500 mg twice a day dose (alternative) for treatment of Trichomonas vaginalis (TV) among HIV+ women. Phase IV randomized clinical trial; HIV+ women with culture confirmed TV were randomized to treatment arm: MTZ 2-gm single dose or MTZ 500 mg twice a day 7-day dose. All women were given 2-gm MTZ doses to deliver to their sex partners. Women were recultured for TV at a test-of-cure (TOC) visit occurring 6-12 days after treatment completion. TV-negative women at TOC were again recultured at a 3-month visit. Repeat TV infection rates were compared between arms. Two hundred seventy HIV+/TV+ women were enrolled (mean age = 40 years, ±9.4; 92.2% African American). Treatment arms were similar with respect to age, race, CD4 count, viral load, antiretroviral therapy status, site, and loss-to-follow up. Women in the 7-day arm had lower repeat TV infection rates at TOC [8.5% (11 of 130) versus 16.8% (21 of 125) (relative risk: 0.50, 95% confidence interval = 0.25, 1.00; P TV among HIV+ women.

Development of γ dose rate monitor based on FPGA and single-chip microcomputer

International Nuclear Information System (INIS)

He Zhiguo; Ling Qiu; Guo Lanying; Yang Binhua

2009-01-01

A novelγdose rate monitor with multiple channels signal collection in which takes the FPGA as the core process chip and single-chip microcomputer as the data processor had been developed. This paper introduced the communication interface design between FPGA and MCU, and gave the data acquisition module and the function simulation chart designed by FPGA. In addition, the software and hardware design diagrams of MCU had been given in this paper. The maximum digitallization was carried on in the designing process. The experiments showed that the scheme for the system matched to the requests completely. (authors)

Patch test dose-response study: polysensitized individuals do not express lower elicitation thresholds than single/double-sensitized individuals

DEFF Research Database (Denmark)

Carlsen, B C; Fischer, Louise Arup; Sosted, H

2009-01-01

with nickel sulphate, methyldibromo glutaronitrile (MDBGN) and p-phenylenediamine (PPD) in dilution series. The ratio between the doses eliciting a response in 50% of patients in the two groups was used as the measure for relative sensitivity. RESULTS: The dose-response curves of the polysensitized group...... for MDBGN and PPD were shifted to the right, and for nickel sulphate shifted to the left, compared with the single/double-sensitized group. The relative sensitivity for each of the three allergens and a combined relative sensitivity for all three allergens were not significantly different when comparing...

Bolus dose response characteristics of single chain urokinase plasminogen activator and tissue plasminogen activator in a dog model of arterial thrombosis.

Science.gov (United States)

Badylak, S F; Voytik, S; Klabunde, R E; Henkin, J; Leski, M

1988-11-15

Tissue plasminogen activator (t-PA) and single chain urokinase-plasminogen activator (scu-PA) are relatively "fibrin-specific" thrombolytic drugs with short plasma half lives of 6-8 minutes. Most treatment regimens with these agents utilize a bolus injection followed by continuous drug infusion, usually combined with anticoagulant therapy. The purpose of this study was to establish the dose-response characteristics for scu-PA and t-PA, when given as a single intravenous bolus injection, in a dog model of arterial thrombosis. Eight groups of 6 dogs each were given one of the following doses of scu-PA (mg/kg): 0.20, 0.50, 1.00, 2.00; or t-PA: 0.05, 0.10, 0.20; or an equivalent amount of saline (control group). All doses were given as a single bolus injection 60 minutes after formation of a totally occlusive femoral artery thrombus. Thrombolysis was measured by monitoring the continuous decrement of 125I activity from a radiolabelled thrombus. Ninety minutes after drug injection, all scu-PA treated dogs showed greater thrombolysis (30%, 45%, 56%, and 67%, respectively) than the control group (15%, p less than 0.01). The 0.10 and 0.20 mg/kg t-PA treated dogs showed greater thrombolysis (35% and 49%, respectively) than the control group (15%, p less than 0.01). Both scu-PA and t-PA caused a partial and dose-dependent decrease in alpha 2-antiplasmin activity but scu-PA caused a greater depletion (72% vs. 18%, respectively, p less than 0.05) at 60 minutes after the highest dose of drug administration. Both drugs showed a longer than expected thrombolytic effect based upon the known half lives. Neither drug caused significant changes in the prothrombin time, activated partial thromboplastin time, thrombin time, hematocrit, platelet count, or fibrin degradation product concentration. Single bolus injections of scu-PA and t-PA produce safe and effective thrombolysis in this dog model of arterial thrombosis.

Radiation dose levels in pediatric chest CT: experience in 499 children evaluated with dual-source single-energy CT

Energy Technology Data Exchange (ETDEWEB)

Martine, Remy-Jardin; Colas, Lucie; Jean-Baptiste, Faivre; Remy, Jacques [CHU Lille (EA 2694) University of Lille, Department of Thoracic Imaging, Hospital Calmette, Lille (France); Santangelo, Teresa [CHU Lille (EA 2694) University of Lille, Department of Thoracic Imaging, Hospital Calmette, Lille (France); Bambino Gesu Children' s Hospital, Department of Imaging, Rome (Italy); Duhamel, Alain [University of Lille (EA 2694), Department of Biostatistics, CHU Lille, Lille (France); Deschildre, Antoine [CHU Lille - University of Lille, Department of Pediatric Pulmonology, Lille (France)

2017-02-15

The availability of dual-source technology has introduced the possibility of scanning children at lower kVp with a high-pitch mode, combining high-speed data acquisition and high temporal resolution. To establish the radiation dose levels of dual-source, single-energy chest CT examinations in children. We retrospectively recorded the dose-length product (DLP) of 499 consecutive examinations obtained in children <50 kg, divided into five weight groups: group 1 (<10 kg, n = 129); group 2 (10-20 kg, n = 176); group 3 (20-30 kg, n = 99), group 4 (30-40 kg, n = 58) and group 5 (40-49 kg, n = 37). All CT examinations were performed with high temporal resolution (75 ms), a high-pitch mode and a weight-adapted selection of the milliamperage. CT examinations were obtained at 80 kVp with a milliamperage ranging between 40 mAs and 90 mAs, and a pitch of 2.0 (n = 162; 32.5%) or 3.0 (n = 337; 67.5%). The mean duration of data acquisition was 522.8 ± 192.0 ms (interquartile range 390 to 610; median 490). In the study population, the mean CT dose index volume (CTDIvol{sub 32}) was 0.83 mGy (standard deviation [SD] 0.20 mGy; interquartile range 0.72 to 0.94; median 0.78); the mean DLP{sub 32} was 21.4 mGy.cm (SD 9.1 mGy.cm; interquartile range 15 to 25; median 19.0); and the mean size-specific dose estimate (SSDE) was 1.7 mGy (SD 0.4 mGy; interquartile range 1.5 to 1.9; median 1.7). The DLP{sub 32}, CTDI{sub vol32} and SSDE were found to be statistically significant in the five weight categories (P < 0.0001). This study establishes the radiation dose levels for dual-source, single-kVp chest CT from a single center. In the five weight categories, the median values varied 15-37 mGy.cm for the DLP{sub 32}, 0.78-1.25 mGy for the CTDI{sub vol32} and 1.6-2.1 mGy for the SSDE. (orig.)

Radiation dose levels in pediatric chest CT: experience in 499 children evaluated with dual-source single-energy CT

International Nuclear Information System (INIS)

Martine, Remy-Jardin; Colas, Lucie; Jean-Baptiste, Faivre; Remy, Jacques; Santangelo, Teresa; Duhamel, Alain; Deschildre, Antoine

2017-01-01

The availability of dual-source technology has introduced the possibility of scanning children at lower kVp with a high-pitch mode, combining high-speed data acquisition and high temporal resolution. To establish the radiation dose levels of dual-source, single-energy chest CT examinations in children. We retrospectively recorded the dose-length product (DLP) of 499 consecutive examinations obtained in children <50 kg, divided into five weight groups: group 1 (<10 kg, n = 129); group 2 (10-20 kg, n = 176); group 3 (20-30 kg, n = 99), group 4 (30-40 kg, n = 58) and group 5 (40-49 kg, n = 37). All CT examinations were performed with high temporal resolution (75 ms), a high-pitch mode and a weight-adapted selection of the milliamperage. CT examinations were obtained at 80 kVp with a milliamperage ranging between 40 mAs and 90 mAs, and a pitch of 2.0 (n = 162; 32.5%) or 3.0 (n = 337; 67.5%). The mean duration of data acquisition was 522.8 ± 192.0 ms (interquartile range 390 to 610; median 490). In the study population, the mean CT dose index volume (CTDIvol 32 ) was 0.83 mGy (standard deviation [SD] 0.20 mGy; interquartile range 0.72 to 0.94; median 0.78); the mean DLP 32 was 21.4 mGy.cm (SD 9.1 mGy.cm; interquartile range 15 to 25; median 19.0); and the mean size-specific dose estimate (SSDE) was 1.7 mGy (SD 0.4 mGy; interquartile range 1.5 to 1.9; median 1.7). The DLP 32 , CTDI vol32 and SSDE were found to be statistically significant in the five weight categories (P < 0.0001). This study establishes the radiation dose levels for dual-source, single-kVp chest CT from a single center. In the five weight categories, the median values varied 15-37 mGy.cm for the DLP 32 , 0.78-1.25 mGy for the CTDI vol32 and 1.6-2.1 mGy for the SSDE. (orig.)

Fosfomycin trometamol: a review of its use as a single-dose oral treatment for patients with acute lower urinary tract infections and pregnant women with asymptomatic bacteriuria.

Science.gov (United States)

Keating, Gillian M

2013-11-01

Fosfomycin trometamol (fosfomycin tromethamine) [Monuril(®), Monurol(®), Monural(®)] is approved in numerous countries worldwide, mainly for the treatment of uncomplicated urinary tract infections (UTIs). Fosfomycin has good in vitro activity against common uropathogens, such as Escherichia coli (including extended-spectrum β-lactamase-producing E. coli), Proteus mirabilis, Klebsiella pneumoniae and Staphylococcus saprophyticus, and the susceptibility of uropathogens to fosfomycin has remained relatively stable over time. A single oral dose of fosfomycin trometamol 3 g (the approved dosage) achieves high concentrations in urine. Results of recent randomized trials indicate that single-dose fosfomycin trometamol had similar clinical and/or bacteriological efficacy to 3- to 7-day regimens of ciprofloxacin, norfloxacin, cotrimoxazole or nitrofurantoin in women with uncomplicated lower UTIs. In addition, single-dose fosfomycin trometamol had similar bacteriological efficacy to a 5-day course of cefuroxime axetil or a 7-day course of amoxicillin/clavulanic acid in pregnant women with asymptomatic bacteriuria, and similar clinical and/or bacteriological efficacy to a 5-day course of cefuroxime axetil or amoxicillin/clavulanic acid or a 3-day course of ceftibuten in pregnant women with a lower UTI. Single-dose fosfomycin trometamol was generally well tolerated, with gastrointestinal adverse events (e.g. diarrhoea, nausea) reported most commonly. In conclusion, single-dose fosfomycin trometamol is an important option for the first-line empirical treatment of uncomplicated lower UTIs.

Implication of fractionated dose exposures in therapeutic gain

International Nuclear Information System (INIS)

Kim, Hye-Jin; Lee, Min-Ho; Kim, Eun-Hee

2016-01-01

Radiation therapy pursues killing tumor cells while sparing normal cells from the radiation exposure. Stereotactic radiosurgery (SRS) is a cancer treatment modality that delivers a high dose in a single operation. This high-dose single operation shortens the treatment course, but can increase the risk of normal cell damage. Normal cell damage can be reduced by employing multi-directional exposures for an increasing number of isocenters. In this study, we investigated whether therapeutic benefits would be expected by employing new dose fractionation patterns at a high-dose single operation. The conventional single-dose operation in brain tumor radiosurgery is performed by delivering fractionated uniform doses. According to Figs. 2 and 3, the conventional radiosurgery might have obtained some therapeutic benefit by employing the fractionated uniform-dose exposures instead of a single-dose exposure. We suggest that further therapeutic gain be expected by employing the fractionated radiation exposures in an increasing dose pattern. Until ensuring our suggestion, the significance in gain of cell surviving should be verified for all three dose patterns with both normal and tumor cells. The investigation whether normal and tumor cells show the same responses to the fractionated dose exposures at lower and higher than 15 Gy of total dose is also reserved for future work

Single Ascending Dose Safety and Pharmacokinetics of CDRI-97/78: First-in-Human Study of a Novel Antimalarial Drug

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N. Shafiq

2014-01-01

Full Text Available Background. CDRI 97/78 has shown efficacy in animal models of falciparum malaria. The present study is the first in-human phase I trial in healthy volunteers. Methods. The study was conducted in 50 healthy volunteers in a single, ascending dose, randomized, placebo-controlled, double blind design. The dose ranges evaluated were from 80 mg to 700 mg. Volunteers were assessed for clinical, biochemical, haematological, radiographic, and electrocardiographic parameters for any adverse events in an in-house facility. After evaluation of safety study results, another cohort of 16 participants were administered a single oral dose of 200 mg of the drug and a detailed pharmacokinetic analysis was undertaken. Results. The compound was found to be well tolerated. MTD was not reached. The few adverse events noted were of grade 2 severity, not requiring intervention and not showing any dose response relationship. The laboratory and electrocardiographic parameters showed statistically significant differences, but all were within the predefined normal range. These parameters were not associated with symptoms/signs and hence regarded as clinically irrelevant. Mean values of T1/2, MRT, and AUC0-∞ of the active metabolite 97/63 were 11.85±1.94 h, 13.77±2.05 h, and 878.74±133.15 ng·h/mL, respectively Conclusion. The novel 1,2,4 trioxane CDRI 97/78 is safe and will be an asset in malarial therapy if results are replicated in multiple dose studies and benefit is shown in confirmatory trials.

Pharmacokinetics of a single oral dose of vitamin D3 (70,000 IU in pregnant and non-pregnant women

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Roth Daniel E

2012-12-01

Full Text Available Abstract Background Improvements in antenatal vitamin D status may have maternal-infant health benefits. To inform the design of prenatal vitamin D3 trials, we conducted a pharmacokinetic study of single-dose vitamin D3 supplementation in women of reproductive age. Methods A single oral vitamin D3 dose (70,000 IU was administered to 34 non-pregnant and 27 pregnant women (27 to 30 weeks gestation enrolled in Dhaka, Bangladesh (23°N. The primary pharmacokinetic outcome measure was the change in serum 25-hydroxyvitamin D concentration over time, estimated using model-independent pharmacokinetic parameters. Results Baseline mean serum 25-hydroxyvitamin D concentration was 54 nmol/L (95% CI 47, 62 in non-pregnant participants and 39 nmol/L (95% CI 34, 45 in pregnant women. Mean peak rise in serum 25-hydroxyvitamin D concentration above baseline was similar in non-pregnant and pregnant women (28 nmol/L and 32 nmol/L, respectively. However, the rate of rise was slightly slower in pregnant women (i.e., lower 25-hydroxyvitamin D on day 2 and higher 25-hydroxyvitamin D on day 21 versus non-pregnant participants. Overall, average 25-hydroxyvitamin D concentration was 19 nmol/L above baseline during the first month. Supplementation did not induce hypercalcemia, and there were no supplement-related adverse events. Conclusions The response to a single 70,000 IU dose of vitamin D3 was similar in pregnant and non-pregnant women in Dhaka and consistent with previous studies in non-pregnant adults. These preliminary data support the further investigation of antenatal vitamin D3 regimens involving doses of ≤70,000 IU in regions where maternal-infant vitamin D deficiency is common. Trial registration ClinicalTrials.gov (NCT00938600

Single-dose, subcutaneous recombinant phenylalanine ammonia lyase conjugated with polyethylene glycol in adult patients with phenylketonuria: an open-label, multicentre, phase 1 dose-escalation trial.

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Longo, Nicola; Harding, Cary O; Burton, Barbara K; Grange, Dorothy K; Vockley, Jerry; Wasserstein, Melissa; Rice, Gregory M; Dorenbaum, Alejandro; Neuenburg, Jutta K; Musson, Donald G; Gu, Zhonghua; Sile, Saba

2014-07-05

Phenylketonuria is an inherited disease caused by impaired activity of phenylalanine hydroxylase, the enzyme that converts phenylalanine to tyrosine, leading to accumulation of phenylalanine and subsequent neurocognitive dysfunction. Phenylalanine ammonia lyase is a prokaryotic enzyme that converts phenylalanine to ammonia and trans-cinnamic acid. We aimed to assess the safety, tolerability, pharmacokinetic characteristics, and efficacy of recombinant Anabaena variabilis phenylalanine ammonia lyase (produced in Escherichia coli) conjugated with polyethylene glycol (rAvPAL-PEG) in reducing phenylalanine concentrations in adult patients with phenylketonuria. In this open-label, phase 1, multicentre trial, single subcutaneous injections of rAvPAL-PEG were given in escalating doses (0·001, 0·003, 0·010, 0·030, and 0·100 mg/kg) to adults with phenylketonuria. Participants aged 18 years or older with blood phenylalanine concentrations of 600 μmol/L or higher were recruited from among patients attending metabolic disease clinics in the USA. The primary endpoints were safety and tolerability of rAvPAL-PEG. Secondary endpoints were the pharmacokinetic characteristics of the drug and its effect on concentrations of phenylalanine. Participants and investigators were not masked to assigned dose group. This study is registered with ClinicalTrials.gov, number NCT00925054. 25 participants were recruited from seven centres between May 6, 2008, and April 15, 2009, with five participants assigned to each escalating dose group. All participants were included in the safety population. The most frequently reported adverse events were injection-site reactions and dizziness, which were self-limited and without sequelae. Two participants had serious adverse reactions to intramuscular medroxyprogesterone acetate, a drug that contains polyethylene glycol as an excipient. Three of five participants given the highest dose of rAvPAL-PEG (0·100 mg/kg) developed a generalised skin rash

Single Enteral Loading Dose of Phenobarbital for Achieving Its Therapeutic Serum Levels in Neonates

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Turhan, Ali H.; Atici, Aytug; Okuyaz, Cetin; Uysal, Sercan

2010-01-01

Aim To investigate whether therapeutic serum drug levels may be achieved with a single enteral loading dose of phenobarbital. Methods The study was performed at the Mersin University Hospital in Turkey between April 2004 and August 2006, and included 29 newborn babies with seizure. After the acute treatment of the seizure with midazolam at a dose of 0.1 mg/kg, phenobarbital was administered by orogastric route at a loading dose of 20 mg/kg. Serum phenobarbital concentrations were measured at 0.5, 3, 6, and 12 hours after the loading. Serum phenobarbital levels between 10-30 μg/mL were considered as the therapeutic range. Results The serum phenobarbital levels reached therapeutic values in 9 (31%), 19 (66%), 21 (72%), and 23 (79%) patients at 0.5, 3, 6, and 12 hours after loading, respectively, while they did not reach therapeutic values in 6 patients (21%) after 12 hours. Four of the patients in whom there was no increase in serum phenobarbital levels had hypoxic-ischemic encephalopathy. Conclusion Enteral loading of phenobarbital can achieve therapeutic serum levels in the large majority of newborn babies with seizure and may be safely used in babies with the intact gastrointestinal tract. PMID:20564764

The atypical excretion profile of meldonium: Comparison of urinary detection windows after single- and multiple-dose application in healthy volunteers.

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Görgens, Christian; Guddat, Sven; Bosse, Christina; Geyer, Hans; Pop, Valentin; Schänzer, Wilhelm; Thevis, Mario

2017-05-10

Following a one-year monitoring program providing unequivocal analytical evidence for a high prevalence in international elite sports, meldonium has been included in the World Anti-Doping Agency's (WADA) list of prohibited substances that came into effect on 1 January 2016. Despite of the polar and hydrophilic nature of the molecule, an unusual long detection window was observed in pilot elimination studies. Consequently, in the present study, urinary excretion profiles after single-dose (5 volunteers, 1×500mg) and multiple-dose oral application (5 volunteers; 2×500mg/day for 6days) were determined in order to facilitate the result management concerning meldonium findings in doping controls. Particularly the option to differentiate between recent use and tapering concentrations was studied. Urinary meldonium concentrations were determined using an analytical approach based on hydrophilic interaction liquid chromatography and high resolution tandem mass spectrometry. The study corroborates the hypothesis of a non-linear, dose-depended and biphasic excretion profile after oral application of meldonium and demonstrates that urinary detection windows are of considerable extent with up to 65 and 117days (concentrations>LOQ of 10ng/mL) following single- and multiple-dose applications, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Successful comeback of the single-dose live oral cholera vaccine CVD 103-HgR.

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Herzog, Christian

2016-01-01

Effective and easy to administer cholera vaccines are in need more than ever, for at risk populations and travellers alike. In many parts of the world cholera is still endemic, causing outbreaks and constituting repeatedly serious public health problems. The oral live cholera vaccine CVD 103-HgR (Orochol, Mutachol), the first genetically modified organism (GMO) used as vaccine, was in its time (launched 1993, Switzerland) the ideal cholera vaccine: single-dose, protective efficacy of 80-100% against moderate to severe cholera, acting within 8 days and exhibiting excellent safety, indiscernible from placebo. However, there were strong headwinds: In the 1990s the indication for cholera vaccines was generally downplayed by experts and in 1997 the European Commission called for a moratorium of GMOs which blocked the registration in the European Union. Thus, demand for this vaccine remained low and in 2003 it was taken off the market for economic reasons. After a decade in obscurity it (Vaxchora) has resurfaced again, now produced in the U.S. and equipped with a U.S. FDA license (June 10, 2016). What had happened? This commentary gives a critical account of an almost unbelievable string of misadventures, emerging adverse circumstances and man-made failures which nearly killed this single-dose live oral cholera vaccine. The good news is that patience and persistence lead to success in the end, allowing good science to prevail for the benefit of those in need. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of immune persistence among inactivated and live attenuated hepatitis a vaccines 2 years after a single dose

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Zhang, Xiaoshu; An, Jing; Tu, Aixia; Liang, Xuefeng; Cui, Fuqiang; Zheng, Hui; Tang, Yu; Liu, Jianfeng; Wang, Xuxia; Zhang, Ningjing; Li, Hui

2016-01-01

ABSTRACT Objective: Compare immune persistence from one dose of each of 3 different hepatitis A vaccines when given to school-age children: a domestic, live attenuated hepatitis A vaccine (H2 vaccine); a domestic inactivated hepatitis A vaccine (Healive®); and an imported, inactivated hepatitis A vaccine (Havrix®),.Methods: School-age children were randomized into 1 of 4 groups to receive a single dose of a vaccine: H2 vaccine, Healive®, Havrix®, or hepatitis B vaccine [control]. Serum samples were collected 12 and 24 months after vaccination for measurement of anti-HAV IgG using microparticle enzyme immunoassay. Seropositivity was defined as ≥ 20 mUI/ml. We compared groups on seropositivity and geometric mean concentration (GMC). Results: Seropositive rates for the H2, Healive®, Havrix®, and control groups were 64%, 94.4%, 73%, and 1.0%, respectively, 12-months post-vaccination; and 63%, 95.6%, 72%, and 1.0%, respectively 24-months post-vaccination. Seropositivity was greater for Healive® than for H2 and Havrix® at 12 months (p-values a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine. PMID:27494260

Evaluation of Geometrically Optimized Single- and Double-plane Interstitial High Dose Rate Implants with Respect to Conformality and Homogeneity

International Nuclear Information System (INIS)

Major, Tibor; Polgar, Csaba; Fodor, Janos; Takacsi-nagy, Zoltan; Mangel, Laszlo; Nemeth, Gyoergy

2003-01-01

The use of a stepping source in high dose rate brachytherapy supported with dwell-time optimization makes it possible to deviate from the classical dosimetry systems. Dose distributions of single- and double-plane implants were analysed for conformality and homogeneity at idealized target volumes. The Paris system was used for catheter positioning and target volume determination. Geometric optimization and individual dose prescription were applied. Volumetric indices and dose parameters were calculated at optimal active length, which was found to be equal to target volume length. The mean conformality, homogeneity, external volume and overdose volume indices were 0.78, 0.67, 0.22 and 0.13, respectively. The average minimum target and reference doses were 69% and 86%, respectively. Comparisons between the volumetric indices of geometrical optimized and non-optimized implants were also performed, and a significant difference was found regarding any index. The geometrical optimization resulted in superior conformality and slightly inferior homogeneity. At geometrically optimized implants, the active length can be reduced compared to non-optimized implants. Volumetric parameters and dose-volume histogram-based individual dose prescription are recommended for quantitative assessment of interstitial implants

Neighborhood-targeted and case-triggered use of a single dose of oral cholera vaccine in an urban setting: Feasibility and vaccine coverage.

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Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S

2017-06-01

In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

The Global Programme to Eliminate Lymphatic Filariasis: History and achievements with special reference to annual single-dose treatment with diethylcarbamazine in Samoa and Fiji.

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Kimura, Eisaku

2011-03-01

Diethylcarbamazine (DEC), first introduced in 1947, was shown to have strong efficacy and safety for treatment of human lymphatic filariasis, which is caused mostly by a species Wuchereria bancrofti. Many studies to optimize the dosage and treatment schedule of DEC followed, and, based on the results, control programs with various regimens were implemented in different endemic areas/countries. By the mid 1970s, with endorsement by the WHO Expert Committee on Filariasis (3rd report, 1974), the standard DEC regimen for W. bancrofti infection in mass treatment had been established in principle: a total dose of 72 mg/kg of body weight given in 12 divided doses, once weekly or monthly, at 6 mg/kg each. Not long after the committee report, the efficacy of annual single-dose treatment at 6 mg/kg, which is only one twelfth of the WHO-recommended dose in a year, was reported effective in French Polynesia (study period: 1973-78), and later in Samoa (study period: 1979-81). These results were published between 1978 and 1985 in the Bulletin of WHO but received little attention. In the mid 1980s, the efficacy of ivermectin, the first-choice drug for onchocerciasis, against lymphatic filariae came to light. Since the effect at a single dose was remarkable, and often better than DEC, it was predicted that the newly introduced drug would replace DEC. Treatment experiments with ivermectin increased quickly in number. Meanwhile, annual single-dose mass drug administration (MDA) with DEC at 6 mg/kg was under scrutiny in Samoa and Fiji. In the early 1990s, the Samoan study, which covered the entire population of 160,000 with 3 annual MDAs, reported a significant reduction in microfilaria (mf) prevalence and mean mf density, while in Fiji, the efficacy of 5 rounds of annual MDA (total dose, 30 mg/kg) was shown to be as effective as 28 multi-dose MDA spread over 2 years (6 weekly plus 22 monthly treatments at 5 mg/kg; total dose, 140 mg/kg). Several additional studies carried out in

Sustained Antibody Responses 6 Years Following 1, 2, or 3 Doses of Quadrivalent Human Papillomavirus (HPV) Vaccine in Adolescent Fijian Girls, and Subsequent Responses to a Single Dose of Bivalent HPV Vaccine: A Prospective Cohort Study.

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Toh, Zheng Quan; Russell, Fiona M; Reyburn, Rita; Fong, James; Tuivaga, Evelyn; Ratu, Tupou; Nguyen, Cattram D; Devi, Rachel; Kama, Mike; Matanitobua, Silivia; Tabrizi, Sepehr N; Garland, Suzanne M; Sinha, Rohit; Frazer, Ian; Tikoduadua, Lisi; Kado, Joseph; Rafai, Eric; Mulholland, Edward K; Licciardi, Paul V

2017-04-01

The duration of antibody response following reduced human papillomavirus (HPV) vaccine doses has not been determined. We compared the antibody responses in girls previously vaccinated with zero, 1, 2, or 3 doses of quadrivalent HPV vaccine (4vHPV; Gardasil, Merck) 6 years previously. A prospective cohort study was undertaken in 200 Fijian girls 15-19 years of age. Approximately equal numbers of girls from 2 main ethnic groups (Fijians of Indian descent [FID] and Indigenous Fijians [iTaukei]) in Fiji were recruited for each dosage groups. Blood was drawn before and 28 days following a single dose of bivalent HPV vaccine (2vHPV; Cervarix, GlaxoSmithKline). We measured neutralizing antibodies (NAb) against HPV-6, -11, -16, and -18 using the pseudovirion-based neutralization assay. After 6 years (before a dose of 2vHPV was given), the geometric mean NAb titers for all 4 HPV types were not statistically different between 2-dose (2D) and 3-dose (3D) recipients: HPV-6 (3D: 2216 [95% confidence interval {CI},1695-2896]; 2D: 1476 [95% CI, 1019-2137]; P = .07), HPV-11 (3D: 4431 [95% CI, 3396-5783]; 2D: 2951 [95% CI, 1984-4390]; P = .09), HPV-16 (3D: 3373 [95% CI, 2511-4530]; 2D: 3275 [95% CI, 2452-4373]; P = .89); HPV-18 (3D: 628 [95% CI: 445-888]; 2D: 606 [95% CI, 462-862]; P = .89), and were higher in FID than iTaukei girls. Although 1-dose recipients had significantly lower NAb titers than 2-/3-dose recipients, their NAb titers were 5- to 30-fold higher than unvaccinated girls. Post-2vHPV NAb titers against HPV-16 and -18 were not statistically different between girls who received 1, 2, or 3 doses of 4vHPV previously. Two doses of 4vHPV provide similar NAb titers as 3 doses for 6 years, although the clinical significance is unknown. A single dose of 4vHPV elicits antibodies that persisted for at least 6 years, and induced immune memory, suggesting possible protection against HPV vaccine types after a single dose of 4vHPV. © The Author 2016. Published by Oxford University

Comparative assessment of efficacy of two different pretreatment single oral doses of betamethasone on inter-appointment and postoperative discomfort: An in vivo clinical evaluation.

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Gyanani, Hitesh; Chhabra, Naveen; Parmar, Ghanshyam R

2016-01-01

Study aimed to evaluate the efficacy of two different pretreatment single oral doses of betamethasone on the incidence of inter-appointment flare up and postoperative discomfort. Fifty-four patients aged 18-59 years requiring endodontic treatment were selected and randomly assigned to three groups; single pretreatment oral dose of placebo or betamethasone in two different oral doses of 0.5 mg and 1 mg, respectively. Endodontic therapy was completed in two visits using triple antibiotic paste as intracanal medicament. Patients were given a questionnaire to record their pain at 1, 2, 3, and 7 days after treatment. In the second visit, obturation was done, and the patients were again instructed to record their pain scores after treatment and discharged. The verbal rating scale was used for recording the pain scores. Statistical analysis was done using ANOVA and the Friedman test. 0.5 mg betamethasone group showed least mean pain scores among all experimental groups; however, there was no statistically significant difference between any of the groups ( P > 0.05). Pretreatment single oral dose of betamethasone is an effective in managing endodontic flare-ups; however, the results were statistically insignificant.

Radiation-induced heart disease due to intrathonacic tumor radiotherapy of a single dose to the rabbits' heart

International Nuclear Information System (INIS)

Zhou Weibing; Feng Yan; Chen Jiayi; Luo Quanyong

2007-01-01

Objective: To observe the changes of radiation-induced heart disease (RIHD) in the rabbits irradiated in clinical related dose, and to evaluate the apoptosis and hypoxia in the irradiated heart by the new scintigraphic agents of 99 Tc m -HL91 and 99 Tc m -Annexin V of heart SPECT. Methods: Tenty-four New Zealand white rabbits 4-month old and 2-3 kg by weight were divided into two groups. Group 1 (clinical related dose group): 16 irradiated by a single close from 0 to 18 Gy. Group 2 (high dose group): 8 irradiated dose from 22 to 80 Gy. The serum cTnI/CKMB, ECG, and heart SPECT(using 99 Tc m -MIBI, 99 Tc m -HL91 and 99 Tc m -Annexin V as agents) were detected before and after irradiation. The animals were followed for 5 months. Then biopsy of rabbit heart was performed and pathologic examination was made by H.E. stain. Results: In the 16 rabbits of clinical related dose group, none died of RIHD. Whereas 2 rabbits died of RIHD in the high dose group. One died of myocardial infarction and the other of congestive heart failure. According to the Stewart introduced heart lesion grading system, of the clinical close ann, there were moderate in 1 rabbit, minimal in 14; and of the high dose ann, it was severe in 2, marked in 1, moderate in 5. The parallel relation was observed between the ECG results and the pathological changes (χ 2 =0.08, P=0.771). Serum value of cTnI, was elevated at the 12th hour after irradiation reaching the peak and maintained for 4 months. However, it came down in the 5th month. The difference of serum cTnI value before and after radiation was statistically significant. Myocardial perfusion scintigraphy tested by heart SPECT ( 99 Tc m -MIBI) showed defects was present in all irradiated rabbits. The relationship between the defects and radiation dose or between the defects and the real RIHD was uncertain. The SPECT images displayed that 99 Tc m -HL91 and 99m Tc-Annexin V did not accumulate in the irradiated heart. Conclusions: No serious damage is

Pharmacokinetics of lansoprazole and its main metabolites after single intravenous doses in healthy Chinese subjects.

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Zhang, Dan; Yang, Man; Liu, Man; Zhang, Yanan; Wang, Xiaolin; Xiao, Xue; Liu, Huichen

2012-11-01

The aim of the study was to evaluate the pharmacokinetics (PK) of lansoprazole (LPZ) and its main metabolites 5'-hydroxy lansoprazole (HLPZ) and lansoprazole sulphone (LPZS) after single intravenous (i.v.) doses of LPZ in healthy Chinese subjects, and the relationship between the cytochrome P450 (CYP) 2C19 phenotypes and the plasma concentrations of LPZS at the time-points in the elimination phase of LPZ. Twelve subjects were given lansoprazole by i.v. infusion. Blood samples were collected at designated time points up to 24 h. Plasma concentrations of LPZ, HLPZ and LPZS were quantified by a selective and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. After single i.v. doses of 15, 30 and 60 mg LPZ, C(max) and area under the plasma concentration-time curve (AUC(0-t)) of LPZ were 725 ± 151, 1480 ± 190, 3130 ± 480 µg · L(-1) and 1690 ± 1210, 3630 ± 2530, 8080 ± 4550 µg · h · L(-1), respectively. LPZ was generally well tolerated in healthy Chinese subjects, and displayed linear PK in the range of 15-60 mg. There were significant differences in the elimination of LPZ and the formation of LPZS between the single CYP2C19 poor metabolizer (PM) and the CYP2C19 extensive metabolizers (EM). The concentration of LPZS at the time-points in the elimination phase of LPZ could be monitored for CYP2C19 phenotyping. As a probe drug for CYP2C19 phenotyping, LPZ for injection might be more suitable than LPZ oral formulations.

Estimating skin sensitization potency from a single dose LLNA.

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Roberts, David W

2015-04-01

Skin sensitization is an important aspect of safety assessment. The mouse local lymph node assay (LLNA) developed in the 1990 s is an in vivo test used for skin sensitization hazard identification and characterization. More recently a reduced version of the LLNA (rLLNA) has been developed as a means of identifying, but not quantifying, sensitization hazard. The work presented here is aimed at enabling rLLNA data to be used to give quantitative potency information that can be used, inter alia, in modeling and read-across approaches to non-animal based potency estimation. A probit function has been derived enabling estimation of EC3 from a single dose. This has led to development of a modified version of the rLLNA, whereby as a general principle the SI value at 10%, or at a lower concentration if 10% is not testable, is used to calculate the EC3. This version of the rLLNA has been evaluated against a selection of chemicals for which full LLNA data are available, and has been shown to give EC3 values in good agreement with those derived from the full LLNA. Copyright © 2015 Elsevier Inc. All rights reserved.

In vivo assessment of catheter positioning accuracy and prolonged irradiation time on liver tolerance dose after single-fraction 192Ir high-dose-rate brachytherapy

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Kropf Siegfried

2011-09-01

Full Text Available Abstract Background To assess brachytherapy catheter positioning accuracy and to evaluate the effects of prolonged irradiation time on the tolerance dose of normal liver parenchyma following single-fraction irradiation with 192 Ir. Materials and methods Fifty patients with 76 malignant liver tumors treated by computed tomography (CT-guided high-dose-rate brachytherapy (HDR-BT were included in the study. The prescribed radiation dose was delivered by 1 - 11 catheters with exposure times in the range of 844 - 4432 seconds. Magnetic resonance imaging (MRI datasets for assessing irradiation effects on normal liver tissue, edema, and hepatocyte dysfunction, obtained 6 and 12 weeks after HDR-BT, were merged with 3D dosimetry data. The isodose of the treatment plan covering the same volume as the irradiation effect was taken as a surrogate for the liver tissue tolerance dose. Catheter positioning accuracy was assessed by calculating the shift between the 3D center coordinates of the irradiation effect volume and the tolerance dose volume for 38 irradiation effects in 30 patients induced by catheters implanted in nearly parallel arrangement. Effects of prolonged irradiation were assessed in areas where the irradiation effect volume and tolerance dose volume did not overlap (mismatch areas by using a catheter contribution index. This index was calculated for 48 irradiation effects induced by at least two catheters in 44 patients. Results Positioning accuracy of the brachytherapy catheters was 5-6 mm. The orthogonal and axial shifts between the center coordinates of the irradiation effect volume and the tolerance dose volume in relation to the direction vector of catheter implantation were highly correlated and in first approximation identically in the T1-w and T2-w MRI sequences (p = 0.003 and p p = 0.001 and p = 0.004, respectively. There was a significant shift of the irradiation effect towards the catheter entry site compared with the planned dose

A parallel chiral-achiral liquid chromatographic method for the determination of the stereoisomers of ketamine and ketamine metabolites in the plasma and urine of patients with complex regional pain syndrome

OpenAIRE

Moaddel, Ruin; Venkata, Swarajya Lakshmi Vattem; Tanga, Mary J.; Bupp, James E.; Green, Carol E.; Iyer, Lalitha; Furimsky, Anna; Goldberg, Michael E.; Torjman, Marc C.; Wainer, Irving W.

2010-01-01

A parallel chiral/achiral LC-MS/MS assay has been developed and validated to measure the plasma and urine concentrations of the enantiomers of ketamine, (R)- and (S)-Ket, in Complex Regional Pain Syndrome (CRPS) patients receiving a 5-day continuous infusion of a sub-anesthetic dose of (R,S)-Ket. The method was also validated for the determination of the enantiomers of the Ket metabolites norketamine, (R)-and (S)-norKet and dehydronorketamine, (R)- and (S)-DHNK, as well as the diastereomeric ...

Safety-efficacy balance of S-ketamine and S-norketamine in acute and chronic pain

OpenAIRE

Noppers, Ingeborg Marieke

2011-01-01

The balance between safety and efficacy is important in pharmacotherapy. When the indication of a registered drug shifts to another disease or a different patient population, studies on safety and efficacy need to be performed. Ketamine is a relatively ‘old’ drug and used for almost 50 years as an anesthetic. Recently there has been a renewed interest for the treatment of therapy-resistant chronic pain with subanesthetic doses of ketamine. This thesis describes the effects of S-ketamine in pa...

Single-dose FTY720 pharmacokinetics, food effect, and pharmacological responses in healthy subjects

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Kovarik, John M; Schmouder, Robert; Barilla, Denise; Wang, Yibin; Kraus, Gerolf

2004-01-01

Aims FTY720 is a sphingosine-1-phosphate receptor agonist that redirects lymphocytes from the circulation to lymph nodes without impairing lymphocyte function. It is being developed as an immunomodulator for the prevention of acute rejection after organ transplantation. This study was performed to provide guidance on administration with respect to meals and to measure pharmacologic responses in healthy subjects. Methods In this randomized, two-period, crossover study, 14 healthy subjects received placebo on day −1 of each period with baseline circadian measurements of lymphocyte count and heart rate. Subjects subsequently received a single 1 mg oral dose of FTY720 on day 1 under fasting conditions and after a high fat meal. Blood FTY720 concentrations, lymphocyte count, and supine heart rate were assessed over an 8 day period after each FTY720 dose. The effect of food on FTY720 pharmacokinetics was assessed by standard bioequivalence testing. Results Both the peak concentration (0.65 ± 0.17 vs 0.64 ± 0.18 ng ml−1) and total exposure (AUC 149 ± 65 vs 139 ± 43 ng ml−1 h) did not differ significantly between fasting and fed states, respectively. The corresponding fed/fasting ratios and 90% confidence intervals were 1.00 (0.86, 1.17) for Cmax and 0.98 (0.86, 1.11) for AUC. Under both treatment conditions peripheral blood lymphocyte count decreased from baseline by 38 ± 9% over the first 2 days postdose and then increased towards predose values over the subsequent week. Whereas a circadian rhythm in supine heart rate was preserved in the presence of FTY720, the heart rate vs time curve was shifted downwards by 10% over the first day postdose and then recovered to prestudy values by days 3–5 postdose. These changes were asymptomatic. Conclusions Single 1 mg doses of FTY720 were well tolerated in healthy subjects and elicited a moderate decrease in peripheral blood lymphocyte count and a transient decrease in heart rate consistent with its pharmacological

Comparison of single-dose and multiple-dose antibiotics for lower urinary tract infection in pregnancy.

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Usta, Taner A; Dogan, Ozgur; Ates, Ugur; Yucel, Burak; Onar, Zehra; Kaya, Erdal

2011-09-01

To compare the efficacy of fosfomycin trometamol, cefuroxime axetil, and amoxicillin clavulanate antibiotics, and to assess the difference in patient compliance, in the treatment of urinary tract infections during pregnancy. Between September 2007 and May 2008, 90 out of 324 pregnant women with complaints of lower urinary tract infection, who were followed at the outpatient clinic or referred to the emergency department of Vakif Gureba Education and Research Hospital, were enrolled in a prospective study. Patients were randomized into 3 equal groups for treatment with single-dose fosfomycin trometamol, or 5-day courses of amoxicillin clavulanate or cefuroxime axetil. After follow-up, study data were obtained for 28, 27, and 29 patients, respectively. The treatment groups did not differ significantly in terms of demographics, clinical success rate, microbiological cure rate, or adverse effects. Significantly higher drug compliance was observed in the fosfomycin trometamol group than in the other 2 groups (PUTI as the standard course of treatment with amoxicillin clavulanate or cefuroxime axetil. Fosfomycin trometamol may be a preferable treatment for UTI because of its simpler use and better rates of compliance. Copyright © 2011 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Ketamine-Induced Changes in the Signal and Noise of Rule Representation in Working Memory by Lateral Prefrontal Neurons.

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Ma, Liya; Skoblenick, Kevin; Seamans, Jeremy K; Everling, Stefan

2015-08-19

Working memory dysfunction is an especially debilitating symptom in schizophrenia. The NMDA antagonist ketamine has been successfully used to model working memory deficits in both rodents and nonhuman primates, but how it affects the strength and the consistency of working memory representations remains unclear. Here we recorded single-neuron activity in the lateral prefrontal cortex of macaque monkeys before and after the administration of subanesthetic doses of ketamine in a rule-based working memory task. The rule was instructed with a color cue before each delay period and dictated the correct prosaccadic or antisaccadic response to a peripheral stimulus appearing after the delay. We found that acute ketamine injections both weakened the rule signal across all delay periods and amplified the trial-to-trial variance in neural activities (i.e., noise), both within individual neurons and at the ensemble level, resulting in impaired performance. In the minority of postinjection trials when the animals responded correctly, the preservation of the signal strength during the delay periods was predictive of their subsequent success. Our findings suggest that NMDA receptor function may be critical for establishing the optimal signal-to-noise ratio in information representation by ensembles of prefrontal cortex neurons. In schizophrenia patients, working memory deficit is highly debilitating and currently without any efficacious treatment. An improved understanding of the pathophysiology of this symptom may provide critical information to treatment development. The NMDA antagonist ketamine, when injected at a subanesthetic dose, produces working memory deficit and other schizophrenia-like symptoms in humans and other animals. Here we investigated the effects of ketamine on the representation of abstract rules by prefrontal neurons, while macaque monkeys held the rules in working memory before responding accordingly. We found that ketamine weakened the signal

Single-dose Live Oral Cholera Vaccine CVD 103-HgR Protects Against Human Experimental Infection With Vibrio cholerae O1 El Tor.

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Chen, Wilbur H; Cohen, Mitchell B; Kirkpatrick, Beth D; Brady, Rebecca C; Galloway, David; Gurwith, Marc; Hall, Robert H; Kessler, Robert A; Lock, Michael; Haney, Douglas; Lyon, Caroline E; Pasetti, Marcela F; Simon, Jakub K; Szabo, Flora; Tennant, Sharon; Levine, Myron M

2016-06-01

No licensed cholera vaccine is presently available in the United States. Cholera vaccines available in other countries require 2 spaced doses. A single-dose cholera vaccine that can rapidly protect short-notice travelers to high-risk areas and help control explosive outbreaks where logistics render 2-dose immunization regimens impractical would be a major advance.PXVX0200, based on live attenuated Vibrio cholerae O1 classical Inaba vaccine strain CVD 103-HgR, elicits seroconversion of vibriocidal antibodies (a correlate of protection) within 10 days of a single oral dose. We investigated the protection conferred by this vaccine in a human cholera challenge model. Consenting healthy adult volunteers, 18-45 years old, were randomly allocated 1:1 to receive 1 oral dose of vaccine (approximately 5 × 10(8) colony-forming units [CFU]) or placebo in double-blind fashion. Volunteers ingested approximately 1 × 10(5) CFU of wild-type V. cholerae O1 El Tor Inaba strain N16961 10 days or 3 months after vaccination and were observed on an inpatient research ward for stool output measurement and management of hydration. The vaccine was well tolerated, with no difference in adverse event frequency among 95 vaccinees vs 102 placebo recipients. The primary endpoint, moderate (≥3.0 L) to severe (≥5.0 L) diarrheal purge, occurred in 39 of 66 (59.1%) placebo controls but only 2 of 35 (5.7%) vaccinees at 10 days (vaccine efficacy, 90.3%; P < .0001) and 4 of 33 (12.1%) vaccinees at 3 months (vaccine efficacy, 79.5%; P < .0001). The significant vaccine efficacy documented 10 days and 3 months after 1 oral dose of PXVX0200 supports further development as a single-dose cholera vaccine. NCT01895855. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

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Wilhelmus, Micha Mm; Hay, Justin L; Zuiker, Rob Gja; Okkerse, Pieter; Perdrieu, Christelle; Sauser, Julien; Beaumont, Maurice; Schmitt, Jeroen; van Gerven, Joop Ma; Silber, Beata Y

2017-02-01

Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study.

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Maha M Eissa

Full Text Available Miltefosine (MFS is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD. This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%, good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs

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

DEFF Research Database (Denmark)

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

2016-01-01

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

Singlet oxygen and ROS in a new light: low-dose subcellular photodynamic treatment enhances proliferation at the single cell level.

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Blázquez-Castro, Alfonso; Breitenbach, Thomas; Ogilby, Peter R

2014-09-01

Two-photon excitation of a sensitizer with a focused laser beam was used to create a spatially-localized subcellular population of reactive oxygen species, ROS, in single HeLa cells. The sensitizer used was protoporphyrin IX, PpIX, endogenously derived from 5-aminolevulinic acid delivered to the cells. Although we infer that singlet oxygen, O2(a(1)Δg), is one ROS produced upon irradiation of PpIX under these conditions, it is possible that the superoxide ion, O2(-˙), may also play a role in this system. With a "high" dose of PpIX-sensitized ROS, the expected death of the cell was observed. However, under "low dose" conditions, clear signs of cell proliferation were observed. The present results facilitate studies of ROS-mediated signalling in imaging-based single cell experiments.

The effect of a single dose of morphine on muscle fatigue indices in male rats

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Sedigheh Amiresmaili

2016-09-01

Full Text Available Background and Aim: Endogenous opioids and addictive opiate drugs change many body functions. . Previous studies have referred to the effects of morphine on smooth and pulmonary muscles ., but the  effects of opioids on skeletal muscles is not known well. Thus, the current study aimed at assessing the effect of a single dose of morphine on muscle fatigue in male rats. Materials and Methods: In this experimental study, 40 male Wistar rats weighing 220-270 g were randomly divided into four equal groups: control (the mice were kept in their cages and received food and water, morphine receiving group, fatigue group (the mice in this group were kept running on  a treadmill . for120 minutes at a rate of 20 meters per minute, and morphine plus fatigue group. At the end of the experiments, blood samples were obtained from the corner of their eyes and were sent to the laboratory for measurement of muscle fatigue indexes including lactate dehydrogenase (LDH and creatine phosphokinase (CPK. Results: Administration of morphine to the fatigue group decreased running time compared with the control group (P=0.009. Furthermore, administration of morphine to the fatigue group significantly increased serum levels of LDH (P=0.009 and CPK (P=0.008. Conclusion: The present study showed that administration of a single dose of morphine in rats increases muscle fatigue biomarkers (LDH, CPK.

Long-term Dose Stability of OnabotulinumtoxinA Injection for Adductor Spasmodic Dysphonia: A 19-Year Single Institution Experience

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Paul Paddle

2017-11-01

Full Text Available ObjectivesAdductor spasmodic dysphonia (AdSD is a focal dystonia predominantly involving the laryngeal adductor muscles. AdSD is reported to be a largely non-progressive neurological disorder, though fluctuations in symptom severity do occur. Repeated laryngeal onabotulinumtoxinA (BTX-A injections are the primary management for AdSD. A number of studies have demonstrated long-term dose stability as evidence of this long-term disease stability.MethodsA retrospective review was performed on all patients undergoing BTX-A injections for AdSD from April 1994 to September 2013 by a single laryngologist at a tertiary referral laryngology center. Patient demographics, injection doses, use of diazepam and/or lidocaine, and self-reported vocal function were recorded. Multiple linear regression analyses were performed.Results83 patients underwent a total of 1,168 injections over 19 years. The mean starting dose was 2.35 MU (0.79 SD. The mean long-term dose was 2.36 MU (0.79 SD. After adjusting for confounders, the change in the relative dose of BTX-A, with every year elapsed since initial dose was 0.13% (95% confidence interval −0.31 to 0.57%, p = 0.568.ConclusionBTX-A dose is stable over time in our large cohort of patients treated with bilateral thyroarytenoid injections for AdSD.

GSK1265744 pharmacokinetics in plasma and tissue after single-dose long-acting injectable administration in healthy subjects.

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Spreen, William; Ford, Susan L; Chen, Shuguang; Wilfret, David; Margolis, David; Gould, Elizabeth; Piscitelli, Stephen

2014-12-15

GSK1265744 (744) is an HIV-1 integrase inhibitor in clinical development as a long-acting (LA) injectable formulation. This study evaluated plasma and tissue pharmacokinetics after single-dose administration of 744 LA administered by intramuscular (IM) or subcutaneous injections. This was a phase I, open-label, 9-cohort, parallel study of 744 in healthy subjects. 744 was administered as a 200 mg/mL nanosuspension at doses of 100-800 mg IM and 100-400 mg subcutaneous. Eight (6 active and 2 placebo) male and female subjects participated in each of the first 7 cohorts. All 8 subjects, 4 males and 4 females, received active 744 LA in cohorts 8 and 9 and underwent rectal and cervicovaginal tissue sampling, respectively. Plasma pharmacokinetic sampling was performed for a minimum of 12 weeks or until 744 concentrations were ≤0.1 μg/mL. Rectal and cervicovaginal tissue biopsies were performed at weeks 2 and 8 (cohort 8) and weeks 4 and 12 (cohort 9). 744 LA was generally safe and well tolerated after single injections. A majority of subjects reported injection site reactions, all graded as mild in intensity. Plasma concentration-time profiles were prolonged with measureable concentrations up to 52 weeks after dosing. 744 LA 800 mg IM achieved mean concentrations above protein adjusted-IC90 for approximately 16 weeks. Rectal and cervicovaginal tissue concentrations ranged from injection has potential application as a monthly or less frequent HIV treatment or prevention agent.

Randomized, open-label, single-dose, crossover, relative bioavailability study in healthy adults, comparing the pharmacokinetics of rabeprazole granules administered using soft food or infant formula as dosing vehicle versus suspension.

Science.gov (United States)

Thyssen, An; Solanki, Bhavna; Treem, William

2012-07-01

A sprinkle capsule formulation containing enteric-coated, delayed-release rabeprazole granules is being developed for the treatment of children with gastrointestinal reflux disease. The granules are designed to be mixed with vehicles that facilitate delivery to children, who may be unable to swallow solid formulations. The primary objective of this study-conducted on the sponsor's initiative-was to compare the bioavailability of rabeprazole granules when mixed with various dosing vehicles (small amount of soft food or infant formula) with that of a rabeprazole suspension with inactive vehicle granules (reference), to determine which dosing vehicle can be used to deliver rabeprazole in children. Tolerability was also assessed. This single-center, single-dose, randomized, open-label, 5-period crossover study was conducted in 35 healthy adult subjects. In a randomized sequence, fasting subjects received a single dose of 10-mg rabeprazole granules per treatment period, mixed with small amounts of 1 of 5 dosing vehicles (a strawberry-flavored suspension of rabeprazole granules with inactive vehicle granules reconstituted with water, yogurt [1 tablespoon], applesauce [1 tablespoon], or infant formula [5 mL], or a suspension of rabeprazole granules with inactive vehicle tablet reconstituted with water). Full plasma pharmacokinetic (PK) profiles of rabeprazole and its thioether metabolite were collected; concentrations were estimated via LC-MS/MS. PK properties were estimated using noncompartmental methods; 90% CIs around least squares mean test-to-reference ratios were calculated for C(max) and AUC values. All treatment-emergent adverse events (TEAEs) were recorded and assessed for severity (mild, moderate, or severe) and relationship to study drug. A total of 35 subjects were enrolled (mean age, 38 years; 54.3% female; 100% white; mean weight, 71.4 kg). Thirty-four subjects completed the study. Rabeprazole and rabeprazole thioether plasma PK properties were comparable

Estimated radiation doses to different organs among patients treated for ankylosing spondylitis with a single course of X rays

International Nuclear Information System (INIS)

Lewis, C.A.; Smith, P.G.; Stratton, I.M.; Darby, S.C.; Doll, R.

1988-01-01

A follow-up study of over 14000 patients treated with a single course of X rays for ankylosing spondylitis demonstrated substantial excess risk of developing cancer. Previously the excess risk of leukaemia has been related to the estimated mean radiation dose to active bone marrow but detailed estimates were not made of the radiation doses to other organs. Data extracted from the original treatment records of a random sample of one in 15 patients have been used to make dose estimates, using Monte Carlo methods, for 30 specific organs or body regions and 12 bone marrow sites. Estimates of mean and median organ doses, standard deviations and ranges have been tabulated. Detailed distributions are presented for six organs (lung, bronchi, stomach, oesophagus, active bone marrow and total body). Comparison with the earlier bone marrow estimates and more recent theoretical estimates shows good agreement. (author)

In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

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Maeda, Azusa [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Wouters, Bradly G. [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); DaCosta, Ralph S., E-mail: rdacosta@uhnres.utoronto.ca [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Techna Institute, University Health Network, Toronto, Ontario (Canada)

2017-01-01

Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.

Stability in the rumen and effect on plasma status of single oral doses of vitamin D and vitamin E in high-yielding dairy cows

DEFF Research Database (Denmark)

Hymøller, Lone; Jensen, Søren Krogh

2010-01-01

The ruminal fate of the fat-soluble vitamins D and E was studied in dairy cows. Ten to 15 kg of ruminal contents was taken from each cow through a ruminal fistula. A sample was taken out (0-h sample) and the rest of the contents were mixed with 4,360 mg of all-rac-α-tocopheryl acetate (vitamin E;...... a single dose of α-tocopheryl acetate led to the conclusion that oral single dose therapy with all-rac-α-tocopheryl acetate is of limited physiological value....

Single Dose Toxicity of Chukyu (spine-healing Pharmacopuncture Injection in the Muscle of Rats

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Jeong Hohyun

2014-03-01

Full Text Available Objectives: This study was performed to analyze the single dose toxicity of Chukyu (spine-healing pharmacopuncture. Methods: All experiments were conducted at the Biotoxtech, an institution authorized to perform non-clinical studies under the regulations of Good Laboratory Practice (GLP regulations. Sprague-Dawley rats were chosen for the pilot study. Doses of Chukyu (spine-healing pharmacopuncture, 0.1, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was conducted under the approval of the Institutional Animal Ethic Committee. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues except in one case, where interstitial infiltrating macrophages were found in one female rat in the 0.5-mL/animal experimental group. Conclusion: The above findings suggest that treatment with Chukyu (spine-healing pharmacopuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

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Guastella, Adam J; Ward, Philip B; Hickie, Ian B; Shahrestani, Sara; Hodge, Marie Antoinette Redoblado; Scott, Elizabeth M; Langdon, Robyn

2015-11-01

Schizophrenia is associated with significant impairments in both higher and lower order social cognitive performance and these impairments contribute to poor social functioning. People with schizophrenia report poor social functioning to be one of their greatest unmet treatment needs. Recent studies have suggested the potential of oxytocin as such a treatment, but mixed results render it uncertain what aspects of social cognition are improved by oxytocin and, subsequently, how oxytocin might best be applied as a therapeutic. The aim of this study was to determine whether a single dose of oxytocin improved higher-order and lower-order social cognition performance for patients with schizophrenia across a well-established battery of social cognition tests. Twenty-one male patients received both a single dose of oxytocin nasal spray (24IU) and a placebo, two weeks apart in a randomized within-subjects placebo controlled design. Following each administration, participants completed the social cognition tasks, as well as a test of general neurocognition. Results revealed that oxytocin particularly enhanced performance on higher order social cognition tasks, with no effects on general neurocognition. Results for individual tasks showed most improvement on tests measuring appreciation of indirect hints and recognition of social faux pas. These results suggest that oxytocin, if combined to enhance social cognition learning, may be beneficial when targeted at higher order social cognition domains. This study also suggests that these higher order tasks, which assess social cognitive processing in a social communication context, may provide useful markers of response to oxytocin in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.

Serial Myocardial Imaging after a Single Dose of Thallium-201

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Takahiko Kamata

2014-10-01

Full Text Available Although thallium-201 exercise scintigraphy has been established for the detection of myocardial ischemia and viability, little is known regarding the myocardial thallium-201 kinetics during angioplasty. Herein, we report a 77-year old man with angina pectoris, in whom serial myocardial imaging after a single dose of thallium-201 was helpful in identifying not only the culprit lesion and myocardial viability, but also the dynamic changes in myocardial perfusion during angioplasty. Thallium-201 images after exercise showed a perfusion defect in the inferior wall, with a trivial redistribution 3 hours after the exercise and a marked improvement 24 hours later. Coronary angiography, performed 27 hours after exercise scintigraphy, showed severe stenosis in the right coronary artery. Guidewire crossing of the lesion interrupted the antegrade flow, which was restored after balloon dilation and stent implantation. Thallium-201 images, 2 hours after angioplasty (i.e., 30 hours after exercise, showed a decreased tracer uptake in the inferior wall, which improved the next day (i.e., 48 hours after exercise. Cardiac biomarkers were negative in the clinical course.

Derivation of an occupational exposure limit (OEL) for methylene chloride based on acute CNS effects and relative potency analysis.

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Storm, J E; Rozman, K K

1998-06-01

The Occupational Safety and Health Administration (OSHA) methylene chloride Permissible Exposure Level (PEL) or 25 ppm is quantitatively derived from mouse tumor results observed in a high-exposure National Toxicology Program bioassay. Because this approach depends on controversial interspecies and low-dose extrapolations, the PEL itself has stimulated heated debate. Here, an alternative safety assessment for methylene chloride is presented. It is based on an acute human lowest-observed-adverse-effect level (LOAEL) of 200 ppm for subtle central nervous system (CNS) depression. Steep, parallel exposure-response curves for anesthetic and subanesthetic CNS effects associated with compounds mechanistically and structurally related to methylene chloride are shown to support a safety factor of two to account for inter-individual variability in response. LOAEL/no-observed-adverse-effect ratios for subtle CNS effects associated with structurally related solvents are shown to support a safety factor range of two to four to account for uncertainty in identifying a subthreshold exposure level. Anesthetic relative potencies and anesthetic/subanesthetic effect level ratios are shown to be constant for the compounds evaluated, demonstrating that subanesthetic relative potencies are also constant. Relative potencies among similarly derived occupational exposure limits (OELs) for solvents structurally related to methylene chloride are therefore used to validate the derived methylene chloride OEL range of 25-50 ppm. Because this safety assessment is based on human (rather than rodent) data and empirical (rather than theoretical) exposure-response relationships and is supported by relative potency analysis, it is a defensible alternative to to the OSHA risk assessment and should positively contribute to the debate regarding the appropriate basis and value for a methylene chloride PEL.

Effect of single-dose albendazole and vitamin A supplementation on the iron status of pre-school children in Sichuan, China.

Science.gov (United States)

Chen, Ke; Xie, Hu Mina; Tian, Weizheng; Zheng, Xiaoling; Jiang, Alice C

2016-04-01

The aim of this study was to explore the effect of single-dose albendazole and vitamin A intervention on the anaemic status and Fe metabolism of pre-school children. This study was a randomised, placebo-controlled and double-blinded intervention trial. All eligible anaemic pre-school children were randomly divided into three groups: group 1 received no intervention, which served as the control group, group 2 received 400 mg single-dose albendazole administration and group 3 received a 60000 μg vitamin A capsule combined with 400 mg single-dose albendazole at the beginning of the study. The follow-up period was for 6 months. Anthropometry and biochemical index about Fe metabolism were measured before and after intervention. A total of 209 pre-school anaemic children were randomly divided into three intervention groups (sixty-four, sixty-two and sixty for groups 1, 2 and 3, respectively). The mean age of the children in the study was 4·4 (sd 0·7) years and 50·5 % of the children were female (94/186). After a follow-up period of 6 months, the levels of serum retinol, ferritin, transferrin receptor-ferritin index and body total Fe content of children in group 3 were significantly higher compared with children in groups 1 and 2 (PAlbendazole plus vitamin A administration showed more efficacy on the improvement of serum retinol and Fe metabolic status.

The Influence of Dosing Modes of Coagulate on Arsenic Removal

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Zhibin Zhang

2014-01-01

Full Text Available Three different dosing modes, including one single dosing mode and two sequential dosing modes, were applied in high-arsenic contaminated water treatment. The results illustrated that the As (V soluble and the As (V nonspecifically sorbed were the insignificant species from Fe-As (V samples in the sequential dosing mode, while they were higher in the single dosing mode. However, it could be further concluded that the mobility of the Fe-As (V in sequential dosing mode was greater than that in single dosing mode. Besides, the main arsenic speciation governing the arsenic-borne coagulates was the As (V associated with poorly crystalline hydrous oxides of Fe in sequential or single dosing mode. Moreover, the particle size distribution analysis indicated that the sequential dosing mode was more prevalent in neutralizing and adsorbing the As (V compared with the single dosing mode. In the FT-IR spectra, the presence of arsenic was highlighted by a well resolved band at 825–829 cm−1. The positions of the As–O stretching vibration bands were shifted gradually as the dosing mode changed from the single to the sequential. This result could be related to the distribution of arsenic speciation in different dosing modes.

Pharmacokinetic Properties of Three Forms of Vaginal Progesterone Administered in Either Single Or Multiple Dose Regimen in Healthy Post-menopausal Chinese Women

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Jianzhong Shentu

2017-04-01

Full Text Available Objective: A generic vaginal progesterone gel has recently been developed in China. Little is known about its pharmacokinetic properties in Chinese subjects. The purpose of our study was to investigate the pharmacokinetics of three forms of vaginal progesterone gel (test formulations at 4 and 8% strength vs. a reference formulation: Crinone 8% in Chinese healthy post-menopausal women.Methods: This study consisted of two parts study. The part 1 study was a single-center, open-label, 3-period study. Twelve healthy post-menopausal women were to evaluate the safety and pharmacokinetics of 45 mg vaginal progesterone gel (Test 4% following single dose and multiple doses administered once every other day (q.o.d. for six times or once daily (q.d. for 6 days. The part 2 study was a randomized, open-label, 3-stage crossover study. Twelve post-menopausal women received 90 mg vaginal progesterone gel (Test 8% or 90 mg Crinone (Reference 8% following single dose and multiple doses (q.o.d. or q.d.. Plasma concentrations of progesterone were measured up to 72 h by using a validated liquid chromatography tandem-mass spectrometry method. The primary pharmacokinetic parameters, maximum plasma concentration (Cmax and area under the plasma concentration–time curve (AUC from time zero to last measurable concentration (AUC0-t and extrapolated to infinity (AUC0-∞ were compared by an analysis of variance using log-transformed data.Results: Totally 24 subjects were enrolled in and completed the study. Following single dose, The geometric mean Cmax values for Test 4%, Test 8%, and Crinone 8% were 6.35, 10.34, 10.45 ng/mL, and their geometric mean AUC0-t (AUC0-∞ were 113.73 (118.00, 169.39 (173.98, and 190.07 (201.13 ng⋅h/mL, respectively. The mean T1/2 values of progesterone were 11.00, 10.92, and 11.40 h, respectively. For 8% test formulation vs. reference, the 90% CIs of the least squares mean test/reference ratios of Cmax, AUC0-t, and AUC0-∞ were 78.32–124

Lack of protective effect of thromboxane synthetase inhibitor (CGS-13080) on single dose radiated canine intestine

International Nuclear Information System (INIS)

Barter, J.F.; Marlow, D.; Kamath, R.K.; Harbert, J.; Torrisi, J.R.; Barnes, W.A.; Potkul, R.K.; Newsome, J.T.; Delgado, G.

1991-01-01

The effect of a thromboxane A2 synthetase inhibitor (CGS-13080) on canine intestine was studied using a single dose of radiation, and radioactive microspheres were used to determine resultant blood flow. Thromboxane A2 causes vasospasm and platelet aggregation and may play a dominant role in radiation injury. However, there was no effect on the intestinal blood flow diminution occurring after radiation in this laboratory model using this thromboxane A2 synthetase inhibitor

Pocket total dose meter

International Nuclear Information System (INIS)

Brackenbush, L.W.; Endres, G.W.R.

1984-10-01

Laboratory measurements have demonstrated that it is possible to simultaneously measure absorbed dose and dose equivalent using a single tissue equivalent proportional counter. Small, pocket sized instruments are being developed to determine dose equivalent as the worker is exposed to mixed field radiation. This paper describes the electronic circuitry and computer algorithms used to determine dose equivalent in these devices

Gamma radiation-induced Impairment of hippocampal neurogenesis, comparison of single and fractionated dose regimens

International Nuclear Information System (INIS)

Khoshbin khoshnazar, A. R; Jahanshahi, M; Azami, N. S

2012-01-01

Radiation therapy of the brain is associated with many consequences, including cognitive disorders. Pathogenesis of radiation induced cognitive disorder is not clear, but reduction of neurogenesis in hippocampus may be an underlying reason. 24 adult male rats entered to study. Radiation absorbed dose to midbrain was 10 Gy, delivered by routine cobalt radiotherapy machine which its output was measured 115.24 cGy/min. The rats were divided in four groups of sixes, including groups of control, single fraction 10 Gy, fractionated 10 Gy and finally anaesthesia sham group. Number of pyramidal nerve cells was counted in two regions of hippocampus formation (CA1 and CA3). The radiation could reduce the number of cells in two regions of hippocampus significantly (p=0.000). It seems fractionated 10 Gy irradiation to more efficient than single fraction, while role of anaesthesia drug should be cautiously assessed. Moreover the rate of neurogenesis reduction was determined the same in these regions of hippocampus meaning the same radiosensitivity of cells

The evolution of anti-ulcer therapy with cimetidine. Is a single large nocturnal dose of cimetidine the right therapy for duodenal ulcer?

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Barbara, L; Corinaldesi, B; Stanghellini, V; Paternicò, A; Fabbri, L; Sacco, T

1986-01-01

Peptic ulcer results from the prevalence of agents causing endoluminal lesions over the defence mechanisms of the mucosa of the upper GI tract. Particularly, in the case of duodenal ulcer, the pathogenetic relevance of non-buffered acid secretion of the early nighttime period has been emphasized. This is indeed confirmed by the fact that a single night dose of 800 mg cimetidine has apparently been proved able--in numerous controlled clinical trials--to provide results that are similar to those obtained with the classic dose of 1 g daily or 400 mg twice daily. Our centre carried out a crossover double-blind controlled trial aimed at evaluating titrable acidity and pH during the 24-h period in seven patients with active duodenal ulcer. The single nighttime dose of cimetidine resulted in a significant and long-lasting inhibition of acid secretion during the entire night. During the day, secretory values returned to levels similar to those obtained with placebo, hence allowing normal digestive functions.

Reliability of single aliquot regenerative protocol (SAR) for dose estimation in quartz at different burial temperatures: A simulation study

International Nuclear Information System (INIS)

Koul, D.K.; Pagonis, V.; Patil, P.

2016-01-01

The single aliquot regenerative protocol (SAR) is a well-established technique for estimating naturally acquired radiation doses in quartz. This simulation work examines the reliability of SAR protocol for samples which experienced different ambient temperatures in nature in the range of −10 to 40 °C. The contribution of various experimental variables used in SAR protocols to the accuracy and precision of the method is simulated for different ambient temperatures. Specifically the effects of paleo-dose, test dose, pre-heating temperature and cut-heat temperature on the accuracy of equivalent dose (ED) estimation are simulated by using random combinations of the concentrations of traps and centers using a previously published comprehensive quartz model. The findings suggest that the ambient temperature has a significant bearing on the reliability of natural dose estimation using SAR protocol, especially for ambient temperatures above 0 °C. The main source of these inaccuracies seems to be thermal sensitization of the quartz samples caused by the well-known thermal transfer of holes between luminescence centers in quartz. The simulations suggest that most of this inaccuracy in the dose estimation can be removed by delivering the laboratory doses in pulses (pulsed irradiation procedures). - Highlights: • Ambient temperatures affect the reliability of SAR. • It overestimates the dose with increase in burial temperature and burial time periods. • Elevated temperature irradiation does not correct for these overestimations. • Inaccuracies in dose estimation can be removed by incorporating pulsed irradiation procedures.

Randomized controlled trial comparing different single doses of intravenous paracetamol for placement of peripherally inserted central catheters in preterm infants

NARCIS (Netherlands)

D.W.E. Roofthooft (Daniella); S.H. Simons (Sinno); R.A. Lingen (Richard); D. Tibboel (Dick); J.N. van den Anker (John); I.K.M. Reiss (Irwin); M. van Dijk (Monique)

2017-01-01

markdownabstract__Background:__ The availability of a safe and effective pharmacological therapy to reduce procedural pain in preterm infants is limited. The effective analgesic single dose of intravenous paracetamol in preterm infants is unknown. Comparative studies on efficacy of different

Interaction between single-dose Mycoplasma hyopneumoniae and porcine reproductive and respiratory syndrome virus vaccines on dually infected pigs.

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Park, Su-Jin; Seo, Hwi Won; Park, Changhoon; Chae, Chanhee

2014-06-01

The objective of this study was to determine the effects of Mycoplasma hyopneumoniae and/or porcine reproductive and respiratory syndrome virus (PRRSV) vaccination on dually infected pigs. In total, 72 pigs were randomly divided into nine groups (eight pigs per group), as follows: five vaccinated and challenged groups, three non-vaccinated and challenged groups, and a negative control group. Single-dose vaccination against M. hyopneumoniae alone decreased the levels of PRRSV viremia and PRRSV-induced pulmonary lesions, whereas single-dose vaccination against PRRSV alone did not decrease nasal shedding of M. hyopneumoniae and mycoplasma-induced pulmonary lesions in the dually infected pigs. The M. hyopneumoniae challenge impaired the protective cell-mediated immunity induced by the PRRSV vaccine, whereas the PRRSV challenge did not impair the protective cell-mediated immunity induced by the M. hyopneumoniae vaccine. The present study provides swine practitioners and producers with efficient vaccination regimes; vaccination against M. hyopneumoniae is the first step in protecting pigs against co-infection with M. hyopneumoniae and PRRSV. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dataset for Phase I randomized clinical trial for safety and tolerability of GET 73 in single and repeated ascending doses including preliminary pharmacokinetic parameters.

Science.gov (United States)

Haass-Koffler, Carolina L; Goodyear, Kimberly; Long, Victoria M; Tran, Harrison H; Loche, Antonella; Cacciaglia, Roberto; Swift, Robert M; Leggio, Lorenzo

2017-12-01

The data in this article outline the methods used for the administration of GET 73 in the first time-in-human manuscript entitled "Phase I randomized clinical trial for the safety, tolerability and preliminary pharmacokinetics of the mGluR5 negative allosteric modulator GET 73 following single and repeated doses in healthy male volunteers" (Haass-Koffler et al., 2017) [1]. Data sets are provided in two different manners. The first series of tables provided includes procedural information about the experiments conducted. The next series of tables provided includes Pharmacokinetic (PK) parameters for GET 73 and its main metabolite MET 2. This set of data is comprised by two experiments: Experiment 1 references a single ascending dose administration of GET 73 and Experiment 2 references a repeated ascending dose administration of GET 73.

The effect of single low-dose dexamethasone on vomiting during awake craniotomy.

Science.gov (United States)

Kamata, Kotoe; Morioka, Nobutada; Maruyama, Takashi; Komayama, Noriaki; Nitta, Masayuki; Muragaki, Yoshihiro; Kawamata, Takakazu; Ozaki, Makoto

2016-12-01

Intraoperative vomiting leads to serious respiratory complications that could influence the surgical decision-making process for awake craniotomy. However, the use of antiemetics is still limited in Japan. The aim of this study was to investigate the effect of prophylactically administered single low-dose dexamethasone on the incidence of vomiting during awake craniotomy. The frequency of hyperglycemia was also examined. We conducted a retrospective case review of awake craniotomy for glioma resection between 2012 and 2015. Of the 124 patients, 91 were included in the analysis. Dexamethasone was not used in 43 patients and the 48 remaining patients received an intravenous bolus of 4.95 mg dexamethasone at anesthetic induction. Because of stable operating conditions, no one required conscious sedation throughout functional mapping and tumor resection. Although dexamethasone pretreatment reduced the incidence of intraoperative vomiting (P = 0.027), the number of patients who complained of nausea was comparable (P = 0.969). No adverse events related to vomiting occurred intraoperatively. Baseline blood glucose concentration did not differ between each group (P = 0.143), but the samples withdrawn before emergence (P = 0.018), during the awake period (P awake craniotomy cases. However, as even a small dose of dexamethasone increases the risk for hyperglycemia, antiemetic prophylaxis with dexamethasone should be administered after careful consideration. Monitoring of perioperative blood glucose concentration is also necessary.

Dose-ranging pharmacokinetics of colistin methanesulphonate (CMS) and colistin in rats following single intravenous CMS doses.

Science.gov (United States)

Marchand, Sandrine; Lamarche, Isabelle; Gobin, Patrice; Couet, William

2010-08-01

The aim of this study was to evaluate the effect of colistin methanesulphonate (CMS) dose on CMS and colistin pharmacokinetics in rats. Three rats per group received an intravenous bolus of CMS at a dose of 5, 15, 30, 60 or 120 mg/kg. Arterial blood samples were drawn at 0, 5, 15, 30, 60, 90, 120, 150 and 180 min. CMS and colistin plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of CMS and colistin were calculated by non-compartmental analysis. Linear relationships were observed between CMS and colistin AUCs to infinity and CMS doses, as well as between CMS and colistin C(max) and CMS doses. CMS and colistin pharmacokinetics were linear for a range of colistin concentrations covering the range of values encountered and recommended in patients even during treatment with higher doses.

Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma

NARCIS (Netherlands)

Scicchitano, R; Aalbers, R; Ukena, D; Manjra, A; Fouquert, L; Centanni, S; Boulet, LP; Naya, IP; Hultquist, C

Objectives:This study evaluated the efficacy and safety of a novel asthma management strategy - budesonide/formoterol for both maintenance and symptom relief (Symbicort Single Inhaler Therapy*) - compared with a higher maintenance dose of budesonide in patients with moderate to severe asthma.

A study on mice exposure dose for low-dose gamma-irradiation using glass dosimeter

Energy Technology Data Exchange (ETDEWEB)

Noh, Sung Jin; Kim, Hyo Jin; Kim, Hyun; Jeong, Dong Hyeok; Son, Tae Gen; Kim, Jung Ki; Yang, Kwang Mo; Kang, Yeong Rok [Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of); Nam, Sang Hee [Dept. of Biomedical Engineering, Inje University, Gimhae (Korea, Republic of)

2015-12-15

The low dose radiation is done for a long period, thus researchers have to know the exact dose distribution for the irradiated mouse. This research has been conducted in order to find out methods in transmitting an exact dose to mouse in a mouse irradiation experiment carried out using {sup 137}C{sub s} irradiation equipment installed in the DIRAMS (Dongnam Institution of Radiological and Medical Sciences) research center. We developed a single mouse housing cage and shelf with adjustable geometric factors such as distance and angle from collimator. The measurement of irradiated dose showed a maximal 42% difference of absorbed dose from the desired dose in the conventional irradiation system, whereas only 6% difference of the absorbed dose was measured in the self-developed mouse apartment system. In addition, multi mice housing showed much difference of the absorbed dose in between head and body, compared to single mouse housing in the conventional irradiation system. This research may allow further research about biological effect assessment for the low dose irradiation using the self-developed mouse apartment to provide more exact doses which it tries to transmit, and to have more reliability for the biological analysis results.

SU-E-T-556: Monte Carlo Generated Dose Distributions for Orbital Irradiation Using a Single Anterior-Posterior Electron Beam and a Hanging Lens Shield

International Nuclear Information System (INIS)

Duwel, D; Lamba, M; Elson, H; Kumar, N

2015-01-01

Purpose: Various cancers of the eye are successfully treated with radiotherapy utilizing one anterior-posterior (A/P) beam that encompasses the entire content of the orbit. In such cases, a hanging lens shield can be used to spare dose to the radiosensitive lens of the eye to prevent cataracts. Methods: This research focused on Monte Carlo characterization of dose distributions resulting from a single A-P field to the orbit with a hanging shield in place. Monte Carlo codes were developed which calculated dose distributions for various electron radiation energies, hanging lens shield radii, shield heights above the eye, and beam spoiler configurations. Film dosimetry was used to benchmark the coding to ensure it was calculating relative dose accurately. Results: The Monte Carlo dose calculations indicated that lateral and depth dose profiles are insensitive to changes in shield height and electron beam energy. Dose deposition was sensitive to shield radius and beam spoiler composition and height above the eye. Conclusion: The use of a single A/P electron beam to treat cancers of the eye while maintaining adequate lens sparing is feasible. Shield radius should be customized to have the same radius as the patient’s lens. A beam spoiler should be used if it is desired to substantially dose the eye tissues lying posterior to the lens in the shadow of the lens shield. The compromise between lens sparing and dose to diseased tissues surrounding the lens can be modulated by varying the beam spoiler thickness, spoiler material composition, and spoiler height above the eye. The sparing ratio is a metric that can be used to evaluate the compromise between lens sparing and dose to surrounding tissues. The higher the ratio, the more dose received by the tissues immediately posterior to the lens relative to the dose received by the lens

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

Science.gov (United States)

Azman, Andrew S.; Luquero, Francisco J.; Ciglenecki, Iza; Grais, Rebecca F.; Sack, David A.; Lessler, Justin

2015-01-01

Background In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. Methods and Findings Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%–56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%–88%) for two doses and 44% (95% CI −27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%–88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943–86,205) cases in Zimbabwe, 78,317 (95% PI 57,435–100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490–3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study.

Directory of Open Access Journals (Sweden)

Andrew S Azman

2015-08-01

Full Text Available In 2013, a stockpile of oral cholera vaccine (OCV was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both.Using mathematical models we determined the minimum relative single-dose efficacy (MRSE at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%-56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%. This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%-88% for two doses and 44% (95% CI -27% to 76% for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%-88%, which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943-86,205 cases in Zimbabwe, 78,317 (95% PI 57,435-100,150 in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490-3,170 cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture uncertainty due to imperfect

Single-dose Intramuscular-injection Toxicology Test of Water-soluble Carthami-flos and Cervi cornu parvum Pharmacopuncture in a Rat Model

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Sunju Park

2015-09-01

Full Text Available Objectives: The aim of the study is to investigate both the single-dose intramuscular injection toxicity and the approximate lethal dose of water-soluble Carthami-flos and Cervi cornu parvum pharmacopuncture (WCFC in male and female Sprague-Dawley (SD rats. Methods: The study was conducted at Biotoxtech Co. according to the Good Laboratory Practice (GLP regulation and the toxicity test guidelines of the Ministry of Food and Drug Safety (MFDS after approval of the Institutional Animal Care and Use Committee. Dosages for the control, high dose, middle dose and low dose groups were 0.5 mL/animal of saline and 0.5, 0.25 and 0.125 mL/animal of WCFC, respectively. WCFC was injected into the muscle of the left femoral region by using a disposable syringe (1 mL, 26 gauge. The general symptoms and mortality were observed 30 minutes, 1, 2, 4, and 6 hours after the first injection and then daily for 14 days after the injection. The body weights of the SD rats were measured on the day of the injection (before injection and on the third, seventh, and fourteenth days after the injection. Serum biochemical and hematologic tests, necropsy examinations, and histopathologic examinations at the injection site were performed after the observation period. Results: No deaths, abnormal clinical symptoms, or significant weight changes were observed in either male or female SD rats in the control or the test (0.125, 0.25, and 0.5 mL/animal groups during the observation period. No significant differences in hematology and serum biochemistry and no macroscopic abnormalities at necropsy were found. No abnormal reactions at injection sites were noted on the topical tolerance tests. Conclusion: The results of this single-dose toxicity study show that WCFC is safe, its lethal doses in male and female SD rats being estimated to be higher than 0.5 mL/animal.

Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose.

Science.gov (United States)

Viscardi, Rose M; Othman, Ahmed A; Hassan, Hazem E; Eddington, Natalie D; Abebe, Elias; Terrin, Michael L; Kaufman, David A; Waites, Ken B

2013-05-01

Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.) dose of azithromycin (10 mg/kg of body weight) is safe but inadequate to eradicate Ureaplasma spp. in preterm infants. We performed a nonrandomized, single-arm open-label study of the pharmacokinetics (PK) and safety of intravenous 20-mg/kg single-dose azithromycin in 13 mechanically ventilated neonates with a gestational age between 24 weeks 0 days and 28 weeks 6 days. Pharmacokinetic data from 25 neonates (12 dosed with 10 mg/kg i.v. and 13 dosed with 20 mg/kg i.v.) were analyzed using a population modeling approach. Using a two-compartment model with allometric scaling of parameters on body weight (WT), the population PK parameter estimates were as follows: clearance, 0.21 liter/h × WT(kg)(0.75) [WT(kg)(0.75) indicates that clearance was allometrically scaled on body weight (in kilograms) with a fixed exponent of 0.75]; intercompartmental clearance, 2.1 liters/h × WT(kg)(0.75); central volume of distribution (V), 1.97 liters × WT (kg); and peripheral V, 17.9 liters × WT (kg). There was no evidence of departure from dose proportionality in azithromycin exposure over the tested dose range. The calculated area under the concentration-time curve over 24 h in the steady state divided by the MIC90 (AUC24/MIC90) for the single dose of azithromycin (20 mg/kg) was 7.5 h. Simulations suggest that 20 mg/kg for 3 days will maintain azithromycin concentrations of >MIC50 of 1 μg/ml for this group of Ureaplasma isolates for ≥ 96 h after the first dose. Azithromycin was well tolerated with no drug-related adverse events. One of seven (14%) Ureaplasma-positive subjects and three of six (50%) Ureaplasma-negative subjects developed physiologic BPD. Ureaplasma was eradicated in all treated Ureaplasma-positive subjects. Simulations suggest that a multiple-dose regimen may be efficacious for microbial

Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus.

Science.gov (United States)

Lu, P; Fleischmann, R; Curtis, C; Ignatenko, S; Clarke, S H; Desai, M; Wong, S L; Grebe, K M; Black, K; Zeng, J; Stolzenbach, J; Medema, J K

2018-02-01

Objective The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) may contribute to the pathogenesis of systemic lupus erythematosus. The safety, tolerability, and pharmacodynamics of the selective Bcl-2 inhibitor venetoclax (ABT-199) were assessed in women with systemic lupus erythematosus. Methods A phase 1, double-blind, randomized, placebo controlled study evaluated single ascending doses (10, 30, 90, 180, 300, and 500 mg) and multiple ascending doses (2 cycles; 30, 60, 120, 240, 400, and 600 mg for 1 week, and then 3 weeks off per cycle) of orally administered venetoclax. Eligible participants were aged 18-65 years with a diagnosis of systemic lupus erythematosus for 6 months or more receiving stable therapy for systemic lupus erythematosus (which could have included corticosteroids and/or stable antimalarials). Results All patients (48/48) completed the single ascending dose, 25 continued into the multiple ascending dose, and 44/50 completed the multiple ascending dose; two of the withdrawals (venetoclax 60 mg and 600 mg cohorts) were due to adverse events. Adverse event incidences were slightly higher in the venetoclax groups compared with the placebo groups, with no dose dependence. There were no serious adverse events with venetoclax. The most common adverse events were headache, nausea, and fatigue. Venetoclax 600 mg multiple ascending dose treatment depleted total lymphocytes and B cells by approximately 50% and 80%, respectively. Naive, switched memory, and memory B-cell subsets enriched in autoreactive B cells exhibited dose-dependent reduction of up to approximately 80%. There were no consistent or marked changes in neutrophils, natural killer cells, hemoglobin, or platelets. Conclusions Venetoclax was generally well tolerated in women with systemic lupus erythematosus and reduced total lymphocytes and disease-relevant subsets of antigen-experienced B cells. Registration ClinicalTrials.gov: NCT01686555.

Microbial contamination of single-and multiple-dose vials after opening in a pulmonary teaching hospital

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Shadi Baniasadi

Full Text Available OBJECTIVES: Intravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections. We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials in the largest pulmonary teaching hospital in Iran. METHODS: In a period of 2 months, opened single- and multiple-dose vials from different wards were sampled by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media. RESULTS: Microbial contamination was identified in 11 of 205 (5.36% of vials. The highest contamination rate was 14.28% for vials used in interventional bronchoscopy unit. The most frequent contaminated medication was insulin. Gram-positive bacteria (81.82% were more significantly involved than gram-negative ones (9.09% and fungi (9.09%, with the highest frequency for Staphylococcus epidermidis . CONCLUSIONS: Our data demonstrate that repeated use of vials especially if basic sterility measures are disobeyed can cause microbial contamination of administered products to the patients. Infection preventionists are responsible to train health care workers regarding aseptic techniques and apply guidelines for aseptic handling of intravenous solutions.

Microbial contamination of single-and multiple-dose vials after opening in a pulmonary teaching hospital

Directory of Open Access Journals (Sweden)

Shadi Baniasadi

2013-02-01

Full Text Available OBJECTIVES: Intravenous therapy is a complex procedure usually requiring the preparation of the medication in the clinical area before administration to the patient. Breaches in aseptic technique may result in microbial contaminations of vials which is a potential cause of different avoidable infections. We aimed to investigate the prevalence and pattern of microbial contamination of single- and multiple-dose vials in the largest pulmonary teaching hospital in Iran. METHODS: In a period of 2 months, opened single- and multiple-dose vials from different wards were sampled by a pharmacist. The name of the medication, ward, labeling of the vials, the date of opening, and storing temperature were recorded for each vial. Remained contents of each vial were cultured using appropriate bacterial and fungal growth media. RESULTS: Microbial contamination was identified in 11 of 205 (5.36% of vials. The highest contamination rate was 14.28% for vials used in interventional bronchoscopy unit. The most frequent contaminated medication was insulin. Gram-positive bacteria (81.82% were more significantly involved than gram-negative ones (9.09% and fungi (9.09%, with the highest frequency for Staphylococcus epidermidis . CONCLUSIONS: Our data demonstrate that repeated use of vials especially if basic sterility measures are disobeyed can cause microbial contamination of administered products to the patients. Infection preventionists are responsible to train health care workers regarding aseptic techniques and apply guidelines for aseptic handling of intravenous solutions.

Population pharmacokinetics of artesunate and dihydroartemisinin following single- and multiple-dosing of oral artesunate in healthy subjects

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Kirsch Lee E

2009-12-01

Full Text Available Abstract Background The population pharmacokinetics of artesunate (AS and its active metabolite dihydroartemisinin (DHA were studied in healthy subjects receiving single- or multiple-dosing of AS orally either in combination with pyronaridine (PYR or as a monotherapy with or without food. Methods Data from 118 concentration-time profiles arising from 91 healthy Korean subjects were pooled from four Phase I clinical studies. Subjects received 2-5 mg/kg of single- and multiple-dosing of oral AS either in combination with PYR or as a monotherapy with or without food. Plasma AS and DHA were measured simultaneously using a validated liquid chromatography- mass spectrometric method with a lower limit of quantification of 1 ng/mL for both AS and DHA. Nonlinear mixed-effect modelling was used to obtain the pharmacokinetic and variability (inter-individual and residual variability parameter estimates. Results A novel parent-metabolite pharmacokinetic model consisting of a dosing compartment, a central compartment for AS, a central compartment and a peripheral compartment for DHA was developed. AS and DHA data were modelled simultaneously assuming stoichiometric conversion to DHA. AS was rapidly absorbed with a population estimate of absorption rate constant (Ka of 3.85 h-1. The population estimates of apparent clearance (CL/F and volume of distribution (V2/F for AS were 1190 L/h with 36.2% inter-individual variability (IIV and 1210 L with 57.4% IIV, respectively. For DHA, the population estimates of apparent clearance (CLM/F and central volume of distribution (V3/F were 93.7 L/h with 28% IIV and 97.1 L with 30% IIV, respectively. The population estimates of apparent inter-compartmental clearance (Q/F and peripheral volume of distribution (V4/F for DHA were 5.74 L/h and 18.5 L, respectively. Intake of high-fat and high-caloric meal prior to the drug administration resulted in 84% reduction in Ka. Body weight impacted CLM/F, such that a unit change in

Single dose total lymphoid irradiation combined with cyclophosphamide as immunosuppression for human marrow transplantation in aplastic anemia

International Nuclear Information System (INIS)

Kim, T.H.; Kersey, J.H.; Khan, F.M.; Sewchand, W.; Ramsey, N.; Krivit, W.; Coccia, P.; Nesbit, M.E.; Levitt, S.H.

1979-01-01

Six patients with aplastic anemia underwent bone marrow transplantation following conditioning with high dose cyclophosphamide and single dose total lymphoid irradiation with 750 rad, 26 rad/min at the midplane of the patient. They all received bone marrow from human leukocyte antigens/mixed lymphocyte culture (HLA/MLC) matched siblings. Five of 6 patients were alive without complications at 12, 11, 7, 4 and 4 months respectively. The remaining patient died from sepis which he had prior to transplantation. There were no graft rejection, graft-vs-Host Disease (GVHD) or interstitial pneumonitis among these patients. The procedure was well tolerated with minimal side effects. The results will be compared with those of groups whose bone marrow was previously transplanted with different immunosuppressive methods

The origin of dose distributions in fluvial sediments, and the prospect of dating single grains from fluvial deposits using optically stimulated luminescence

CERN Document Server

Olley, J M; Roberts, R G

1999-01-01

We examine the causes of the asymmetric distributions of dose observed from measurements of the optically stimulated luminescence emitted by small aliquots of fluvial quartz, and deduce that the asymmetry arises as a result of samples being composed of a mix of mainly well bleached grains with grains that were effectively unbleached at the time of deposition. We demonstrate that the shapes of the dose distributions can be used to assess the likelihood that aliquots consist only of grains that were well-bleached at the time of deposition. The more asymmetric the distribution, the greater the probability that the aliquots with the lowest dose most closely represent the true burial dose. Single grains with differing doses are present in each of the samples examined, and the population with the lowest dose gives an optical age consistent with the expected burial age. This result implies that the beta-dose heterogeneity in these deposits is small, and that the effects of micro-dosimetric variations on optical dati...

SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

International Nuclear Information System (INIS)

Ding, C; Hrycushko, B; Jiang, S; Meyer, J; Timmerman, R

2014-01-01

Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm 3 ) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan, the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment

Dose rate and dose fractionation studies in total body irradiation of dogs

International Nuclear Information System (INIS)

Kolb, H.J.; Netzel, B.; Schaffer, E.; Kolb, H.

1979-01-01

Total body irradiation (TBI) with 800-900 rads and allogeneic bone marrow transplantation according to the regimen designated by the Seattle group has induced remissions in patients with otherwise refractory acute leukemias. Relapse of leukemia after bone marrow transplantation remains the major problem, when the Seattle set up of two opposing 60 Co-sources and a low dose rate is used in TBI. Studies in dogs with TBI at various dose rates confirmed observations in mice that gastrointestinal toxicity is unlike toxicity against hemopoietic stem cells and possibly also leukemic stem cells depending on the dose rate. However, following very high single doses (2400 R) and marrow infusion acute gastrointestinal toxicity was not prevented by the lowest dose rate studied (0.5 R/min). Fractionated TBI with fractions of 600 R in addition to 1200 R (1000 rads) permitted the application of total doses up to 300 R followed by marrow infusion without irreversible toxicity. 26 dogs given 2400-3000 R have been observed for presently up to 2 years with regard to delayed radiation toxicity. This toxicity was mild in dogs given single doses at a low dose rate or fractionated TBI. Fractionated TBI is presently evaluated with allogeneic transplants in the dog before being applied to leukemic patients

Absorbed dose estimates from a single measurement one to three days after the administration of 177Lu-DOTATATE/-TOC.

Science.gov (United States)

Hänscheid, Heribert; Lapa, Constantin; Buck, Andreas K; Lassmann, Michael; Werner, Rudolf A

2017-01-01

To retrospectively analyze the accuracy of absorbed dose estimates from a single measurement of the activity concentrations in tumors and relevant organs one to three days after the administration of 177 Lu-DOTA-TATE/TOC assuming tissue specific effective half-lives. Activity kinetics in 54 kidneys, 30 neuroendocrine tumor lesions, 25 livers, and 27 spleens were deduced from series of planar images in 29 patients. After adaptation of mono- or bi-exponential fit functions to the measured data, it was analyzed for each fit function how precise the time integral can be estimated from fixed tissue-specific half-lives and a single measurement at 24, 48, or 72 h after the administration. For the kidneys, assuming a fixed tissue-specific half-life of 50 h, the deviations of the estimate from the actual integral were median (5 % percentile, 95 % percentile): -3 °% (-15 %>; +16 °%) for measurements after 24 h, +2 %> (-9 %>; +12 %>) for measurements after 48 h, and 0 % (-2 %; +12 %) for measurements after 72 h. The corresponding values for the other tissues, assuming fixed tissue-specific half-lives of 67 h for liver and spleen and 77 h for tumors, were +2 % (-25 %; +20 %) for measurements after 24 h, +2 °% (-16 %>; +17 %>) for measurements after 48 h, and +2 %> (-11 %>; +10 %>) for measurements after 72 h. Especially for the kidneys, which often represent the dose limiting organ, but also for liver, spleen, and neuroendocrine tumors, a meaningful absorbed dose estimate is possible from a single measurement after 2, more preferably 3 days after the administration of 177 Lu-DOTA-TATE/-TOC assuming fixed tissue specific effective half-lives. Schattauer GmbH.

Protective effects of orally applied fullerenol nano particles in rats after a single dose of doxorubicin

Directory of Open Access Journals (Sweden)

Ičević Ivana Đ.

2011-01-01

Full Text Available Polyhydroxylated, water soluble, fullerenol C60(OH24 nano particles (FNP in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX (8 mg/kg (i.p. 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP, in H2O:DMSO (80:20, w/w solution given orally in final doses of 10, 14.4, and 21.2 mg/kg three days successively, has the protective (hepatoprotective and nephroprotective effect against doxorubicin-induced cytotoxicity via its antioxidant properties.

Pharmacokinetics of surotomycin from phase 1 single and multiple ascending dose studies in healthy volunteers.

Science.gov (United States)

Chandorkar, Gurudatt; Zhan, Qiao; Donovan, Julie; Rege, Shruta; Patino, Hernando

2017-03-28

Surotomycin, a novel, orally administered, cyclic, lipopeptide antibacterial in development for the treatment of Clostridium difficile-associated diarrhea, has demonstrated minimal intestinal absorption in animal models. Safety, tolerability, and plasma pharmacokinetics of single and multiple ascending oral doses (SAD/MAD) of surotomycin in healthy volunteers were characterized in two randomized, double-blind, placebo-controlled, phase 1 studies. Participants were sequentially enrolled into one of four SAD (500, 1000, 2000, 4000 mg surotomycin) or three MAD (250, 500, 1000 mg surotomycin twice/day for 14 days) cohorts. Ten subjects were randomized 4:1 into each cohort to receive surotomycin or placebo. Surotomycin plasma concentrations rose as dose increased (maximum plasma concentration [C max ]: 10.5, 21.5, 66.6, and 86.7 ng/mL). Systemic levels were generally low, with peak median surotomycin plasma concentrations observed 6-12 h after the first dose. In the MAD study, surotomycin plasma concentrations were higher on day 14 (C max : 25.5, 37.6, and 93.5 ng/mL) than on day 1 (C max : 6.8, 11.0, and 21.1 ng/mL for increasing doses), indicating accumulation. In the SAD study, <0.01% of the administered dose was recovered in urine. Mean surotomycin stool concentration from the 1000 mg MAD cohort was 6394 μg/g on day 5. Both cohorts were well tolerated with all adverse events reported as mild to moderate. Both SAD and MAD studies of surotomycin demonstrated minimal systemic exposure, with feces the primary route of elimination following oral administration; consistent with observations with similar compounds, such as fidaxomicin. Results of these phase 1 studies support the continued clinical development of surotomycin for the treatment of Clostridium difficile-associated diarrhea. NCT02835118 and NCT02835105 . Retrospectively registered, July 13 2016.

Phase I/II trial of single-fraction high-dose-rate brachytherapy-boosted hypofractionated intensity-modulated radiation therapy for localized adenocarcinoma of the prostate.

Science.gov (United States)

Myers, Michael A; Hagan, Michael P; Todor, Dorin; Gilbert, Lynn; Mukhopadhyay, Nitai; Randolf, Jessica; Heimiller, Jeffrey; Anscher, Mitchell S

2012-01-01

A Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of intensity-modulated radiation therapy (IMRT) with a single-fraction high-dose-rate (HDR) brachytherapy implant. From 2001 through 2006, 26 consecutive patients were treated on the trial. The primary objective was to demonstrate a high rate of completion without experiencing a treatment-limiting toxicity. Eligibility was limited to patients with T stage ≤2b, prostate-specific antigen (PSA) ≤20, and Gleason score ≤7. Treatment began with a single HDR fraction of 6Gy to the entire prostate and 9Gy to the peripheral zone, followed by IMRT optimized to deliver in 28 fractions with a normalized total dose of 70Gy. Patients received 50.4Gy to the pelvic lymph node. The prostate dose (IMRT and HDR) resulted in an average biologic equivalent dose >128Gy (α/β=3). Patients whose pretreatment PSA was ≥10ng/mL, Gleason score 7, or stage ≥T2b received short-term androgen ablation. Median followup was 53 months (9-68 months). There were no biochemical failures by either the American Society of Therapeutic Radiology and Oncology or the Phoenix definitions. The median nadir PSA was 0.32ng/mL. All the 26 patients completed the treatment as prescribed. The rate of Grade 3 late genitourinary toxicity was 3.8% consisting of a urethral stricture. There was no other Grade 3 or 4 genitourinary or gastrointestinal toxicities. Single-fraction HDR-boosted IMRT is a safe effective method of dose escalation for localized prostate cancer. Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Balancing Radiation and Contrast Media Dose in Single-Pass Abdominal Multidetector CT: Prospective Evaluation of Image Quality.

Science.gov (United States)

Camera, Luigi; Romano, Federica; Liccardo, Immacolata; Liuzzi, Raffaele; Imbriaco, Massimo; Mainenti, Pier Paolo; Pizzuti, Laura Micol; Segreto, Sabrina; Maurea, Simone; Brunetti, Arturo

2015-11-01

As both contrast and radiation dose affect the quality of CT images, a constant image quality in abdominal contrast-enhanced multidetector computed tomography (CE-MDCT) could be obtained balancing radiation and contrast media dose according to the age of the patients. Seventy-two (38 Men; 34 women; aged 20-83 years) patients underwent a single-pass abdominal CE-MDCT. Patients were divided into three different age groups: A (20-44 years); B (45-65 years); and C (>65 years). For each group, a different noise index (NI) and contrast media dose (370 mgI/mL) was selected as follows: A (NI, 15; 2.5 mL/kg), B (NI, 12.5; 2 mL/kg), and C (NI, 10; 1.5 mL/kg). Radiation exposure was reported as dose-length product (DLP) in mGy × cm. For quantitative analysis, signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated for both the liver (L) and the abdominal aorta (A). Statistical analysis was performed with a one-way analysis of variance. Standard imaging criteria were used for qualitative analysis. Although peak hepatic enhancement was 152 ± 16, 128 ± 12, and 101 ± 14 Hounsfield units (P contrast media dose (mL) administered were 476 ± 147 and 155 ± 27 for group A, 926 ± 291 and 130 ± 16 for group B, and 1981 ± 451 and 106 ± 15 for group C, respectively (P contrast media dose administered to patients of different age. Copyright © 2015 AUR. Published by Elsevier Inc. All rights reserved.

SU-E-I-98: Dose Comparison for Pulmonary Embolism CT Studies: Single Energy Vs. Dual Energy

International Nuclear Information System (INIS)

Mahmood, U; Erdi, Y

2014-01-01

Purpose: The purpose of this study was to assess and compare the size specific dose estimate (SSDE), dose length product (DLP) and noise relationship for pulmonary embolism studies evaluated by single source dual energy computed tomography (DECT) against conventional CT (CCT) studies in a busy cancer center and to determine the dose savings provided by DECT. Methods: An IRB-approved retrospective study was performed to determine the CTDIvol and DLP from a subset of patients scanned with both DECT and CCT over the past five years. We were able to identify 30 breast cancer patients (6 male, 24 female, age range 24 to 81) who had both DECT and CCT studies performed. DECT scans were performed with a GE HD 750 scanner (140/80 kVp, 480 mAs and 40 mm) and CCT scans were performed with a GE Lightspeed 16 slice scanner (120 kVp, 352 mAs, 20 mm). Image noise was measured by placing an ROI and recording the standard deviation of the mean HU along the descending aorta. Results: The average DECT patient size specific dose estimate was to be 14.2 ± 1.7 mGy as compared to 22.4 ± 2.7 mGy from CCT PE studies, which is a 37% reduction in the SSDE. The average DECT DLP was 721.8 ± 84.6 mGy-cm as compared to 981.8 ± 106.1 mGy-cm for CCT, which is a 26% decrease. Compared to CCT the image noise was found to decrease by 19% when using DECT for PE studies. Conclusion: DECT SSDE and DLP measurements indicate dose savings and image noise reduction when compared to CCT. In an environment that heavily debates CT patient doses, this study confirms the effectiveness of DECT in PE imaging

Dose banding as an alternative to body surface area-based dosing of chemotherapeutic agents

NARCIS (Netherlands)

E. Chatelut (Etienne); M.L. White-Koning (M.); A.H.J. Mathijssen (Ron); F. Puisset (F.); S.D. Baker (Sharyn); A. Sparreboom (Alex)

2012-01-01

textabstractBackground: Dose banding is a recently suggested dosing method that uses predefined ranges (bands) of body surface area (BSA) to calculate each patients dose by using a single BSA-value per band. Thus, drugs with sufficient long-term stability can be prepared in advance. The main

Dissociable effects of a single dose of ecstasy (MDMA) on psychomotor skills and attentional performance.

Science.gov (United States)

Lamers, C T J; Ramaekers, J G; Muntjewerff, N D; Sikkema, K L; Samyn, N; Read, N L; Brookhuis, K A; Riedel, W J

2003-12-01

Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a psychoactive recreational drug widely used by young people visiting dance parties, and has been associated with poor cognitive function. The current study assessed the influence of a single dose of MDMA 75 mg and alcohol 0.5 g/kg on cognition, psychomotor performance and driving-related task performance. Twelve healthy recreational ecstasy users participated in an experimental study conducted according to a double-blind, double-dummy, placebo-controlled three-way cross-over design. MDMA improved psychomotor performance, such as movement speed and tracking performance in a single task, as well as in a divided attention task. MDMA impaired the ability to predict object movement under divided attention. However, the inability to accurately predict object movement after MDMA may indicate impairment of particular performance skills relevant to driving. There was no effect of MDMA on visual search, planning or retrieval from semantic memory.

Radiation sensitivity for delayed reproductive death (DRD) following single or split-dose irradiation

International Nuclear Information System (INIS)

Hagemann, G.; Lipfert, C.H.; Wueppen, G.

2001-01-01

Materials and Methods: CHO-cells of a sub clone of the line T71 have a spontaneous cell loss rate of l of the DRD can be defined as the proportional factor of the linear relationship between the MCD on one side and the dose K x the cell division factor m on the other side. E l is dependent on the age of the cells during irradiation and the cell line. The slope of the dually logarithmic growth curve of the cell population is: s=1-E l . K. Experimentally E l was found to be equal for single and split dose irradiation and amounted to E l =0.065 with s d =±0.004. - Literature analysis for the mathematical estimation of E l . K was based on reports of measurements of the local tumor recurrence growth of carcinomas and sarcomas of rodents and pulmonary metastases of sarcomas in humans, respectively, after fractional irradiation. We obtained values of ≤E l . K≤0.77. Values for E l are independent of the dose and lie considerably below data derived from in-vitro measurements of different cell cultures. Conclusions: Since recurrence kinetics of tumors are determined by the radiation sensitivity E l of the DRD, E l can be used for estimating the kinetics of tumor recurrence. As lately described, MCD is linearly proportional to the micro-nucleus frequency. Determinations of the micro-nucleus frequencies in tumor cell biopsies pre and post radiation onset offer the option for developing a fast predictive assay. Organ malformations of embryos after exposition to ionizing radiation can be mathematically deduced by DRD to the partial cell mortality. (orig.) [de

Ketamine: A New Antidepressant?

Directory of Open Access Journals (Sweden)

Feride Karacaer

2015-03-01

Full Text Available Standart antidepressants are needed for the many individuals with major depressive disorder. However they do not respond adequately to treatment and because of a delay of weeks before the emergence of therapeutic effects. Recent studies show that subanesthetic dose of ketamine is efficacy and safety for the treatment of depression. Antidepressant effects of ketamine have been found to be short-lived and its psychotomimetic properties may limit the use of ketamine to depressive patients. Future research studies should focus on identifying predictors of response (pharmalogical and clinical , investigating application of different doses and routes of administration and maintaining antidepressant effect. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2015; 7(1: 30-40

Effects of propranolol on conversational reciprocity in autism spectrum disorder: a pilot, double-blind, single-dose psychopharmacological challenge study.

Science.gov (United States)

Zamzow, Rachel M; Ferguson, Bradley J; Stichter, Janine P; Porges, Eric C; Ragsdale, Alexandra S; Lewis, Morgan L; Beversdorf, David Q

2016-04-01

Pharmacological intervention for autism spectrum disorder (ASD) is an important addition to treatment, yet currently available agents target co-morbid psychiatric concerns, such as aggression and irritability. Propranolol, a beta-adrenergic antagonist with anxiolytic effects, has been shown to improve verbal fluency and working memory in adults and adolescents with ASD in single-dose challenges. The present pilot study explores the acute effects of propranolol on a measure of conversational reciprocity in this population. We also examined whether autonomic activity and anxiety moderate or mediate response to the drug, given relationships between these variables and ASD, as well as the drug's effects. In a within-subject crossover design, 20 individuals with ASD received a single dose of propranolol or placebo during two sessions in a double-blinded, counterbalanced manner. After drug administration, participants performed a conversational reciprocity task by engaging in a short conversation with the researcher. Measurements of autonomic activity and anxiety were obtained before and after drug administration. Propranolol significantly improved performance on the conversational reciprocity task total [d = 0.40] and nonverbal communication domain scores when compared to the placebo condition. However, neither autonomic activity nor anxiety was significantly associated with drug response. Acute propranolol administration improved conversational reciprocity in ASD. Further exploration of these preliminary findings, as well as other potential treatment response predictors, with serial doses is warranted.

Treatment of advanced pancreatic carcinoma with 90Y-Clivatuzumab Tetraxetan: a phase I single-dose escalation trial.

Science.gov (United States)

Gulec, Seza A; Cohen, Steven J; Pennington, Kenneth L; Zuckier, Lionel S; Hauke, Ralph J; Horne, Heather; Wegener, William A; Teoh, Nick; Gold, David V; Sharkey, Robert M; Goldenberg, David M

2011-06-15

Humanized antibody hPAM4 specifically binds a mucin glycoprotein expressed in pancreatic adenocarcinomas. This phase I study evaluated a single dose of (90)Y-clivatuzumab tetraxetan ((90)Y-labeled hPAM4) in patients with advanced pancreatic cancer. Twenty-one patients (4 stage III; 17 stage IV) received (111)In-hPAM4 for imaging and serum sampling before (90)Y-hPAM4. Study procedures evaluated adverse events, safety laboratories, computed tomography (CT) scans, biomarkers, pharmacokinetics, radiation dosimetry, and immunogenicity (HAHA). (111)In-hPAM4 showed normal biodistribution with radiation dose estimates to red marrow and solid organs acceptable for radioimmunotherapy and with tumor targeting in 12 patients. One patient withdrew before (90)Y-hPAM4; otherwise, 20 patients received (90)Y doses of 15 (n = 7), 20 (n = 9), and 25 mCi/m(2) (n = 4). Treatment was well tolerated; the only significant drug-related toxicities were (NCI CTC v.3) grade 3 to 4 neutropenia and thrombocytopenia increasing with (90)Y dose. There were no bleeding events or serious infections, and most cytopenias recovered to grade 1 within 12 weeks. Three patients at 25 mCi/m(2) encountered dose-limiting toxicity with grade 4 cytopenias more than 7 days, establishing 20 mCi/m(2) as the maximal tolerated (90)Y dose. Two patients developed HAHA of uncertain clinical significance. Most patients progressed rapidly and with CA19-9 levels increasing within 1 month of therapy, but 7 remained progression-free by CT for 1.5 to 5.6 months, including 3 achieving transient partial responses (32%-52% tumor diameter shrinkage). (90)Y-Clivatuzumab tetraxetan was well tolerated with manageable hematologic toxicity at the maximal tolerated (90)Y dose, and is a potential new therapeutic for advanced pancreatic cancer. ©2011 AACR.

Efficacy of a single dose of milbemycin oxime/praziquantel combination tablets, Milpro(®), against adult Echinococcus multilocularis in dogs and both adult and immature E. multilocularis in young cats.

Science.gov (United States)

Cvejic, Dejan; Schneider, Claudia; Fourie, Josephus; de Vos, Christa; Bonneau, Stephane; Bernachon, Natalia; Hellmann, Klaus

2016-03-01

Two single-site, laboratory, negatively controlled, masked, randomised dose confirmation studies were performed: one in dogs, the other in cats. After a period of acclimatisation, both the dogs and cats were orally infected with Echinococcus multilocularis protoscoleces. In the dog study, 10 dogs received a single dose of Milpro® tablets at a minimum dose of 0.5 mg/kg milbemycin oxime and 5 mg/kg praziquantel 18 days post-infection and 10 dogs received no treatment. In the cat study, 10 cats received a single dose of Milpro® tablets at a minimum dose of 2 mg/kg milbemycin oxime and 5 mg/kg praziquantel 7 days post-infection, 10 cats received a single dose of the treatment 18 days post-infection and 10 cats remained untreated. In both studies, intestinal worm counts were performed 23 days post-infection at necropsy. No worms were retrieved from any of the 30 treated animals. Nine of 10 control dogs had multiple worms (geometric mean 91, arithmetic mean 304) and all 10 control cats had multiple worms (geometric mean 216, arithmetic mean 481). The difference in worm counts between all three treated groups and their controls was highly significant (ANOVA p values of log transformed data dogs and cats as well as for elimination of immature E. multilocularis in cats as evidenced by the effectiveness of treatment 7 days post-infection. The treatments were well accepted and tolerated, and there were no adverse drug reactions observed.

Estimation and comparison of effective dose (E) in standard chest CT by organ dose measurements and dose-length-product methods and assessment of the influence of CT tube potential (energy dependency) on effective dose in a dual-source CT.

Science.gov (United States)

Paul, Jijo; Banckwitz, Rosemarie; Krauss, Bernhard; Vogl, Thomas J; Maentele, Werner; Bauer, Ralf W

2012-04-01

To determine effective dose (E) during standard chest CT using an organ dose-based and a dose-length-product-based (DLP) approach for four different scan protocols including high-pitch and dual-energy in a dual-source CT scanner of the second generation. Organ doses were measured with thermo luminescence dosimeters (TLD) in an anthropomorphic male adult phantom. Further, DLP-based dose estimates were performed by using the standard 0.014mSv/mGycm conversion coefficient k. Examinations were performed on a dual-source CT system (Somatom Definition Flash, Siemens). Four scan protocols were investigated: (1) single-source 120kV, (2) single-source 100kV, (3) high-pitch 120kV, and (4) dual-energy with 100/Sn140kV with equivalent CTDIvol and no automated tube current modulation. E was then determined following recommendations of ICRP publication 103 and 60 and specific k values were derived. DLP-based estimates differed by 4.5-16.56% and 5.2-15.8% relatively to ICRP 60 and 103, respectively. The derived k factors calculated from TLD measurements were 0.0148, 0.015, 0.0166, and 0.0148 for protocol 1, 2, 3 and 4, respectively. Effective dose estimations by ICRP 103 and 60 for single-energy and dual-energy protocols show a difference of less than 0.04mSv. Estimates of E based on DLP work equally well for single-energy, high-pitch and dual-energy CT examinations. The tube potential definitely affects effective dose in a substantial way. Effective dose estimations by ICRP 103 and 60 for both single-energy and dual-energy examinations differ not more than 0.04mSv. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis

Directory of Open Access Journals (Sweden)

Satoshi Takahashi

2014-04-01

Full Text Available To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011–2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33. The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43 and 37.2% (16/43, respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50. The microbiological eradication rates for the pathogens were 90.9% (30/33 for Neisseria gonorrhoeae, 91.5% (43/47 for Chlamydia trachomatis, 71.4% (5/7 for Mycoplasma genitalium, and 100% (13/13 for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120. The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

Clinical Efficacy of a Single Two Gram Dose of Azithromycin Extended Release for Male Patients with Urethritis.

Science.gov (United States)

Takahashi, Satoshi; Kiyota, Hiroshi; Ito, Shin; Iwasawa, Akihiko; Hiyama, Yoshiki; Uehara, Teruhisa; Ichihara, Koji; Hashimoto, Jiro; Masumori, Naoya; Sunaoshi, Kenichi; Takeda, Koichi; Suzuki, Nobukazu; Hosobe, Takahide; Goto, Hirokazu; Suzuki, Hidenori; Onodera, Shoichi

2014-04-02

To clarify the clinical efficacy of a single oral 2 g dose of azithromycin extended-release for heterosexual male patients with urethritis, and the current antimicrobial sensitivity of Neisseria gonorrhoeae to azithromycin, a prospective clinical trial was conducted from 2011-2013. In patients with gonococcal urethritis, the eradication rate was 90.9% (30 of 33). The susceptibility rates of isolated Neisseria gonorrhoeae strains to ceftriaxone, spectinomycin, cefixime and azithromycin were 100%, 100%, 95.3% (41/43) and 37.2% (16/43), respectively. In the patients with nongonococcal urethritis, the eradication rate was 90.0% (45 of 50). The microbiological eradication rates for the pathogens were 90.9% (30/33) for Neisseria gonorrhoeae, 91.5% (43/47) for Chlamydia trachomatis, 71.4% (5/7) for Mycoplasma genitalium, and 100% (13/13) for Ureaplasma urealyticum. The main adverse event was diarrhea and its manifestation rate was 35.2% (32 of 120). The symptom of diarrhea was mostly temporary and resolved spontaneously. The conclusion was that the treatment regimen with a single oral 2 g dose of azithromycin extended-release would be effective for patients with urethritis. However, the antimicrobial susceptibilities of Neisseria gonorrhoeae and Mycoplasma genitalium should be carefully monitored because of possible treatment failure.

Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

Science.gov (United States)

Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

2015-01-01

Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.