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Sample records for single therapeutic dose

  1. 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

  2. Therapeutic dosage assessment based on population pharmacokinetics of a novel single-dose transdermal donepezil patch in healthy volunteers.

    Science.gov (United States)

    Choi, Hee Youn; Kim, Yo Han; Hong, Donghyun; Kim, Seong Su; Bae, Kyun-Seop; Lim, Hyeong-Seok

    2015-08-01

    We performed population pharmacokinetic (PK) analysis of a novel transdermal donepezil patch in healthy subjects who participated in a phase I trial. We also studied the optimal dosage regimen with repeated patch application for achieving a therapeutic range using a PK simulation model. This study used data from a randomized, single-dose escalation phase I clinical trial conducted in Korea. The population PK analysis was performed using NONMEM software, version 7.3. From the final PK model, we simulated repeat patch application results assuming various transdermal absorption rates. Based on the clinical trial data, novel donepezil patches with doses of 43.75 mg/12.5 cm(2), 87.5 mg/25 cm(2), and 175 mg/50 cm(2) were placed on each subject. A linear one-compartment, first-order elimination with sequential zero- and first-order absorption model best described the donepezil plasma concentrations after patch application. Simulated results on the basis of the PK model showed that repeat application of the patches of 87.5 mg/25 cm(2) and 175 mg/50 cm(2) every 72 h would cover the therapeutic range of donepezil and reach steady-state faster with fewer fluctuations in concentration compared to typical oral administrations. A linear one-compartment with sequential zero- and first-order absorption model was effective for describing the PKs of donepezil after application of patch. Based on this analysis, 87.5 mg/25 cm(2) or 175 mg/50 cm(2) patch application every 72 h is expected to achieve the desired plasma concentration of donepezil.

  3. Dose optimisation of voriconazole with therapeutic drug monitoring in children: a single-centre experience in China.

    Science.gov (United States)

    Liu, Liang; Zhou, Xing; Wu, Tingting; Jiang, Hongliang; Yang, Sitao; Zhang, Yang

    2017-04-01

    The pharmacokinetic profile of voriconazole is highly variable, rendering inconsistent and/or inadequate dosing, especially in children voriconazole with at least one plasma trough level (C trough ) monitored. Statistical analyses were performed to examine the dose-exposure relationship as well as other factors potentially affecting voriconazole C trough in children of different ages. A total of 107 paediatric patients were included, of whom 75 were voriconazole C trough was highly variable in patients aged voriconazole exposure. Co-administration of omeprazole significantly increased the voriconazole level (P = 0.032), likely through CYP2C19 inhibition. This is the largest series to date describing voriconazole dose-exposure relationships in children aged <2 years. A starting maintenance dose of 5 to <7 mg/kg intravenously twice daily may be required for most children of Asian origin to reach the therapeutic target. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  4. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single [14C]-Labeled Therapeutic Dose.

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K; Tompkins, E M; Boocock, D J; Martin, E A; Farmer, P B; Turteltaub, K W; Ubick, E; Hemingway, D; Horner-Glister, E; White, I H

    2007-05-23

    Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the U.S. for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated but much interest has focussed on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to ten women as a single [{sup 14}C]-labeled therapeutic (20 mg) dose, {approx}18 h prior to undergoing colon resections. Using the sensitive technique of accelerator mass spectrometry, coupled with HPLC separation of enzymatically digested DNA, a peak corresponding to authentic dG-N{sup 2}-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/10{sup 9} nucleotides. No [{sup 14}C]-radiolabel associated with tamoxifen or its major metabolites was detected. The presence of detectable CYP3A4 protein in all colon samples suggests this tissue has the potential to activate tamoxifen to {alpha}-hydroxytamoxifen, in addition to that occurring in the systemic circulation, and direct interaction of this metabolite with DNA could account for the binding observed. Although the level of tamoxifeninduced damage displayed a degree of inter-individual variability, when present it was {approx}10-100 times higher than that reported for other suspect human colon carcinogens such as PhIP. These findings provide a mechanistic basis through which tamoxifen could increase the incidence of colon cancers in women.

  5. 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

  6. 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

  7. Pharmacist-managed dose adjustment feedback using therapeutic drug monitoring of vancomycin was useful for patients with methicillin-resistant Staphylococcus aureus infections: a single institution experience

    Directory of Open Access Journals (Sweden)

    Hirano R

    2016-10-01

    Full Text Available Ryuichi Hirano,1 Yuichi Sakamoto,2 Junichi Kitazawa,2 Shoji Yamamoto,1 Naoki Tachibana2 1Department of Pharmacy, 2Laboratory Medicine and Blood Transfusion, Aomori Prefectural Central Hospital, Aomori-shi, Japan Background: Vancomycin (VCM requires dose adjustment based on therapeutic drug monitoring. At Aomori Prefectural Central Hospital, physicians carried out VCM therapeutic drug monitoring based on their experience, because pharmacists did not participate in the dose adjustment. We evaluated the impact of an Antimicrobial Stewardship Program (ASP on attaining target VCM trough concentrations and pharmacokinetics (PK/pharmacodynamics (PD parameters in patients with methicillin-resistant Staphylococcus aureus (MRSA infections. Materials and methods: The ASP was introduced in April 2012. We implemented a prospective audit of prescribed VCM dosages and provided feedback based on measured VCM trough concentrations. In a retrospective pre- and postcomparison study from April 2007 to December 2011 (preimplementation and from April 2012 to December 2014 (postimplementation, 79 patients were treated for MRSA infection with VCM, and trough concentrations were monitored (pre, n=28; post, n=51. In 65 patients (pre, n=15; post, n=50, 24-hour area under the ­concentration–time curve (AUC 0–24 h/minimum inhibitory concentration (MIC ratios were calculated. Results: Pharmacist feedback, which included recommendations for changing dose or using alternative anti-MRSA antibiotics, was highly accepted during postimplementation (88%, 29/33. The number of patients with serum VCM concentrations within the therapeutic range (10–20 μg/mL was significantly higher during postimplementation (84%, 43/51 than during preimplementation (39%, 11/28 (P<0.01. The percentage of patients who attained target PK/PD parameters (AUC 0–24 h/MIC >400 was significantly higher during postimplementation (84%, 42/50 than during preimplementation (53%, 8/15; P=0.013. There were

  8. Dose computation for therapeutic electron beams

    Science.gov (United States)

    Glegg, Martin Mackenzie

    The accuracy of electron dose calculations performed by two commercially available treatment planning computers, Varian Cadplan and Helax TMS, has been assessed. Measured values of absorbed dose delivered by a Varian 2100C linear accelerator, under a wide variety of irradiation conditions, were compared with doses calculated by the treatment planning computers. Much of the motivation for this work was provided by a requirement to verify the accuracy of calculated electron dose distributions in situations encountered clinically at Glasgow's Beatson Oncology Centre. Calculated dose distributions are required in a significant minority of electron treatments, usually in cases involving treatment to the head and neck. Here, therapeutic electron beams are subject to factors which may cause non-uniformity in the distribution of dose, and which may complicate the calculation of dose. The beam shape is often irregular, the beam may enter the patient at an oblique angle or at an extended source to skin distance (SSD), tissue inhomogeneities can alter the dose distribution, and tissue equivalent material (such as wax) may be added to reduce dose to critical organs. Technological advances have allowed the current generation of treatment planning computers to implement dose calculation algorithms with the ability to model electron beams in these complex situations. These calculations have, however, yet to be verified by measurement. This work has assessed the accuracy of calculations in a number of specific instances. Chapter two contains a comparison of measured and calculated planar electron isodose distributions. Three situations were considered: oblique incidence, incidence on an irregular surface (such as that which would be arise from the use of wax to reduce dose to spinal cord), and incidence on a phantom containing a small air cavity. Calculations were compared with measurements made by thermoluminescent dosimetry (TLD) in a WTe electron solid water phantom. Chapter

  9. Therapeutic effects of low radiation doses

    Energy Technology Data Exchange (ETDEWEB)

    Trott, K.R. (Dept. of Radiation Biology, St. Bartholomew' s Medical College, London (United Kingdom))

    1994-01-01

    This editorial explores the scientific basis of radiotherapy with doses of < 1 Gy for various non-malignant conditions, in particular dose-effect relationships, risk-benefit considerations and biological mechanisms. A review of the literature, particularly clinical and experimental reports published more than 50 years ago was conducted to clarify the following problems. 1. The dose-response relationships for the therapeutic effects on three groups of conditions: non-malignant skin disease, arthrosis and other painful degenerative joint disorders and anti-inflammatory radiotherapy; 2. risks after radiotherapy and after the best alternative treatments; 3. the biological mechanisms of the different therapeutic effects. Radiotherapy is very effective in all three groups of disease. Few dose-finding studies have been performed, all demonstrating that the optimal doses are considerable lower than the generally recommended doses. In different conditions, risk-benefit analysis of radiotherapy versus the best alternative treatment yields very different results: whereas radiotherapy for acute postpartum mastitis may not be justified any more, the risk-benefit ratio of radiotherapy of other conditions and particularly so in dermatology and some anti-inflammatory radiotherapy appears to be more favourable than the risk-benefit ratio of the best alternative treatments. Radiotherapy can be very effective treatment for various non-malignant conditions such as eczema, psoriasis, periarthritis humeroscapularis, epicondylitis, knee arthrosis, hydradenitis, parotitis and panaritium and probably be associated with less acute and long-term side effects than similarly effective other treatments. Randomized clinical studies are required to find the optimal dosage which, at present, may be unnecessarily high.

  10. Therapeutic dose from a pyroelectric electron accelerator.

    Science.gov (United States)

    Fullem, T Z; Fazel, K C; Geuther, J A; Danon, Y

    2009-11-01

    Simple heating of pyroelectric crystals has been used as the basis for compact sources of X rays, electrons, ions and neutrons. We report on the evaluation of the feasibility of using a portable pyroelectric electron accelerator to deliver a therapeutic dose to tissue. Such a device could be mass produced as a handheld, battery-powered instrument. Experiments were conducted with several crystal sizes in which the crystal was heated inside a vacuum chamber and the emitted electrons were allowed to penetrate a thin beryllium window into the surrounding air. A Faraday cup was used to count the number of electrons that exited the window. The energy of these electrons was determined by measuring the energy spectrum of the X rays that resulted from the electron interactions with the Faraday cup. Based on these measurements, the dose that this source could deliver to tissue was calculated using Monte Carlo calculations. It was found that 10(13) electrons with a peak energy of the order of 100 keV were emitted from the beryllium window and could deliver a dose of 1664 Gy to a 2-cm-diameter, 110-microm-deep region of tissue located 1.5 cm from the window with air between the window and the tissue. This dose level is high enough to consider this technology for medical applications in which shallow energy deposition is beneficial.

  11. Intestinal absorbtion from therapeutic iron doses

    International Nuclear Information System (INIS)

    Werner, E.

    1977-01-01

    On a total of 105 persons with normal iron stores, iron depletion, and iron deficiency the intestinal absorption from therapeutic iron doses (100 mg Fe and 50 mg Fe as ferrous glycocoll sulphate) of a special galenic form was measured. The measurements were performed by means of a whole-body counter and preparations labelled with radio iron ( 59 Fe). Mean values of absorption rates from 100 mg Fe in healthy males were 5.0% and in healthy females 5.6% whereas in latent iron deficiency and in iron deficiency anemia mean values of 10% and 13% were obtained, respectively. The maximum absorption rate of 20 to 25% is reached already in the late stage of latent iron deficiency. Advancing severeness of iron deficiency is not followed by an increase of iron absorption. Investigations an 21 persons showed no significant difference between absorption rates of the galenic preparations used when administered orally before or after breakfast, respectively. (orig.) [de

  12. 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, ...

  13. 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.

  14. Acetaminophen-cysteine adducts during therapeutic dosing and following overdose

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    Judge Bryan S

    2011-03-01

    Full Text Available Abstract Background Acetaminophen-cysteine adducts (APAP-CYS are a specific biomarker of acetaminophen exposure. APAP-CYS concentrations have been described in the setting of acute overdose, and a concentration >1.1 nmol/ml has been suggested as a marker of hepatic injury from acetaminophen overdose in patients with an ALT >1000 IU/L. However, the concentrations of APAP-CYS during therapeutic dosing, in cases of acetaminophen toxicity from repeated dosing and in cases of hepatic injury from non-acetaminophen hepatotoxins have not been well characterized. The objective of this study is to describe APAP-CYS concentrations in these clinical settings as well as to further characterize the concentrations observed following acetaminophen overdose. Methods Samples were collected during three clinical trials in which subjects received 4 g/day of acetaminophen and during an observational study of acetaminophen overdose patients. Trial 1 consisted of non-drinkers who received APAP for 10 days, Trial 2 consisted of moderate drinkers dosed for 10 days and Trial 3 included subjects who chronically abuse alcohol dosed for 5 days. Patients in the observational study were categorized by type of acetaminophen exposure (single or repeated. Serum APAP-CYS was measured using high pressure liquid chromatography with electrochemical detection. Results Trial 1 included 144 samples from 24 subjects; Trial 2 included 182 samples from 91 subjects and Trial 3 included 200 samples from 40 subjects. In addition, we collected samples from 19 subjects with acute acetaminophen ingestion, 7 subjects with repeated acetaminophen exposure and 4 subjects who ingested another hepatotoxin. The mean (SD peak APAP-CYS concentrations for the Trials were: Trial 1- 0.4 (0.20 nmol/ml, Trial 2- 0.1 (0.09 nmol/ml and Trial 3- 0.3 (0.12 nmol/ml. APAP-CYS concentrations varied substantially among the patients with acetaminophen toxicity (0.10 to 27.3 nmol/ml. No subject had detectable APAP

  15. Methodology for management of therapeutic dose of I-131

    International Nuclear Information System (INIS)

    Basteris M, J.; Gomez D, R.

    2007-01-01

    The present work suggests the use of measures guided to eliminate the resulting chronic sialoadenitis of the treatment previously described with a therapeutic dose bigger than ablative of Iodine 131, as well as the use of citric fruits to stimulate the salivation, the administration of liquid post-dose is included to accelerate the gastric emptying avoiding the secondary effects as the vomit. (Author)

  16. Dose optimisation in single plane interstitial brachytherapy.

    Science.gov (United States)

    Tanderup, Kari; Hellebust, Taran Paulsen; Honoré, Henriette Benedicte; Nielsen, Søren Kynde; Olsen, Dag Rune; Grau, Cai; Lindegaard, Jacob Christian

    2006-10-01

    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. In 14 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 (OI), homogeneity index (HI), conformal index (COIN), minimum target dose, and high dose volumes were evaluated. The dependence of OI, HI, and COIN on target volume and implant regularity was evaluated. In addition, 12 theoretical implant configurations were analyzed. Geometrical and graphical optimisation improved the dose plans significantly with graphical optimisation being superior. Graphically optimised dose plans showed a significant decrease of 18%+/-9% in high dose volume (pusability of these parameters for comparison of dose plans between patients. Dwell time optimisation significantly improved the dose distribution regarding homogeneity, conformity, minimum target dose, and size of high dose volumes. Graphical optimisation is fast, reproducible and superior to geometric optimisation.

  17. Effect of a therapeutic dose of pseudoephedrine on swimmers ...

    African Journals Online (AJOL)

    To investigate the effect of therapeutic PSE use on performance in aerobic and explosive sprint swimming events. Method. A double-blinded cross-over study design was used. Participants in the control group initially received a placebo and those in the experimental group received a divided PSE dose of 90 mg/d.

  18. Dose optimisation in single plane interstitial brachytherapy

    DEFF Research Database (Denmark)

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

    2006-01-01

    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...... 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...... (OI),       homogeneity index (HI), conformal index (COIN), minimum target dose, and       high dose volumes were evaluated. The dependence of OI, HI, and COIN on       target volume and implant regularity was evaluated. In addition, 12       theoretical implant configurations were analyzed. RESULTS...

  19. Radiation doses by therapeutical practices with iodine 131

    International Nuclear Information System (INIS)

    Di Trano, J.L.; Rojo, A.M.; Gomez Parada, I.M.; Grassi, E.; Gatica, N.; Kunst, J.J.; Gonzalez, M.

    1998-01-01

    The aim of this document is to estimate the doses to workers and public due to therapeutical practices with iodine 131. Environmental and personal doses by external irradiation were determined using thermoluminescent dosimeters (TLD). The environmental dosimetry resulted in an equivalent dose H * (10) of approximately 0,1 mSv. The calculated personal equivalent dose Hp (10) was of the order of 0,1 mSv. The exposition rate was measured, being the values obtained in the range of 0,20 and 0,35 mSv/h. (1m from the abdominal wall). Concentrations of iodine 131 were determinate in the air of the room, during the first day in the hospital. Values obtained were between 0,04 Bq/l and 0,20 Bq/l. Surface samples were taken in the service, obtaining levels of contamination in the range of 0,001 and 0,4 Bq/cm 2 . The surface samples obtained in the hospital room were about 0,15 Bq/cm 2 . Urine samples were collected resulting in an eliminated activity of iodine 131, during the first 24 hours, of about 60 % of the administered activity. Samples of sweat of different cutaneous regions were obtained, the maximum values of the activity measured reached 200 Bq/cm 2 . According to the obtained results it is important to elaborate guides to be given to patients as an instrument to reduce the external exposure and to avoid internal contamination. (author)

  20. Single dose regorafenib-induced hypertensive crisis.

    Science.gov (United States)

    Yilmaz, B; Kemal, Y; Teker, F; Kut, E; Demirag, G; Yucel, I

    2014-06-01

    Gastrointestinal stromal tumors (GISTs) are uncommon tumors of the gastrointestinal (GI) tract. Regorafenib is a new multikinase inhibitor and is approved for the treatment of GISTs in patients who develop resistance to imatinib and sunitinib. The most common drug-related adverse events with regorafenib are hypertension, hand-foot skin reactions, and diarrhea. Grade IV hypertensive side effect has never been reported after a single dose. In this report, we present a case of Grade IV hypertensive side effect (hypertensive crisis and seizure) after a single dose of regorafenib. A 54-year-old male normotensive GIST patient was admitted to the emergency department with seizure and encephalopathy after the first dosage of regorafenib. His blood pressure was 240/140 mmHg upon admission. After intensive treatment with nitrate and nitroprusside, his blood pressure returned to normal levels in five days. Regorafenib was discontinued, and he did not experience hypertension again. This paper reports the first case of Grade IV hypertension after the first dosage of regorafenib. We can suggest that hypertension is an idiosyncratic side effect unrelated to the dosage.

  1. Therapeutic rationale for low dose doxepin in insomnia patients

    Directory of Open Access Journals (Sweden)

    Jigar Katwala

    2013-08-01

    Full Text Available Histamine is an excitatory neurotransmitter in central nervous system. It plays an important role in the regulation of the sleep-wake cycle. Antidepressant with sleep-promoting effects, for example, doxepin, promotes sleep not through a sedative action but through resynchronisation of circadian cycle. The stimulation of the H1 receptor is thought to play an important role in mediating arousal. Doxepin has a high affinity for the H1 receptor, making it a selective H1 antagonist at low dose and it has been shown to display sedating properties. Compared to other sedative antidepressant, low dose doxepin is the only tricyclic drug which has been evaluated by well-designed, randomised, double blind, placebo controlled studies in both adult and elderly patients. Doxepin is not designated as controlled substance/unscheduled drugs and thus may be of special advantage to use in patients with a history of substance abuse. Hence, welldocumented therapeutic efficacy, tolerability and lack of important adverse effects make the low dose doxepin as a unique, rational drug for the treatment of insomnia in adult and elderly patients.

  2. A comparative study of Multiple versus Single infection doses of ...

    African Journals Online (AJOL)

    kemrilib

    auratus) were compared with those of single exposure. Multiple infections with low doses of the parasite did not seem to be protective, as suggested by; more worms, worse gross and histopathology in multiple low dose group compared to single high dose group. Most probably there is an antigenic threshold, which needs ...

  3. Reporting and validation of gynaecological Groupe Euopeen de Curietherapie European Society for Therapeutic Radiology and Oncology (ESTRO) brachytherapy recommendations for MR image-based dose volume parameters and clinical outcome with high dose-rate brachytherapy in cervical cancers: a single-institution initial experience.

    Science.gov (United States)

    Mahantshetty, Umesh; Swamidas, Jamema; Khanna, Nehal; Engineer, Reena; Merchant, Nikhil H; Deshpande, Deepak D; Shrivastava, Shyamkishore

    2011-08-01

    The objectives are to report the dosimetric analysis, preliminary clinical outcome, and comparison with published data of 3-dimensional magnetic resonance-based high dose rate brachytherapy (BT) in cervical cancer. The data set of 24 patients with cervical cancer treated with high dose-rate brachytherapy applications was analyzed. All patients received radiation with or without chemotherapy (10 patients received concomitant chemoradiation). Point A, International Commission on Radiation Units and Measurement (ICRU) point doses, and Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology dose volume parameters, namely, high-risk clinical target volume (HR-CTV), D90 and D100 doses, and dose to D0.1cc and D2cc, for rectum, bladder, and sigmoid, were calculated and correlated. Mean ± SD HR-CTV was 45.2 ± 15.8 cc. The mean ± SD point A dose was 73.4 ± 4.5 Gy (median, 74.3 Gy) total biologically equivalent dose in 2 Gy per fraction (EQD2), whereas mean ± SD D90 doses were 70.9 ± 10.6 GyEQD2 (median, 68). The mean ± SD ICRU rectal and bladder points were 63.5 ± 8.1 and 80.4 ± 34.4 GyEQD2, respectively. The D0.1cc and D2cc for rectum were 66.0 ± 9.9 GyEQD2 (median, 64.5) and 57.8 ± 7.7 GyEQD2 (median, 58.8), for bladder 139.1 ± 54.7 GyEQD2 (median, 131.9) and 93.4 ± 24.6 GyEQD2 (median, 91), and sigmoid were 109.4 ± 45.2 GyEQD2 (median, 91) and 74.6 ± 19.6 GyEQD2 (median, 69.6). With a median follow-up of 24 months, 3 patients had local nodal failure, 1 had right external iliac nodal failure, and 1 had left supraclavicular nodal failure. The 3-D magnetic resonance image-based high dose-rate brachytherapy approach in cervical cancers is feasible. In our experience, the HR-CTV volumes are large, and D0.1cc and D2cc doses to bladder and sigmoid are higher than published literature so far.

  4. [Treatment of Kawasaki disease by different doses of immunoglobulin: a Mata analysis of therapeutic effects].

    Science.gov (United States)

    Chen, Jing; Ma, Bin; Lin, Li-Xing; Xue, Yi-Ming

    2011-08-01

    To assess the therapeutic effects and safety of different doses of immunoglobulin in the treatment of Kawasaki disease. The papers related to the treatment of Kawasaki disease were electronically searched in the databases of PubMed, EMBASE, Cochrane Library, CNKI, VIP and Wanfang. Randomized clinical trials (RCT) on the treatment of Kawasaki disease with different doses of immunoglobulin were included and assessed for quality. A Mata analysis was performed by RevMan 5.0. Twenty-eight RCTs involved 2596 cases were included. The results of Meta analysis showed that there were no significant differences in the incidences of coronary artery injuries at various phases, adverse effects and fever disappearance time between the immunoglobulin treatment groups at the doses of 1 g/(kg•d) for 1-2 days and 2 g/(kg•d) for single use. The fever disappearance time in the immunoglobulin treatment group at the dose of 1 g/(kg•d) for 1-2 days was significantly shorter than that in the immunoglobulin treatment group at the dose of 400 mg/(kg•d) for 4-5 days, but there were no significant differences in the incidences of coronary artery injuries at the acute phase and 6 months after treatment and adverse effects between the two groups. The incidence of coronary artery injuries at the acute phase and 6 months was lower and the fever disappearance time was shorter in the immunoglobulin treatment group at the dose of 2 g/(kg•d) for single use than those in the immunoglobulin treatment group at the dose of 400 mg/(kg•d) for 4-5 days, but there were no significant differences in the incidences of coronary artery injuries at the subacute phase and 12 months after treatment and adverse effects between the two groups. There are similar therapeutic effects for Kawasaki disease between the immunoglobulin treatment groups at the doses of 1 g/(kg•d) for 1-2 days and 2 g/(kg•d) for single use. The fever disappearance time in the two groups is shorter than that in the treatment

  5. Deferasirox at therapeutic doses is associated with dose-dependent hypercalciuria.

    Science.gov (United States)

    Wong, Phillip; Polkinghorne, Kevan; Kerr, Peter G; Doery, James C G; Gillespie, Matthew T; Larmour, I; Fuller, Peter J; Bowden, Donald K; Milat, Frances

    2016-04-01

    Deferasirox is an oral iron chelator used widely in the treatment of thalassemia major and other transfusion-dependent hemoglobinopathies. Whilst initial long-term studies established the renal safety of deferasirox, there are now increasing reports of hypercalciuria and renal tubular dysfunction. In addition, urolithiasis with rapid loss of bone density in patients with β thalassemia major has been reported. We conducted a cross-sectional cohort study enrolling 152 adult patients comprising of β thalassemia major (81.5%), sickle cell disease (8%), thalassemia intermedia (2%), HbH disease (6.5%) and E/β thalassemia (2%). Cases were matched with normal control subjects on age, gender and serum creatinine. Iron chelator use was documented and urine calcium to creatinine ratios measured. At the time of analysis, 88.8% of patients were receiving deferasirox and 11.2% were on deferoxamine. Hypercalciuria was present in 91.9% of subjects on deferasirox in a positive dose-dependent relationship. This was not seen with subjects receiving deferoxamine. At a mean dose of 30.2±8.8mg/kg/day, deferasirox was associated with an almost 4 fold increase in urine calcium to creatinine ratio (UCa/Cr). Hypercalciuria was present at therapeutic doses of deferasirox in a dose-dependent manner and warrants further investigation and vigilance for osteoporosis, urolithiasis and other markers of renal dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Single dose pharmacokinetics of mefloquine in healthy Nigerian ...

    African Journals Online (AJOL)

    Single dose pharmacokinetics of mefloquine was determined in SJ ic healthy Nigerian male subjects. Mefloquine 500mg single dose was administered and blood sa mples were collected 11t intervals. Plasma concentrations were determined by RP-HPLC method after sample pretreated step by solid phase extraction ...

  7. single dose pharmacokinetics of mefloquine in healthy nigerian ...

    African Journals Online (AJOL)

    BSN

    Single dose pharmacokinetics of mefloquine was determined in SJ ic healthy Nigerian male subjects. Mefloquine 500mg single dose was administered and blood samples were collected. 11t intervals. Plasma concentrations were determined by RP-HPLC method after sample pre- treated step by solid phase extraction ...

  8. single dose pharmacokinetics of mefloquine in healthy nigerian ...

    African Journals Online (AJOL)

    BSN

    University of Jos, Jos Nigeria. Single dose pharmacokinetics of mefloquine was determined in SJ ic healthy Nigerian male subjects. ... INTRODUCTION. Mefloquine is a quinolinemethanol antimalarial found to be effective as single dose therapy for all species ..... ·ographic using electron capture. LB. a'"lrl Rcmbo L., (1993).

  9. Single-Domain Antibodies As Therapeutics against Human Viral Diseases

    Directory of Open Access Journals (Sweden)

    Yanling Wu

    2017-12-01

    Full Text Available In full-size formats, monoclonal antibodies have been highly successful as therapeutics against cancer and immune diseases. However, their large size leads to inaccessibility of some epitopes and relatively high production costs. As an alternative, single-domain antibodies (sdAbs offer special advantages compared to full-size antibodies, including smaller size, larger number of accessible epitopes, relatively low production costs and improved robustness. Currently, sdAbs are being developed against a number of viruses, including human immunodeficiency virus-1 (HIV-1, influenza viruses, hepatitis C virus (HCV, respiratory syncytial virus (RSV, and enteric viruses. Although sdAbs are very potent inhibitors of viral infections, no sdAbs have been approved for clinical use against virial infection or any other diseases. In this review, we discuss the current state of research on sdAbs against viruses and their potential as therapeutics against human viral diseases.

  10. Therapeutic doses of radiation alter proliferation and attachment of osteoblasts to implant surfaces.

    Science.gov (United States)

    Ahmad, Mansur; Sampair, Christopher; Nazmul-Hossain, Abu N M; Khurana, Neerja; Nerness, Andrew; Wutticharoenmongkol, Patcharaporn

    2008-09-15

    Osseointegration of implants in irradiated bone is inadequate. The effect of radiation on cell-implant material interaction has not been adequately studied. The goal of this study was to investigate the effects of ionizing radiationon the proliferation, differentiation, and attachment of osteoblasts to commercially pure titanium (cpTi). Human fetal osteoblasts (hFOB) were irradiated either before or after plating in tissue culture (TC) dishes with or without cpTi disks. Radiation was single dose of 10 cGy, 25 cGy, 50 cGy, 1 Gy, 2 Gy, 4 Gy or 8 Gy. Cell proliferation was determined by counting trypsinized cells on 7 days after irradiation. Attachment of irradiated hFOB was measured indirectly by counting cells 2 and 6 h after plating. Differentiation was evaluated by alkaline phosphatase activity. Compared with nonirradiated sham controls, higher doses of radiation significantly reduced cell attachment and proliferation. Both proliferation and attachment were significantly lower on cpTi compared with TC. Attachment decreased based on the length of postirradiation period. Although differentiation was significantly enhanced by a dose of 8 Gy, proliferation was lowest. These initial studies show that effects of therapeutic doses of radiation on osteoblasts varied depending on the surface, time-elapsed, and amount of radiation.

  11. Tolerance of the human spinal cord to single dose radiosurgery

    International Nuclear Information System (INIS)

    Ryu, S.; Zhu, G.; Yin, F.-F.; Ajlouni, M.; Kim, J.H.

    2003-01-01

    Tolerance of the spinal cord to the single dose of radiation is not well defined. Although there are cases of human spinal cord tolerance from re-irradiation to the same cord level, the information about the tolerance of human spinal cord to single large dose of radiosurgery is not available. We carried out spinal radiosurgery to treat spinal metastasis and studied the single dose tolerance of the human spinal cord in an ongoing dose escalation paradigm. A total of 39 patients with 48 lesions of spinal metastasis were treated with single dose radiosurgery at Henry Ford Hospital. The radiosurgery dose was escalated from 8 Gy to 16 Gy at 2 Gy increment. The radiation dose was prescribed to periphery of the spinal tumor. The radiation dose to the spinal cord was estimated by computerized dosimetry. The median follow-up time was 10 months (range 6-18 months) from the radiosurgery. The endpoint of the study was to demonstrate the efficacy of the spinal radiosurgery and to determine the tolerance of human spinal cord to single dose radiosurgery. The dose to the spinal cord was generally less than 50 % of the prescribed radiation dose. The volume of the spinal cord that received higher than this dose was less than 20 % of the anterior portion of the spinal cord. Maximum single dose of 8 Gy was delivered to the anterior 20 % of the spinal cord in this dose escalation study. The dose volume histogram will be presented. There was no acute or subacute radiation toxicity detected clinically and radiologically during the maximum follow-up of 20 months. Further dose escalation is in progress. The single tolerance dose of the human spinal cord appears to be at least 8 Gy when it was given to the 20 % of the cord volume, although the duration of follow up is not long enough to detect severe late cord toxicity. This study offers a valuable radiobiological basis of the normal spinal cord tolerance, and opens spinal radiosurgery as a safe treatment for spinal metastasis

  12. Specification of absorbed dose for reporting a therapeutic irradiation

    International Nuclear Information System (INIS)

    Wambersie, A.; Chassagne, D.

    1981-01-01

    The problem of dose specification in external beam therapy with photons and electrons has been dealt with in ICRU Report 29 (1978). This problem arises from the fact that the absorbed dose distribution is usually not uniform in the target volume and that for the purpose of treatment reporting a nominal absorbed dose - which will be called target absorbed dose - has to be selected. When comparing the clinical results obtained between radiotherapy centres, the differences in the reported target absorbed doses which can be introduced by differences in the methods of dose specification often are much larger than the differences related to the dosimetric procedures themselves. This shows the importance of the problem. In this paper, some definitions of terms and concepts currently used in radiotherapy are first recalled: tumour volume, target volume, treatment volume, etc. These definitions have been proposed in ICRU Report 29 for photon and electron beams; they can be extended to any kind of irradiation. For external beam therapy with photons and electrons, the target absorbed dose is defined as the absorbed dose at selected point(s) (specification point(s)) having a meaningful relation to the target volume and/or the irradiation beams. Examples are discussed for typical cases. As far as interstitial and intracavitary therapy is concerned, the problem is more complex and no recommendations have so far been made by the ICRU Commission. A major difficulty arises from the sharp dose gradient as a function of the distance to the sources. The particular case of the treatment of cervix carcinoma is considered and some possible methods of specification are discussed: (1) the indication of the sources (in adequate units) and the duration of the application, (2) the absorbed doses at selected reference points (bladder, rectum, bony structures) and (3) the description of the tissue volume (height, width, thickness) encompassed by a given isodose surface (60Gy). (author)

  13. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

    Directory of Open Access Journals (Sweden)

    Jan B W J Cornelissen

    Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

  14. 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

  15. Rhabdomyolysis induced by a single dose of a statin

    OpenAIRE

    Jamil, S; Iqbal, P

    2004-01-01

    Statins have been shown to cause myotoxicity and rhabdomyolysis. In most cases rhabdomyolysis occurs following the use of these drugs for at least one week. A case of rhabdomyolysis after just a single dose of simvastatin is reported.

  16. Methodology to administer therapeutic dose of I-131

    International Nuclear Information System (INIS)

    Basteris M, J.; Gomez D, R.

    2007-01-01

    The present work suggests the use of measures guided to eliminate the resulting chronic sialoadenitis of the treatment of the thyroid cancer with Iodine-131, as well as the use of citric fruits to stimulate the salivation, the post-dose administration of liquids to accelerate the gastric emptying avoiding the secondary effects as the vomit is included. (Author)

  17. 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

  18. Employing the therapeutic operating characteristic (TOC) graph for individualised dose prescription.

    Science.gov (United States)

    Hoffmann, Aswin L; Huizenga, Henk; Kaanders, Johannes H A M

    2013-03-07

    In current practice, patients scheduled for radiotherapy are treated according to 'rigid' protocols with predefined dose prescriptions that do not consider risk-taking preferences of individuals. The therapeutic operating characteristic (TOC) graph is applied as a decision-aid to assess the trade-off between treatment benefit and morbidity to facilitate dose prescription customisation. Historical dose-response data from prostate cancer patient cohorts treated with 3D-conformal radiotherapy is used to construct TOC graphs. Next, intensity-modulated (IMRT) plans are generated by optimisation based on dosimetric criteria and dose-response relationships. TOC graphs are constructed for dose-scaling of the optimised IMRT plan and individualised dose prescription. The area under the TOC curve (AUC) is estimated to measure the therapeutic power of these plans. On a continuous scale, the TOC graph directly visualises treatment benefit and morbidity risk of physicians' or patients' choices for dose (de-)escalation. The trade-off between these probabilities facilitates the selection of an individualised dose prescription. TOC graphs show broader therapeutic window and higher AUCs with increasing target dose heterogeneity. The TOC graph gives patients and physicians access to a decision-aid and read-out of the trade-off between treatment benefit and morbidity risks for individualised dose prescription customisation over a continuous range of dose levels.

  19. Employing the therapeutic operating characteristic (TOC) graph for individualised dose prescription

    International Nuclear Information System (INIS)

    Hoffmann, Aswin L; Huizenga, Henk; Kaanders, Johannes HAM

    2013-01-01

    In current practice, patients scheduled for radiotherapy are treated according to ‘rigid’ protocols with predefined dose prescriptions that do not consider risk-taking preferences of individuals. The therapeutic operating characteristic (TOC) graph is applied as a decision-aid to assess the trade-off between treatment benefit and morbidity to facilitate dose prescription customisation. Historical dose-response data from prostate cancer patient cohorts treated with 3D-conformal radiotherapy is used to construct TOC graphs. Next, intensity-modulated (IMRT) plans are generated by optimisation based on dosimetric criteria and dose-response relationships. TOC graphs are constructed for dose-scaling of the optimised IMRT plan and individualised dose prescription. The area under the TOC curve (AUC) is estimated to measure the therapeutic power of these plans. On a continuous scale, the TOC graph directly visualises treatment benefit and morbidity risk of physicians’ or patients’ choices for dose (de-)escalation. The trade-off between these probabilities facilitates the selection of an individualised dose prescription. TOC graphs show broader therapeutic window and higher AUCs with increasing target dose heterogeneity. The TOC graph gives patients and physicians access to a decision-aid and read-out of the trade-off between treatment benefit and morbidity risks for individualised dose prescription customisation over a continuous range of dose levels

  20. Effects of therapeutic and supratherapeutic doses of oral tedizolid phosphate on cardiac repolarisation in healthy volunteers: a randomised controlled study.

    Science.gov (United States)

    Flanagan, Shawn; Litwin, Jeffrey; Fang, Edward; Prokocimer, Philippe

    2016-07-01

    Drug-induced prolongation of the QT interval on the electrocardiogram (ECG) infrequently results in Torsades de pointes, a potentially fatal arrhythmia. Therefore, thorough QT analysis of new drugs is a regulatory requirement. The objective of this phase 1 study was to assess the effects of oral tedizolid phosphate on the QT interval corrected with Fridericia's formula (QTcF) in healthy adult subjects. A single therapeutic dose (200 mg) and a supratherapeutic dose (1200 mg) of tedizolid phosphate were administered to characterise QTc changes following typical systemic exposure and with markedly higher exposures, respectively. This was a four-way crossover study with 48 subjects randomly assigned to receive therapeutic and supratherapeutic doses of tedizolid phosphate, moxifloxacin (positive control for QT interval prolongation) and placebo (negative control). A continuous 12-lead ECG was recorded from 1 h before drug administration to 23 h after administration. Adverse events, which were generally mild, occurred most frequently with moxifloxacin or with a supratherapeutic dose of tedizolid phosphate; however, all treatments were well tolerated. This study demonstrated that therapeutic or supratherapeutic doses of the antibacterial tedizolid had no clinically significant effect on QT interval in healthy adults [ClinicalTrials.gov registration no.: NCT01461460]. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  1. Absorption kinetics and steady-state plasma concentrations of theophylline following therapeutic doses of two sustained-release preparations

    DEFF Research Database (Denmark)

    Andersen, O; Nielsen, M K; Eriksen, P B

    1983-01-01

    Ten healthy volunteers received two sustained-release preparations as a single and multiple dose regimen in an open crossover study. Plasma theophylline concentrations were measured by an enzyme immunoassay. The limited fluctuation of the theophylline levels at steady state, with twice daily...... formulation, whereas this was not the case for the other (r = 0.27 and 0.49). The daily dose necessary to keep the plasma concentration within the therapeutic range of 55-110 mumole/liter varied from 7.9 to 22.9 mg/kg. Only mild side effects were recorded, but they were not correlated to the plasma...... theophylline concentration....

  2. 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.

  3. Enhanced activity of deoxycytidine kinase after pulsed low dose rate and single dose gamma irradiation

    NARCIS (Netherlands)

    Sigmond, J.; Haveman, J.; Kreder, N. Castro; Loves, W. J.; van Bree, C.; Franken, N. A.; Peters, G. J.

    2006-01-01

    In both pulsed low dose rate (LDR) and single high dose radiation schedules, gemcitabine pretreatment sensitizes tumor cells to radiation. These radiosensitizing effects could be the result of decreased DNA repair. In this study, the effect of irradiation on the deoxycytidine kinase (dCK) needed for

  4. Therapeutic termination of second trimester pregnancies with low dose misoprostol

    International Nuclear Information System (INIS)

    Liaquat, N.F.; Javed, I.; Shuja, S.; Shoaib, T.; Bano, K.; Waheed, S.; Ansar, A.

    2006-01-01

    To determine the effectiveness of 50 micro g misoprostol for midtrimester termination of pregnancies. The study subjects were 54 pregnant women admitted during the 2nd trimester (14-26 weeks) of gestation, willing or requiring termination of pregnancy. Those patients were included in the study who were admitted with closed cervical os, either had intrauterine death, fetal anomaly, medical disorder (hypertension or diabetes) or history of previous ceasrean section. Cases of placenta previa, acute asthma, glaucoma, cardiac diseases and allergy to prostaglandins were excluded. Each patient received 50 micro g misoprostol intravaginally. Maximum 4 doses were given at 4 hours interval and state of cervical os was assessed by vaginal examination before insertion of next dose or at the onset of uterine contractions. After 4 doses of misoprostol, patients were kept under observation and watched for uterine contractions to start or for expulsion of products. Syntocinon infusion was started to augment labour where products of conception failed to expel out inspite of open os. Outcome measures include success rate of termination within 12, 24, 36 and 48 hours, mean induction - abortion time interval and maternal side effects. Results: The success rate of termination within 12, 24, 36 and 48 hours were 27.7%, 83.3%, 94.4% and 96.3% respectively. Mean induction to abortion time interval, in case of abortion within 48 hours, was found to be 18.9 +- 11.58 (range 4-48 hours). Dead fetuses were aborted earlier than alive fetuses. The mean induction abortion time interval was 17.01+-8.7 hours in dead and 23.4 +- 15.9 hours in alive fetuses (t -value:1.9, p: 0.05). Two patients failed to deliver within 48 hours of induction. Two patients suffered from febrile illness. Vaginal administration of 50 micro g misoprostol every 4 hourly is an effective and safe agent for ripening of cervix and convenient way of inducing abortion during 2nd trimester of pregnancy in a women either with

  5. Radiosterilisation of the vagina in therapeutic doses - does it exist

    Energy Technology Data Exchange (ETDEWEB)

    Gerstner, G.; Kucera, H.; Weghaupt, K.; Rotter, M.

    1986-11-01

    The endogenous genital flora is a major source of infections of the female genital tract, especially in patients with cervical or endometrial cancer. Until recently the 'radiosterilisation of the vagina', respectively a prophylactic and/or therapeutic effect of irradiation (external highvoltage as well as intracavitary-radium) concerning infections was postulated in the literature. This theory was disproved in a prospective clinical and bacteriological study covering 48 patients with advanced cervical cancer undergoing primary intracavitary radium-irradiation and 38 patients with inoperable endometrical cancer, undergoing primary iridium-192-afterloading. Following intracavitary radium for cervical cancer some typical nosocomial pathogens like Streptococcus faecalis, Enterobacter, Klebsiella, Proteus and Pseudomonas were isolated significantly more frequently than before treatment. Likewise, the mean number of aerobic bacterial species increased significantly after irradiation. Also primary Ir-192 (afterloading) irradiation did not alter the frequency of isolation of the resident flora in endometrial cancer patients. Therefore, 'radiosterilisation' of the vagina as result of radiotherapy does not exist.

  6. Radiosterilisation of the vagina in therapeutic doses - does it exist

    International Nuclear Information System (INIS)

    Gerstner, G.; Kucera, H.; Weghaupt, K.; Rotter, M.; Vienna Univ.

    1986-01-01

    The endogenous genital flora is a major source of infections of the female genital tract, especially in patients with cervical or endometrial cancer. Until recently the 'radiosterilisation of the vagina', respectively a prophylactic and/or therapeutic effect of irradiation (external highvoltage as well as intracavitary-radium) concerning infections was postulated in the literature. This theory was disproved in a prospective clinical and bacteriological study covering 48 patients with advanced cervical cancer undergoing primary intracavitary radium-irradiation and 38 patients with inoperable endometrical cancer, undergoing primary iridium-192-afterloading. Following intracavitary radium for cervical cancer some typical nosocomial pathogens like Streptococcus faecalis, Enterobacter, Klebsiella, Proteus and Pseudomonas were isolated significantly more frequently than before treatment. Likewise, the mean number of aerobic bacterial species increased significantly after irradiation. Also primary Ir-192 (afterloading) irradiation did not alter the frequency of isolation of the resident flora in endometrial cancer patients. Therefore, 'radiosterilisation' of the vagina as result of radiotherapy does not exist. (orig.) [de

  7. Single dose methotrexate therapy: application to interstitial ectopic pregnancy.

    Science.gov (United States)

    Borgatta, L; Burnhill, M; Stubblefield, P

    1998-03-01

    A woman with a small (6-mm gestational sac) interstitial pregnancy had complete resolution after medical therapy alone. A single cycle of methotrexate 50 mg/m2 was used as outpatient treatment without any operative procedure either for diagnosis or intervention. The guidelines that have evolved for selection of women for single dose methotrexate treatment for both intrauterine and tubal ectopic pregnancies may be applicable to interstitial ectopic pregnancy as well. A suggested framework for treatment decisions is presented.

  8. The therapeutic effect of high-dose esomeprazole on stress ulcer bleeding in trauma patients.

    Science.gov (United States)

    Cui, Li-Hong; Li, Chao; Wang, Xiao-Hui; Yan, Zhi-Hui; He, Xing; Gong, San-Dong

    2015-01-01

    To compare the therapeutic effects of different doses of intravenous esomeprazole on treating trauma patients with stress ulcer bleeding. A total of 102 trauma patients with stress ulcer bleeding were randomly divided into 2 groups: 52 patients were assigned to the high-dose group who received 80 mg intravenous esomeprazole, and then 8 mg/h continuous infusion for 3 days; 50 patients were assigned to the conventional dose group who received 40 mg intravenous esomeprazole sodium once every 12 h for 72 h. Compared with the conventional dose group, the total efficiency of the high-dose group and conventional dose group was 98.08% and 86.00%, respectively (p esomeprazole have good hemostatic effects on stress ulcer bleeding in trauma patients. The high-dose esomeprazole is better for hemostasis.

  9. Combined low dose local anesthetics and opioids versus single use ...

    African Journals Online (AJOL)

    2014-09-24

    Sep 24, 2014 ... stay of the patients. Therefore, reducing the side effects associated with intrathecal anesthesia is quite helpful to support better postoperative management. Combined low dose local anesthetics and opioids versus single use of LA for transurethral urological surgery: A meta‑analysis. Y Ding, M Li, L Chen1, ...

  10. Comparative study of analgesic effectiveness of single doses of ...

    African Journals Online (AJOL)

    Method: This study employed the visual analogue scale to measure the effectiveness of single doses of ibuprofen and paracetamol over a six-hour period, following a third molar surgery in a homogenous study population, matched for age, body mass index (BMI) and gender. Alarms were set to remind patients to score pain ...

  11. An optimised age-based dosing regimen for single low-dose primaquine for blocking malaria transmission in Cambodia.

    Science.gov (United States)

    Leang, Rithea; Khu, Naw Htee; Mukaka, Mavuto; Debackere, Mark; Tripura, Rupam; Kheang, Soy Ty; Chy, Say; Kak, Neeraj; Buchy, Philippe; Tarantola, Arnaud; Menard, Didier; Roca-Felterer, Arantxa; Fairhurst, Rick M; Kheng, Sim; Muth, Sinoun; Ngak, Song; Dondorp, Arjen M; White, Nicholas J; Taylor, Walter Robert John

    2016-10-27

    In 2012, the World Health Organization recommended the addition of single low-dose primaquine (SLDPQ, 0.25 mg base/kg body weight) to artemisinin combination therapies to block the transmission of Plasmodium falciparum without testing for glucose-6-phosphate dehydrogenase deficiency. The targeted group was non-pregnant patients aged ≥ 1 year (later changed to ≥ 6 months) with acute uncomplicated falciparum malaria, primarily in countries with artemisinin-resistant P. falciparum (ARPf). No dosing regimen was suggested, leaving malaria control programmes and clinicians in limbo. Therefore, we designed a user-friendly, age-based SLDPQ regimen for Cambodia, the country most affected by ARPf. By reviewing primaquine's pharmacology, we defined a therapeutic dose range of 0.15-0.38 mg base/kg (9-22.5 mg in a 60-kg adult) for a therapeutic index of 2.5. Primaquine doses (1-20 mg) were tested using a modelled, anthropometric database of 28,138 Cambodian individuals (22,772 healthy, 4119 with malaria and 1247 with other infections); age distributions were: 0.5-4 years (20.0 %, n = 5640), 5-12 years (9.1 %, n = 2559), 13-17 years (9.1 %, n = 2550), and ≥ 18 years (61.8 %, n = 17,389). Optimal age-dosing groups were selected according to calculated mg base/kg doses and proportions of individuals receiving a therapeutic dose. Four age-dosing bands were defined: (1) 0.5-4 years, (2) 5-9 years, (3) 10-14 years, and (4) ≥15 years to receive 2.5, 5, 7.5, and 15 mg of primaquine base, resulting in therapeutic doses in 97.4 % (5494/5640), 90.5 % (1511/1669), 97.7 % (1473/1508), and 95.7 % (18,489/19,321) of individuals, respectively. Corresponding median (1st-99th centiles) mg base/kg doses of primaquine were (1) 0.23 (0.15-0.38), (2) 0.29 (0.18-0.45), (3) 0.27 (0.15-0.39), and (4) 0.29 (0.20-0.42). This age-based SLDPQ regimen could contribute substantially to malaria elimination and requires urgent evaluation in Cambodia and

  12. Optimization of the therapeutic dose of 131I for thyroid differentiated carcinoma

    International Nuclear Information System (INIS)

    Lima, Fabiana Farias de

    2002-09-01

    I-131 thyroid cancer therapy is based on the strategy of concentrating radioactive iodine in the thyroid tissue, to completetly eliminate thyroid tissue and functioning thyroid cancer metastases remaining after thyroidectomy. In Brazil, fixed activities of 131 I generally are given, sometimes either delivering insufficient activities to ablate all of the remnants, or unnecessarily high activities, with patients remaining in the hospital for some period of time. This investigation proposes a protocol of individualized planning of ablative doses, based on individual patients metabolisms and measured thyroid remnant masses. Simulated thyroid remnants were fabricated in various forms, volumes and activities, and optimum image acquisition parameters were determined using Single-Photon Emission Computed Tomography 9SPECT). Resultant images were evaluated, to determine the apparent volumes and the 131 I concentrations. I-131 metabolism was studied in 9 patients who had undergone thyroidectomies. Their thyroid remnant masses were determined applying the same parameters used in SPECT simulation studies, and the optimum activity for their therapy was calculated and compared to the established fixed activity of 3.7 GBq (100 mCi), which would have normally been assigned. Background subtraction using the method of percent maximum counts, using a value of 67.5%, combined with scatter correction (triple energy window method), was shown to be optimum for SPECT quantification of volumes between 3-10 ml. Errors in the method were below 9% for sources with regular geometries and around 11% for sources with irregular geometries. In the patient studies, it was observed that 78% of patients could have received reduced activities of 131 (from 0.8-3-2. GBq (20-87 nCi). In addition, 33% of these patients could have received low enough activities to have discharged from the hospital, using an individualized administration scheme. This could also have resulted in a dose reduction for many

  13. Vaxchora: A Single-Dose Oral Cholera Vaccine.

    Science.gov (United States)

    Cabrera, Adriana; Lepage, Jayne E; Sullivan, Karyn M; Seed, Sheila M

    2017-07-01

    To review trials evaluating the efficacy and safety of Vaxchora, a reformulated, single-dose, oral, lyophilized Vibrio cholerae CVD 103-HgR vaccine for the prevention of travel-related cholera caused by V cholerae serogroup O1. A literature search was conducted using MEDLINE (1946 to January week 3, 2017) and EMBASE (1996 to 2017 week 3). Keywords included oral cholera vaccine, single-dose, Vaxchora, and CVD 103-HgR. Limits included human, clinical trials published in English since 2010. ClinicalTrials.gov was used as a source for unpublished data. Additional data sources were obtained through bibliographic review of selected articles. Studies that addressed the safety and efficacy of Vaxchora, the reformulated, single-dose oral CVD 103-HgR cholera vaccine, were selected for analysis. Approval of Vaxchora, was based on efficacy of the vaccine in human trials demonstrating 90.3% protection among those challenged with V cholerae 10 days after vaccination and in immunogenicity studies with 90% systemic vibriocidal antibody conversion at 6 months after a single-dose of vaccine. Tolerability was acceptable, with the most common adverse effects reported to be fatigue, headache, and abdominal pain. Vaxchora is the only FDA-approved, single-dose oral vaccine for the prevention of cholera caused by V cholerae serogroup O1 in adult travelers from the United States going to cholera-affected areas. Safety and efficacy has not been established in children, immunocompromised persons, and pregnant or breastfeeding women or those living in cholera-endemic areas.

  14. Comparison of post cesarean infection after single dose versus three doses of prophylactic antibiotic regimen

    Directory of Open Access Journals (Sweden)

    Farnaz Mohammadian

    2013-04-01

    Full Text Available Background: Cesarean delivery is a surgical operation which is applied to prevent maternal and fetal complications. Cesarean delivery isn’t without complication and has some complications such as infection. Postoperative infection includes endometritis, wound infection and septic pelvic thrombophlebitis that depend to prophylactic antibiotics and surgical technique. The aim of this study was comparison of post operative infection after single dose and three doses of prophylactic antibiotic regimens. . Material and Methods: This double blind randomized clinical trial was performed on all pregnant women referd to the Vali-Asr Hospital of Zanjan University of Medical Sciences and underwent cesarean delivery during one year from starting study. Participants subsequently were randomized into two groups: A (recieved single dose of prophylactic antibiotic and B (recieved three doses of prophylactic antibiotic. Subjects were checked up for the clinical signs of infection during hospitalization and 10 days after discharge. The results were analyzed by SPSS Software Ver16 and Chi-Square Test. Results: During one year, 146 pregnant women with cesarean delivery entered 2 equal groups (A and B which each group had 73 subjects. During hospitalization after cesarean delivery, 5(6.8% patients of group A and 2(2.7% patients of group B had fever. There was no significant correlation between the two groups. Conclusion: There was no significant correlation between single dose and three doses of prophylactic antibiotic regimens in groups A and B. Therefore, it seems thatthere is no need to use three doses of prophylactic antibiotic for cesarean delivery.Therfore, because of drug resistance and economic loss, single dose of prophylactic antibiotic is recommended for prevention of post cesarean infection

  15. Role of sulfite additives in wine induced asthma: single dose and cumulative dose studies

    OpenAIRE

    Vally, H; Thompson, P

    2001-01-01

    BACKGROUND—Wine appears to be a significant trigger for asthma. Although sulfite additives have been implicated as a major cause of wine induced asthma, direct evidence is limited. Two studies were undertaken to assess sulfite reactivity in wine sensitive asthmatics. The first study assessed sensitivity to sulfites in wine using a single dose sulfited wine challenge protocol followed by a double blind, placebo controlled challenge. In the second study a cumulative dose su...

  16. 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.

  17. Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum.

    Science.gov (United States)

    Hansson, Anna; Rasmussen, Thomas; Kraiczi, Holger

    2017-04-01

    Under-dosing is a recognized problem with current nicotine replacement therapy (NRT). Therefore, a new 6mg nicotine gum has been developed. To compare the nicotine uptake from the 6mg gum versus currently available NRT products, two pharmacokinetic studies were performed. In one randomized crossover study, 44 healthy adult smokers received single doses of 6, 4, and 2mg nicotine gum, and 4mg nicotine lozenge on separate occasions. In a separate randomized crossover multiple-dose study over 11 hours, 50 healthy adult smokers received one 6mg gum every hour and 90 minutes, respectively, one 4mg gum every hour, and one 4mg lozenge every hour. In both studies, blood samples were collected over 12 hours to determine single-dose and multiple-dose pharmacokinetic variables. In the single-dose study, the amount of nicotine released from the 2, 4, and 6mg gums (1.44, 3.36, and 4.94mg) as well as the resulting maximum concentration and area under the curve (5.9, 10.1, and 13.8ng/mL, and 17.1, 30.7, 46.2ng/mL × h, respectively) increased with dose. The maximum concentration and area under the curve of the 6mg gum were 44% and 30% greater, respectively, than those for 4mg lozenge. Upon hourly administration, the steady-state average plasma nicotine concentration with 6mg gum (37.4ng/mL) was significantly higher than those for 4mg lozenge (28.3ng/mL) and 4mg gum (27.1ng/mL). Nicotine delivery via the 6mg gum results in higher plasma nicotine concentrations after a single dose and at steady state than with currently available oral NRT. Under-dosing is a recognized problem with current NRT. Therefore, a new 6mg nicotine gum has been developed. Our studies show that upon single-dose and multiple-dose administration, the 6mg gum releases and delivers more nicotine to the systemic circulation than 2mg gum, 4mg gum, and 4mg lozenge. Thus, each 6mg nicotine gum provides a higher degree of nicotine substitution and/or lasts for a longer period of time than currently available nicotine

  18. Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate

    International Nuclear Information System (INIS)

    Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J.; Ravelli, Raimond B. G.

    2011-01-01

    The effects of dose and dose-rate were investigated for single-particle cryo-electron microscopy using stroboscopic data collection. A dose-rate effect was observed favoring lower flux densities. Radiation damage is an important resolution limiting factor both in macromolecular X-ray crystallography and cryo-electron microscopy. Systematic studies in macromolecular X-ray crystallography greatly benefited from the use of dose, expressed as energy deposited per mass unit, which is derived from parameters including incident flux, beam energy, beam size, sample composition and sample size. In here, the use of dose is reintroduced for electron microscopy, accounting for the electron energy, incident flux and measured sample thickness and composition. Knowledge of the amount of energy deposited allowed us to compare doses with experimental limits in macromolecular X-ray crystallography, to obtain an upper estimate of radical concentrations that build up in the vitreous sample, and to translate heat-transfer simulations carried out for macromolecular X-ray crystallography to cryo-electron microscopy. Stroboscopic exposure series of 50–250 images were collected for different incident flux densities and integration times from Lumbricus terrestris extracellular hemoglobin. The images within each series were computationally aligned and analyzed with similarity metrics such as Fourier ring correlation, Fourier ring phase residual and figure of merit. Prior to gas bubble formation, the images become linearly brighter with dose, at a rate of approximately 0.1% per 10 MGy. The gradual decomposition of a vitrified hemoglobin sample could be visualized at a series of doses up to 5500 MGy, by which dose the sample was sublimed. Comparison of equal-dose series collected with different incident flux densities showed a dose-rate effect favoring lower flux densities. Heat simulations predict that sample heating will only become an issue for very large dose rates (50 e − Å −2 s

  19. Employing the therapeutic operating characteristic (TOC) graph for individualised dose prescription

    NARCIS (Netherlands)

    Hoffmann, A.L.; Huizenga, H.; Kaanders, J.H.A.M.

    2013-01-01

    BACKGROUND: In current practice, patients scheduled for radiotherapy are treated according to 'rigid' protocols with predefined dose prescriptions that do not consider risk-taking preferences of individuals. The therapeutic operating characteristic (TOC) graph is applied as a decision-aid to assess

  20. Single oral dose safety of D-allulose in dogs.

    Science.gov (United States)

    Nishii, Naohito; Nomizo, Toru; Takashima, Satoshi; Matsubara, Tatsuya; Tokuda, Masaaki; Kitagawa, Hitoshi

    2016-07-01

    Healthy dogs were administered acute oral doses of D-allulose (also called D-psicose) to evaluate its toxicity. Six dogs received oral doses of either a placebo or D-allulose solution (1 and 4 g/kg) on three different study days. One dog experienced vomiting, and five dogs showed transient diarrhea when 4 g/kg of D-allulose was administered. All dogs were active and had a good appetite throughout the study period. Blood glucose concentration slightly decreased without a rise in plasma insulin concentration 2 hr after D-allulose administration. Plasma alkaline phosphatase activities showed a mild increase between 12 and 48 hr after D-allulose administration. These data suggested that a single oral dose of D-allulose does not show severe toxicity in dogs.

  1. Impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat.

    Science.gov (United States)

    Shah, Jan Muhammad; Qureshi, Toufique Ahmed; Shah, Tahmina; Shah, Qurban Ali; Arain, Muhammad Asif; Bhutto, Zohaib Ahmed; Saeed, Muhammad; Siyal, Farman Ali

    2016-10-01

    The aim of this study was to evaluate the impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat species. Six mature, healthy goats (combine breed and sex) with average weight 25 kg were selected for this study. The therapeutic (20 mg/kg b.w.) and high doses (40 and 60 mg) of florfenicol were administered for 3 days with 24 h interval. Blood samples were collected at 0, 24, 48, 72, 96, and 120 h following the each administered dose. The results showed that the therapeutic dose of florfenicol produced nonsignificant effect on serum urea, creatinine, total protein (TP), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and bilirubin on all timings, and increased (pflorfenicol (40 and 60 mg) significantly altered the kidney and liver functional indicators in the blood. In contrast with control, the serum urea level was (pflorfenicol produced reversible dose-dependent effects on functional indicators of kidney and liver such as urea, creatinine, TP, ALP, SGOT, SGPT, GGT, and bilirubin.

  2. Impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat

    Science.gov (United States)

    Shah, Jan Muhammad; Qureshi, Toufique Ahmed; Shah, Tahmina; Shah, Qurban Ali; Arain, Muhammad Asif; Bhutto, Zohaib Ahmed; Saeed, Muhammad; Siyal, Farman Ali

    2016-01-01

    Aim: The aim of this study was to evaluate the impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat species. Materials and Methods: Six mature, healthy goats (combine breed and sex) with average weight 25 kg were selected for this study. The therapeutic (20 mg/kg b.w.) and high doses (40 and 60 mg) of florfenicol were administered for 3 days with 24 h interval. Blood samples were collected at 0, 24, 48, 72, 96, and 120 h following the each administered dose. Results: The results showed that the therapeutic dose of florfenicol produced nonsignificant effect on serum urea, creatinine, total protein (TP), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) and bilirubin on all timings, and increased (pflorfenicol (40 and 60 mg) significantly altered the kidney and liver functional indicators in the blood. In contrast with control, the serum urea level was (pflorfenicol produced reversible dose-dependent effects on functional indicators of kidney and liver such as urea, creatinine, TP, ALP, SGOT, SGPT, GGT, and bilirubin. PMID:27847425

  3. Impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat

    Directory of Open Access Journals (Sweden)

    Jan Muhammad Shah

    2016-10-01

    Full Text Available Aim: The aim of this study was to evaluate the impact of therapeutic and high doses of florfenicol on kidney and liver functional indicators in goat species. Materials and Methods: Six mature, healthy goats (combine breed and sex with average weight 25 kg were selected for this study. The therapeutic (20 mg/kg b.w. and high doses (40 and 60 mg of florfenicol were administered for 3 days with 24 h interval. Blood samples were collected at 0, 24, 48, 72, 96, and 120 h following the each administered dose. Results: The results showed that the therapeutic dose of florfenicol produced nonsignificant effect on serum urea, creatinine, total protein (TP, alkaline phosphatase (ALP, gamma-glutamyl transferase (GGT and bilirubin on all timings, and increased (p<0.05 the serum glutamic oxaloacetic transaminase (SGOT and serum glutamate-pyruvate transaminase (SGPT levels for 48 h. Whereas the high doses of florfenicol (40 and 60 mg significantly altered the kidney and liver functional indicators in the blood. In contrast with control, the serum urea level was (p<0.01 increased at all timing points. Creatinine values were altered (p<0.01, <0.05 in increasing manner from 24 to 96 h. The high dose of 40 mg decreased the TP (p<0.05 for 72 h and 60 mg persisted same effect (p<0.01 up to 120 h. The indices of ALP, GGT, SGOT, and SGPT were raised (p<0.01, <0.05 at all timings. The bilirubin indexes also (p<0.05 elevated from 48 to 72. Conclusion: It was concluded that the high doses of florfenicol produced reversible dose-dependent effects on functional indicators of kidney and liver such as urea, creatinine, TP, ALP, SGOT, SGPT, GGT, and bilirubin.

  4. Voriconazole dosing and therapeutic drug monitoring in children: experience from a paediatric tertiary care centre.

    Science.gov (United States)

    Boast, Alison; Curtis, Nigel; Cranswick, Noel; Gwee, Amanda

    2016-07-01

    Therapeutic drug monitoring (TDM) of voriconazole is recommended to achieve trough concentrations of 1-5 mg/L. In children, this is challenging due to age-related variability in voriconazole pharmacokinetics. This study describes our experience with voriconazole, focusing on dosing regimens, dose adjustment and TDM. We reviewed the medical records of immunocompromised children who received voriconazole from July 2009 to January 2015 and had TDM. Demographic, clinical and voriconazole dosing and monitoring data were collected. Fifty-five children received 62 courses of voriconazole and had TDM, with a total of 256 samples taken. Only 71.0% of courses (44/62) had TDM at the correct time, and at least one therapeutic level was achieved in only 52.3% (23/44) of these. Twenty-six courses had at least one sub-therapeutic level and in only 61.5% was the dose adjusted. Patients aged 12 years required median intravenous doses of 8.8, 7.5 and 4.0 mg/kg twice daily, respectively (P 12 years required median doses of 4.7 and 4.3 mg/kg twice daily, respectively (P = 0.307). Levels within the target range were observed to fall below 1 mg/L in 36.4% of unchanged dosing regimens. Photosensitive skin reactions (20.0%) and hepatotoxicity (12.7%) were the most frequent adverse events and occurred in children with voriconazole levels voriconazole concentrations in children, particularly in children <6 years of age. This warrants repeated TDM throughout treatment. Standardized guidelines for TDM and dose adjustment are required in children. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. 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

    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...

  6. Pharmacokinetics of Solithromycin (CEM-101) after Single or Multiple Oral Doses and Effects of Food on Single-Dose Bioavailability in Healthy Adult Subjects▿

    OpenAIRE

    Still, J. Gordon; Schranz, Jennifer; Degenhardt, Thorsten P.; Scott, Drusilla; Fernandes, Prabhavathi; Gutierrez, Maria J.; Clark, Kay

    2011-01-01

    The pharmacokinetics of orally administered solithromycin (CEM-101), a novel fluoroketolide, were evaluated in healthy subjects in three phase 1 studies. In two randomized, double-blinded, placebo-controlled studies, escalating single oral doses of solithromycin (50 to 1,600 mg) or seven oral daily doses (200 to 600 mg) of solithromycin were administered. A third study evaluated the effects of food on the bioavailability of single oral doses (400 mg) of solithromycin. Following single doses, ...

  7. Low-dose methotrexate - a therapeutical kick in TNF-alpha antagonist treatment for recalcitrant psoriasis vulgaris.

    Science.gov (United States)

    Wilsmann-Theis, Dagmar; Fronhoffs, Kristina; Ehler, Lin-Kristin; Wenzel, Joerg; Bieber, Thomas; Klingmueller, Karin

    2014-01-01

    In contrast to the treatment of rheumatoid arthritis, there are few data in psoriasis vulgaris regarding the efficacy of combining tumor necrosis factor (TNF)-alpha inhibitors and methotrexate (MTX). Indeed, combination of MTX with different TNF-alpha inhibitors may enhance the therapeutic effects and reduce side effects because of less dosage of the single agent. The present authors present five cases in which low-dose MTX combined with TNF-alpha inhibitors led to impressive improvement in Psoriasis Area and Severity Index scores. Here, the present authors initiated very low-dose MTX treatment in addition to existing TNF-alpha inhibitor therapy to exhaust current therapy and prevent premature change of the biologic. These observations support the concept of combined treatment in recalcitrant cases of psoriasis, which need a systemically lifelong treatment when both first-line and second-line monotherapies fail to provide sufficient clinical response. © 2013 Wiley Periodicals, Inc.

  8. Interstitial pregnancy treated with a single-dose of systemic methotrexate: A successful management

    Directory of Open Access Journals (Sweden)

    Serena Corioni

    2015-01-01

    Full Text Available Interstitial pregnancy is an ectopic pregnancy at high hemorrhagic risk. It often poses a diagnostic and therapeutic challenge to the clinician, with a significant risk of morbidity and mortality. It presents a difficult management problem with no absolute standard of care; the most appropriate treatment technique for these pregnancies remains controversial. We describe a case of unruptured interstitial pregnancy successfully treated with a single-dose of systemic methotrexate with subsequent ultrasound and serum beta human chorionic gonadotropin monitoring. Medical management can be a safe and successful option in selected cases that satisfy specific criteria and in women who are able to be monitored after treatment.

  9. Effect of therapeutic dose X rays on mechanical and chemical properties of esthetic dental materials

    Directory of Open Access Journals (Sweden)

    Adriana Dibo da Cruz

    2008-09-01

    Full Text Available The aim of this study was to investigate the influence of therapeutic dose X rays on the microhardness (MH and degree of conversion (DC of two different esthetic restorative dental materials. The materials were photo-activated with a LED light-curing unit using three cure-times: 5, 20 and 40 seconds. The photo-activation was carried out in two distinct periods: before and after irradiation with doses of 5, 35 and 70 Gy, from a 6 MV X rays beam. In accordance with the methodology used, it was conclude that a therapeutic dose does not have a detrimental effect on the photoinitiator molecules, because the photo-activation occurred after they were irradiated. When the irradiation was applied before photo-activation, the materials showed MH improvement, but when photo-activation was performed after irradiation, there was less improvement. However, there was no correlation between MH and DC. Thus, a therapeutic dose applied to cured material can promote linking and breaking of chain bonds in a non-linear way.

  10. 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

  11. Role of sulfite additives in wine induced asthma: single dose and cumulative dose studies.

    Science.gov (United States)

    Vally, H; Thompson, P J

    2001-10-01

    Wine appears to be a significant trigger for asthma. Although sulfite additives have been implicated as a major cause of wine induced asthma, direct evidence is limited. Two studies were undertaken to assess sulfite reactivity in wine sensitive asthmatics. The first study assessed sensitivity to sulfites in wine using a single dose sulfited wine challenge protocol followed by a double blind, placebo controlled challenge. In the second study a cumulative dose sulfited wine challenge protocol was employed to establish if wine sensitive asthmatics as a group have an increased sensitivity to sulfites. In study 1, 24 asthmatic patients with a strong history of wine induced asthma were screened. Subjects showing positive responses to single blind high sulfite (300 ppm) wine challenge were rechallenged on separate days in a double blind, placebo controlled fashion with wines of varying sulfite levels to characterise their responses to these drinks. In study 2, wine sensitive asthmatic patients (n=12) and control asthmatics (n=6) were challenged cumulatively with wine containing increasing concentrations of sulfite in order to characterise further their sensitivity to sulfites in wine. Four of the 24 self-reporting wine sensitive asthmatic patients were found to respond to sulfite additives in wine when challenged in a single dose fashion (study 1). In the double blind dose-response study all four had a significant fall in forced expiratory volume in one second (FEV(1)) (>15% from baseline) following exposure to wine containing 300 ppm sulfite, but did not respond to wines containing 20, 75 or 150 ppm sulfite. Responses were maximal at 5 minutes (mean (SD) maximal decline in FEV(1) 28.7 (13)%) and took 15-60 minutes to return to baseline levels. In the cumulative dose-response study (study 2) no significant difference was observed in any of the lung function parameters measured (FEV(1), peak expiratory flow (PEF), mid phase forced expiratory flow (FEF(25-75))) between wine

  12. Role of single dose prophylactic antibiotic in elective caesarean section

    Directory of Open Access Journals (Sweden)

    Hasna Hena Pervin

    2016-08-01

    Full Text Available Background: Maternal morbidity related to infection after caesarean section has been reported to be higher than that of vaginal delivery. The prevention of infection in patients undergoing caesarean section is a major challenge, particularly in hospitals, where there is frequent chance of cross infection due to overcrowding. Objective: The present study was undertaken to see the efficacy of single dose cetriaxone as a prophylaxis in elective caesarean section to prevent postop­erative infection. Methods: This cross sectional study was conducted on 100 patients who underwent elective caesarean section where single dose of Ceftriaxone was used as prophylaxis in the Department of Obstetrics & Gynaecology, Bang­abandhu Sheikh Mujib Medical University Hospital, between January to June 2010. The outcomes measures were post­operative febrile morbidity, wound infe-ction and other infections (urinary tract infection, chest infection. Data were analysed using statistical package for social sciences (SPSS version 11.5.Results: Over one-third (38% patients age group was between 18 -25 years, 56% in between 25 -35 years and 6% were over 35 years old. Nearly half(46% was anemic (haemoglobin< 11 g/dl and 16% was obese (BMI≥28 kg/m2. All the patients were operated by obstetricians of same level. Three per cent patients developed wound infection, 5% developed other infections like UTI and chest infection and 7% had febrile illness. Among the several factors suspected to be associated with post operative complications, preoperative anaemia, long duration of operation (>60 minutes and prolonged hospital stay (>1 week were found to be significantly assocated with postoperative complications.Conclusion: The present study suggests that single dose prophylactic antibiotic ceftriaxone given 1 hour before operation in patients with cesarean section deliveries reduces the chance of postoperative infection to a bare minimum.

  13. Immunogenicity of single dose live attenuated hepatitis a vaccine.

    Science.gov (United States)

    Bhave, Sheila; Bavdekar, Ashish; Sapru, Amita; Bawangade, Seema; Pandit, Anand

    2011-02-01

    A long-term immunogenicity study of a single dose live attenuated H2 strain hepatitis A vaccine is being conducted in healthy Indian children at KEM Hospital, Pune. 131 of the original 143 children vaccinated in 2004, were evaluated for anti-HAV antibodies 30 months post vaccination (2007). Seroprotective antibody levels >20 mIU/mL were demonstrated in 87.8 % subjects with an overall GMT of 92.02 mIU/mL. No hepatitis like illness was recorded in any of the subjects since vaccination.

  14. Time-dose relationship in radiotherapy of gingival carcinoma. Therapeutic results

    International Nuclear Information System (INIS)

    Maciejewski, B.; Wojcieszek, Z.; Majewski, S.

    1982-01-01

    Therapeutic results were analysed in 30 patients with gingival carcinoma irradiated with 60 Co at the Institute of Oncology in Gliwice. Three-year asymptomatic survival rate was 26%. Administration of 1950 rets dose was associated with a high probability of cure and low risk of complications. Tumour diameter exceeding 3 cm, involvement of adjacent anatomical structures and metastases to cervical lymph nodes worsened considerably the prognosis. (author)

  15. Dosimetric evaluation of sucrose and granulated cane sugar in the therapeutic dose range.

    Science.gov (United States)

    Davidson, Melanie T M; Jordan, Kevin J

    2009-04-01

    Granulated cane sugar has been used as a dosimetric material to report dose in high dose accidental irradiations. The purpose of this study was to assess whether clinical dosimetry is also plausible with such a commonly available material. The behavior of cane sugar was explored with respect to therapeutically relevant radiation quantities (dose, dose rate) and qualities (energy, radiation type) as well as under different temperature conditions. The stability of the signal postirradiation was also measured. Absorbed dose was measured by spectrophotometric readout of a ferrous ammonium sulfate xylenol orange (FX)-sugar solution in 10 cm path length cells. A visible color change was produced as a function of dose when the irradiated sugar samples were dissolved in FX solution (10% dilution by mass). A comparison of the optical absorbance spectra and dose response of cane sugar with analytical grade sucrose was done to establish a benchmark standard from which subsequent dosimetry measurements can be validated. The response of the sugar dosimeter read at 590 nm was found to be linear over the dose range of 100-2000 cGy, independent of energy (6-18 MV) and of the average dose rate (100-500 cGy/min). The readout of sugar samples irradiated with mixed photon and electron fields was also shown to be independent of radiation type (photons and electrons). Sugar temperature (20-40 degrees C) during irradiation did not affect dose estimates, making it a promising dosimeter for in vivo dosimetry, particularly in cases where the dosimeter must remain in contact with the patient for an extended period of time. Sugar can be used as an integrating dosimeter, since it exhibits no fractionation effects. Granulated cane sugar is cost effective, safe, soft tissue equivalent, and can be used under various experimental conditions, making it a suitable dosimeter for some radiotherapy applications.

  16. Radiation exposure to examiners and patients during therapeutic ERCP: Dose optimisation and risk estimation

    International Nuclear Information System (INIS)

    Sulieman, A.; Kappas, K.; Theodorou, K.; Paroutoglou, G.; Kapatenakis, A.; Kapsoritakis, A.; Potamianos, S.; Vlychou, M.; Fezoulidis, I.

    2008-01-01

    Aim: This study intended to optimise the radiation dose during therapeutic ERCP, and to estimate the risk for examiners and patients, to compare the doses based on available data obtained by other researchers and reference levels recommended by international organizations, and to evaluate the technique applied in order to reduce patient and examiners doses. Materials and Methods: 153 patients were studied in two Gastroenterology Departments, (group A, 111; group B, 42). Thermoluminescent dosimeters (TLD) were used to measure the staff and patients entrance surface dose (ESD) at different body sites. Results: The mean ESD, exit and thyroid surface dose per procedure was estimated to be 68.75 mGy, 3.45 mGy and 0.67 mGy, respectively. The mean patient effective dose was 3.44 mSv, and the cancer risk per procedure was estimated to be 190 x10 -6 . The effective dose for the first, second and third examiner was 0.4 μSv, 0.2 μSv and 5.0 μSv, respectively. Conclusion: The patient dose can be optimized by the presence of two experienced examiners and reduction of radiographic images. The examiners should use a wrap around lead apron since the highest dose originating from the X-ray tube, is incident on their side and back. The current formulae, which exist, underestimate the effective dose to the examiners, when they are applied for ERCP procedures. For both patients and examiners, our results were up to 60% lower compared to the lowest values found in previous studies. (authors)

  17. Acute pancreatitis related to therapeutic dosing with colchicine: a case report

    Directory of Open Access Journals (Sweden)

    Ting Joseph

    2007-08-01

    Full Text Available Abstract Background Colchicine is used in the treatment and prophylaxis of gout. It possesses a narrow therapeutic window, frequently resulting in dose-limiting gastrointestinal side-effects such as diarrhoea and emesis. As colchicine is a cellular anti-mitotic agent, the most serious effects include myelosuppression, myoneuropathy and multiple organ failure. This occurs with intentional overdose or with therapeutic dosing in patients with reduced clearance of colchicine due to pre-existing renal or hepatic impairment. Acute pancreatitis has rarely been reported, and only in association with severe colchicine overdose accompanied by multi-organ failure. Case presentation We report a case of acute pancreatitis without other organ toxicity related to recent commencement of colchicine for acute gout, occurring in an elderly male with pre-existing renal impairment. Conclusion 1 Colchicine should be used with care in elderly patients or patients with impaired renal function. 2 Aside from myelosuppression, myoneuropathy and multiple organ failure, colchicine may now be associated with acute pancreatitis even with therapeutic dosing; this has not previously being reported.

  18. Rhabdomyolysis associated with single-dose intravenous esomeprazole administration

    Science.gov (United States)

    Jeon, Dae-Hong; Kim, Yire; Kim, Min Jeong; Cho, Hyun Seop; Bae, Eun Jin; Chang, Se-Ho; Park, Dong Jun

    2016-01-01

    Abstract Background: Proton pump inhibitors are usually safe, although serious adverse effects can occur. We report the first case of rhabdomyolysis associated with single-dose intravenous esomeprozole administration. Methods: A 45-year-old Korean male visited our emergency room because of persistent lower chest discomfort that started 10 hours before. He had been diagnosed with diabetes and coronary heart disease, but discontinued oral hypoglycemic agents 1 month earlier. He continued to take medications for coronary heart disease. There was no abnormality on an electrocardiogram or in cardiac enzymes. Initial laboratory findings did not show abnormalities for muscle enzymes. Esomeprozole 40 mg was administrated intravenously for the control of his ambiguous chest discomfort. Then, 12 hours later, he complained of abrupt severe right buttock pain. An area of tender muscle swelling 8 cm in diameter was seen on his right buttock area. Creatine kinase and lactate dehydrogenase were elevated to 40,538 and 1326 U/L, respectively. A bone scan using 20 mCi of 99mTc-hydroxymethylene diphosphonate was compatible with rhabdomyolysis. Results: His muscular symptoms, signs, and laboratory findings improved markedly with conservative management, including hydration and urine alkalinization. He is being followed in the outpatient department with no evidence of recurrence. Conclusion: We should keep in mind that single-dose intravenous administration of esomeprazole can induce rhabdomyolysis. PMID:27442680

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Effects of single dose intranasal oxytocin on social cognition in schizophrenia.

    Science.gov (United States)

    Davis, Michael C; Lee, Junghee; Horan, William P; Clarke, Angelika D; McGee, Mark R; Green, Michael F; Marder, Stephen R

    2013-07-01

    Deficits in social cognition are common in schizophrenia and predict poor community functioning. Given the current limitations of psychosocial treatments and the lack of pharmacological treatments for social cognitive deficits, the development of novel therapeutic agents could greatly enhance functional recovery in schizophrenia. This study evaluated whether a single dose of intranasal oxytocin acutely improves social cognitive functioning in schizophrenia. Twenty-three male veterans with schizophrenia completed baseline assessments of social cognition that were divided into lower-level (facial affect perception, social perception, detection of lies) and higher-level (detection of sarcasm and deception, empathy) processes. One week later, patients received the same battery after being randomized to a single dose of 40 IU intranasal oxytocin or placebo. Though the groups did not differ significantly on the social cognition composite score, oxytocin improved performance for the higher-level social cognitive tasks (Cohen's d=1.0, p=0.045). Subjects were unable to accurately guess which treatment they had received. The improvements found in higher-level social cognition encourage further studies into the therapeutic potential of oxytocin in schizophrenia. Published by Elsevier B.V.

  1. Evaluation of thromboembolic disease using single dose dual phase scintigraphy

    International Nuclear Information System (INIS)

    Sharma, A.R.; Charan, S.; Silva, I.

    2004-01-01

    Introduction: Clinical presentation of thromboembolic disease (TED) is caused by three mechanisms 1) obstruction to venous outflow 2) vascular inflammation and 3) pulmonary emboli. Single Dose (Tc-99m MAA) Dual Phases (Veno-Pulmonary) scintigraphy is theoretically capable of evaluating two of three above mentioned patho-physiological factors. Therefore, a prospective study was designed to explore potential of Single Dose Dual Phase (SDDP) scintigraphy in the evaluation of thromboembolic disease. Materials and methods: Sixty consecutive patients with high clinical likelihood of thromboembolic disease (onset of painful and edematous lower limb, chest pain, shortness of breath, presence of risk factors for DVT, H/o of previous episode of DVT, right ventricular strain on ECHO, hypoxaemia on blood gas analysis), were included in this study. There were 43 men and 17 women (mean age 36 years). They were subjected to single dose dual phase (SDDP) scintigraphy using Tc-99m MAA (4 mci). Firstly venous phase of imaging was obtained with simultaneous injection of Tc-99m MAA diluted in 10 ml normal saline in syringe into superficial veins of dorsum of both feet (large volume continuous flow technique) in whole body acquisition mode on Dual Detectors Gamma Camera; followed by lung perfusion scintigraphy in conventional projections as second phase of study. Venous phase (Venography) was interpreted as per Ziffer's criteria in four venous segments (Unpaired- Inferior Vena Cava, 3 paired - Iliac, Femoral and Popliteal). Interpretation of lung perfusion scan was made as per PIOPED Criteria. Results: Forty-one of sixty patients (67%) showed scintigraphic evidence of venous occlusion (DVT) during venous phase. Out of these, 17 patients eventually had high probability lung scan for pulmonary embolism (29%). None of the patient with negative venous phase (n=19) showed perfusion defects on lung perfusion scan. Venous thrombosis most commonly affected the left lower limb (n=29, 71%). In 5

  2. PHARMACOKINETICS OF ORALLY ADMINISTERED VORICONAZOLE IN AFRICAN PENGUINS (SPHENISCUS DEMERSUS) AFTER SINGLE AND MULTIPLE DOSES.

    Science.gov (United States)

    Hyatt, Michael W; Wiederhold, Nathan P; Hope, William W; Stott, Katharine E

    2017-06-01

    Aspergillosis is a common respiratory fungal disease in African penguins ( Spheniscus demersus ) under managed care, and treatment failures with itraconazole due to drug resistance are increasingly common, leading to recent use of voriconazole. Empirical dosing with voriconazole based on other avian studies has resulted in adverse clinical drug effects in penguins. The objective of this study was to determine oral voriconazole pharmacokinetics (PK) in African penguins (n = 18). Single and once daily multiple oral doses of 5 mg/kg voriconazole were evaluated with a 4-mo washout period between trials. Plasma voriconazole concentrations were determined via high-performance liquid chromatography. Data was modeled using 3-compartamental population methodologies that supported first-order elimination. Observed mean peak concentration (1.89 μg/ml) after single dosing PK analysis was determined within the first hour following voriconazole administration. In the multiple-dose trial average plasma voriconazole concentrations were significantly higher on days 4 and 7 as compared with day 2. The mean estimates for volume of distribution (V/F) and clearance (Cl/F) for the multiple-dose study were 3.34 L and 0.18 L/hr, respectively. Monte Carlo simulations determined the median area under the curve (AUC 0-24 ) at 84 hr was 37.7 μg·h/ml. As this assessment was comparable with the average AUC in humans receiving the recommended human oral dosage 200 mg b.i.d., it suggests that 5 mg/kg p.o. s.i.d. could be a safe and effective regimen in African penguins for treatment of aspergillosis. However, due to potential drug accumulation and subsequent toxicity, therapeutic drug monitoring with dosage adjustments is recommended to individualize dosing.

  3. Main clinical, therapeutic and technical factors related to patient's maximum skin dose in interventional cardiology procedures

    Science.gov (United States)

    Journy, N; Sinno-Tellier, S; Maccia, C; Le Tertre, A; Pirard, P; Pagès, P; Eilstein, D; Donadieu, J; Bar, O

    2012-01-01

    Objective The study aimed to characterise the factors related to the X-ray dose delivered to the patient's skin during interventional cardiology procedures. Methods We studied 177 coronary angiographies (CAs) and/or percutaneous transluminal coronary angioplasties (PTCAs) carried out in a French clinic on the same radiography table. The clinical and therapeutic characteristics, and the technical parameters of the procedures, were collected. The dose area product (DAP) and the maximum skin dose (MSD) were measured by an ionisation chamber (Diamentor; Philips, Amsterdam, The Netherlands) and radiosensitive film (Gafchromic; International Specialty Products Advanced Materials Group, Wayne, NJ). Multivariate analyses were used to assess the effects of the factors of interest on dose. Results The mean MSD and DAP were respectively 389 mGy and 65 Gy cm−2 for CAs, and 916 mGy and 69 Gy cm−2 for PTCAs. For 8% of the procedures, the MSD exceeded 2 Gy. Although a linear relationship between the MSD and the DAP was observed for CAs (r=0.93), a simple extrapolation of such a model to PTCAs would lead to an inadequate assessment of the risk, especially for the highest dose values. For PTCAs, the body mass index, the therapeutic complexity, the fluoroscopy time and the number of cine frames were independent explanatory factors of the MSD, whoever the practitioner was. Moreover, the effect of technical factors such as collimation, cinematography settings and X-ray tube orientations on the DAP was shown. Conclusion Optimising the technical options for interventional procedures and training staff on radiation protection might notably reduce the dose and ultimately avoid patient skin lesions. PMID:22457404

  4. 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

  5. A novel dose-volume metric for optimizing therapeutic ratio through fractionation: retrospective analysis of lung cancer treatments.

    Science.gov (United States)

    Keller, Harald; Hope, Andrew; Meier, Gabriel; Davison, Matt

    2013-08-01

    To explore the potential of a novel dose-volume based metric to assist in the selection of optimal fractionation schedules for lung cancer patients. Selecting the dose per fraction that maximizes the therapeutic ratio via a linear-quadratic effect on normal tissue complication probability and tumor cell survival is an optimization problem. The mathematical solution reveals that the optimal fractionation schedule is determined by a generalized dose ratio between the normal tissue and the tumor, here termed the bifurcation number B, that can be derived from the dose-volume histogram of the normal tissue. The bifurcation number characterizes the volume effect of a normal tissue and its dependency on the fractionation schedule. The clinical relevance of the bifurcation number was evaluated in 46 patients previously treated for nonsmall cell lung cancer (NSCLC) according to various fractionation protocols. Bifurcation numbers were computed for both lung and esophagus as the normal tissues. The value of the bifurcation number determines whether the volume effect reverses the traditional radiobiological advantage of small dose per fraction for the normal tissue. If B is smaller than the ratio of alpha/beta ratios between normal tissue and tumor, then a single fraction is optimal; otherwise the optimal treatment is an infinite number of doses (hence the name "bifurcation" number). These fractionation schedules correspond clinically to hypo- and standard/hyperfractionation, respectively. Compared with traditional dose-volume metrics, the bifurcation number is a unitless ratio and independent of dose fractionation. The B-numbers derived from the clinical treatment plans are also strongly consistent with historically prescribed clinical fractionation protocols for NSCLC treatments. The B-numbers for esophagus and lung for all patients receiving a high dose per fraction protocol (>7.5 Gy/fraction) were all smaller than the B-numbers for the patients receiving standard 2 Gy

  6. 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

  7. Restless Legs Syndrome After Single Low Dose Quetiapine Administration.

    Science.gov (United States)

    Soyata, Ahmet Z; Celebi, Fahri; Yargc, Lutfi I

    2016-01-01

    Restless legs syndrome is an underdiagnosed sensori-motor disorder and psychotropic drugs are one of the main secondary causes of the illness. The most common psychotropic agents that cause restless legs syndrome are antidepressants; however, antipsychotics have also been reported to induce restless legs syndrome. The prevalence, vulnerability factors and the underlying mechanism of antipsychotic-induced restless legs syndrome are unclear. A possible explanation is that dopaminergic blockade is the main precipitator of the syndrome. Quetiapine-induced restless legs syndrome is another point of interest because of its low binding to D2 receptors. We herein report the case of a restless legs syndrome that emerged after a single low dose quetiapine administration.

  8. 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

  9. Estimation of Maximum Recommended Therapeutic Dose Using Predicted Promiscuity and Potency.

    Science.gov (United States)

    Liu, T; Oprea, T; Ursu, O; Hasselgren, C; Altman, R B

    2016-12-01

    We report a simple model that predicts the maximum recommended therapeutic dose (MRTD) of small molecule drugs based on an assessment of likely protein-drug interactions. Previously, we reported methods for computational estimation of drug promiscuity and potency. We used these concepts to build a linear model derived from 238 small molecular drugs to predict MRTD. We applied this model successfully to predict MRTDs for 16 nonsteroidal antiinflammatory drugs (NSAIDs) and 14 antiretroviral drugs. Of note, based on the estimated promiscuity of low-dose drugs (and active chemicals), we identified 83 proteins as "high-risk off-targets" (HROTs) that are often associated with low doses; the evaluation of interactions with HROTs may be useful during early phases of drug discovery. Our model helps explain the MRTD for drugs with severe adverse reactions caused by interactions with HROTs. © 2016 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  10. Study of the therapeutic dose and the clinical effect on Graves' disease with I-131 treatment

    International Nuclear Information System (INIS)

    Dang, Y.

    2005-01-01

    Full text: Graves' disease is being treated with I-131 for more than 40 years in China. Previously the dose of I-131 used to be calculated using the 'Quimby' formula. We have now observed that the dose of I-131 administered to patients is now lower in recent years than the early years. The radioactive iodine uptake by the thyroid gland has also changed significantly over a period of time. In this paper we intend to explore these reasons and to research the relationship between the dose and the effect as well as the main cause of the incidence of the hypothyroidism. The parameters in 'Quimby' formula including I-131 uptake, effective half-life and thyroid weight were analyzed and compared with each year data from 1961 to 1988 and subjected to multiple regression analysis to determine the influence on the calculation of dose in 4465 patients. The therapeutic effects were compared with the data of the clinical follow-up of patients between 1961-1973 and 1978-1988 in 748 patients. The factors which might lead to the hypothyroidism were investigated with the non-condition logistic regression. The I-131 uptake was repeatedly measured within one week in 100 patients to identify the changing pattern of the I-131 uptake and its influence on the administered therapeutic dose. We observed an increase in the value of I-131 uptake. The value of I-131 uptake showed an increase after 1977, as well as a prolongation of effective half-life after 1973. The main reason for these changes being a replacement of the equipment in 1977 (G-M counter tube was replaced by scintillation counter), and the other reason being salt iodization in China in 1973. These two factors resulted in a significant reduction in the administered dose of I-131 during the period 1974-1988 as compared to the previous period 1961-1973; the mean administered doses being 168.35MBq and 330.33MBq respectively. The result of multiple regression analyses suggested that the thyroid weight and the effective half

  11. Systematic review and meta-analysis of single-dose and non-single-dose methotrexate protocols in the treatment of ectopic pregnancy.

    Science.gov (United States)

    Yuk, Jin-Sung; Lee, Jung Hun; Park, Won I; Ahn, Hyeong Sik; Kim, Hyun Jung

    2018-02-27

    It remains unclear which methotrexate protocol for the treatment of ectopic pregnancy has a higher success rate or a higher adverse effect rate. To compare the treatment success rates and adverse effect rates of single-dose and non-single-dose (two-dose and multi-dose) methotrexate protocols in the treatment of ectopic pregnancy. Various databases including Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched on July 1, 2017, using search terms including "methotrexate" and "pregnancy." Randomized controlled trials comparing different methotrexate protocols for the treatment of ectopic pregnancy were included. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated to compare treatment success rates and adverse effect rates. The single-dose and non-single-dose protocols had similar success rates (RR 1.00, 95% CI 0.96-1.04; 11 trials, 1121 patients, I 2 =18%). The non-single-dose protocols had a higher adverse effect rate than did the single-dose protocol (RR 0.73, 95% CI 0.59-0.91; nine trials, 934 patients, I 2 =0%). The single-dose methotrexate protocol was the optimal protocol for the medical treatment of ectopic pregnancy. © 2018 International Federation of Gynecology and Obstetrics.

  12. Protective and Therapeutic Role of Low Dose Gamma Radiation on Streptozotocin Induced Diabetes in Rats

    International Nuclear Information System (INIS)

    Mansour, H.H.; Hafez, H.F.; Shouman, S.A.

    2011-01-01

    Diabetes mellitus is a multi-factorial disease which is characterized by vascular and renal complication. This study was initiated to investigate the protective and the therapeutic effect of low dose of gamma radiation (LDR) on diabetic complications. A total of 30 adult male rats were divided into 5 groups: Group I: served as control and injected intraperitoneally with 0.2 ml of 0.1 mol/l citrate buffer (ph 4.5), group II: rats became diabetic via intraperitoneal injection with 60 mg/kg streptozotocin (STZ) dissolved in 0.2 ml of 0.1 mol/l citrate buffer (ph 4.5), group III irradiated rats (IRR): submitted to fractionated dose of whole body gamma rays; 0.25 Gy for 2 consecutive days (whole dose 0.5 Gy), group IV diabetic irradiated rats (STZ + IRR): rats became diabetic as group II then four weeks after diabetes induction (day 28), rats were submitted to 2 fractions of whole body gamma rays as in group III, and group V irradiated diabetic rats (IRR + STZ): rats were injected intraperitoneally with 0.2 ml of 0.1 mol/l citrate buffer then submitted to whole body gamma rays; 0.25 Gy for 2 consecutive days then one hour after the last IRR dose, rats were made diabetic as group II. In pre and post-irradiation of STZ rats, significant changes were observed in serum lipid profiles, hepatic and cardiac serum enzymes. Significant decrease in hepatic and cardiac malondialdehyde (MDA) and total nitrate/nitrite (NO(x)) levels, and significant increase in superoxide dismutase (SOD) and glutathione (GSH) levels were observed as compared to diabetic group. The study suggests that LDR may provide useful protective and therapeutic option in the reversal of oxidative stress induced in diabetic rats

  13. [Therapeutic efficacy of nootropil different doses in attention deficit hyperactivity disorder].

    Science.gov (United States)

    Zavadenko, N N; Suvorinova, S Iu

    2004-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is the most common cause of behavioral and learning problems in childhood. Therapeutic efficiency of nootropil (piracetam) in two different doses has been evaluated in the open control study of 80 children with ADHD, 70 boys and 10 girls, aged 6-11 years, being divided into 3 groups. Two groups received nootropil, as a monotherapy, for a month: 1st group (30 patients)--in the dosage of 70 mg/kg daily and 2nd group (30 patients)--40 mg/kg daily orally. The control group of 20 patients did not receive any treatment. All children were examined twice with one month interval. A procedure of assessment included of structured questionnaire to parents, neurological examination with scored evaluation of subtle signs and psychological testing. Nootropil therapy in ADHD children resulted in the improvement of behavioral characteristics, motor coordination as well as continuous, selective and divided attention. A response rate was 60% in patients received 70 mg/kg of nootropil and 43% for nootropil dosage of 40 mg/kg. The results of the study suggest more considerable positive therapeutic effects of nootropil higher dose on behavioral, motor and attention characteristics in children with ADHD.

  14. Single-dose versus two-dose administration of methotrexate for the treatment of ectopic pregnancy: a randomized controlled trial.

    Science.gov (United States)

    Song, Taejong; Kim, Mi Kyoung; Kim, Mi-La; Jung, Yong Wook; Yun, Bo Seong; Seong, Seok Ju

    2016-02-01

    Can a two-dose methotrexate treatment protocol improve the treatment success rate compared with a single-dose protocol in women with an ectopic pregnancy? The two-dose protocol was not superior to the single-dose protocol for the treatment of ectopic pregnancy. Although the two-dose methotrexate protocol for ectopic pregnancy was recently introduced to combine the efficacy and convenience of the fixed multi-dose and single-dose protocols, studies comparing the success rates, treatment satisfaction and acceptability of the single-dose and two-dose treatment protocols for ectopic pregnancy are currently lacking. A randomized trial was conducted on 92 participants with tubal ectopic pregnancy, between May 2013 and April 2015. Patients who were diagnosed with tubal ectopic pregnancy and who elected to undergo systemic methotrexate treatment were randomly assigned to follow either the single-dose (n = 46) or two-dose protocol (n = 46). The primary outcome measure was treatment success without surgical intervention. The secondary outcome measures were the incidence of methotrexate-associated side effects, β-human chorionic gonadotrophin (β-hCG) resolution time, cost of care received and treatment satisfaction. There were no differences in baseline characteristics between the groups. The success rates between the single-dose and two-dose groups did not show a significant difference [82.6 versus 87.0%; relative risk (RR) 0.95; 95% confidence interval (CI) 0.80-1.13]. However, the success rate in a subgroup of participants with a pretreatment β-hCG level of >5000 mIU/ml appeared to be higher in the two-dose group than in the single-dose group (80.0 versus 58.8%), although the difference was not statistically significant. No significant differences in methotrexate-associated side effects, cost or treatment satisfaction were observed between the groups. The two-dose group required a lower number of days for the β-hCG level to decrease to ectopic pregnancy. None. www

  15. Gender-specific distribution of mefloquine in the blood following the administration of therapeutic doses.

    Science.gov (United States)

    Wernsdorfer, Walther H; Noedl, Harald; Rendi-Wagner, Pamela; Kollaritsch, Herwig; Wiedermann, Gerhard; Mikolasek, Andrea; Karbwang, Juntra; Na-Bangchang, Kesara

    2013-12-09

    The objectives of the study were to elucidate the gender-specific distribution of mefloquine in cellular and fluid blood compartments when given at therapeutic dosage, to assess its correlation with the occurrence of treatment-related adverse events, and to explore the necessity of adjusting treatment guidelines for females. The distribution of mefloquine following the administration of standard therapeutic doses (1,250 mg mefloquine in split dose) to 22 healthy Caucasian volunteers was assessed in whole blood, serum, plasma, red blood cells (RBCs), white blood cells, and platelets using high performance liquid chromatography. Plasma mefloquine concentrations after 14 hours were considerably higher in female subjects than in males (2,778 vs 1,017 ng/ml at H14), concordant with a significantly higher frequency, duration, and severity of adverse reactions. However, mean drug concentrations of RBC appeared slightly higher in male volunteers (857 vs 719 ng/ml). At H48, a similar situation prevailed, and at H168 the mefloquine concentrations in plasma continued to be higher in females compared to males (1,353 vs 666 ng/ml), while the concentrations of RBC were similar in females (389 vs 375 ng/ml). Since the observations relate to healthy individuals, they do not take into account selective uptake of mefloquine by Plasmodium-infected erythrocytes as in the case of therapeutic drug use. Although plasma mefloquine concentrations in female healthy volunteers are considerably higher and the concentrations of the RBCs are initially lower compared to males, they do not seem to justify an adjustment of treatment guidelines for mefloquine in female Caucasian individuals.

  16. 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)

  17. Serial Myocardial Imaging after a Single Dose of Thallium-201

    Directory of Open Access Journals (Sweden)

    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.

  18. 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)

  19. Adderall XR: long acting stimulant for single daily dosing.

    Science.gov (United States)

    Sallee, Floyd R; Smirnoff, Alexander V

    2004-11-01

    Adderall XR (SLI381) is the latest addition to the group of psychostimulant formulations, which provides the mixed amphetamine salts contained in Adderall as a single-daily dose formulation. Adderall XR is indicated for the treatment of attention deficit hyperactivity disorder in children and adolescents, with recent US Food and Drug Administration approval for attention deficit hyperactivity disorder in adults. Novel and important aspects of Adderall XR is its 12 h duration of action, relative superior efficacy to nonstimulant atomoxetine in a comparator trial, and significant quality of life impact in children, confirmed by the largest effectiveness trial yet to be performed for any attention deficit hyperactivity disorder therapy. Potentially important benefits of Adderall XR are proven safety and efficacy in adults with attention deficit hyperactivity disorder and positive postmarketing findings in treating oppositional defiant disorder -- the most common comorbidity in children with attention deficit hyperactivity disorder. This review summarizes the important properties of Adderall XR, to include a distinct two-stage delivery system and combination of active ingredients, offering unique advantages. Relevant clinical trials and the newest data from meeting reports are also discussed.

  20. Methodology for management of therapeutic dose of I-131; Metodologia para administrar dosis terapeutica de I-131

    Energy Technology Data Exchange (ETDEWEB)

    Basteris M, J.; Gomez D, R. [Universidad Autonoma de Yucatan, Facultad de Medicina, Merida, Yucatan (Mexico)

    2007-07-01

    The present work suggests the use of measures guided to eliminate the resulting chronic sialoadenitis of the treatment previously described with a therapeutic dose bigger than ablative of Iodine 131, as well as the use of citric fruits to stimulate the salivation, the administration of liquid post-dose is included to accelerate the gastric emptying avoiding the secondary effects as the vomit. (Author)

  1. Therapeutic efficacy and toxicity of a single and double application of boron neutron capture therapy (BNCT) in a hamster cheek pouch oral precancer model

    International Nuclear Information System (INIS)

    Monti Hughes, A; Pozzi, E C C; Thorp, S; Garabalino, M A; Farias, R O; Gonzalez, S J; Heber, E M; Itoiz, M E; Aromando, R F; Molinari, A J; Miller, M; Nigg, D W; Curotto, P; Trivillin, V A; Schwint, A E

    2012-01-01

    Tumor development from tissue with potentially malignant disorders (PMD) gives rise to second primary tumors. We previously demonstrated the partial inhibitory effect on tumor development of Boron Neutron Capture Therapy (BNCT) mediated by the boron compounds BPA (boronophenylalanine) and decahydrodecaborate (GB-10) in a hamster pouch oral precancer model. Seeking to optimize BNCT, the aim of the present study was to contribute to the knowledge of BNCT radiobiology for oral precancer and assess new BNCT protocols in terms of inhibition of tumor development and radiotoxicity. Groups of cancerized hamsters were locally exposed to single or double applications (2 weeks apart) of BPA-BNCT or (GB-10 + BPA)-BNCT at a total dose of 8Gy to tissue with PMD; to a single application of BPA-BNCT at 6Gy and to a double application (4 weeks apart) of BPA-BNCT or (BPA + GB-10)-BNCT at a total dose of 10Gy. Cancerized, sham-irradiated hamsters served as controls. Clinical status, tumor development from tissue with PMD and mucositis were followed for 8 months. The marked therapeutic efficacy of single applications of BNCT at 6 and 8Gy were associated to severe radiotoxicity. Dose fractionation into 2 applications reduced mucositis but also reduced therapeutic efficacy, depending on dose and interval between applications. A double application (4 weeks apart) of (GB-10 + BPA)-BNCT at a total dose of 10Gy rendered the best therapeutic advantage, i.e. 63% - 100% inhibition of tumor development with only slight mucositis in 67% of cases. The data reported herein show that issues such as dose levels and dose fractionation, interval between applications, and choice of boron compounds are pivotal to therapeutic advantage and must be tailored for a particular pathology and anatomic site. The present study determined treatment conditions that would contribute to optimize BNCT for precancer and that would warrant cautious assessment in a clinical scenario (author)

  2. Developing equations to predict surface dose and therapeutic interval in bolused electron fields: A Monte Carlo Study

    Science.gov (United States)

    Jabbari, Nasrollah; Khalkhali, Hamid Reza

    2017-07-01

    In this research, we aim to investigate the influence of different materials, as a bolus, on the low-energy electron beam dose distributions and to develop equations for predicting surface dose based on bolus thickness, as well as the therapeutic interval based on surface dose. All the Monte Carlo (MC) calculations and measurements were conducted on a Siemens PRIMUS linac. Based on EGSnrc MC code, BEAMnrc system was used to model a Siemens linac and generate phase-space files for three electron beams (6, 8, and 10 MeV). The particles were transported from the phase-space files to the bolus materials and the simulated water phantom using DOSXYZnrc. Various materials with different thicknesses were examined as a bolus, and appropriate equations were determined for each material and electron beam. The comparison of percent depth dose (PDD) curves and beam profiles, using MC, with the measured data demonstrated that the calculated values properly matched with the measurements. The results indicated that the use of bolus materials with the density of higher than soft tissue can increase both surface dose and therapeutic interval simultaneously. This finding arises from the fact that the required bolus thickness for achieving the therapeutic surface dose decreases in the case of high-density materials. Two series of prediction equations were proposed for predicting the surface dose based on bolus thickness and the therapeutic interval based on surface dose. These equations are able to calculate properly the bolus thickness required for producing a therapeutic surface dose (above 90%) for any therapeutic interval.

  3. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination.

    Science.gov (United States)

    Pardi, Norbert; Hogan, Michael J; Pelc, Rebecca S; Muramatsu, Hiromi; Andersen, Hanne; DeMaso, Christina R; Dowd, Kimberly A; Sutherland, Laura L; Scearce, Richard M; Parks, Robert; Wagner, Wendeline; Granados, Alex; Greenhouse, Jack; Walker, Michelle; Willis, Elinor; Yu, Jae-Sung; McGee, Charles E; Sempowski, Gregory D; Mui, Barbara L; Tam, Ying K; Huang, Yan-Jang; Vanlandingham, Dana; Holmes, Veronica M; Balachandran, Harikrishnan; Sahu, Sujata; Lifton, Michelle; Higgs, Stephen; Hensley, Scott E; Madden, Thomas D; Hope, Michael J; Karikó, Katalin; Santra, Sampa; Graham, Barney S; Lewis, Mark G; Pierson, Theodore C; Haynes, Barton F; Weissman, Drew

    2017-03-09

    Zika virus (ZIKV) has recently emerged as a pandemic associated with severe neuropathology in newborns and adults. There are no ZIKV-specific treatments or preventatives. Therefore, the development of a safe and effective vaccine is a high priority. Messenger RNA (mRNA) has emerged as a versatile and highly effective platform to deliver vaccine antigens and therapeutic proteins. Here we demonstrate that a single low-dose intradermal immunization with lipid-nanoparticle-encapsulated nucleoside-modified mRNA (mRNA-LNP) encoding the pre-membrane and envelope glycoproteins of a strain from the ZIKV outbreak in 2013 elicited potent and durable neutralizing antibody responses in mice and non-human primates. Immunization with 30 μg of nucleoside-modified ZIKV mRNA-LNP protected mice against ZIKV challenges at 2 weeks or 5 months after vaccination, and a single dose of 50 μg was sufficient to protect non-human primates against a challenge at 5 weeks after vaccination. These data demonstrate that nucleoside-modified mRNA-LNP elicits rapid and durable protective immunity and therefore represents a new and promising vaccine candidate for the global fight against ZIKV.

  4. Pediatric vancomycin dosing: Trends over time and the impact of therapeutic drug monitoring.

    Science.gov (United States)

    Balch, Alfred H; Constance, Jonathan E; Thorell, Emily A; Stockmann, Chris; Korgenski, Ernest K; Campbell, Sarah C; Spigarelli, Michael G; Sherwin, Catherine M T

    2015-02-01

    Monitoring of vancomycin trough concentrations is recommended for pediatric patients in the product label and by several professional societies. However, among a network of freestanding children's hospitals vancomycin therapeutic drug monitoring (TDM) practices were reported to be highly variable. In this study, we sought to evaluate whether trends in vancomycin use and TDM changed across a large healthcare delivery system in Utah and Idaho from 2006 to 2012. Children ≤18 years who received ≥2 vancomycin doses were included. Overall, vancomycin TDM was performed during 5,035 (80%) of 6,259 hospital encounters, in which 85,442 doses were administered and 7,935 concentrations were obtained. Across this time period, the median trough concentration increased from 10.9 to 13.7 µg/mL (P vancomycin TDM is commonly performed among children and the majority of abnormal trough concentrations were associated with an appropriate modification to the dosing regimen. © 2014, The American College of Clinical Pharmacology.

  5. 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.

  6. 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.

  7. Retrospective dosimetry: Estimation of the dose to quartz using the single-aliquot regenerative-dose protocol

    DEFF Research Database (Denmark)

    Banerjee, D.; Bøtter-Jensen, L.; Murray, A.S.

    2000-01-01

    We report on the application of the single-aliquot regenerative-dose protocol to retrospective dosimetry, using the optically stimulated luminescence (OSL) from quartz extracted from fired bricks. These bricks had previously been exposed to enhanced levels of ionising radiation while part...... meets the fundamental requirement of the single-aliquot regenerative-dose protocol, in that any change in the luminescence recombination probability can be corrected for by using the OSL response to a fixed test dose. The response of a particular aliquot is examined after three different treatments...

  8. Correcting Effect of Therapeutic Doses of Optical Radiation on Hematological Parameters of Blood Irradiated In Vivo

    Science.gov (United States)

    Zalesskaya, G. A.; Laskina, O. V.

    2017-07-01

    We studied the effect of therapeutic doses of optical radiation on the hematological parameters of blood irradiated in vivo: hemoglobin concentration, hematocrit, and the number of erythrocytes in the peripheral blood of patients during courses of extracorporeal, overvein, and intravenous blood irradiation and after treatment. The reversible changes during the procedures were found to differ from the changes obtained after treatment completion. At the end of the treatment course, the hematological parameters had changed in different directions and became higher, the same, or lower than the initial parameters depending on the initial parameters and photoinduced changes in blood oxygenation. A compensatory effect was found for photohemotherapy on oxygen-dependent processes altering the oxygen inflow into cells as well as the generation of active oxygen species and their inhibition by antioxidant systems.

  9. Maximum likelihood estimation of dose-response parameters for therapeutic operating characteristic (TOC) analysis of carcinoma of the nasopharynx

    International Nuclear Information System (INIS)

    Metz, C.E.; Tokars, R.P.; Kronman, H.B.; Griem, M.L.

    1982-01-01

    A Therapeutic Operating Characteristic (TOC) curve for radiation therapy plots, for all possible treatment doses, the probability of tumor ablation as a function of the probability of radiation-induced complication. Application of this analysis to actual therapeutic situation requires that dose-response curves for ablation and for complication be estimated from clinical data. We describe an approach in which ''maximum likelihood estimates'' of these dose-response curves are made, and we apply this approach to data collected on responses to radiotherapy for carcinoma of the nasopharynx. TOC curves constructed from the estimated dose-response curves are subject to moderately large uncertainties because of the limitations of available data.These TOC curves suggest, however, that treatment doses greater than 1800 rem may substantially increase the probability of tumor ablation with little increase in the risk of radiation-induced cervical myelopathy, especially for T1 and T2 tumors

  10. Combined low dose local anesthetics and opioids versus single use ...

    African Journals Online (AJOL)

    Introduction: The combination of reduced dose of local anesthetics (LA) and highly lipid‑soluble synthetic opioids for patients undergoing transurethral surgery could reduce block duration and side‑effects. However, it remains unclear what are the most appropriate levels of low dose and the extent to which the side‑effects ...

  11. Single dose oral tenoxicam for acute postoperative pain in adults.

    Science.gov (United States)

    Moore, Owen A; McIntyre, Mairead; Moore, R Andrew; Derry, Sheena; McQuay, Henry J

    2009-07-08

    Tenoxicam is a non-steroidal anti-inflammatory drug (NSAID) licensed for use in rheumatic disease and other musculoskeletal disorders in the UK, and is widely available in other countries worldwide. This review sought to evaluate the efficacy and safety of oral tenoxicam in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties. To assess the efficacy of single dose oral tenoxicam in acute postoperative pain, and any associated adverse events. We searched The Cochrane Library (Issue 1, 2009), MEDLINE (March 2009); EMBASE via Ovid (March 2009); the Oxford Pain Relief Database. Randomised, double-blind, placebo-controlled clinical trials of oral tenoxicam for relief of acute postoperative pain in adults. Two review authors independently assessed trial quality and extracted data. The area under the "pain relief versus time" curve was used to derive the proportion of participants with tenoxicam experiencing least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals was also collected. Not one of sixteen studies identified by the searches and examined in detail studied oral tenoxicam in patients with established postoperative pain and therefore no results are available. In the absence of evidence of efficacy for oral tenoxicam in acute postoperative pain, its use in this indication is not justified at present. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be

  12. Single dose pharmacokinetics of the novel transdermal donepezil patch in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Kim YH

    2015-03-01

    Full Text Available Yo Han Kim,1 Hee Youn Choi,1 Hyeong-Seok Lim,1 Shi Hyang Lee,1 Hae Sun Jeon,1 Donghyun Hong,2 Seong Su Kim,2 Young Kweon Choi,2 Kyun-Seop Bae1 1Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea; 2iCure Pharmaceutical lncorporated, Anseong, Gyeonggi-do, Republic of Korea Background: Donepezil is an acetylcholinesterase inhibitor indicated for Alzheimer’s disease. The aim of this randomized, single-blind, placebo-controlled, single-dose, dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics of the donepezil patch in healthy male subjects. Methods: Each healthy male subject received a single transdermal donepezil patch (72 hours patch-on periods of 43.75 mg/12.5 cm2, 87.5 mg/25 cm2, or 175 mg/50 cm2. Serial blood samples were collected up to 312 hours after patch application. The plasma concentrations of donepezil were determined by using a validated liquid chromatography–tandem mass spectrometry method. Pharmacokinetic parameters were obtained by noncompartmental analysis. Tolerability of the patches and performance of the patches (adhesion, skin irritation, residual donepezil content in the patch were assessed throughout the study. Results: The study was completed by 36 healthy subjects. After patch application, the maximal plasma donepezil concentration (Cmax and the area under the curve (AUC increased in a dose-proportional manner. Median time to Cmax was ~74–76 hours (~2–4 hours after patch removal, and mean t1/2ß was ~63.77–93.07 hours. The average donepezil residue in the patch after 72 hours was ~73.9%–86.7% of the loading dose. There were neither serious adverse events nor adverse events that lead to discontinuation. Skin adhesion of the patch was good in 97.2% of the subjects. All skin irritations after patch removal were mild and were resolved during the study period. Conclusion: The donepezil patch

  13. Comparative evaluation of 2 g single dose versus conventional dose azithromycin in uncomplicated skin and skin structure infections.

    Science.gov (United States)

    Dey, Sudipta Kumar; Das, Amal Kanti; Sen, Sumit; Hazra, Avijit

    2015-01-01

    Uncomplicated skin and skin structure infections (uSSSIs) are a common clinical problem. Majority are caused by staphylococci and streptococci. Different oral antibiotics are used for uSSSI, with comparable efficacy but varying treatment duration, cost, and adverse event profile. Azithromycin is used in uSSSI in adults conventionally in a dose of 500 mg once for 5 days. The extensive tissue distribution of the drug and its long elimination half-life prompted us to explore whether a single 2 g dose of the drug would produce a response in uSSSI comparable to conventional dosing. We conducted a parallel group, open-label, randomized, controlled trial (CTRI/2015/07/005969) with subjects of either sex, ≥12 years of age, presenting with uSSSI to the dermatology outpatient department. One group (n = 146) received 2 g single supervised dose while the other (n = 146) received conventional dose of 500 mg once daily for 5 days. Subjects were followed up on day 4 and day 8. Complete clinical cure implied complete healing of lesions, without residual signs or symptoms, within 7 days. High cure rate was observed in both arms (97.97% and 98.63%, respectively) along with noticeable improvement in symptom profile from baseline but without statistically significant difference between groups. However, excellent adherence (defined as no tablets missed) was better in single dosing arm (98.65% vs. 86.30%). Tolerability was also comparable between groups with the majority of adverse events encountered being gastrointestinal in nature and mild. Single 2 g azithromycin dose achieved the same result as conventional azithromycin dosing in uSSSI with comparable tolerability but with the advantage of assured adherence. This dose can, therefore, be recommended as an alternative and administration supervised if feasible.

  14. Protective effect of a low single dose inhaled steroid against exercise induced bronchoconstriction

    NARCIS (Netherlands)

    Visser, R.; Wind, M.; de Graaf, B.; de Jongh, Franciscus H.C.; van der Palen, Jacobus Adrianus Maria; Thio, B.J.

    2015-01-01

    Objective Daily use of inhaled corticosteroids (ICS) reduces exercise induced bronchoconstriction (EIB) in asthmatic children. A high single dose of ICS also provided acute protection against EIB. Objective of this study is to investigate whether a low single dose of ICS offers protection against

  15. 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...

  16. Nonconvulsive status epilepticus in the elderly associated with newer antidepressants used at therapeutic doses: A report of three cases

    OpenAIRE

    Go Taniguchi; Miho Miyajima; Masako Watanabe; Yoshiko Murata; Daichi Sone; Yutaka Watanabe; Mitsutoshi Okazaki; Motonori Kobayashi-Kimura; Masaaki Kato; Teiichi Onuma

    2015-01-01

    Classic antidepressants have been known to induce convulsive seizures and nonconvulsive status epilepticus (NCSE). On the other hand, many reports have emphasized the safety of novel antidepressants. However, we encountered three cases of NCSE in the elderly associated with the use of newer antidepressants at therapeutic doses. All three patients were male and were 73?years of age or older. One patient was recently diagnosed with temporal lobe epilepsy and treated with low-dose lamotrigine. I...

  17. Toxicity to the hematopoietic and lymphoid organs of piglets treated with a therapeutic dose of florfenicol.

    Science.gov (United States)

    Hu, Dongfang; Zhang, Taixiang; Zhang, Zhendong; Wang, Guangwen; Wang, Fangkun; Qu, Yajin; Niu, Yujuan; Liu, Sidang

    2014-12-15

    Florfenicol (FLO) is a broad-spectrum antibacterial agent for treatment of bacteriosis of piglets in veterinary practice. To study the toxicity to the hematopoietic and lymphoid organs of piglets treated with a therapeutic dose of FLO, 20 healthy weaned piglets were selected and randomly divided into two groups. Piglets in the FLO group were fed with fodder supplemented with 30mg/kg BW of FLO twice a day for 10 days. Blood samples were drawn at four time points: 1 day before FLO administration and 1, 7, and 14 days post-withdrawal. Three or four piglets were euthanized at each time point post-withdrawal and tissue samples (bone marrow, thymus and spleen) were collected for fixation and cryostorage. The levels of classical swine fever virus (CSFV) antibody against the vaccine, the concentrations of Hsp70 and IL-6 in serum and Hsp70 in tissues, and the mRNA expression levels of B-cell lymphoma 2 (bcl-2) and tumor suppressor p53 were detected, the hematology of the piglets were analyzed, and the histopathology and the status of apoptosis of the hematopoietic and lymphoid organs was examined. The results showed changes in several indicators in the FLO group 1 day post-withdrawal: the concentration of red blood cells (RBCs) was decreased, and that of platelets (PLTs) was significantly lower (p<0.05); the volumes of RBC and PLT were increased; the sum of blood lymphocytes was statistically decreased (p<0.05); the concentration of IL-6 was significantly increased (p<0.05); the concentrations of Hsp70 in serum and tissues were increased; obvious atrophy of the hematopoietic cell lines and partial replacement by fat cells were observed in bone marrow; thymus and spleen tissues showed lower concentrations and sparser arrangement of lymphocytes in the thymic medulla and white pulp of the spleen respectively; and the mRNA expression levels of bcl-2 in the three tissues were up-regulated, while that of p53 was down-regulated. With time after cessation of FLO administration, the

  18. Single oral dose safety of D-allulose in dogs

    OpenAIRE

    NISHII, Naohito; NOMIZO, Toru; TAKASHIMA, Satoshi; MATSUBARA, Tatsuya; TOKUDA, Masaaki; KITAGAWA, Hitoshi

    2016-01-01

    Healthy dogs were administered acute oral doses of D-allulose (also called D-psicose) to evaluate its toxicity. Six dogs received oral doses of either a placebo or D-allulose solution (1 and 4 g/kg) on three different study days. One dog experienced vomiting, and five dogs showed transient diarrhea when 4 g/kg of D-allulose was administered. All dogs were active and had a good appetite throughout the study period. Blood glucose concentration slightly decreased without a rise in plasma insulin...

  19. Therapeutic drug monitoring and use of an adjusted body weight strategy for high-dose voriconazole therapy.

    Science.gov (United States)

    Richards, Patrick G; Dang, Kimberlyn M; Kauffman, Carol A; Stalker, Kay Lyn; Sudekum, David; Kerr, Lisa; Brinker-Bodley, Michelle; Cheriyan, Beena; West, Nina; Collins, Curtis D; Polega, Shikha; Malani, Anurag N

    2017-04-01

    A high-dose 12 mg/kg/day (6 mg/kg twice daily) voriconazole regimen was recommended by the CDC to treat patients injected with contaminated methylprednisolone acetate that caused a multi-state fungal outbreak in 2012-13. Therapeutic drug monitoring results of this unique regimen are unknown, as is the most appropriate dosing weight for obese patients. We evaluated voriconazole trough measurements for this dosing scheme, as well as the use of adjusted body weight dosing for obese patients. Voriconazole trough levels were analysed in obese (BMI ≥35 kg/m 2 ) and non-obese (BMI voriconazole troughs were supratherapeutic (>5 mg/L) in 65 (47%) patients, therapeutic (2-5 mg/L) in 57 (41%) patients and subtherapeutic (Voriconazole doses >11 and >8 mg/kg/day produced mainly first steady-state supratherapeutic troughs in 44 obese and 94 non-obese patients, respectively. An initial 12 mg/kg/day was progressively lowered to a median maintenance dose of 8.5 mg/kg/day in the obese and 8.6 mg/kg/day in the non-obese. A high-dose voriconazole regimen produced initial supratherapeutic troughs that required dose adjustment downward by nearly 30%. Adjusted body weight dosing in obese patients resulted in a similar maintenance dose to total body weight dosing in the non-obese, and appears to be a sensible dosing strategy for these patients.

  20. A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia.

    Science.gov (United States)

    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.

  1. Effects of a Single Dose of Caffeine on Resting Cardiovascular ...

    African Journals Online (AJOL)

    The objective of this study was to determine the effect of 5mg/kg body weight dose of caffeine on cardiovascular system of normal young adult males of Black African Origin. Twenty normal young adult male volunteers participated. A repeated measures 2 randomized Crosse over (counter balanced) double blind design was ...

  2. Effects of a Single Dose of Caffeine on Resting Cardiovascular ...

    African Journals Online (AJOL)

    Administrator

    The objective of this study was to determine the effect of. 5mg/kg body weight dose of caffeine on cardiovascular system of normal young adult males of Black African Origin. Twenty normal young adult male volunteers participated. A repeated measures 2 randomized Crosse over (counter balanced) double blind design was ...

  3. An acute, non-therapeutic dose of methylphenidate disrupts partner preference in female rats.

    Science.gov (United States)

    Gomez, Alexa; Petrucci, Alexandra N; Dance, Lauren; Morales-Valenzuela, Jessica; Gibbs, Nicole; Dahlhausen, Cara C; Villatoro, Jessica R; Frohardt, Russell F; Guarraci, Fay A

    (counterbalancing previous MPH exposure). Once again MPH increased locomotor activity. In conclusion, the effects of MPH were equally as robust in naturally cycling subjects as in the more commonly used OVX-hormone primed subjects. The results of the present study suggest that an acute, non-therapeutic dose of MPH disrupts approach and interest in a male stimulus during a test of partner preference. This avoidance of the male stimulus may be the result of a decrease in the incentive value of a sexual partner. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Therapeutic dose of Ginkgo biloba extract 761 may alter the urine excretion of Wistar rats

    Directory of Open Access Journals (Sweden)

    Monica S. C. Dalmacio

    2012-08-01

    Full Text Available Wistar rats (n=20 were divided in two groups: G1 received 2 mg/kg of GBE (Ginkgo biloba extract 761, whereas G2 received the same volume of a sodium chloride solution (0.9%, both for 10 days. After a 7-day interval, the treatment was repeated for 8 days. Urine volume and food and water intake were measured daily during this protocol. Histological assessments were performed. No significant difference (p>0.05 was observed in food and water intake of animals during treatment with GBE. Animals who received GBE had a smaller urine volume and increase of weight with a significance difference (p<0.05 during the first and second exposure period. No histological alteration was observed in tissues, except for the kidney of the experimental group, which revealed a higher concentration of red cells in the glomerulus with a strong staining for Vascular Endothelial Growth Factor (VEGF. The introduction of GBE (therapeutic dose in health rats may promote alterations in the physiology of the kidney, but no sufficient to modify the glomerulus architecture, including at ultra structural level (electron microscopy.

  5. Therapeutic dose of Ginkgo biloba extract 761 may alter the urine excretion of Wistar rats

    Directory of Open Access Journals (Sweden)

    Monica S. C. Dalmacio

    2012-10-01

    Full Text Available Wistar rats (n=20 were divided in two groups: G1 received 2 mg/kg of GBE (Ginkgo biloba extract 761, whereas G2 received the same volume of a sodium chloride solution (0.9%, both for 10 days. After a 7-day interval, the treatment was repeated for 8 days. Urine volume and food and water intake were measured daily during this protocol. Histological assessments were performed. No significant difference (p>0.05 was observed in food and water intake of animals during treatment with GBE. Animals who received GBE had a smaller urine volume and increase of weight with a significance difference (p<0.05 during the first and second exposure period. No histological alteration was observed in tissues, except for the kidney of the experimental group, which revealed a higher concentration of red cells in the glomerulus with a strong staining for Vascular Endothelial Growth Factor (VEGF. The introduction of GBE (therapeutic dose in health rats may promote alterations in the physiology of the kidney, but no sufficient to modify the glomerulus architecture, including at ultra structural level (electron microscopy.

  6. Effect of therapeutic doses of enrofloxacin on circulating lymphocyte subpopulations in pigs

    Directory of Open Access Journals (Sweden)

    Pomorska-Mól Małgorzata

    2015-06-01

    Full Text Available Twenty pigs of similar genetics (PIC were used. Pigs were randomly divided into two groups: experimental (ENRO, n = 10 and control (C, n = 10. From day 0 to day 4, pigs from ENRO group received enrofloxacin at the recommended therapeutic dose. Pigs from C group received PBS instead of enrofloxacin. Blood samples were collected on days 0 (before antibiotic administration, 2, 4 (during antibiotic therapy, 9, and 13 of the study (after enrofloxacin administration. Haematological examination and flow cytometry were used to establish the relative and absolute counts of various leukocyte subsets. Lymphocyte subpopulations were measured by fluorochrom-labelled antibodies according to following definitions: CD3+ (T cells, CD21+ (B cells, CD4+CD8- (helper T cells, Th, CD4-CD8+ (cytolytic T cells, CLT, CD4+CD8+ (cytolytic and memory T cells. The present study revealed the modulating effect of enrofloxacin on the composition of circulating lymphocytes in pigs. Concentration and percentage of CD8+ cells decreased significantly after treatment with enrofloxacin and as a result the absolute CD4/CD8 ratio increased significantly as compared to control group (P < 0.05.These findings should prompt further studies on the practical significance of the results obtained in terms of clinical implications. In view of the results, it cannot be excluded that enrofloxacin may also have immunomodulatory effects on host response to infection.

  7. Five-Week Outcomes From a Dosing Trial of Therapeutic Massage for Chronic Neck Pain

    Science.gov (United States)

    Sherman, Karen J.; Cook, Andrea J.; Wellman, Robert D.; Hawkes, Rene J.; Kahn, Janet R.; Deyo, Richard A.; Cherkin, Daniel C.

    2014-01-01

    PURPOSE This trial was designed to evaluate the optimal dose of massage for individuals with chronic neck pain. METHODS We recruited 228 individuals with chronic nonspecific neck pain from an integrated health care system and the general population, and randomized them to 5 groups receiving various doses of massage (a 4-week course consisting of 30-minute visits 2 or 3 times weekly or 60-minute visits 1, 2, or 3 times weekly) or to a single control group (a 4-week period on a wait list). We assessed neck-related dysfunction with the Neck Disability Index (range, 0–50 points) and pain intensity with a numerical rating scale (range, 0–10 points) at baseline and 5 weeks. We used log-linear regression to assess the likelihood of clinically meaningful improvement in neck-related dysfunction (≥5 points on Neck Disability Index) or pain intensity (≥30% improvement) by treatment group. RESULTS After adjustment for baseline age, outcome measures, and imbalanced covariates, 30-minute treatments were not significantly better than the wait list control condition in terms of achieving a clinically meaningful improvement in neck dysfunction or pain, regardless of the frequency of treatments. In contrast, 60-minute treatments 2 and 3 times weekly significantly increased the likelihood of such improvement compared with the control condition in terms of both neck dysfunction (relative risk = 3.41 and 4.98, P = .04 and .005, respectively) and pain intensity (relative risk = 2.30 and 2.73; P = .007 and .001, respectively). CONCLUSIONS After 4 weeks of treatment, we found multiple 60-minute massages per week more effective than fewer or shorter sessions for individuals with chronic neck pain. Clinicians recommending massage and researchers studying this therapy should ensure that patients receive a likely effective dose of treatment. PMID:24615306

  8. A dramatic response to a single dose of infliximab in a patient with prolonged pustular psoriasis derived from inverse psoriasis.

    Science.gov (United States)

    Li, Mengmeng; Dai, Weiwei; Yan, Wei; Liu, Yuanzhen; Wang, Lian; Li, Wei

    2017-07-01

    We report a case of a 25-year-old Chinese man with an exceptionally prolonged history of pustular psoriasis derived from inverse psoriasis who was unsatisfied with conventional treatment and was successfully treated with a single dose of infliximab without noticeable adverse effects. No recurrence or flaring was observed after 3 months of follow-up. This case illustrates that infliximab may be an effective and safe therapeutic option for patients with refractory pustular psoriasis derived from inverse psoriasis. © 2017 Wiley Periodicals, Inc.

  9. Maintenance of cytosolic calcium is crucial to extend l-arginine therapeutic benefits during continuous dosing.

    Science.gov (United States)

    Mohan, Srinidi; Harding, Lisa

    2016-10-01

    The therapeutic benefits associated with short-term l-arginine supplementation are lost during continuous dosing. AMP-activated protein kinase (AMPK) functional modulation has been correlated with l-arginine therapeutic effectiveness, and with tolerance development during continuous supplementation. However, the metabolic link that is responsible for AMPK functional modulation during continuous l-arginine exposure is currently not known. To explore this, we incubated HUVECs for 7 days with 100 μmol/L l-arginine, in the presence or absence of other agents; and monitored their effects for eNOS function, and on tolerance sparing effects (viz, cellular glucose accumulation, and oxidative stress). HUVEC co-incubation with 100 μmol/L l-arginine and ≤1200 mg/mL calcium (Ca 2+ ) for 7 days avoided tolerance development, with an at least 1-fold increase in the eNOS and AMPK functional activity; and an 1-fold increase in overall cellular glucose uptake. The overall cellular cytosolic Ca 2+ was below 200 nmol/L, with no change in cellular glucose and superoxide/peroxynitrite (O 2 •- /ONOO - ) level from control. However, tolerance sparing effects of at least 70% decrease in eNOS and AMPK functional response, with an 1-fold reduction in glucose uptake, and at least 2-fold increase in O 2 •- /ONOO - were observed in cells exposed for 7 days to 100 μmol/L l-arginine at Ca 2+ co-incubation concentration of >1200 mg/mL. The >1200 mg/mL Ca2+ co-incubation condition, also improved the overall cellular Ca 2+ to >200 nmol/L. Similar tolerance response was observed in cells co-treated with 100 μmol/L l-arginine and ≤1200 mg/mL Ca 2+ in the presence of Ca 2+ influx inhibitor (20 μmol/L 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetra acetic acid), or eNOS activity inhibitor (30 μmol/L l-N G -nitroarginine methyl ester). No tolerance response was seen in cells incubated for 7 days with 100 μmol/L l-arginine and ≤1200 mg/mL Ca 2+ ; even in the presence of the inhibitor for

  10. Observational infant exploratory [14C]-paracetamol pharmacokinetic microdose/therapeutic dose study with accelerator mass spectrometry bioanalysis

    NARCIS (Netherlands)

    Garner, C.R.; Park, K.B.; French, N.S.; Earnshaw, C.; Schipani, A.; Selby, A.M.; Byrne, L.; Siner, S.; Crawley, F.P.; Vaes, W.H.J.; Duijn, E. van; ligt, R. de; Varendi, H.; Lass, J.; Grynkiewicz, G.; Maruszak, W.; Turner, M.A.

    2015-01-01

    Aims The aims of the study were to compare [14C]-paracetamol ([14C]-PARA) paediatric pharmacokinetics (PK) after administration mixed in a therapeutic dose or an isolated microdose and to develop further and validate accelerator mass spectrometry (AMS) bioanalysis in the 0-2 year old age group.

  11. Influence of time-dose-relationships in therapeutic nuclear medicine applications on biological effectiveness of irradiation. Consequences for dosimetry

    International Nuclear Information System (INIS)

    Oehme, L.; Kotzerke, J.; Doerr, W.; Wust, P.

    2008-01-01

    Aim: The biological effectiveness of irradiation is influenced not only by the total dose but also the rate at which this dose is administered. Tolerance dose estimates from external radiation therapy with a conventional fractionation protocol require adaptation for application in targeted radionuclide therapy. Methods: The linear-quadratic model allows for calculation of the biologically effective dose (BED) and takes into consideration tissue specific factors (recovery capacity) as well as dose rate effects (recovery kinetics). It can be applied in radionuclide therapy as well. For relevant therapeutic radionuclides (e. g. 188 Re, 90 Y, 177 Lu, and 131 I), the effect of different physical decay times and variable biological half-lives on BED was calculated for several organs. Results: BED is markedly increased using 188 Re compared to longer-lived radionuclides. The effect is dose-dependent and tissue-specific, resulting, for example, in higher effects on the kidneys compared to bone marrow. Therefore, in unfavourable conditions (e. g. reduced recovery capacity due to concomitant diseases or previous therapy), the BED may exceed organ dose tolerance. Conclusion: Time-dose-relationships have to be taken into consideration by the calculation of BED for internal radionuclide therapy. The biological effectiveness depends on dose- and tissue-specific factors and is much more pronounced in 188 Re than in 90 Y and other longer living radionuclides. Determination of organ tolerance dose values should take into account these radiobiological differences, since it is currently not considered in dosimetry programs. (orig.)

  12. Long-term immunity in young adults after a single dose of inactivated Hepatitis A vaccines.

    Science.gov (United States)

    Orr, Nadav; Klement, Eyal; Gillis, David; Sela, Tamar; Kayouf, Raid; Derazne, Estela; Grotto, Itamar; Balicer, Ran; Huerta, Michael; Aviram, Lisa; Ambar, Ruhama; Epstein, Yoram; Heled, Yuval; Cohen, Dani

    2006-05-15

    We evaluated in a prospective study the immune response of naïve subjects to a single dose of inactivated Hepatitis A vaccine. Ninety-seven percent of the vaccinees sero-converted 1 month after vaccination and 93% were still positive 2 years later. All of the vaccinees had a strong booster response 2 years after the single dose. Avaxim was more immunogenic than Vaqta for the primary dose (p = 0.01 for sero-positivity, p<0.001 for antibody level) but no differences were found after boosting with Avaxim. Performance of intense physical activity during the first month after a single vaccine dose was associated with lower antibody levels (p = 0.004). This study indicates that a single dose of inactivated HAV vaccine elicits protective immune memory for at least 2 years.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Efficacy of high therapeutic doses of iodine-131 in patients with differentiated thyroid cancer and detectable serum thyroglobulin

    Energy Technology Data Exchange (ETDEWEB)

    Keizer, B. de; Rijk, P.P. van; Klerk, J.M.H. de [Dept. of Nuclear Medicine, University Medical Center Utrecht (Netherlands); Koppeschaar, H.P.F.; Zelissen, P.M.J.; Lips, C.J.M. [Dept. of Endocrinology, University Medical Center Utrecht (Netherlands); Dijk, A. van [Dept. of Hospital Pharmacy, University Medical Center Utrecht (Netherlands)

    2001-02-01

    Serum thyroglobulin (Tg) is usually the best marker of residual or metastatic disease after treatment of differentiated thyroid cancer. We evaluated the effect of so-called blind therapeutic doses of iodine-131 in patients with detectable Tg during suppressive levothyroxine treatment (Tg-on), and in patients with a negative diagnostic scintigram but detectable Tg during the hypothyroid phase (Tg-off). Twenty-two patients with differentiated thyroid carcinoma underwent total thyroidectomy and radioiodine ablation. During the follow-up, six patients with detectable Tg-on and 16 patients with detectable Tg-off were identified. All patients were treated with a blind therapeutic dose of 7,400 MBq iodine-131. Diagnostic scintigrams were compared with post-treatment scintigrams. Tg-off was measured in 16 cases, 1 year after the administration of the blind therapeutic dose, at the time of the follow-up diagnostic scintigram. Six patients were followed up by Tg-on only. Post-therapy scintigrams revealed previously undiagnosed local recurrence or distant metastases in 13/22 cases (59%); the remaining nine post-therapy scintigrams were negative. At the time of the blind therapeutic doses, Tg-off values ranged from 8 to 608 {mu}g/l. After 1 year of follow-up, Tg-off decreased in 14/16 (88%) patients. In all patients who were followed by Tg-on only (n=6), a decrease in Tg values was measured. It is concluded that blind therapeutic doses resulted in a decrease in Tg levels in the majority of patients with suspected recurrence or metastases. The post-treatment scintigrams revealed pathological uptake in 59% of patients. (orig.)

  15. Optimization of the therapeutic dose of {sup 131}I for thyroid differentiated carcinoma; Otimizacao da dose terapeutica com {sup 131}I para carcinoma diferenciado da tiroide

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Fabiana Farias de

    2002-09-01

    I-131 thyroid cancer therapy is based on the strategy of concentrating radioactive iodine in the thyroid tissue, to completetly eliminate thyroid tissue and functioning thyroid cancer metastases remaining after thyroidectomy. In Brazil, fixed activities of {sup 131} I generally are given, sometimes either delivering insufficient activities to ablate all of the remnants, or unnecessarily high activities, with patients remaining in the hospital for some period of time. This investigation proposes a protocol of individualized planning of ablative doses, based on individual patients metabolisms and measured thyroid remnant masses. Simulated thyroid remnants were fabricated in various forms, volumes and activities, and optimum image acquisition parameters were determined using Single-Photon Emission Computed Tomography 9SPECT). Resultant images were evaluated, to determine the apparent volumes and the {sup 131} I concentrations. I-131 metabolism was studied in 9 patients who had undergone thyroidectomies. Their thyroid remnant masses were determined applying the same parameters used in SPECT simulation studies, and the optimum activity for their therapy was calculated and compared to the established fixed activity of 3.7 GBq (100 mCi), which would have normally been assigned. Background subtraction using the method of percent maximum counts, using a value of 67.5%, combined with scatter correction (triple energy window method), was shown to be optimum for SPECT quantification of volumes between 3-10 ml. Errors in the method were below 9% for sources with regular geometries and around 11% for sources with irregular geometries. In the patient studies, it was observed that 78% of patients could have received reduced activities of {sup 131} (from 0.8-3-2. GBq (20-87 nCi). In addition, 33% of these patients could have received low enough activities to have discharged from the hospital, using an individualized administration scheme. This could also have resulted in a dose

  16. Bioelectrical impedimetric sensor for single cell analysis based on nanoroughened quartz substrate; suitable for cancer therapeutic purposes.

    Science.gov (United States)

    Gharooni, Milad; Abdolahad, Mohammad

    2017-08-05

    Single cells analysis has been interested in recent decade. Apart from scientific benefits to achieve new biological phenomena in cell study, many diagnostic and therapeutic protocols in non-communicable diseases were introduced by single cell analysis. Moreover, non-invasive methods to maintain the investigated cell for time dependent monitoring has been widely studied because of its importance in some crucial cases such as drug resistance in cancer. Bioelectrical monitoring is one of such methods Although the procedures reported based on electrical probing might not induce cell disruption, indirect connection between recording electrodes and cell membrane (mostly in microfluidic approaches) reduced the quality of response and limited the precision of the results. Here, a bioelectronic sensor for monitoring the effect of anticancer drugs on single breast cancer cells was fabricated based on nano-roughened gold electrodes on a quartz substrate applied direct contacts to cell membrane. Whole of the surface except a microcircle surrounded the sensing region was passivated by overbaked photoresist layer. Cells were dropped on the sensor without the assistance of any micropipette or microfluidic systems and just individual regions for attachment of one cell has been opened on the sensing region arrays. MCF-7 cancer cells were time tracked under the effect of Paclitaxel and Mebendazole anti-tubulin drugs in low and high doses. Inducing non regulated depolymerization and polymerization in tubulin structures of the single cancer cells were monitored by the electrical signals recorded before and after drug treatment. Electrical responses of single cells to their incubation with drugs completely reflected their vitality and biological states which were confirmed by confocal imaging. This is one of the first investigation on bioelectrical monitoring of single cell's resistance to anticancer drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Pharmacokinetics of solithromycin (CEM-101) after single or multiple oral doses and effects of food on single-dose bioavailability in healthy adult subjects.

    Science.gov (United States)

    Still, J Gordon; Schranz, Jennifer; Degenhardt, Thorsten P; Scott, Drusilla; Fernandes, Prabhavathi; Gutierrez, Maria J; Clark, Kay

    2011-05-01

    The pharmacokinetics of orally administered solithromycin (CEM-101), a novel fluoroketolide, were evaluated in healthy subjects in three phase 1 studies. In two randomized, double-blinded, placebo-controlled studies, escalating single oral doses of solithromycin (50 to 1,600 mg) or seven oral daily doses (200 to 600 mg) of solithromycin were administered. A third study evaluated the effects of food on the bioavailability of single oral doses (400 mg) of solithromycin. Following single doses, the median time to peak concentration (Tmax) ranged from 1.5 h to 6 h. The mean maximum measured plasma concentration (Cmax) ranged from 0.0223 μg/ml to 19.647 μg/ml, and the area under the concentration-versus-time curve from time zero to time t (AUC0-t) ranged from 0.0402 μg·h/ml to 28.599 μg·h/ml. There was no effect of high-fat food on the oral bioavailability of solithromycin. In the multiple-dose study, after 7 days, the mean maximum measured plasma solithromycin concentration at steady-state (Cmax,ss) ranged from 0.248 to 1.50 μg/ml, and the area under the concentration-versus-time curve over the final dosing interval (AUCτ) ranged from 2.310 to 18.41 μg·h/ml. These values indicate a greater than proportional increase in exposure at 200 and 400 mg but a proportional exposure at 600 mg. Median Tmax values remained constant between day 1 and day 7. Moderate accumulation ratios of solithromycin were observed after 7 days of dosing. All dose regimens of solithromycin were well tolerated, and no discontinuations due to an adverse event occurred. The human pharmacokinetic profile and tolerability of solithromycin, combined with its in vitro potency and efficacy in animal models against a broad spectrum of pathogens, support further development of solithromycin.

  18. Pharmacokinetic study of single- and multiple-dosing with metolazone tablets in healthy Chinese population.

    Science.gov (United States)

    Li, Xueqing; Wang, Rutao; Liu, Yang; Liu, Yun; Zheng, Heng; Feng, Yabo; Zhao, Na; Geng, Hongbin; Zhang, Wanzhi; Wen, Aidong

    2017-11-16

    Metolazone is a diuretic, saluretic and antihypertensive chemical compound from the quinazoline category that possesses medicinal features similar to those of other thiazide diuretic drugs. However, the pharmacokinetics of metolazone in the Chinese population has rarely been studied. This study aimed to examine the pharmacokinetic characteristics, safety characteristic, and tolerability of metolazone in healthy Chinese subjects after single and multiple doses taken orally as well as the effects that food and gender have on oral metolazone pharmacokinetic parameters. An open-label, randomized, and single- and multiple-dosing investigation was performed in healthy Chinese subjects. The investigation included 3 study groups: the 0.5 mg, 1 mg and 2 mg dose groups were the single-dose study groups in the first stage. Eligible volunteers were randomly and orally administered a single 0.5 mg, 1 mg, or 2 mg metolazone tablet. The 0.5 mg dose group was also part of the multiple-dose study group, and the 1 mg dose group was the food-effect study group in the second stage. Human plasma samples were gathered pre-dosing and up to 48 h after dosing. The human plasma sample concentration of metolazone was quantified using a validated liquid chromatography tandem mass spectrometry method. Pharmacokinetic data were calculated by a noncompartmental analysis method using WinNonlin version 6.4. Tolerability was evaluated based on adverse events, medical examination, 12-lead ECG, and other clinical laboratory exams. Thirty eligible subjects (15 men and 15 women) were registered in our investigation and completed all of the study stages. The AUC and C max showed dose proportionality after a single dose based on the linear-regression analysis. A comparison of the pharmacokinetic data revealed that the differences between the male and female groups were not statistically significant. The t max of metolazone was increased by approximately 100% in the fed condition. Metolazone was

  19. 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

  20. Intrapartum single-dose carbamazepine reduces nevirapine levels faster and may decrease resistance after a single dose of nevirapine for perinatal HIV prevention.

    NARCIS (Netherlands)

    Muro, E.P.; Fillekes, Q.; Kisanga, E.R.; L'homme, R.F.A.; Aitken, S.C.; Mariki, G.; Ven, A.J.A.M. van der; Dolmans, W.M.V.; Schuurman, R.; Walker, A.S.; Gibb, D.M.; Burger, D.M.

    2012-01-01

    BACKGROUND: World Health Organization guidelines recommend zidovudine + lamivudine for 7 days from labor onset in HIV-infected women receiving single-dose nevirapine (sdNVP) to cover prolonged subtherapeutic nevirapine concentrations. Although effective, this is complicated and does not eliminate

  1. The pharmacokinetic and safety profiles of blonanserin in healthy Chinese volunteers after single fasting doses and single and multiple postprandial doses.

    Science.gov (United States)

    Chen, Xia; Wang, Hongyun; Jiang, Ji; Chen, Rui; Zhou, Ying; Zhong, Wen; Liu, Hongzhong; Hu, Pei

    2014-03-01

    Blonanserin is a novel atypical antipsychotic drug acting as a mixed serotonin 5-HT2A and dopamine D2 receptor antagonist. This study investigated the pharmacokinetics and safety of blonanserin in healthy Chinese males. This was an open-label trial with two parts. Twenty-four subjects were enrolled in part A to receive a single fasting dose of 4 or 8 mg blonanserin (each n = 12); part B recruited 12 subjects and administered single and sequentially twice-daily multiple postprandial doses of blonanserin 2 mg for 9 days. Serial blood samples were taken for the bioassay of plasma blonanserin and its four metabolites during both sub-studies. Safety was assessed, including repeat measurements of fasting serum prolactin, insulin, triglyceride and cholesterol. Blonanserin was rapidly absorbed, accompanied with immediate plasma concentration elevation of the N-oxide form (M2) and gradual rises of the N-deethylated form (M1) and its downstream metabolites. The mean elimination half-life of blonanserin (7.7-11.9 h) was much longer than that of M2 (1.2-1.3 h) but shorter than that of M1 (26.4-31.4 h) after single fasting doses. After food intake, a single dose of 2 mg blonanserin resulted in total exposure and peak concentrations of blonanserin similar to those observed with a single fasting dose of blonanserin 4 mg. Moreover, the relationship of metabolite over parent compound ratio was different between M1 and M2 after single and multiple postprandial administrations (single dose vs multiple dose: M1, 0.33 vs 0.75; M2, 0.13 vs 0.067). Mild but transient increases of prolactin, insulin and triglyceride were observed. The pharmacokinetics of blonanserin in Chinese subjects were similar to those observed in Japanese subjects. This study suggested that food intake not only increases the bioavailability of blonanserin but differently affects the pharmacokinetics of its metabolites as well. The drug was safe and well tolerated in healthy Chinese males.

  2. Single, repeated dose toxicity and genotoxicity assessment of herb formula KIOM2012H

    Directory of Open Access Journals (Sweden)

    Hwayong Park

    2017-12-01

    Full Text Available Background: Traditional medicine and herbal prescriptions are becoming more popular, and they account for a large share of the world’s healthcare research studies, developments, and market demands. Increasing scientific evidence of the substantive efficacies such as preventive health keeping pharmaceutical materials and dietary supplements can be found elsewhere. Above all, safety should be the critical premise for considering developmental materials such as pharmaceuticals without side effects and toxicity. Methods: The authors formulated KIOM2012H (K2H using four herbs that were reported to have medicinal effects—including anticancer, antiaging, antimicrobial, inflammation, and neuroprotective properties. In order to examine the toxicity, single and repeated dose toxicity, and genotoxicities of bacterial mutation, micronucleus, and chromosomal aberration assays were conducted. Results: All experimental observations and results showed normal findings. Toxicities or abnormal signs were not observed in all experimental assays, including oral administration, animal behavior, clinical findings, and changes in body weight in vivo. In vitro bacterial cultures produced no revertant colonies, and no increased numbers of structural or numerical aberrant metaphases were found in the metaphase chromosomes examined. Moreover, no significant increased frequency of micronucleus was observed in any of the doses used. Overall, no acute toxicity or genotoxicity was found in all analysis parameters in all the assays conducted. Conclusion: Reviewing the results as a whole, K2H extract was regarded as a safe material with no toxicity, and can be applied for the research and development of complementary and alternative medicines with improved efficacy in current therapeutic healthcare, based on traditional medicine and herb resources. Keywords: genotoxicity, herb, toxicity, traditional medicine

  3. Randomized clinical trial of extended versus single-dose perioperative antibiotic prophylaxis for acute calculous cholecystitis

    NARCIS (Netherlands)

    Loozen, C. S.; Kortram, K.; Kornmann, V. N. N.; van Ramshorst, B.; Vlaminckx, B.; Knibbe, C. A. J.; Kelder, J. C.; Donkervoort, S. C.; Nieuwenhuijzen, G. A. P.; Ponten, J. E. H.; van Geloven, A. A. W.; van Duijvendijk, P.; Bos, W. J. W.; Besselink, M. G. H.; Gouma, D. J.; van Santvoort, H. C.; Boerma, D.

    2017-01-01

    Many patients who have surgery for acute cholecystitis receive postoperative antibiotic prophylaxis, with the intent to reduce infectious complications. There is, however, no evidence that extending antibiotics beyond a single perioperative dose is advantageous. This study aimed to determine the

  4. Differentiated thyroid cancer treatment with therapeutic doses of 131I calculated by dosimetry: our experience

    International Nuclear Information System (INIS)

    Fadel, Ana M.; Chebel, G.M.; Valdivieso, C.M.; Degrossi, Osvaldo J.; Cabrejas, R.; Cabrejas, M.L.

    2006-01-01

    The optimum dose for the differentiated thyroid cancer treatment is a motive of controversy. There exist two ways of deciding the dose to administer: the empirical method (fixed doses) and dosimetric calculation method. The use of fixed doses has demonstrated safety and effectiveness. Nevertheless there are cases in which the use of several small doses not resolves the metastases illness of the patients. Using the Benua-Leeper method for dosimetric calculation we have evaluated the maximum dose treatment that could be administered to 20 patients who showed persistent disease after several treatments with 131 I. (author) [es

  5. 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.

  6. Single- and Multiple-Dose Pharmacokinetics and Absolute Bioavailability of Tedizolid

    OpenAIRE

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

    2014-01-01

    Objectives 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. Design Double-blind, single-ascending dose, multiple-dose pharmacokinetics study, as well as tolerability and open-label crossover studies. Setting Single center in the United States (Covance Clini...

  7. 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.

  8. Population pharmacokinetics of piperacillin in the early phase of septic shock – does standard dosing result in therapeutic plasma concentrations?

    DEFF Research Database (Denmark)

    Öbrink-Hansen, Kristina Margareta; Juul, Rasmus Vestergaard; Storgaard, Merete

    2015-01-01

    of administration. Time above the minimal inhibitory concentration (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/L). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50% fT>4xMIC and 100% f T>MIC. A population PK model was developed...... between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets compared to patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent...... bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug need to be considered....

  9. Clinicopathogenetic reasoning of the use of therapeutic dosed “Nordic walking” in patients with combined cardiovascular disease

    Directory of Open Access Journals (Sweden)

    E. A. Gozhenko

    2013-08-01

    Full Text Available The problem of using the methods of climatotherapy and kinetotherapy when providing medical rehabilitation for patients with combined cardiovascular abnormity is connected with cardiovascular adaptive abilities decrease in patients, low rehabilitation potential, that generates negative outlook on ability to work, quality of life and overall cardiovascular risk. The aim of the study: reasoning of the use of therapeutic dosed “Nordic walking” in rehabilitation of the patients with combined cardiovascular disease. Materials and methods of research: On sanatorium-resort stage of medical rehabilitation 30 patients with coronary heart disease associated with arterial hypertension of 1-3 degrees, were under dynamic observation. In the observed group, 12 (40% patients were female and 18 (60% male, mean age of the patients was (54.00 ± 1.65 years. All patients received complex treatment: diet therapy (diet number 10, magnetotherapy of segmental areas of the heart, massage of collar area, classes of therapeutic dosed «Nordic» walking. If necessary, patients received drug therapy (ACE inhibitors, beta-blockers, antiplatelet agents. To study the possibility of applying and the principles of dosing of the therapeutic dosed "Nordic" walking, clinical condition of the patient, the main indicators of the electrocardiogram, changes in heart rate and blood pressure before, during and after classes, were studied in dynamics (on day 1, the third and last day of application of the proposed methods. Ambulatory blood pressure monitoring, assessment of tolerance to physical loads and degree of reduction in physical performance were done before and after treatment. Results and discussion: analysis of the dynamics of growth of heart rate in response to the classes of therapeutic dosed «Nordic» walking, its growth was marked and this indicator reaches its largest value by the end of the sanatory stage of treatment (p<0.05. Such dynamics shows the training

  10. Absorbed dose to active red bone marrow from diagnostic and therapeutic uses of radiation

    International Nuclear Information System (INIS)

    Solomon, S.B.

    1980-06-01

    The bone-marrow dose arising from radiological procedures as carried out in Australia have been determined as part of a survey of population doses. This paper describes the method of calculation of the radiation doses to the active bone marrow from diagnostic radiography, fluoroscopy and radiotherapy. The results of the calculations are compared with the results of other models of bone-marrow dose for a number of diagnostic X-ray procedures

  11. 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)

  12. 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.

    Directory of Open Access Journals (Sweden)

    John A Todd

    2016-10-01

    Full Text Available 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.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 = -0.052, 0.254 and 0.497

  13. Efficacy of single dose antihistamine vs. single dose valerian-hops in subjective sleep measures among war refugees: a comparison trial

    Directory of Open Access Journals (Sweden)

    Omar Salem Gammoh

    Full Text Available Abstract Background Many sedatives and anxiolytics are used in single dose or chronically to aid sleep. Clinically important sedatives include valerian-hops and antihistamines as they are used over the counter and are highly accessible and safe agents. Objectives To evaluate and compare a single dose of chlorpheniramine versus valerian-hops combination in modulating subjective sleep measures in insomniac war refugees. Methods Insomnia among refugees was screened using the Insomnia Severity Index (ISI. Insomniac subjects were randomized to received a single dose valerian-hops (320/80 mg (n = 65, or chlorpheneramine (4 mg (n = 50 or placebo (n = 76 two hours prior sleeping. Participants were instructed to complete Leeds Sleep Evaluation Questionnaire (LSEQ, visual analogue scales of anxiety and sedation. Also sleep latency, total hours slept and self-rated improvement were obtained. Results Almost 75% of screened refugees had insomnia. Chlorpheneramine reduced sleep latency and anxiety significantly, however it resulted in poor sleep quality. Valerian-hops group showed marked anxiolysis one hour after dosing, a sleep quality similar to placebo and better than chlorpheneramine, and better alertness compared to placebo. Participants satisfaction was higher with chlorpheneramine and there was no difference in the total hours slept. Discussion Valerian-hops combination may provide better sleep quality than antihistamines.

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

    Directory of Open Access Journals (Sweden)

    Taylor DR

    2013-07-01

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

  15. Single dose versus fractionated stereotactic radiotherapy for meningiomas

    International Nuclear Information System (INIS)

    Lo, S.S.; Cho, K.H.; Hall, W.A.

    2002-01-01

    To evaluate the safety and efficacy of stereotactic radiosurgery (SRS) compared to fractionated stereotactic radiation therapy (FSRT) for meningiomas treated over a seven year period. Of the 53 patients (15 male and 38 female) with 63 meningiomas, 35 were treated with SRS and the 18 patients with tumors adjacent to critical structures or with large tumors were treated with FSRT. The median doses for the SRS and the FSRT groups were 1400 cGy (500- 4500 cGy) and 5400 cGy (4000-6000 cGy) respectively. Median target volumes for SRS and FSRT were 6.8 ml and 8.8 ml respectively. The median follow-up for the SRS and FSRT groups were 38 months (4.1-97 months) and 30.5 months (6.0-63 months) respectively. The five-year tumor control probability (TC) for benign versus atypical meningiomas were 92.7% vs. 31% (P=.006). The three-year TC were 92.7% vs. 93.3% for SRS vs. FSRT groups respectively (P=.62). For benign meningiomas, the three-year TC were 92.9% vs. 92.3% for the SRS group (29 patients) vs. FSRT group (14 patients) respectively (P=.77). Two patients in the SRS group and one in the FSRT group developed late complications. Preliminary data suggest that SRS is a safe and effective treatment for patients with benign meningiomas. Fractionated stereotactic radiation therapy with conventional fractionation appeared to be an effective and safe treatment alternative for patients not appropriate for SRS. A longer follow-up is required to determine the long-term efficacy and the toxicity of these treatment modalities. (author)

  16. 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.

  17. 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

  18. Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

    Science.gov (United States)

    Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Cieszkowski, Jakub; Dembiński, Marcin; Sendur, Ryszard; Bonior, Joanna; Jaworek, Jolanta; Ambroży, Tadeusz; Olszanecki, Rafał; Kuśnierz-Cabala, Beata; Tomasz, Kaczmarzyk; Tomaszewska, Romana; Dembiński, Artur

    2017-04-21

    Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

  19. Adverse effects of a single dose of gentamicin in adults: a systematic review.

    Science.gov (United States)

    Hayward, Rachel S; Harding, Jan; Molloy, Rob; Land, Lucy; Longcroft-Neal, Kate; Moore, David; Ross, Jonathan D C

    2018-02-01

    To systematically review the frequency and type of adverse events associated with a single dose of intravenous or intramuscular gentamicin in adults, for any indication, in studies where a comparator was available. A review protocol was developed and registered (PROSPERO: CRD42013003229). Studies were eligible for review if they: recruited participants aged ≥16 years; used gentamicin intramuscularly or intravenously as a single one-off dose; compared gentamicin to another medication or placebo; and monitored adverse events. MEDLINE, EMBASE, Cochrane Library, trial registries, conference proceedings and other relevant databases were searched up to November 2016. Risk of bias was assessed on all included studies. In total, 15 522 records were identified. After removal of duplicates, screening of title/abstracts for relevance and independent selection of full texts by two reviewers, 36 studies were included. Across all the included studies, 24 107 participants received a single one-off dose of gentamicin (doses ranged from 1 mg kg -1 to 480 mg per dose). Acute kidney injury was described in 2520 participants receiving gentamicin. The large majority of cases were reversible. There were no cases of ototoxicity reported in patients receiving gentamicin. A meta-analysis was not performed due to study heterogeneity. A significant number of patients saw a transient rise in creatinine after a single dose of gentamicin at doses up to 480 mg. Persistent renal impairment and other adverse events were relatively rare. © 2017 The British Pharmacological Society.

  20. DBD plasma source operated in single-filamentary mode for therapeutic use in dermatology

    Energy Technology Data Exchange (ETDEWEB)

    Rajasekaran, Priyadarshini; Mertmann, Philipp; Bibinov, Nikita; Awakowicz, Peter [Institute for Electrical Engineering and Plasma Technology, Ruhr-Universitaet Bochum, Universitaetsstr. 150, 44801 Bochum (Germany); Wandke, Dirk [CINOGY GmbH, Max-Naeder-Str. 15, 37114 Duderstadt (Germany); Vioel, Wolfgang, E-mail: rajasekaran@aept.rub.d, E-mail: mertmann@aept.rub.d, E-mail: Nikita.Bibinov@rub.d, E-mail: dirk.wandke@cinogy.co, E-mail: vioel@hawk-hhg.d, E-mail: awakowicz@aept.rub.d [University of Applied Sciences and Arts, Faculty of Natural Sciences and Technology, Von-Ossietzky-Str. 99, 37085 Goettingen (Germany)

    2009-11-21

    Our dielectric barrier discharge (DBD) plasma source for bio-medical application comprises a copper electrode covered with ceramic. Objects of high capacitance such as the human body can be used as the opposite electrode. In this study, the DBD source is operated in single-filamentary mode using an aluminium spike as the opposite electrode, to imitate the conditions when the discharge is ignited on a raised point, such as hair, during therapeutic use on the human body. The single-filamentary discharge thus obtained is characterized using optical emission spectroscopy, numerical simulation, voltage-current measurements and microphotography. For characterization of the discharge, averaged plasma parameters such as electron distribution function and electron density are determined. Fluxes of nitric oxide (NO), ozone (O{sub 3}) and photons reaching the treated surface are simulated. The calculated fluxes are finally compared with corresponding fluxes used in different bio-medical applications.

  1. 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.

  2. Compatibility of the repairable-conditionally repairable, multi-target and linear-quadratic models in converting hypofractionated radiation doses to single doses.

    Science.gov (United States)

    Iwata, Hiromitsu; Matsufuji, Naruhiro; Toshito, Toshiyuki; Akagi, Takashi; Otsuka, Shinya; Shibamoto, Yuta

    2013-03-01

    We investigated the applicability of the repairable-conditionally repairable (RCR) model and the multi-target (MT) model to dose conversion in high-dose-per-fraction radiotherapy in comparison with the linear-quadratic (LQ) model. Cell survival data of V79 and EMT6 single cells receiving single doses of 2-12 Gy or 2 or 3 fractions of 4 or 5 Gy each, and that of V79 spheroids receiving single doses of 5-26 Gy or 2-5 fractions of 5-12 Gy, were analyzed. Single and fractionated doses to actually reduce cell survival to the same level were determined by a colony assay. Single doses used in the experiments and surviving fractions at the doses were substituted into equations of the RCR, MT and LQ models in the calculation software Mathematica, and each parameter coefficient was computed. Thereafter, using the coefficients and the three models, equivalent single doses for the hypofractionated doses were calculated. They were then compared with actually-determined equivalent single doses for the hypofractionated doses. The equivalent single doses calculated using the RCR, MT and LQ models tended to be lower than the actually determined equivalent single doses. The LQ model seemed to fit relatively well at doses of 5 Gy or less. At 6 Gy or higher doses, the RCR and MT models seemed to be more reliable than the LQ model. In hypofractionated stereotactic radiotherapy, the LQ model should not be used, and conversion models incorporating the concept of the RCR or MT models, such as the generalized linear-quadratic models, appear to be more suitable.

  3. Dose contributions from large-angle scattered particles in therapeutic carbon beams

    International Nuclear Information System (INIS)

    Kusano, Yohsuke; Kanai, Tatsuaki; Kase, Yuki; Matsufuji, Naruhiro; Komori, Masataka; Kanematsu, Nobuyuki; Ito, Atsushi; Uchida, Hirohisa

    2007-01-01

    In carbon therapy, doses at center of spread-out Bragg peaks depend on field size. For a small field of 5x5 cm 2 , the central dose reduces to 96% of the central dose for the open field in case of 400 MeV/n carbon beam. Assuming the broad beam injected to the water phantom is made up of many pencil beams, the transverse dose distribution can be reconstructed by summing the dose distribution of the pencil beams. We estimated dose profiles of this pencil beam through measurements of dose distributions of broad uniform beams blocked half of the irradiation fields. The dose at a distance of a few cm from the edge of the irradiation field reaches up to a few percent of the central dose. From radiation quality measurements of this penumbra, the large-angle scattered particles were found to be secondary fragments which have lower LET than primary carbon beams. Carbon ions break up in beam modifying devices or in water phantom through nuclear interaction with target nuclei. The angular distributions of these fragmented nuclei are much broader than those of primary carbon particles. The transverse dose distribution of the pencil beam can be approximated by a function of the three-Gaussian form. For a simplest case of mono-energetic beam, contributions of the Gaussian components which have large mean deviations become larger as the depth in the water phantom increases

  4. Therapeutic angiogenesis due to balanced single-vector delivery of VEGF and PDGF-BB

    Science.gov (United States)

    Banfi, Andrea; von Degenfeld, Georges; Gianni-Barrera, Roberto; Reginato, Silvia; Merchant, Milton J.; McDonald, Donald M.; Blau, Helen M.

    2012-01-01

    Therapeutic angiogenesis by delivery of vascular growth factors is an attractive strategy for treating debilitating occlusive vascular diseases, yet clinical trials have thus far failed to show efficacy. As a result, limb amputation remains a common outcome for muscle ischemia due to severe atherosclerotic disease, with an overall incidence of 100 per million people in the United States per year. A challenge has been that the angiogenic master regulator vascular endothelial growth factor (VEGF) induces dysfunctional vessels, if expressed outside of a narrow dosage window. We tested the hypothesis that codelivery of platelet-derived growth factor-BB (PDGF-BB), which recruits pericytes, could induce normal angiogenesis in skeletal muscle irrespective of VEGF levels. Coexpression of VEGF and PDGF-BB encoded by separate vectors in different cells or in the same cells only partially corrected aberrant angiogenesis. In marked contrast, coexpression of both factors in every cell at a fixed relative level via a single bicistronic vector led to robust, uniformly normal angiogenesis, even when VEGF expression was high and heterogeneous. Notably, in an ischemic hindlimb model, single-vector expression led to efficient growth of collateral arteries, revascularization, increased blood flow, and reduced tissue damage. Furthermore, these results were confirmed in a clinically applicable gene therapy approach by adenoviral-mediated delivery of the bicistronic vector. We conclude that coordinated expression of VEGF and PDGF-BB via a single vector constitutes a novel strategy for harnessing the potency of VEGF to induce safe and efficacious angiogenesis.—Banfi, A., von Degenfeld, G., Gianni-Barrera, R., Reginato, S., Merchant, M. J., McDonald, D. M., Blau, H. M. Therapeutic angiogenesis due to balanced single-vector delivery of VEGF and PDGF-BB. PMID:22391130

  5. 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.

  6. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers.

    Science.gov (United States)

    Hirawat, Samit; Welch, Ellen M; Elfring, Gary L; Northcutt, Valerie J; Paushkin, Sergey; Hwang, Seongwoo; Leonard, Eileen M; Almstead, Neil G; Ju, William; Peltz, Stuart W; Miller, Langdon L

    2007-04-01

    Nonsense (premature stop codon) mutations are causative in 5% to 15% of patients with monogenetic inherited disorders. PTC124, a 284-Dalton 1,2,4-oxadiazole, promotes ribosomal readthrough of premature stop codons in mRNA and offers therapeutic potential for multiple genetic diseases. The authors conducted 2 phase I studies of PTC124 in 62 healthy adult volunteers. The initial, single-dose study evaluated doses of 3 to 200 mg/kg and assessed fed-fasting status on pharmacokinetics following a dose of 50 mg/kg. The subsequent multiple-dose study evaluated doses from 10 to 50 mg/kg/dose twice per day (bid) for up to 14 days. PTC124 administered orally as a liquid suspension was palatable and well tolerated through single doses of 100 mg/kg. At 150 and 200 mg/kg, PTC124 induced mild headache, dizziness, and gastrointestinal events. With repeated doses through 50 mg/kg/dose bid, reversible transaminase elevations Duchenne muscular dystrophy.

  7. Controllable dose: a discussion on the control of individual doses from single sources

    International Nuclear Information System (INIS)

    Clarke, R.H.

    1999-01-01

    Contaminated land is an issue of considerable interest in many countries. It arises as a result of accidental releases, as from Chernobyl, and from manmade activities including atmospheric testing of nuclear weapons. Contamination is also an historic liability from, for example, plants using radium, or from excessive effluent discharges. A particular issue at present is the decommissioning of nuclear facilities, old reactors and weapons fabrication facilities. These liabilities require the expenditure of considerable amounts of money and some people think that too much money is being, and will be, spent to achieve low levels of residual contamination. If contaminated land is not cleaned up there is public concern and in some countries there will be litigation, charging that the environmental risk is too great. These concerns have led to an increased pressure from some individuals to propose a threshold in the dose-response relationship in order to reduce the expenditure. It is true that, increasingly, our science is judged in the courts rather than by national academies os science. Judge and jury will decide on the issue of the threshold and it is they who must be convinced as to whether there are no risks at low doses of radiation. The issue is primarily in relation to public non occupational exposure, and because of the continuing lack of definitive scientific evidence, a new approach to protection could be considered (author)

  8. Controllable dose: a discussion on the control of individual doses from single sources

    International Nuclear Information System (INIS)

    Clarke, R.

    1999-01-01

    Contaminated land is an issue of considerable interest in many countries. It arises as a result of accidental releases, as from Chernobyl, and from manmade activities including atmospheric testing of nuclear weapons. Contamination is also an historic liability from, for example, plants using radium, or from excessive effluent discharges. A particular issue at present is the decommissioning of nuclear facilities, old reactors and weapons fabrication facilities. These liabilities require the expenditure of considerable amounts of money and some people think that too much money is being, and will be, spent to achieve low levels of residual contamination. If contaminated land is not cleaned up these is public concern and in some countries there will be litigation, charging that the environmental risk is too great. These concerns have led to an increased pressure from some individuals to propose a threshold in the dose-responses relationship in order to reduce the expenditure. It is true that, increasingly, our science is judged in the courts rather by national academies of sciences. Judge and jury decide on the issue to the threshold and it is they who must convinced as to whether there are no risks at low doses of radiation. The issue is primarily in relation to public not occupational exposure, and because of the continuing lack of definitive scientific evidence, a new approach to protection could be considered. (author)

  9. Study on LET distribution and dose distribution in heterogeneity for therapeutic carbon ion beams

    International Nuclear Information System (INIS)

    Kohno, Ryosuke; Yasuda, Nakahiro; Komori, Masataka; Matsufuji, Naruhiro; Kanematsu, Nobuyuki; Kanai, Tatsuaki; Himukai, Takeshi; Kase, Yuki; Ochiai, Keiko

    2005-01-01

    In order to develop and verify dose averaged linear energy transfer (LET) calculation algorithm for carbon ion radiotherapy, we used a CR-39 solid state track detector as an LET distribution detector. First, depth dose averaged LET distributions in water obtained using the CR-39 for mono-energetic beam and spread-out Bragg peak beam were compared with calculations by treatment planning. We confirmed that the CR-39 could measure the high LET particles which contribute dominantly to dose averaged LET. On the other hand, the CR-39 overestimated in tail region of distal fall-off in depth-dose distributions, since its detection limits for lower LET particles. However, as physical dose in the region is considerably small, effect of this discrepancy on the biological dose distribution turn out to be small. Therefore, we conclude that it is useful for LET distribution measurements in carbon ion radiotherapy to use the CR-39 detector. Then, we would like to modify into more precise carbon ion dose calculation algorithm to be able to predict lateral dose averaged LET distributions. Therefore, lateral dose averaged LET distributions for collimated beams were also measured using the CR-39 detectors and analyzed. (author)

  10. Pharmacokinetics of Solithromycin (CEM-101) after Single or Multiple Oral Doses and Effects of Food on Single-Dose Bioavailability in Healthy Adult Subjects▿

    Science.gov (United States)

    Still, J. Gordon; Schranz, Jennifer; Degenhardt, Thorsten P.; Scott, Drusilla; Fernandes, Prabhavathi; Gutierrez, Maria J.; Clark, Kay

    2011-01-01

    The pharmacokinetics of orally administered solithromycin (CEM-101), a novel fluoroketolide, were evaluated in healthy subjects in three phase 1 studies. In two randomized, double-blinded, placebo-controlled studies, escalating single oral doses of solithromycin (50 to 1,600 mg) or seven oral daily doses (200 to 600 mg) of solithromycin were administered. A third study evaluated the effects of food on the bioavailability of single oral doses (400 mg) of solithromycin. Following single doses, the median time to peak concentration (Tmax) ranged from 1.5 h to 6 h. The mean maximum measured plasma concentration (Cmax) ranged from 0.0223 μg/ml to 19.647 μg/ml, and the area under the concentration-versus-time curve from time zero to time t (AUC0–t) ranged from 0.0402 μg · h/ml to 28.599 μg · h/ml. There was no effect of high-fat food on the oral bioavailability of solithromycin. In the multiple-dose study, after 7 days, the mean maximum measured plasma solithromycin concentration at steady-state (Cmax,ss) ranged from 0.248 to 1.50 μg/ml, and the area under the concentration-versus-time curve over the final dosing interval (AUCτ) ranged from 2.310 to 18.41 μg · h/ml. These values indicate a greater than proportional increase in exposure at 200 and 400 mg but a proportional exposure at 600 mg. Median Tmax values remained constant between day 1 and day 7. Moderate accumulation ratios of solithromycin were observed after 7 days of dosing. All dose regimens of solithromycin were well tolerated, and no discontinuations due to an adverse event occurred. The human pharmacokinetic profile and tolerability of solithromycin, combined with its in vitro potency and efficacy in animal models against a broad spectrum of pathogens, support further development of solithromycin. PMID:21282444

  11. Therapeutic immunization and local low-dose tumor irradiation, a reinforcing combination

    NARCIS (Netherlands)

    Draghiciu, Oana; Walczak, Mateusz; Hoogeboom, Baukje Nynke; Franken, Kees L M C; Melief, Kees J M; Nijman, Hans W; Daemen, Toos

    2014-01-01

    Therapeutic cancer vaccines show promise in preclinical studies, yet their clinical efficacy is limited. Increased recruitment of immune cells into tumors and suppression of the immune suppressive tumor environment are critical components toward effective cancer immunotherapies. Here, we report how

  12. Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations?

    Science.gov (United States)

    Öbrink-Hansen, Kristina; Juul, Rasmus Vestergaard; Storgaard, Merete; Thomsen, Marianne Kragh; Hardlei, Tore Forsingdal; Brock, Birgitte; Kreilgaard, Mads; Gjedsted, Jakob

    2015-11-01

    Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the MIC (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50% fT>4×MIC and 100% fT>MIC. A population PK model was developed using NONMEM, and data were best described by a two-compartment model. Central and intercompartmental clearances were 3.6 liters/h (relative standard error [RSE], 15.7%) and 6.58 liters/h (RSE, 16.4%), respectively, and central and peripheral volumes were 7.3 liters (RSE, 11.8%) and 3.9 liters (RSE, 9.7%), respectively. Piperacillin plasma concentrations varied considerably between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets than were patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug needs to be considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02306928.). Copyright © 2015, American Society for Microbiology

  13. 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

  14. [Randomized Comparison of Two Approaches to Initial Warfarin Dosing: Time in Therapeutic Range of International Normalized Ratio During Hospitalization].

    Science.gov (United States)

    Gordeev, I G; Averkov, O V; Mishchenko, L N; Levchuk, N N; Vechorko, V I

    2017-09-01

    To perform a randomized, open-label comparison of average time in therapeutic range (TTR) of international normalized ratio (INR) using two approaches to initial warfarin dosing during hospitalization: the standard method and the one using individual patient characteristics (clinical algorithm - the studied approach). We randomly assigned 60 patients with different indications for vitamin K antagonist therapy to the studied approach (n=31, intervention group) or to the standard method (n=29, control group). А target INR range for all patients was 2.0 to 3.0. The average TTR and portions of INR values within target range during the whole time of drug dosing turned out to be small. TTR was 22.4% with standard method and 21.4% with clinical algorithm, which was well below desired 60%. The opportunities for achieving target INR in inpatient settings, regardless of warfarin dosing regimen, are limited.

  15. New method for the induction of therapeutic amenorrhea: low dose endometrial afterloading irradiation. Clinical and hormonal studies

    Energy Technology Data Exchange (ETDEWEB)

    Gronroos, M.; Turunen, T.; Raekallio, J.; Ruotsalinen, P.; Salmi, T. (Turku Univ. (Finland). Dept. of Obstetrics and Gynecology)

    1982-08-01

    The authors present a new method for the induction of therapeutic amenorrhea: low dose endometrial afterloading irradiation. The problem with this method has been how to inactivate the endometrium while maintaining the physiological function of the ovaries. In 5/29 young patients regular or irregular bleedings occurred after an endometrial dose of 11+-1 Gy. These subjects were given a repeat low dose intrauterine irradiation. Thereafter no bleedings were found in four out of five patients. Two to 9 years after the repeat irradiation the plasma levels of E/sub 1/, E/sub 2/, FSH and LH corresponded closely to those of healthy women in reproductive age in three out of five patients; some high plasma P levels indicated ovulation. In two patients the E/sub 1/, E/sub 2/, and P values were more likely postmenopausal but, on the other hand, FSH and LH values reproductive ones. 19 refs.

  16. A new method for the induction of therapeutic amenorrhea: low dose endometrial afterloading irradiation. Clinical and hormonal studies

    International Nuclear Information System (INIS)

    Gronroos, M.; Turunen, T.; Raekallio, J.; Ruotsalinen, P.; Salmi, T.

    1982-01-01

    The authors present a new method for the induction of therapeutic amenorrhea: low dose endometrial afterloading irradiation. The problem with this method has been how to inactivate the endometrium while maintaining the physiological function of the ovaries. In 5/29 young patients regular or irregular bleedings occurred after an endometrial dose of 11+-1 Gy. These subjects were given a repeat low dose intrauterine irradiation. Thereafter no bleedings were found in four out of five patients. Two to 9 years after the repeat irradiation the plasma levels of E 1 , E 2 , FSH and LH corresponded closely to those of healthy women in reproductive age in three out of five patients; some high plasma P levels indicated ovulation. In two patients the E 1 , E 2 , and P values were more likely postmenopausal but, on the other hand, FSH and LH values reproductive ones. (author)

  17. The influence of single low dose of recombinant human thyrotropin on I-131 treatment of large multi-nodular goitre

    International Nuclear Information System (INIS)

    Mojsak, M.N.; Abdelrazek, S.; Rogowski, F.; Szunowski, P.; Mysliwiec, J.; Kociura-Sawicka, A.

    2015-01-01

    Full text of publication follows. Recombinant human thyrotropin (rhTSH) is a substance that after single intramuscular injection can increase thyroid radioiodine uptake (RAIU) and improve the results of radioiodine therapy (RIT) in patients with nontoxic multi-nodular goitre (MNG). These effects are very important especially in cases of large MNG with relatively low RAIU or contraindications to surgery. The aim of the study: the evaluation of the influence of the single low dose of rhTSH to RAIU and the effects of RIT in patients with benign large nontoxic MNG. Material and methods: 40 patients (14 male, 26 female, age 41-80 yr) with large MNG > 100 grams and with baseline RAIU < 40% (33,37±7,96%) were included to the study and divided into two groups. First group received the single intramuscular injection of 0,03 mg rhTSH and the second received placebo. The RAIU were measured again 48 hours after the rhTSH (24 hours after diagnostic dose of I-131). After this, all the patients were administered the therapeutic doses of I-131 recalculated according to new RAIU. The patients follow up was continued for minimum 12 months. Results: the mean RAIU after rhTSH increased more than twice, to 75% from 33%. One year after RIT the mean volume goitre reduction were significantly greater in group with rhTSH than in patients with placebo (48±16% vs. 37±18%). Decrease of compression symptoms has taken place earlier and was more important in patients after rhTSH. 12 months after RIT two patients stay in hypothyroid state (from the group with rhTSH), other patients are euthyroid. Conclusions: even the single very low dose of rhTSH increases the values of RAIU in significant way. Efficacy of rhTSH-augmented RIT in patients with large nontoxic MNG is greater than standard RIT. It allows to reduce administered doses of I-131, decreases the need of repeating RIT, makes the radiation adsorbed doses for whole body lower and the RIT shorter. (authors)

  18. 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

  19. Enhance Therapeutic Effect Compared with Single Transplantation in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Dandan Wang

    2012-01-01

    Full Text Available The clinical trial of allogenic mesenchymal stem cells (MSCs transplantation for refractory SLE patients has shown significant safety and efficacy profiles. However, the optimum frequency of the MSCs transplantation (MSCT is unknown. This study was undertaken to observe whether double transplantations of MSCs is superior to single transplantation. Fifty-eight refractory SLE patients were enrolled in this study, in which 30 were randomly given single MSCT, and the other 28 were given double MSCT. Patients were followed up for rates of survival, disease remission, and relapse, as well as transplantation-related adverse events. SLE disease activity index (SLEDAI and serologic features were evaluated. Our results showed that no remarkable differences between single and double allogenic MSCT were found in terms of disease remission and relapse, amelioration of disease activity, and serum indexes in an SLE clinical trial with more than one year followup. This study demonstrated that single MSCs transplantation at the dose of one million MSCs per kilogram of body weight was sufficient to induce disease remission for refractory SLE patients.

  20. Dose to the Developing Dentition During Therapeutic Irradiation: Organ at Risk Determination and Clinical Implications

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Reid F., E-mail: Reid.Thompson@uphs.upenn.edu [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Schneider, Ralf A., E-mail: ralf.schneider@psi.ch [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Albertini, Francesca; Lomax, Antony J.; Ares, Carmen; Goitein, Gudrun [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); Hug, Eugen B. [Center for Proton Therapy, Paul Scherrer Institute, Villigen (Switzerland); ProCure Therapy Centers, New York, New York (United States)

    2013-05-01

    Purpose: Irradiation of pediatric facial structures can cause severe impairment of permanent teeth later in life. We therefore focused on primary and permanent teeth as organs at risk, investigating the ability to identify individual teeth in children and infants and to correlate dose distributions with subsequent dental toxicity. Methods and Materials: We retrospectively reviewed 14 pediatric patients who received a maximum dose >20 Gy(relative biological effectiveness, RBE) to 1 or more primary or permanent teeth between 2003 and 2009. The patients (aged 1-16 years) received spot-scanning proton therapy with 46 to 66 Gy(RBE) in 23 to 33 daily fractions for a variety of tumors, including rhabdomyosarcoma (n=10), sarcoma (n=2), teratoma (n=1), and carcinoma (n=1). Individual teeth were contoured on axial slices from planning computed tomography (CT) scans. Dose-volume histogram data were retrospectively obtained from total calculated delivered treatments. Dental follow-up information was obtained from external care providers. Results: All primary teeth and permanent incisors, canines, premolars, and first and second molars were identifiable on CT scans in all patients as early as 1 year of age. Dose-volume histogram analysis showed wide dose variability, with a median 37 Gy(RBE) per tooth dose range across all individuals, and a median 50 Gy(RBE) intraindividual dose range across all teeth. Dental follow-up revealed absence of significant toxicity in 7 of 10 patients but severe localized toxicity in teeth receiving >20 Gy(RBE) among 3 patients who were all treated at <4 years of age. Conclusions: CT-based assessment of dose distribution to individual teeth is feasible, although delayed calcification may complicate tooth identification in the youngest patients. Patterns of dental dose exposure vary markedly within and among patients, corresponding to rapid dose falloff with protons. Severe localized dental toxicity was observed in a few patients receiving the

  1. A high performance liquid chromatographic assay of mefloquine in saliva after a single oral dose in healthy adult Africans.

    Science.gov (United States)

    Gbotosho, Grace O; Happi, Christian T; Lawal, Omowunmi; Sijuade, Abayomi; Sowunmi, Akin; Oduola, Ayoade

    2012-02-27

    Mefloquine-artesunate is a formulation of artemisinin based combination therapy (ACT) recommended by the World Health Organization and historically the first ACT used clinically. The use of ACT demands constant monitoring of therapeutic efficacies and drug levels, in order to ensure that optimum drug exposure is achieved and detect reduced susceptibility to these drugs. Quantification of anti-malarial drugs in biological fluids other than blood would provide a more readily applicable method of therapeutic drug monitoring in developing endemic countries. Efforts in this study were devoted to the development of a simple, field applicable, non-invasive method for assay of mefloquine in saliva. A high performance liquid chromatographic method with UV detection at 220 nm for assaying mefloquine in saliva was developed and validated by comparing mefloquine concentrations in saliva and plasma samples from four healthy volunteers who received single oral dose of mefloquine. Verapamil was used as internal standard. Chromatographic separation was achieved using a Hypersil ODS column. Extraction recoveries of mefloquine in plasma or saliva were 76-86% or 83-93% respectively. Limit of quantification of mefloquine was 20 ng/ml. Agreement between salivary and plasma mefloquine concentrations was satisfactory (r = 0.88, p mefloquine in saliva paralleled that in plasma, making salivary quantification of mefloquine potentially useful in therapeutic drug monitoring. © 2012 Gbotosho et al; licensee BioMed Central Ltd.

  2. A high performance liquid chromatographic assay of Mefloquine in saliva after a single oral dose in healthy adult Africans

    Directory of Open Access Journals (Sweden)

    Gbotosho Grace O

    2012-02-01

    Full Text Available Abstract Background Mefloquine-artesunate is a formulation of artemisinin based combination therapy (ACT recommended by the World Health Organization and historically the first ACT used clinically. The use of ACT demands constant monitoring of therapeutic efficacies and drug levels, in order to ensure that optimum drug exposure is achieved and detect reduced susceptibility to these drugs. Quantification of anti-malarial drugs in biological fluids other than blood would provide a more readily applicable method of therapeutic drug monitoring in developing endemic countries. Efforts in this study were devoted to the development of a simple, field applicable, non-invasive method for assay of mefloquine in saliva. Methods A high performance liquid chromatographic method with UV detection at 220 nm for assaying mefloquine in saliva was developed and validated by comparing mefloquine concentrations in saliva and plasma samples from four healthy volunteers who received single oral dose of mefloquine. Verapamil was used as internal standard. Chromatographic separation was achieved using a Hypersil ODS column. Results Extraction recoveries of mefloquine in plasma or saliva were 76-86% or 83-93% respectively. Limit of quantification of mefloquine was 20 ng/ml. Agreement between salivary and plasma mefloquine concentrations was satisfactory (r = 0.88, p Conclusion Disposition of mefloquine in saliva paralleled that in plasma, making salivary quantification of mefloquine potentially useful in therapeutic drug monitoring.

  3. 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.

  4. A single dose of intravenous esomeprazole decreases gastric secretion in healthy volunteers.

    Science.gov (United States)

    Nichita, C; Abdou, A E-W; Maerten, P; Herranz, M; Mouret, N; Thalmann, C; Michetti, P F; Dorta, G

    2009-11-15

    Data suggest that esomeprazole decreases gastric secretion. To assess the effect of a single i.v. esomeprazole dose on gastric secretion volume 3 h after drug administration, as a primary endpoint, and to evaluate, as secondary endpoints, the reduction 1 and 5 h after dosing; time when the gastric pH was bronchoaspiration during anaesthesia induction and in intensive care patients should be investigated in further studies.

  5. Routine β-Human Chorionic Gonadotropin Monitoring for Single-Dose Methotrexate Treatment in Ectopic Pregnancy.

    Science.gov (United States)

    Dai, Yuxin; Zhang, Guorui; Zhu, Lan; Lang, Jinghe; Liu, Zhufeng

    To evaluate an alternative monitoring protocol without day 4 β-human chorionic gonadotropin (β-hCG) measurement for predicting the need for a repeated methotrexate (MTX) dose in patients undergoing single-dose MTX therapy for ectopic pregnancy (EP). Single-center retrospective study (Canadian Task Force classification II-3). University-affiliated hospital. Included in the study were 184 EP patients treated with MTX between January 2009 and December 2016. Single-dose MTX treatment (50 mg/m 2 ). The patients were treated with repeated doses of MTX every 7 days, if necessary, according to Stovall's protocol, or with laparoscopic surgery in cases of tubal rupture. The success of a single-dose of MTX according to the alternative measure was defined as a >50% decrease in the β-hCG level between days 1 and 7 in clinically stable patients. The sensitivity, specificity, false-negative rate, false-positive rate, and attributable risk of this new monitoring measure were calculated and compared with the traditional regimen. The new protocol had a sensitivity and specificity of 100% and 88.7%, respectively, for predicting a required second dose in patients whose day 1 β-hCG levels were <2000 mIU/mL. For patients with day 1 β-hCG level ≥2000 mIU/mL, both monitoring regimens had the same efficiency. The new monitoring model without the day 4 β-hCG measurement may offer both patients and clinicians multiple options to monitor single-dose MTX therapy for selected EP patients, with a comparable clinical efficiency to Stovall's protocol and less expense and follow-up burden to patients. Copyright © 2017 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.

  6. Long-Term Impact of Immunosuppressants at Therapeutic Doses on Male Reproductive System in Unilateral Nephrectomized Rats: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Yehui Chen

    2013-01-01

    Full Text Available Cyclosporine, tacrolimus, and sirolimus are commonly used in renal transplant recipients to prevent rejection. However, information for comparative effects of these agents on the male productive system is extremely limited and controversial. In a physiologically and clinically relevant rat model of unilateral nephrectomy, we demonstrated that long-term oral administration of both cyclosporine and sirolimus at doses equivalent to the therapeutic levels used for postrenal transplant patients significantly affects testicular development and the hypothalamic-pituitary-gonadal axis accompanied by profound histological changes of testicular structures on both light and electron microscopic examinations. Spermatogenesis was also severely impaired as indicated by low total sperm counts along with reduction of sperm motility and increase in sperm abnormality after treatment with these agents, which may lead to male infertility. On the other hand, treatment with therapeutic dose of tacrolimus only induced mild reduction of sperm count without histological evidence of testicular injury. The current study clearly demonstrates that commonly used immunosuppressants have various impacts on male reproductive system even at therapeutic levels. Our data provide useful information for the assessment of male infertility in renal transplant recipients who wish to father children. Clinical trials to address these issues should be urged.

  7. Using Six Sigma to improve once daily gentamicin dosing and therapeutic drug monitoring performance.

    LENUS (Irish Health Repository)

    Egan, Sean

    2012-08-07

    BACKGROUND: Safe, effective therapy with the antimicrobial gentamicin requires good practice in dose selection and monitoring of serum levels. Suboptimal therapy occurs with breakdown in the process of drug dosing, serum blood sampling, laboratory processing and level interpretation. Unintentional underdosing may result. This improvement effort aimed to optimise this process in an academic teaching hospital using Six Sigma process improvement methodology. METHODS: A multidisciplinary project team was formed. Process measures considered critical to quality were defined, and baseline practice was examined through process mapping and audit. Root cause analysis informed improvement measures. These included a new dosing and monitoring schedule, and standardised assay sampling and drug administration timing which maximised local capabilities. Three iterations of the improvement cycle were conducted over a 24-month period. RESULTS: The attainment of serum level sampling in the required time window improved by 85% (p≤0.0001). A 66% improvement in accuracy of dosing was observed (p≤0.0001). Unnecessary dose omission while awaiting level results and inadvertent disruption to therapy due to dosing and monitoring process breakdown were eliminated. Average daily dose administered increased from 3.39 mg\\/kg to 4.78 mg\\/kg\\/day. CONCLUSIONS: Using Six Sigma methodology enhanced gentamicin usage process performance. Local process related factors may adversely affect adherence to practice guidelines for gentamicin, a drug which is complex to use. It is vital to adapt dosing guidance and monitoring requirements so that they are capable of being implemented in the clinical environment as a matter of routine. Improvement may be achieved through a structured localised approach with multidisciplinary stakeholder involvement.

  8. Effect of lactation on single-dose pharmacokinetics of norfloxacin nicotinate in ewes.

    Science.gov (United States)

    Soback, S; Gips, M; Bialer, M; Bor, A

    1994-01-01

    In a three-way crossover trial, six healthy Finnish-Merino-Awassi ewes were given a single intravenous injection of norfloxacin nicotinate (in a dose equivalent to 25 mg of norfloxacin base per kg of body weight) during nursing, 1 day after weaning, and 1 month after weaning. Blood and milk samples were collected at different time intervals following dosing, and norfloxacin concentrations were determined by a high-performance liquid chromatography assay. The serum drug concentration versus time data were analyzed by a noncompartmental approach which was based on the statistical-moment theory. The total body clearance values were 4.2 +/- 1.3 (injection during nursing), 1.6 +/- 0.3 (injection 1 day after weaning), and 3.1 +/- 0.8 ml/min/kg (injection 1 month after weaning). The mean residence times were 335 +/- 83, 797 +/- 129, and 481 +/- 102 min and terminal half-lives were 266 +/- 51, 603 +/- 94, and 372 +/- 68 min for the respective treatments. The estimated volumes of distribution at steady state were 1.3 +/- 0.1, 1.2 +/- 0.1, and 1.4 +/- 0.2 liter/kg for the respective treatments. Milk norfloxacin concentrations were up to 40 times higher than the corresponding concentrations in serum during lactation. Accordingly, in ewes with 1.5 liter of milk in the udder more than half of the drug in the animal appeared to be in the milk. Therapeutic concentrations of norfloxacin could be detected in the sera of suckling lambs, implicating that fluoroquinolone therapy should be discouraged during breast feeding. In lactating ewes and in ewes with full udders, moment analysis calculations did not show a significant difference between the system moment mean residence time and the system matrix mean residence time values. Thus, the pharmacokinetics of norfloxacin in the three groups could be described by the classical two-compartment open-body model with input and output occurring from the central compartment. The results did not support the existence of a distinguishable milk

  9. 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

  10. Comparative single-dose pharmacokinetics of rasagiline in minipigs after oral dosing or transdermal administration via a newly developed patch.

    Science.gov (United States)

    Lin, Yu; Zou, Yanye; Lin, Jialiang; Zhang, Tao; Deng, Jie

    2013-08-01

    1. A rasagiline transdermal patch was developed for the treatment of early and advanced Parkinson's disease. Relevant pharmacokinetic parameters of rasagiline obtained after transdermal administration to minipigs were compared with those of rasagiline after oral administration. 2. A total of 18 minipigs were randomly divided into three groups (six animals for each group). A single dose of 1 mg rasagiline tablet was orally administrated to one group. Meanwhile, single dose of 1.25 and 2.5 mg (2 and 4 cm(2)) rasagiline patches were given (at the postauricular skin) to the other two groups, respectively. The pharmacokinetic parameters such as plasma half-life (t1/2), time to peak plasma-concentration (Tmax), mean residence time (MRT), area under the curve (AUC(0-t)) were significantly (p rasagiline (1.25 mg patch: 11.8 ± 6.5 h, 2.5 mg patch: 12.5 ± 4.7 h) in minipig following transdermal administration was significantly prolonged as compared with that following the oral administration (1 mg tablet: 4.7 ± 2.5 h). The dose-normalized relative bioavailability of rasagiline patch in minipig were 178.5% and 156.4%, respectively, for 1.25 and 2.5 mg patches compared with 1 mg rasagiline tablet. The prolonged t1/2 and increased bioavailability of rasagiline patch suggested a possible longer dosing interval compared with oral tablet.

  11. Single Dose Methotrexate in Treatment of Ectopic Pregnancy: Review of 32 Case

    Directory of Open Access Journals (Sweden)

    Aysun Aybatlı

    2011-03-01

    Full Text Available Objective: To evaluate the efficacy of single dose intramuscular methotrexate in the treatment of ectopic pregnancy.Material and Methods: 32 patients who matched the inclusion criteria were enrolled. Success of treatment was defined as a resolution of ectopic pregnancy without performing surgical intervention. The cases in whom the treatment was successful and those that were not were compared for β-hCG values and clinical features.Results: β-hCG at diagnosis averaged 1293.9 mIU/ml. Of the 32 patients who received methotrexate, 26 were successfully treated. 23 patients (71.8% received a single dose of methotrexate, 3 patients (9.3% received an additional dose of methotrexate, 6 patients (18.7% who had failed methotrexate required surgery for cure. The success rate of single-dose methotrexate was 79.3%. Conclusion: Our study shows that single dose systemic methotrexate treatment can be used as an option in unruptured pregnancies.

  12. Postprandial triglyceridemia after single dose of alcohol in healthy young men.

    Science.gov (United States)

    Mudráková, E; Poledne, R; Kovář, J

    2013-03-01

    Moderate alcohol consumption provides protection against cardiovascular disease primarily due to increase of HDL-cholesterol. However, it also has some adverse effects on metabolism of triglycerides (TG). Therefore, we addressed the question how a single dose of alcohol affects postprandial lipemia and activities of two enzymes playing a critical role in regulation of triglyceridemia, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL). Eight healthy volunteers were given a single dose of alcohol (vodka; 0.6 g of ethanol/kg of body weight) together with a fat load (0.7 g of fat/kg of body weight) in an experimental breakfast or together with dinner 12 h before the experimental breakfast. In comparison to control experiment, alcohol given with breakfast induced increased and prolonged postprandial response of triglyceride-rich lipoproteins (TRL; d Alcohol given in the evening before the experiment increased fasting TG concentration but did not affect changes in TRL and IDL concentrations. LPL activity measured both in vivo using intravenous fat tolerance test and in vitro and HTGL activity were determined at the end of experiments (after 7.5 h of postprandial lipemia study). Neither was affected by a single dose of alcohol. Single dose of alcohol induces immediate and profound changes in metabolism of TRL and IDL. The same dose of alcohol given 12 h before meal does affect baseline TG concentration but not the postprandial changes of triglyceridemia. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Nonconvulsive status epilepticus in the elderly associated with newer antidepressants used at therapeutic doses: A report of three cases

    Directory of Open Access Journals (Sweden)

    Go Taniguchi

    2015-01-01

    All three patients were male and were 73 years of age or older. One patient was recently diagnosed with temporal lobe epilepsy and treated with low-dose lamotrigine. In all patients, newer antidepressants were initiated because of depressive symptoms. After titrating to therapeutic doses (paroxetine 20 mg/day, sertraline 50 mg/day, and combination of sertraline 50 mg/day and mirtazapine 30 mg/day in one patient each, impaired consciousness appeared. Electroencephalography (EEG showed generalized slow waves with intermittent spike–slow-wave complexes. Intravenous injection of antiepileptic drugs improved EEG findings and clinical symptoms. After discontinuance of the abovementioned antidepressants, NCSE did not recur in any of patients. These reports raise the question of whether the newer antidepressants, like classic antidepressants, might also induce NCSE in the elderly, even when used at therapeutic doses. Physicians should consider monitoring for possible NCSE when using newer antidepressants in patients who may have low drug tolerability. Active continuous video-EEG monitoring is essential when behavioral and psychological symptoms or change in consciousness level is suspected.

  14. Equivalent dose estimation using a single aliquot of polymineral fine grains

    DEFF Research Database (Denmark)

    Banerjee, D.; Murray, A.S.; Bøtter-Jensen, L.

    2001-01-01

    We have tested the suitability of a new single-aliquot regenerative-dose protocol for estimating the equivalent dose (D-e) in polymineral fine grains extracted from colluvia from various sites in Germany. First, we report the behaviour of three OSL signals: (i) blue-stimulated, (ii) infrared......C, the post-IR blue signals are stable. The preheat dependence of estimates of D-e obtained using fine grains is presented for the first time, for both blue- and IR-derived signals. Our results are compared with D-e estimates derived from multiple-aliquot additive-dose IR luminescence data, obtained using...

  15. An Optimized Voriconazole Dosing Strategy to Achieve Therapeutic Serum Concentrations in Children Younger than 2 Years Old.

    Science.gov (United States)

    Zembles, Tracy N; Thompson, Nathan E; Havens, Peter L; Kaufman, Bruce A; Huppler, Anna R

    2016-10-01

    To describe our experience with voriconazole in three patients younger than 2 years using an optimized dosing strategy for voriconazole that incorporates intensive therapeutic drug monitoring (TDM). Case series. Large pediatric hospital. Three patients younger than 2 years who received voriconazole therapy and had serum trough concentrations measured between January 1, 2010, and October 31, 2015. A clinical practice guideline developed at our institution was used to standardize initial dosing, appropriate use and timing of TDM, and dosage modifications based on TDM. TDM was used to guide dosing to achieve a target voriconazole serum trough concentration of 2-6 μg/ml. Voriconazole samples were assayed by using a high-performance liquid chromatography analytical method with solid-phase extraction. Initial dosages for the three patients were 9 mg/kg intravenously every 12 hours (one patient) and 9 mg/kg enterally twice/day (two patients). Multiple dose escalations and a more frequent dosing interval were required to achieve trough concentrations within the target range. The final dosages were 12 mg/kg intravenously every 8 hours, 17.7 mg/kg enterally 3 times/day, and 8.5 mg/kg enterally 3 times/day, respectively. In addition to voriconazole trough concentrations, TDM included evaluations for drug toxicities. Visual, neurologic, or hepatic adverse effects were not encountered in the three patients. Our data support higher initial doses and perhaps a 3 times/day dosing schedule to achieve voriconazole serum concentrations in the target range for children younger than 2 years. Implementation of a clinical practice guideline with the participation of pharmacists specializing in pharmacokinetics allows for effective use of voriconazole in young children. © 2016 Pharmacotherapy Publications, Inc.

  16. Single- and Multiple-Day Dosing Studies to Investigate High-Dose Pharmacokinetics of Epelsiban and Its Metabolite, GSK2395448, in Healthy Female Volunteers.

    Science.gov (United States)

    Mahar, Kelly M; Enslin, Mary Beth; Gress, Angie; Amrine-Madsen, Heather; Cooper, Melisa

    2018-01-01

    Open-label single- and double-blind repeat-dose studies in healthy female volunteers were conducted to investigate the pharmacokinetics (PK) and safety/tolerability of epelsiban total daily doses ranging from 600 to 900 mg. In 1 study (n = 12), epelsiban was dosed at 300 or 450 mg twice daily (every 12 hours) for a single day. In the repeat-dose double-blind study, epelsiban and placebo were administered to 31 subjects as 200 mg 3 times daily, 300 mg 3 times daily (TID), or 450 mg twice daily (BID) for 14 days. After both single and 14 daily repeat doses, the PK profiles for epelsiban and its metabolite, GSK2395448, remained linear at all administered doses. The exposures at a given total daily dose were also similar between BID and TID dosing regimens. Exposure (AUC 0-τ ), based on dosing intervals, for both epelsiban and GSK2395448 was similar. However, compared with morning dosing, C max was lower after evening dosing, possibly because of a food effect. The highest accumulation of epelsiban and GSK2395448 exposures (AUC 0-τ ) was approximately 34% for each after repeat dosing, consistent with the short half-life. At total daily doses of 600 and 900 mg, epelsiban was generally well tolerated, and there were no significant safety concerns identified. © 2017, The American College of Clinical Pharmacology.

  17. External dose measurements for patients receiving therapeutic I-131 for thyroid cancer

    International Nuclear Information System (INIS)

    Molfetas, M.; Kottou, S.

    2002-01-01

    Iodine-131 is a well established and effective treatment, supplementing surgery, in differentiated thyroid carcinoma. Iodine-131 except from its β-emission, that generates a cell-killing effect in a small area, has also a γ-emission irradiating distant tissues and even people who are close enough with the treated patient. The International Commission on Radiation Protection, ICRP has estimated the probability of a radiation-induced fatal cancer for the whole population at 5.0 % per sievert for low doses and at low dose rates and at 1.3 % for serious genetic diseases. For elderly people the probability seems to be 3 to 10 times lower, whereas for children up to the age of 10 years, 2-3 times higher. These findings led the ICRP to recommend new dose limits, lower than the previous ones. The European Union has endorsed the ICRP recommendations and the Council issued two directives, with which the Greek legislation complied recently. The current annual public dose limit is 1 mSv, while in the new Greek legislation the concept of dose constrains (0.5 m Sv in Greece) has also been proposed as a goal to reach whenever possible

  18. Pharmacokinetics of meloxicam in rabbits after oral administration of single and multiple doses.

    Science.gov (United States)

    Fredholm, Daniel V; Carpenter, James W; KuKanich, Butch; Kohles, Micah

    2013-04-01

    To determine the pharmacokinetics of meloxicam (1 mg/kg) in rabbits after oral administration of single and multiple doses. 6 healthy rabbits. A single dose of meloxicam (1 mg/kg, PO) was administered to the rabbits. After a 10-day washout period, meloxicam (1 mg/kg, PO) was administered to rabbits every 24 hours for 5 days. Blood samples were obtained from rabbits at predetermined intervals during both treatment periods. Plasma meloxicam concentrations were determined, and noncompartmental pharmacokinetic analysis was performed. The mean peak plasma concentration and area under the plasma concentration-versus-time curve extrapolated to infinity after administration of a single dose of meloxicam were 0.83 μg/mL and 10.37 h•μg/mL, respectively. After administration of meloxicam for 5 days, the mean peak plasma concentration was 1.33 μg/mL, and the area under the plasma concentration-versus-time curve from the time of administration of the last dose to 24 hours after that time was 18.79 h•μg/mL. For single- and multiple-dose meloxicam experiments, the mean time to maximum plasma concentration was 6.5 and 5.8 hours and the mean terminal half-life was 6.1 and 6.7 hours, respectively. Plasma concentrations of meloxicam for rabbits in the present study were proportionally higher than those previously reported for rabbits receiving 0.2 mg of meloxicam/kg and were similar to those determined for animals of other species that received clinically effective doses. A dose of 1 mg/kg may be necessary to achieve clinically effective circulating concentrations of meloxicam in rabbits, although further studies are needed.

  19. 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.

  20. 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

    International Nuclear Information System (INIS)

    Kinner, Sonja; Steinweg, Verena; Maderwald, Stefan; Radtke, Arnold; Sotiropoulos, Georgios; Forsting, Michael; Schroeder, Tobias

    2014-01-01

    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

  1. 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

  2. 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

  3. Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.

    Science.gov (United States)

    Cheng, Yaofeng; Chen, Shenjue; Freeden, Chris; Chen, Weiqi; Zhang, Yueping; Abraham, Pamela; Nelson, David M; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

    2017-09-01

    The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  4. Failure Rate of Single Dose Methotrexate in Managment of Ectopic Pregnancy

    Directory of Open Access Journals (Sweden)

    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.

  5. Amodiaquine-associated adverse effects after inadvertent overdose and after a standard therapeutic dose

    DEFF Research Database (Denmark)

    Adjei, G O; Goka, B Q; Rodrigues, O P

    2009-01-01

    A case of an acute dystonic reaction in a child presumptively treated for malaria with amodiaquine, and a case of persistent asymptomatic bradycardia in another child with mild pulmonary stenosis treated with a standard dose of amodiaquine for parasitologically confirmed uncomplicated malaria, is...

  6. Therapeutic drug monitoring to individualize the dosing of pazopanib: a pharmacokinetic feasibility study

    NARCIS (Netherlands)

    Wit, D. de; Erp, N. van; Hartigh, J. den; Wolterbeek, R..; Hollander-van Deursen, M. den; Labots, M.; Guchelaar (LUMC), H.J.; Verheul, H.M.; Gelderblom, H.

    2015-01-01

    BACKGROUND: Patients treated with the standard dose of pazopanib show a large interpatient variability in drug exposure defined as the area under the plasma concentration-time curve (AUC0-24h). The primary objective of this study was to evaluate the feasibility of pharmacokinetics (PK)-guided

  7. In vitro modeling of skin dose and monitoring of DCA following therapeutic intervention

    International Nuclear Information System (INIS)

    Balajee, Adayabalam S.; Dainiak, Nicholas

    2016-01-01

    Human skin is the largest organ of the body accounting for approximately 16% of the total bodyweight. Skin is readily exposed to ionizing radiation during either accidental or intentional exposure such as radiotherapy or other medical procedures because it constitutes the interface between environment and internal organs. Estimation of accurate entrance skin dose and maximum absorbed dose (MAD) is crucial to prevent serious skin injuries. Cutaneous Radiation Syndrome (CRS) is defined by a number of pathological changes manifested in the skin and severity of these changes depend on Liner Energy Transfer (LET), dose, dose-rate, geometry of exposure and volume of body part exposed. In most of the radiological accident scenarios, reconstructive dosimetry in the skin has been performed using physical (thermoluminescence and optical stimulated luminescence), biological (cytogenetics) and computational methods/models to manage radiation exposed victims.Results of the cytogenetic testing performed at the CBL on a few patients will be discussed to illustrate the potential use of DCA and other cytogenetic techniques such as micronuclei and multicolor FISH in monitoring the health of radiotherapy patients

  8. Methodology to administer therapeutic dose of I-131; Metodologia para administrar dosis terapeutica de I-131

    Energy Technology Data Exchange (ETDEWEB)

    Basteris M, J.; Gomez D, R. [Universidad Autonoma de Yucatan, Facultad de Medicina, Merida, Yucatan (Mexico)

    2007-07-01

    The present work suggests the use of measures guided to eliminate the resulting chronic sialoadenitis of the treatment of the thyroid cancer with Iodine-131, as well as the use of citric fruits to stimulate the salivation, the post-dose administration of liquids to accelerate the gastric emptying avoiding the secondary effects as the vomit is included. (Author)

  9. Therapeutic efficacy of small doses of colchicine combined with glucocorticoid for acute gouty arthritis

    Directory of Open Access Journals (Sweden)

    Ying LIU

    2015-10-01

    Full Text Available Objective To observe the clinical effect of small dose of colchicine combined with glucocorticoid for acute gouty arthritis. Methods Ninety-two patients with acute gouty arthritis were equally and randomly divided into small doses of colchicine combined with dexamethasone treatment group (treatment group and conventional large dose colchicine treatment group (control group between January 2009 and December 2013. The articular lesion scoring and clinical efficacy evaluation were performed at 3, 6, 12, 24, 48, and 72h after treatment. Erythrocyte sedimentation rate (ESR, white blood cells, hepatorenal function and glomerular filtration rate (GFR were determined before and 72h after treatment respectively. The gastrointestinal adverse events and recurrence rate were observed within one month after treatment. Results The articular lesion scores were significantly decreased at 6, 12, 48, and 72h after treatment in treatment group compared with control group (P0.05. Serum uric acid, glutamic-pyruvic transaminase in serum (SGPT, and GFR did not show any change before and 72h after the treatment, and there was also no significant difference between groups (P>0.05. The incidence of gastrointestinal adverse events were obviously higher in control group (76.1% compared with that of the treatment group (P<0.05, and the differences was statistically significant. There was no statistical difference in recurrence rate between the control group and treatment group after a follow-up of one month. Conclusions Compared with conventional large dose colchicine, small dose of colchicine combined with dexamethasone can more rapidly and effectively control acute gouty arthritis, with good tolerability and safety, thus being worthy of popularization clinically. DOI: 10.11855/j.issn.0577-7402.2015.08.10

  10. Therapeutic profile of single-fraction radiosurgery of vestibular schwannoma: unrelated malignancy predicts tumor control.

    Science.gov (United States)

    Wowra, Berndt; Muacevic, Alexander; Fürweger, Christoph; Schichor, Christian; Tonn, Jörg-Christian

    2012-07-01

    Radiosurgery has become an accepted treatment option for vestibular schwannomas. Nevertheless, predictors of tumor control and treatment toxicity in current radiosurgery of vestibular schwannomas are not well understood. To generate new information on predictors of tumor control and cranial nerve toxicity of single-fraction radiosurgery of vestibular schwannomas, we conducted a single-institution long-term observational study of radiosurgery for sporadic vestibular schwannomas. Minimum follow-up was 3 years. Investigated as potential predictors of tumor control and cranial nerve toxicity were treatment technology; tumor resection preceding radiosurgery; tumor size; gender; patient age; history of cancer, vascular disease, or metabolic disease; tumor volume; radiosurgical prescription dose; and isodose line. Three hundred eighty-six patients met inclusion criteria. Treatment failure was observed in 27 patients. History of unrelated cancer (strongest predictor) and prescription dose significantly predicted tumor control. The cumulative incidence of treatment failure was 30% after 6.5 years in patients with unrelated malignancy and 10% after ≥15 years in patients without such cancer (P < .02). Tumor volume was the only predictor of trigeminal neuropathy (observed in 6 patients). No predictor of facial nerve toxicity was found. On the House and Brackmann scale, 1 patient had a permanent one-level drop and 7 a transient drop of 1 to 3 levels. Serviceable hearing was preserved in 75.1%. Tumor hearing before radiosurgery, recurrence, and prescription isodose predicted ototoxicity. Unrelated malignancy is a strong predictor of tumor control. Tumor recurrence predominantly predicts ototoxicity. These findings potentially will aid future clinical decision making in ambiguous cases.

  11. Is dosing of therapeutic immunoglobulins optimal? – A review of a 3-decade long debate in Europe.

    Directory of Open Access Journals (Sweden)

    Jacqueline eKerr

    2014-12-01

    Full Text Available The consumption of immunoglobulins (Ig is increasing due to better recognition of antibody deficiencies, an aging population and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications in Europe. The background to the current regulatory settings in Europe is provided as a backdrop for the latest developments in primary and secondary immunodeficiencies and in immunomodulatory indications. In these heterogeneous areas, clinical trials encompassing different routes of administration, varying intervals and infusion rates are paving the way towards more individualized therapy regimens.In primary antibody deficiencies adjustments in dosing and intervals will depend on the clinical presentation, effective IgG trough levels and IgG metabolism. Ideally, individual pharmacokinetic profiles in conjunction with the clinical phenotype could lead to highly tailored treatment. In practice, incremental dosage increases are necessary to titrate the optimal dose for more severely ill patients. Higher intravenous doses in these patients also have beneficial immunomodulatory effects beyond mere IgG replacement. Better understanding of the pharmacokinetics of Ig therapy is leading to a move away from simplistic ‘per kg’ dosing.Defective antibody production is common in many secondary immunodeficiencies irrespective of whether the causative factor was lymphoid malignancies (established indications, certain autoimmune disorders, immunosuppressive agents or biologics. This antibody failure, as shown by test immunisation, may be amenable to treatment with replacement Ig therapy. In certain immunomodulatory settings (e.g. ITP selection of patients for Ig therapy may be enhanced by relevant biomarkers in order to exclude non-responders and thus obtain higher response rates. In this review the developments in dosing of therapeutic immunoglobulins have been

  12. Single intravenous and oral dose pharmacokinetics of florfenicol in the channel catfish Ictalurus punctatus

    Science.gov (United States)

    Plasma distribution and elimination of florfenicol in channel catfish were investigated after a single dose (10mg/kg) of intravenous i.v.) or oral administration in freshwater at a mean water temperature of 25.4°C. Florfenicol concentrations in plasma were analyzed by means of liquid chromatography...

  13. Efficacy of a single dose of a transdermal diclofenac patch as pre ...

    African Journals Online (AJOL)

    2012-01-25

    Jan 25, 2012 ... Original Research: Efficacy of single dose of transdermal diclofenac patch. 194. 2012;18(4). South Afr J Anaesth Analg. Introduction. Peripheral tissue injury, as seen in postoperative patients, provokes two kinds of modification in the responsiveness of the nervous system. In peripheral sensitisation, there is ...

  14. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Healy, W.L.; Lo, T.C.; Covall, D.J.; Pfeifer, B.A.; Wasilewski, S.A. (Lahey Clinic Medical Center, Burlington, MA (USA))

    1990-12-01

    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.

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

    Science.gov (United States)

    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.

  17. 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...

  18. The feasibility of repeated left ventricular ejection fraction analysis with sequential single-dose radionuclide ventriculography

    NARCIS (Netherlands)

    van der Vleuten, PA; Slart, RHJA; Tio, RA; van der Horst, ICC; van Veldhuisen, DJ; Dierckx, RA; Zijlstra, F

    Objective Repeated left ventricular ejection fraction (LVEF) analyses with sequential single-dose radionuclide ventriculography might be an interesting technique for monitoring the effect of positive inotropic interventions. The aim of the study was to assess the reproducibility of LVEF measurement

  19. Oral microflora and selection of resistance after a single dose of amoxicillin.

    Science.gov (United States)

    Khalil, D; Hultin, M; Rashid, M U; Lund, B

    2016-11-01

    The study aimed to determine the effects of a single-dose antibiotic prophylaxis on normal oral microflora. A single dose of 2 g amoxicillin was given to 29 healthy volunteers. Saliva was collected before antibiotic administration (day 1), and again on days 2, 5, 10, 17 and 24 and subjected to culturing and antibiotic sensitivity analysis. Twenty-one per cent (6/29) of the individuals carried penicillin-V- and amoxicillin-resistant viridans streptococci before antibiotic administration. After a single dose of amoxicillin there was a significant reduction in Streptococcus salivarius on days 2 and 5, a significant reduction in other viridans streptococci on day 2 and the proportion of viridans streptococci with reduced susceptibility to amoxicillin was significantly increased on days 2 and 5. A single dose of amoxicillin can cause an ecological disturbance and induce selection of resistant strains in the oral microflora. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  20. 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

  1. 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.

  2. 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,

  3. 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...

  4. 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.

  5. 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

  6. 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.

  7. Clinical Strategy for Optimal Traditional Chinese Medicine (TCM) Herbal Dose Selection in Disease Therapeutics: Expert Consensus on Classic TCM Herbal Formula Dose Conversion.

    Science.gov (United States)

    Zha, Lin-Hua; He, Li-Sha; Lian, Feng-Mei; Zhen, Zhong; Ji, Hang-Yu; Xu, Li-Peng; Tong, Xiao-Lin

    2015-01-01

    The clinical therapeutics of traditional Chinese medicine (TCM) constitutes a complicated process which involves theory, diagnosis, and formula prescription with specific herbal dosage. Zhang Zhong-Jing's classic work, Treatise on Febrile and Miscellaneous Diseases, has been influencing TCM practice for almost 2000 years. However, during this extended period of time in Chinese history, the Chinese weight measurement system experienced noticeable changes. This change in the weight measurement system inevitably, and perhaps even negatively, affected TCM herbal dosage determination and treatment outcome. Thus, in modern society, a full understanding of the accuracy of herbal dose selection has a critical importance in the TCM daily practice of delivering the best treatment to the patients suffering from different illnesses. In the 973 Project of the Chinese National Basic Research Program, expert consensus on classic TCM formula dose conversion has been reached based on extensive literature review and discussion on the dose-effect relationship of classic TCM formulas. One "liang" in classic TCM formulas is equivalent to 13.8 g. However, based on many TCM basic and clinical studies of variable herbal formula prescriptions and herbal drug preparations, the rule of one liang equals 13.8 g should be adjusted according to different disease conditions. Recommended by the committee on TCM formula dose-effect relationship of the China Association of Chinese Medicine and the World Federation of Chinese Medicine Societies, the following expert consensus has been reached: (i) One liang converts to 6-9 g for the severely and critically ill patients. (ii) One liang converts to 3-6 g for the patients suffering from chronic diseases. (iii) One liang converts to 1-3 g in preventive medicine. The above conversions should be used as a future TCM practice guideline. Using this recommended guideline should enhance the effectiveness of daily TCM practice.

  8. Comparison of two different strategies of treatment with zoledronate in HIV-infected patients with low bone mineral density: single dose versus two doses in 2 years.

    Science.gov (United States)

    Negredo, E; Bonjoch, A; Pérez-Álvarez, N; Ornelas, A; Puig, J; Herrero, C; Estany, C; del Río, L; di Gregorio, S; Echeverría, P; Clotet, B

    2015-08-01

    Given the need for easily managed treatment of osteoporosis in HIV-infected patients, we evaluated the efficacy and tolerability of two doses of zoledronate, by comparing three groups of patients: those with annual administration, those with biennial administration (one dose in 2 years) and a control group with no administration of zoledronate. We randomized (2:1) 31 patients on antiretroviral therapy with low bone mineral density (BMD) to zoledronate (5 mg administered intravenously; 21 patients) plus diet counselling and to a control group (diet counselling; 10 patients). At week 48, patients treated with zoledronate were randomized again to receive a second dose (two-dose group; n = 12) or to continue with diet counselling only (single-dose group; n = 9). Changes in lumbar spine and hip BMD and bone turnover markers were compared. The median percentage change from baseline to week 96 in L1-L4 BMD was -1.74% [interquartile range (IQR) -2.56, 3.60%], 7.90% (IQR 4.20, 16.57%) and 5.22% (IQR 2.02, 7.28%) in the control, two-dose and single-dose groups, respectively (P two doses; P = 0.02, control vs. single dose; P = 0.18, two doses vs. single dose). Hip BMD changed by a median of 2.12% (IQR -0.12, 3.08%), 5.16% (IQR 3.06, 6.74%) and 4.47% (IQR 1, 5.58%), respectively (P = 0.04, control vs. two doses; P = 0.34, two doses vs. single dose). No differences between the two-dose and single-dose groups were detected in bone markers at week 96. The benefits for BMD of a single dose of zoledronate in 2 years may be comparable to those obtained with two doses of the drug after 96 weeks, although this study is insufficiently powered to exclude a real difference. Future studies should explore whether biennial administration of zoledronate is a useful alternative in the treatment of osteoporosis in HIV-infected patients. © 2015 British HIV Association.

  9. Radial dose distributions from carbon ions of therapeutic energies calculated with Geant4-DNA.

    Science.gov (United States)

    Wang, He; Vassiliev, Oleg N

    2017-05-21

    We report on radial dose distributions [Formula: see text] for carbon ions calculated with Geant4-DNA code. These distributions characterize ion tracks on a nanoscale and are important for understanding the biological effects of ion beams. We present data for carbon ion beams in the energy range from 20 to 400 MeV u -1 . To approximate the Monte Carlo results, we developed a simple formula that combines the well-known inverse square distance dependence with a factor correcting [Formula: see text] for small [Formula: see text]. The proposed formula can be used to calculate [Formula: see text] for any energy within the above range and for distances [Formula: see text] from 1 nm to 2 μm with a maximum error not exceeding 14%. This range of distances corresponds to a dose range of over seven orders of magnitude. Differences between our results and those of previously published analytical models are discussed.

  10. The effect of a metal hip prosthesis on the radiation dose in therapeutic photon beam irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Lin, S.-Y.; Chu, T.-C. E-mail: tcchu@mx.nthu.edu.tw; Lin, J.-P.; Liu, M.-T

    2002-07-01

    Prostate and cervical cancer patients are often treated with external X-ray beams of bi-lateral incidence. Such treatment may incur some dose effect that cannot be predicted precisely in commercial treatment planning systems (TPS) for patients having undergone total hip replacement. This study performs a Monte Carlo (MC) simulation and an analytical calculation (convolution superposition algorithm which is implemented in ADAC TPS) of a 6 MV, 5x5 cm{sup 2} X-ray beam incident into water with the existence of hip prosthesis, e.g. Ti6Al4V and CoCrMo alloy. The results indicate that ADAC TPS cannot precisely account for the scatter and backscatter radiation that a metal hip prosthesis causes. For percent depth dose (PDD) curves, the maximum underdosage of ADAC TPS up to 5 mm above the interface between dense material and water is 5%, 20% and 27% for PDD{sub Bone}, PDD{sub Ti} and PDD{sub Co}, respectively. The dose re-buildup, which occurs behind the hip region, becomes more and more obvious for denser medium existed in water. Increasing inhomogeneity also enhances the underdosage of ADAC for greater depth (>10 cm), as the figures of nearly 2% in PDD{sub Bone}, PDD{sub Ti} and 4-5% in PDD{sub Co} reveal. Overestimating the attenuated power of high-density non-water material in ADAC TPS causes this underdosage. For dose profiles, no significant differences were found in Profile{sub Bone} at any depth. Profile{sub Ti} reveals that MC slightly exceeds ADAC at off-axis position 1.0-2.0 cm. Profile{sub Co} reveals this more obviously. This finding means that scatter radiation from these denser materials is significant and cannot be predicted precisely in ADAC.

  11. Pretreatment serum human chorionic gonadotropin cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy.

    Science.gov (United States)

    Kim, Junhwan; Jung, Young Mi; Lee, Da Yong; Jee, Byung Chul

    2017-01-01

    To investigate individual pretreatment serum human chorionic gonadotropin (hCG) cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy. Eighty-five women who received methotrexate for the treatment of tubal ectopic pregnancy during 2003 to 2015 were selected. Fifty-three women received a single-dose regimen and 32 women received a multi-dose regimen. Medical treatment failure was defined as necessity of surgical treatment. The medical treatment success rate was estimated in both regimens and the pretreatment serum hCG titer to predict the success was assessed by receiver operating characteristics curve analysis. Pretreatment clinical and laboratory parameters were similar between group of single-dose regimen and multi-dose regimen. Treatment success rate was 64.2% in the single-dose regimen group and 71.9% in the multi-dose regimen group ( P >0.05). Pretreatment serum hCG titer was an independent prognostic factor for treatment success in each regimen. Serum hCG cutoff value to predict the treatment success was 3,026 IU/L in single-dose regimen group and 3,711 IU/L in multi-dose regimen group. We recommend use of single-dose regimen when pretreatment serum hCG <3,026 IU/L but multi-dose regimen may be favored when initial serum hCG level between 3,026 and 3,711 IU/L.

  12. Optimizing therapeutics in the management of patients with multiple sclerosis: a review of drug efficacy, dosing, and mechanisms of action

    Directory of Open Access Journals (Sweden)

    Damal K

    2013-11-01

    Full Text Available Kavitha Damal, Emily Stoker, John F FoleyRocky Mountain Multiple Sclerosis Research Group, Salt Lake City, UT, USAAbstract: Multiple sclerosis (MS is a debilitating neurological disorder that affects nearly 2 million adults, mostly in their prime of youth. An environmental trigger, such as a viral infection, is hypothesized to initiate the abnormal behavior of host immune cells: to attack and damage the myelin sheath surrounding the neurons of the central nervous system. While several other pathways and disease triggers are still being investigated, it is nonetheless clear that MS is a heterogeneous disease with multifactorial etiologies that works independently or synergistically to initiate the aberrant immune responses to myelin. Although there are still no definitive markers to diagnose the disease or to cure the disease per se, research on management of MS has improved many fold over the past decade. New disease-modifying therapeutics are poised to decrease immune inflammatory responses and consequently decelerate the progression of MS disease activity, reduce the exacerbations of MS symptoms, and stabilize the physical and mental status of individuals. In this review, we describe the mechanism of action, optimal dosing, drug administration, safety, and efficacy of the disease-modifying therapeutics that are currently approved for MS therapy. We also briefly touch upon the new drugs currently under investigation, and discuss the future of MS therapeutics.Keywords: multiple sclerosis, immunomodulation, interferons, glatiramer acetate, monoclonal antibodies, dimethyl fumarate

  13. A model-based analysis of a simplified beam-specific dose output in proton therapy with a single-ring wobbling system.

    Science.gov (United States)

    Kase, Yuki; Yamashita, Haruo; Numano, Masumi; Sakama, Makoto; Mizota, Manabu; Maeda, Yoshikazu; Tameshige, Yuji; Murayama, Shigeyuki

    2015-01-07

    In radiation therapy, it is necessary to preset a monitor unit in an irradiation control system to deliver a prescribed absolute dose to a reference point in the planning target volume. The purpose of this study was to develop a model-based monitor unit calculation method for proton-beam therapy with a single-ring wobbling system. The absorbed dose at a calibration point per monitor unit had been measured for each beam-specific measurement condition without a patient-specific collimator or range compensator before proton therapeutic irradiation at Shizuoka Cancer Center. In this paper, we propose a simplified dose output model to obtain the output ratio between a beam-specific dose and a reference field dose, from which a monitor unit for the proton treatment could be derived without beam-specific measurements. The model parameters were determined to fit some typical data measured in a proton treatment room, called a Gantry 1 course. Then, the model calculation was compared with 5456 dose output ratios that had been measured for 150-, 190- and 220 MeV therapeutic proton beams in two treatment rooms over the past decade. The mean value and standard deviation of the difference between the measurement and the model calculation were respectively 0.00% and 0.27% for the Gantry 1 course, and -0.25% and 0.35% for the Gantry 2 course. The model calculation was in good agreement with the measured beam-specific doses, within 1%, except for conditions less frequently used for treatment. The small variation for the various beam conditions shows the high long-term reproducibility of the measurement and high degree of compatibility of the two treatment rooms. Therefore, the model was expected to assure the setting value of the dose monitor for treatment, to save the effort required for beam-specific measurement, and to predict the dose output for new beam conditions in the future.

  14. [Therapeutic effects of different doses of botulinum toxin A injection on tiptoe deformation in children with cerebral palsy].

    Science.gov (United States)

    Niu, Guo-Hui; Zhang, Xiao-Li; Zhu, Deng-Na; Cai, Zhi-Jun; Li, San-Song; Zhang, Wei

    2014-07-01

    To study the therapeutic effects of different doses of botulinum toxin A (BTX-A) injection on tiptoe deformation in children with cerebral palsy. A total of 256 children with tiptoe deformation due to spastic cerebral palsy were classified into group A (muscle tension levels I-II, n=147) and group B (muscle tension levels III-IV, n=109). Group A was randomly divided into group A1 (injected with high-dose BTX-A, n=73) and group A2 (injected with low-dose BTX-A, n=74). Group B was randomly divided into group B1 (injected with high-dose BTX-A, n=55) and group B2 ( injected with low-dose BTX-A, n=54). The dose of BTX-A was 6 U/kg for groups A1 and B1 and was 3 U/kg for groups A2 and B2. Before the injection and at 1,2,6, and 12 months after injection, the muscle tension of limbs was evaluated with the modified Ashworth Scale, and the recovery of motor function of lower limbs was assessed with the Gross Motor Function Measure (GMFM). Before and after treatment, there were no significant differences in Ashworth and GMFM scores between groups A1 and A2 (P>0.05). After treatment, group B1 had a significantly reduced Ashworth score and a significantly increased GMFM score, and group B1 had a significantly lower Ashworth score and a significantly higher GMFM score compared with group B2 (PAshworth score gradually declined post-treatment, reached the lowest point at 3 months after treatment, and returned to the level before treatment at 12 months after treatment; GMFM score gradually increased post-treatment and reached the peak level at 12 months after treatment (P<0.05). The level of muscle tension should be considered when BTX-A injection is used for treating tiptoe deformation in children with cerebral palsy. It makes no difference to use high- or low-dose BTX-A when the muscle tension level is within I-II, but high-dose BTX-A has a better performance in reducing muscle tension and improving motor function when the muscle tension level is within III-IV.

  15. Pharmacokinetics of single-dose ceftaroline fosamil in children with cystic fibrosis.

    Science.gov (United States)

    Le, Jennifer; Bradley, John S; Hingtgen, Sara; Skochko, Shannon; Black, Nanette; Jones, Ronald N; Lim, Meerana; Capparelli, Edmund V

    2017-11-01

    Single-dose pharmacokinetics (PK) and safety of ceftaroline fosamil with population pharmacokinetic/pharmacodynamic (PK/PD) modeling for staphylococcal pneumonia was performed in children with CF. Subjects between 6 and 18 years old were evaluated in this phase 1, open-label, single-dose, prospective study using 10 mg/kg (up to 600 mg). Non-compartmental analysis and population-based PK analyses with Monte Carlo simulation (for doses 8-20 mg/kg every 8 h, infused over 1-4 h) were conducted. A total of 20 subjects were enrolled. The median age and weight were 12 yr (range 6.3-17.4) and 38.7 kg (range 17.8-94.3), respectively. A 3-compartment linear model incorporating age and weight provided the best fit for the data. Comparing children 6 to ceftaroline CL compared with published data from non-CF children; greater dosages may be required in children with CF to achieve adequate exposure in the treatment of MRSA pneumonia. Pharmacodynamic-based dosing predicts that dosing should also be based on the patient's MRSA MIC. © 2017 Wiley Periodicals, Inc.

  16. Single-dose Intravenous Toxicology Testing of Daebohwalryeok Pharmcopuncture in Sprague-Dawley Rats.

    Science.gov (United States)

    Sun, Seung-Ho; Park, Sunju; Jeong, Jong-Jin; Lee, Kwang-Ho; Yu, Jun-Sang; Seo, Hyung-Sik; Kwon, Ki-Rok

    2015-06-01

    The aims of the study were to test the single-dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP) in Sprague-Dawley (SD) rats and to estimate the crude lethal dose. The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP) laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156). The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group). General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA) by using statistical analysis system (SAS, version 9.2). No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg.

  17. Single-dose Intravenous Toxicology Testing of Daebohwalryeok Pharmcopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Seung-Ho Sun

    2015-06-01

    Full Text Available Objectives: The aims of the study were to test the single-dose intravenous toxicity of Daebohwalryeok pharmacopuncture (DHRP in Sprague-Dawley (SD rats and to estimate the crude lethal dose. Methods: The experiments were conducted at Biotoxtech Co., a Good Laboratory Practice (GLP laboratory, according to the GLP regulation and were approved by the Institutional Animal Care and Use Committee of Biotoxtech Co. (Approval no: 110156. The rats were divided into three groups: DHRP was injected into the rats in the two test groups at doses of 10 mL/kg and 20 mL/kg, respectively, and normal saline solution was injected into the rats in the control group. Single doses of DHRP were injected intravenously into 6 week old SD rats (5 male and 5 female rats per group. General symptoms were observed and weights were measured during the 14 day observation period after the injection. After the observation period, necropsies were done. Then, histopathological tests were performed. Weight data were analyzed with a one-way analysis of variance (ANOVA by using statistical analysis system (SAS, version 9.2. Results: No deaths and no statistical significant weight changes were observed for either male or female SD rats in either the control or the test groups during the observation period. In addition, no treatment related general symptoms or necropsy abnormalities were observed. Histopathological results showed no DHRP related effects in the 20 mL/kg DHRP group for either male or female rats. Conclusion: Under the conditions of this study, the results from single-dose intravenous injections of DHRP showed that estimated lethal doses for both male and female rats were above 20 mL/kg.

  18. Preoperative therapeutic neuroscience education for lumbar radiculopathy: a single-case fMRI report.

    Science.gov (United States)

    Louw, Adriaan; Puentedura, Emilio J; Diener, Ina; Peoples, Randal R

    2015-01-01

    Therapeutic neuroscience education (TNE) has been shown to be effective in the treatment of mainly chronic musculoskeletal pain conditions. This case study aims to describe the changes in brain activation on functional magnetic resonance imaging (fMRI) scanning, before and after the application of a newly-designed preoperative TNE program. A 30-year-old female with a current acute episode of low back pain (LBP) and radiculopathy participated in a single preoperative TNE session. She completed pre- and post-education measures including visual analog scale (VAS) for LBP and leg pain; Oswestry Disability Index (ODI); Fear Avoidance Beliefs Questionnaire (FABQ); Pain Catastrophizing Scale (PCS) and a series of Likert-scale questions regarding beliefs and attitudes to lumbar surgery (LS). After a 30-minute TNE session, ODI decreased by 10%, PCS decreased by 10 points and her beliefs and attitudes shifted positively regarding LS. Immediately following TNE straight leg raise increased by 7° and forward flexion by 8 cm. fMRI testing following TNE revealed 3 marked differences compared to pre-education scanning: (1) deactivation of the periaqueductal gray area; (2) deactivation of the cerebellum; and (3) increased activation of the motor cortex. The immediate positive fMRI, psychometric and physical movement changes may indicate a cortical mechanism of TNE for patients scheduled for LS.

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

    DEFF Research Database (Denmark)

    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...

  20. Safety and pharmacokinetics of dicloxacillin in healthy Chinese volunteers following single and multiple oral doses

    Directory of Open Access Journals (Sweden)

    Wu GL

    2015-10-01

    Full Text Available Guolan Wu, Yunliang Zheng, Huili Zhou, Xingjiang Hu, Jian Liu, You Zhai, Meixiang Zhu, Lihua Wu, Jianzhong Shentu Research Center for Clinical Pharmacy, State Key Laboratory for Diagnosis and Treatment of Infectious Disease, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China Background: Dicloxacillin, a semisynthetic isoxazolyl penicillin antibiotic, has antimicrobial activity against a wide variety of gram-positive bacteria including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumonia, Streptococcus epidermidis, Streptococcus viridans, Streptococcus agalactiae, and Neisseria meningitidis. The objective of this study was to evaluate the safety and pharmacokinetic profile of dicloxacillin after single and multiple oral dose in healthy Chinese volunteers.Methods: A single-center, open-label, randomized, two-phase study was conducted in 16 subjects. In the single-dose phase, subjects were randomly assigned to receive single doses of 0.25, 0.5, 1.0, and 2.0 g of dicloxacillin sodium capsule in a 4-way crossover design with a 5-day washout period between administrations. In the multiple-dose phase, subjects were assigned to receive 0.25 or 0.5 g every 6 hours for 3 days in a 2-way crossover design. Plasma and urine pharmacokinetic samples were assayed by a validated high-performance liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated and analyzed statistically. Safety assessments were conducted throughout the study.Results: Following a single oral dose of 0.25–2.0 g dicloxacillin sodium, the maximum plasma drug concentration (Cmax and the corresponding values for the area under the concentration–time curve from 0 to 10 hours (AUC0–10 h increased in a dose-proportional manner. The mean elimination half-life (t1/2 was in the range of 1.38–1.71 hours. Dicloxacillin was excreted in its unchanged form via the kidney, with no

  1. Single-dose oral fluconazole versus topical clotrimazole in patients with pityriasis versicolor: A double-blind randomized controlled trial.

    Science.gov (United States)

    Dehghan, Mohammad; Akbari, Negin; Alborzi, Nazila; Sadani, Somayeh; Keshtkar, Abas A

    2010-08-01

    This study was designed to compare the therapeutic effects of topical clotrimazole and systemic fluconazole in pityriasis versicolor. A double-blind randomized controlled trial was carried out in the dermatological clinic of Gorgan, northern Iran, between April 2006 and May 2007. All consecutive patients with pityriasis versicolor were included and randomly divided into two groups. In the first group (G1), patients underwent treatment with a single dose of fluconazole capsule (400 mg) and placebo cream. In the second group (G2), patients underwent treatment with clotrimazole cream (twice daily) and placebo capsule. The course of treatment was 2 weeks. All subjects were re-evaluated 2, 4 and 12 weeks after the end of the therapeutic course. After 2 weeks, the rate of complete resolution of disease was significantly higher in G2 than G1 (49.1% vs 30%). After 4 weeks, 41 patients (81.2%) of G1 and 52 patients (94.9%) of G2 showed complete resolution. After 12 weeks, 46 patients (92%) in G1 and 45 patients (81.8%) in G2 showed complete resolution. Recurrence rate in G1 and G2 were 6% and 18.2%, respectively. No complications were seen in either group. In this study, clinical response at week 4 was greater in the clotrimazole group than the fluconazole group. Recurrence at week 12 after treatment was less with oral fluconazole than clotrimazole cream. So, for better evaluation, more studies need to be done.

  2. Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells

    International Nuclear Information System (INIS)

    Iordanskiy, Sergey; Van Duyne, Rachel; Sampey, Gavin C; Woodson, Caitlin M; Fry, Kelsi; Saifuddin, Mohammed; Guo, Jia; Wu, Yuntao; Romerio, Fabio; Kashanchi, Fatah

    2015-01-01

    The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4 + T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4 + T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4 + T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells. - Highlights: • X-ray irradiation (IR) increases

  3. Therapeutic doses of irradiation activate viral transcription and induce apoptosis in HIV-1 infected cells

    Energy Technology Data Exchange (ETDEWEB)

    Iordanskiy, Sergey [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Van Duyne, Rachel [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702 (United States); Sampey, Gavin C; Woodson, Caitlin M; Fry, Kelsi; Saifuddin, Mohammed; Guo, Jia; Wu, Yuntao [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States); Romerio, Fabio [Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Kashanchi, Fatah, E-mail: fkashanc@gmu.edu [School of Systems Biology, Laboratory of Molecular Virology, George Mason University, Manassas, VA 20110 (United States)

    2015-11-15

    The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4{sup +} T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4{sup +} T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4{sup +} T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the “Shock and Kill” strategy for latently HIV-1 infected cells. - Highlights: • X-ray irradiation

  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

  5. Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.

    Science.gov (United States)

    Bernigaud, Charlotte; Fang, Fang; Fischer, Katja; Lespine, Anne; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

    2016-10-01

    Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy. Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.

  6. Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model

    Science.gov (United States)

    Bernigaud, Charlotte; Aho, Ludwig Serge; Dreau, Dominique; Kelly, Andrew; Sutra, Jean-François; Moreau, Francis; Lilin, Thomas; Botterel, Françoise; Guillot, Jacques; Chosidow, Olivier

    2016-01-01

    Background Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. Methodology/Principal Findings Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26–100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite’s entire life cycle and enabling long-lasting efficacy. Conclusions/Significance Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies. PMID:27732588

  7. A study of the effects of therapeutic doses of ionizing radiation in vitro on Lactobacillus isolates originating from the vagina - a pilot study.

    Science.gov (United States)

    Gosiewski, Tomasz; Mróz, Tomasz; Ochońska, Dorota; Pabian, Wojciech; Bulanda, Malgorzata; Brzychczy-Wloch, Monika

    2016-05-31

    Ionizing radiation is used as a therapeutic option in the treatment of certain neoplastic lesions located, among others, in the pelvic region. The therapeutic doses of radiation employed often result in adverse effects manifesting themselves primarily in the form of genital tract infections in patients or diarrhea. The data available in the literature indicate disorders in the microbial ecosystem caused by ionizing radiation, which leads to the problems mentioned above. In the present study, we examined the influence of ionizing radiation on 52 selected strains of bacteria: Lactobacillus crispatus, L. fermentum, L. plantarum, L. reuteri, L. acidophilus L. amylovorus, L. casei, L. helveticus, L. paracasei, L. rhamnosus, L. salivarius and L. gasseri. This collection of Lactobacillus bacteria isolates of various species, obtained from the genital tract and gastrointestinal tract of healthy women, was tested for resistance to therapeutic doses of ionizing radiation. The species studied, were isolated from the genital tract (n = 30) and from the anus (n = 22) of healthy pregnant women. Three doses of 3 Gy (fractionated dose) and 50 Gy (total dose of the whole radiotherapy cycle) were applied. The greatest differences in survival of the tested strains in comparison to the control group (not subjected to radiation) were observed at the dose of 50 Gy. However, the results were not statistically significant. Survival decrease to zero was not demonstrated for any of the tested strains. Therapeutic doses of radiation do not affect the Lactobacillus bacteria significantly.

  8. Pharmacokinetics and egg residues after oral administration of a single dose of meloxicam in domestic chickens (Gallus domesticus).

    Science.gov (United States)

    Souza, Marcy J; Bergman, Joan B; White, Molly S; Gordon, Kristen I; Gerhardt, Lillian E; Cox, Sherry K

    2017-08-01

    OBJECTIVE To determine the pharmacokinetics of meloxicam in domestic hens and duration and quantity of drug residues in their eggs following PO administration of a single dose (1 mg of meloxicam/kg). ANIMALS 8 healthy adult White Leghorn hens. PROCEDURES Hens were administered 1 mg of meloxicam/kg PO once. A blood sample was collected immediately before and at intervals up to 48 hours after drug administration. The hens' eggs were collected for 3 weeks after drug administration. Samples of the hens' plasma, egg whites (albumen), and egg yolks were analyzed by high-performance liquid chromatography. RESULTS The half-life, maximum concentration, and time to maximum concentration of meloxicam in plasma samples were 2.8 hours, 7.21 μg/mL, and 2 hours, respectively. Following meloxicam administration, the drug was not detected after 4 days in egg whites and after 8 days in egg yolks. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that meloxicam administered at a dose of 1 mg/kg PO in chickens appears to maintain plasma concentrations equivalent to those reported to be therapeutic for humans for 12 hours. The egg residue data may be used to aid establishment of appropriate drug withdrawal time recommendations.

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

    Directory of Open Access Journals (Sweden)

    Iyoke CA

    2017-05-01

    significantly between cases and controls (95.7% vs 94.3%; P=0.73. Similarly, the mean increases in hemoglobin following either therapeutic route were comparable (1.03±0.56 g/dL for intravenous iron and 0.97±0.46 g/dL for the oral group; P=0.42. Conclusion: Single total-dose intravenous iron for treatment of puerperal iron-deficiency anemia was as effective as daily single doses of ferric iron tablets. For puerperal patients with iron-deficiency anemia in whom compliance with and tolerability of oral iron are not certain, a single total-dose intravenous iron can be safely offered. Keywords: effect, intravenous, iron, puerperal, anemia

  10. [Oxygen enhancement ratio (OER) and therapeutic gain factor (GF) for low-dose irradiation with californium-252].

    Science.gov (United States)

    Wambersie, A; Van Dam, J; Octave-Prignot, M; Dutreix, A

    1982-01-01

    The potential benefit of the introduction of californium-252 in interstitial and intracavitary therapy is related to the greater efficiency of its neutron emission against anoxic cancer cells. In that respect, the oxygen enhancement ratio (OER) of the 252Cf emission has been determined for a continuous low dose rate irradiation. The biological system is growth inhibition in Vicia faba bean roots. A new Vicia faba "BelB" strain has been used, which better tolerates long periods (up to about 10 hours) of anoxia. In a first series of experiments, for a 252Cf (Dn + gamma) dose rate of 0.11 Gy . h-1, an OER of 1.4 +/- 0.1 was observed (the gamma contribution of D gamma to the total absorbed dose Dn + gamma was 0.35 at the position of the root tips). In a second series of experiments, in somewhat different geometrical conditions with a 252Cf (Dn + gamma) dose rate of 0.13 Gy . h-1, an OER of 1.5 +/- 0.1 was observed (D gamma/Dn + gamma = 0.42). The OER values observed for similar irradiation times, with iridium-192 gamma-rays, were 2.3 +/- 0.2 and 2.6 +/- 0.1 respectively, which leads to therapeutic gain factors (GF) of 1.6 and 1.7 respectively. These GF values are slightly lower than those previously obtained (GF = 1.8) on the same system, with d(50)-Be, p(75)-Be and 15 MeV neutron beams.

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

    International Nuclear Information System (INIS)

    Kook, M.; Lapp, T.; Murray, A.S.; Thomsen, K.J.; Jain, M.

    2015-01-01

    In optically stimulated luminescence (OSL) dating and other retrospective dosimetry studies there is considerable demand for the ability to measure luminescence from individual dosimeters in the size range 50–500 μm diameter, either as separate grains or as part of a matrix. This work tests 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 with associated uncertainties. - Highlights: • A luminescence imaging system for the routine measurement is described. • Optimization of detection efficiency and crosstalk are described. • Noise analysis of EMCCD is described. • The dose response curve and dose distribution of the natural sample are consistent with expectation.

  12. Early prediction for the requirement of second or third dose methotrexate in women with ectopic pregnancy, treated with single-dose regimen.

    Science.gov (United States)

    Yıldırım, Aysegul; Cırık, Derya Akdağ; Altay, Metin; Gelisen, Orhan

    2015-06-01

    To investigate the predictive factors for the requirement of additional doses of methotrexate in women with ectopic pregnancy treated with single-dose methotrexate regimen. This retrospective cohort study was conducted on women treated with single-dose methotrexate regimen for ectopic pregnancy at a tertiary referral center. Control group included the patients who were treated only with a single dose of methotrexate (n = 131) and study group included the patients who need a second dose or third dose methotrexate (n = 76). The sonographic variables such as size of the ectopic mass, the endometrial thickness and biochemical variables were analyzed via Chi square and student t test. Logistic regression analysis used to determine independent predictors of the additional dose requirement. The size of the ectopic mass and the endometrial thickness were similar in both groups. However, all human chorionic gonadotropin values on day 1, 4 and 7 were significantly higher in study group than the control group (p = 0.0001). Logistic regression analysis revealed that the human chorionic gonadotropin changes between day 1 and 4 is a predictive factor for requirement of additional doses of methotrexate (area under curve: 0.763, p 22% reduction from day 1 to 4. Less than 22% reduction in human chorionic gonadotropin levels from day 1 to 4 can be used as a predictive factor for the requirement of an additional dose of methotrexate in single-dose regimen. This cutoff value can be used for patients to inform about the probable longer resolution time and refer to alternative treatment modalities such as two-dose, multiple-dose regimens or surgery.

  13. Single-dose electron beam irradiation in treatment and prevention of keloids and hypertrophic scars

    International Nuclear Information System (INIS)

    Lo, T.C.M.; Salzman, F.A.; Seckel, B.R.; Wright, K.A.

    1990-01-01

    Low megavolt electron beam irradiation was used on 354 sites in 199 patients at Lahey Clinic either for palliation of symptomatic hypertrophic scars or as post operative irradiation in an attempt to prevent formation or recurrence of hypertrophic scars. Electron energies used ranged from 1.5 to 3.5 MeV. The median age of the 59 male patients was 22 years and of the 140 female patients 35 years. All patients had at least one follow-up visit, and the median follow-up was 35 months. Of the 294 sites treated for the first time, 272 (93 per cent) were irradiated with a single fraction with a skin dose ranging from 2 to 20 Gy. Of the 85 sites in 63 patients without excision of symptomatic hypertrophic scars, single-dose electron beam irradiation was of clinically significant value in only 41 sites (48 per cent). No patients have been treated without surgical excision since 1973. Because of a history of formation of hypertrophic scars elsewhere in the body, 13 patients with 19 incisions were treated prophylactically after operation for other diseases. All sites were irradiated with single doses ranging from 8 to 20 Gy, and hypertrophic scars did not subsequently develop in any patient. Altogether, 119 patients with 174 sites were irradiated after surgical excision of hypertrophic scars to prevent recurrence; 168 sites (97 per cent) received singe-fraction irradiation, and 161 received a dose of 8 Gy greater, up to 15 Gy. No statistically significant differences were observed in complete success rates, ranging from 82 to 90 per cent with doses of 9 Gy or greater. An interval of up to 72h between excision and single-fraction irradiation satisfactorily prevented recurrence, and clinically significant chronic telangiectasia was recorded in only one patient. Postoperative low megavolt electron beam irradiation with a single dose of 9 Gy or greater is highly effective in the prevention of formation recurrence of hypertrophic scars or keloids. (author). 31 refs.; 2 figs.; 4 tabs

  14. Deposition of diazepam and its metabolites in hair following a single dose of diazepam

    DEFF Research Database (Denmark)

    Wang, Xin; Johansen, Sys Stybe; Zhang, Yurong

    2017-01-01

    not detected. Diazepam and nordazepam levels at 10 months post-exposure were extremely low (near the LOQ), indicating drug loss by personal hygiene and physical handling. To our knowledge, this is the first single-dose diazepam study using black hair and the first study to include measurements of oxazepam......Only sporadic data are available on hair concentrations of diazepam and some of its metabolites (nordazepam, oxazepam, and temazepam) following a single controlled dose. The aim of this study was to investigate the deposition of diazepam and its metabolites in human hair after eight healthy...... volunteers (four women and four men, ages 24-26, East Asian) consumed 10 mg of diazepam. Hair was collected from all volunteers 1 month after exposure, and also 2 months post-exposure from men and 10 months post-exposure from women. Diazepam and the complete metabolite profile, including oxazepam glucuronide...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

  16. 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.

  17. 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...

  18. Optimization algorithm for absorbed dose calculation during single intake of 131І to rats

    Directory of Open Access Journals (Sweden)

    I. P. Drozd

    2016-02-01

    Full Text Available Original calculation algorithms are proposed for absorbed doses in the thyroid gland and thymus of rats at single income of 131I that enable to simplify the calculations and at the same time ensure high reliability of results in the range of input activities of 1 - 115000 Bq. According to the algorithms, the program is developed in the MATLAB environment, adapted for use on Windows running PC. Relative error of calculations is ±2 %.

  19. Cefodizime in serum and skin blister fluid after single intravenous and intramuscular doses in healthy volunteers.

    OpenAIRE

    Korting, H C; Schäfer-Korting, M; Maass, L; Klesel, N; Mutschler, E

    1987-01-01

    In gonorrhea therapy, cephalosporins are conventionally administered by intramuscular (i.m.) injection, which rather frequently leads to local side effects. To investigate whether the well-tolerated intravenous (i.v.) injection of cephalosporins may be of comparable gonocidal effect, levels of cefodizime, a new broad-spectrum cephalosporin, in serum and tissue fluid (suction blister and cantharides blister fluid) were determined in six healthy men. Single doses of 1 g of cefodizime were injec...

  20. Single Dose IV Peramivir is Safe and Effective in the Treatment of Pediatric Influenza

    Science.gov (United States)

    Vanchiere, John; Plunkett, Stephanie; Annamalai, Rajasekaran; Julien, Katie; Peterson, James; Goisse, Marcy; Christensen, Shane; Mehta, Priyesh; Coleman, Stephen; Munoz, Flor; Flynt, Amy; Dobo, Sylvia; Nagy, Eniko; Kargl, Deborah; Mathis, Amanda; Collis, Phil; Sheridan, William

    2017-01-01

    Abstract Background Peramivir (PVR) is a potent neuraminidase inhibitor with in vitro activity against all influenza virus subtypes. Previous studies demonstrated the efficacy and safety of PVR as a single dose intravenous (IV) treatment for acute uncomplicated influenza in adults. Methods A phase 3 study compared age-appropriate doses of single dose IV PVR to 5 days of oral oseltamivir (OSE) (4:1 randomization, stratified by age) in pediatric subjects age 0 -17 years within 48 hours of onset of acute uncomplicated influenza. Plasma concentrations of PVR were measured up to 6 hours post dose. Serial viral titers were measured from nasopharyngeal swabs. Severity of influenza signs and symptoms were recorded in a diary. Results 122 subjects were enrolled up to a data cutoff of March 31, 2017 (Coleman, BioCryst Pharmaceuticals: Investigator, Research support; F. Munoz, BioCryst Pharmaceuticals: Investigator, Research support; A. Flynt, BioCryst Pharmaceuticals: Consultant, Consulting fee; S. Dobo, BioCryst Pharmaceuticals: Employee, Salary; E. Nagy, BioCryst Pharmaceuticals: Employee, Salary; D. Kargl, BioCryst Pharmaceuticals: Consultant, Consulting fee; A. Mathis, BioCryst Pharmaceuticals: Employee, Salary; P. Collis, BioCryst Pharmaceuticals: Employee, Salary; W. Sheridan, BioCryst Pharmaceuticals: Employee, Salary

  1. Pharmacokinetics of valerenic acid after single and multiple doses of valerian in older women.

    Science.gov (United States)

    Anderson, Gail D; Elmer, Gary W; Taibi, Diana M; Vitiello, Michael V; Kantor, Eric; Kalhorn, Thomas F; Howald, William N; Barsness, Suzanne; Landis, Carol A

    2010-10-01

    Insomnia is a commonly reported clinical problem with as many as 50% of older adults reporting difficulty in falling and/or remaining asleep. Valerian (Valeriana officinalis) is a commonly used herb that has been advocated for promoting sleep. Valerenic acid is used as a marker for quantitative analysis of valerian products with evidence of pharmacological activity relevant to the hypnotic effects of valerian. The objective of this study was to determine the pharmacokinetics of valerenic acid in a group of elderly women after receiving a single nightly valerian dose and after 2 weeks of valerian dosing. There was not a statistically significant difference in the average peak concentration (C(max)), time to maximum concentration (T(max)) area under the time curve (AUC), elimination half-life (T(1/2)) and oral clearance after a single dose compared with multiple dosing. There was considerable inter- and intra-subject variability in the pharmacokinetic parameters. C(max) and AUC deceased and T(1/2) increased with increased body weight. The variability between the capsules was extremely low: 2.2%, 1.4% and 1.4%, for hydroxyvalerenic acid, acetoxyvalerenic acid and valerenic acid, respectively. In conclusion, large variability in the pharmacokinetics of valerenic acid may contribute to the inconsistencies in the effect of valerian as a sleep aid. Copyright © 2010 John Wiley & Sons, Ltd.

  2. 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.

  3. Intranasal administration of a therapeutic HIV vaccine (Vacc-4x induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Kristin Brekke

    Full Text Available Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant.Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-β.Vacc-4x proliferative T cell responses increased only among the vaccinated (p ≤ 0.031. The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037 and developed larger DTH (p = 0.005 than the adjuvant group. Rectal (distal Vacc-4x IgA and IgG antibodies also increased (p = 0.043 in this group. In contrast, the high dose generated higher nasal (local Vacc-4x IgA (p = 0.028 and serum IgG (p = 0.030 antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = -0.82, p < 0.001 and high regulation (r = 0.61, p = 0.010 at baseline.Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation.ClinicalTrials.gov NCT01473810.

  4. 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)

  5. Changes in the avian cochlea after single high-dose gentamicin.

    Science.gov (United States)

    Girod, D A; Park, R H; Park, D L; Durham, D

    2000-01-01

    Define the time course of functional and anatomical damage and subsequent recovery (by regeneration) of hair cells in the chicken inner ear after a single high-dose of gentamicin. Broiler chicks were given a single intraperitoneal dose (200 mg/kg) of gentamicin (n = 39) or saline (n = 39). Functional status was evaluated with auditory brainstem response (ABR) thresholds before injection and before sacrifice at 2, 5, 9, 16, 21, 28, and 70 days postinjection. The cochleae were then examined with scanning electron microscopy (SEM) to assess the extent of damage along the cochlea and absolute hair cell numbers in the basal 15% of the cochlea (high-frequency region). Considerable variability between animals was seen for both ABR and SEM changes. Damage was maximal at 5 days postinjection with an average ABR threshold shift of 12 dB (range -10 to 50 dB) and basal cochlear damage of 28% (range 12%-57%). Hair cell counts were significantly decreased in the basal 15% of the cochlea at 5 days. Hair cell regeneration resulted in rapid anatomical and functional recovery, but evidence of hair cell disorganization persisted at 70 days despite improved thresholds. A single high dose of gentamicin produces a significant but variable anatomical and functional insult in the chick cochlea. Hair cell regeneration results in rapid but incomplete recovery.

  6. 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.

  7. Persistence of Immunity Acquired after a Single Dose of Rubella Vaccine in Japan.

    Science.gov (United States)

    Okafuji, Takao; Okafuji, Teruo; Nakayama, Tetsuo

    2016-05-20

    To date, Takahashi, Matsuura, and TO-336 strains of live-attenuated rubella vaccine have been used in Japan. Japan implemented a single-dose rubella vaccination program until 2006. However, few reports are available on the persistence of immunity after this vaccination program. We collected 276 serum samples from January 2009 to December 2011 at Okafuji Pediatric Clinic and assessed the immune status of these samples against rubella virus during 1-10 years after vaccination with a single dose of Takahashi rubella vaccine. Regional outbreak of rubella did not occur during 1999-2011. The collected serum samples were tested for antibodies against the rubella virus by performing a standard hemagglutination inhibition (HAI) test. Our results showed that all the tested serum samples contained antibodies against the rubella virus 10 years after the vaccination. Geometric mean titer of HAI antibodies was 1:180 and decreased to 1:68 at 10 years after the vaccination. The levels of HAI antibodies decreased logarithmically with time after the vaccination. In conclusion, vaccine-acquired immunity after vaccination with a single dose of live-attenuated Takahashi rubella vaccine was retained for at least 10 years when rubella was under regional control.

  8. 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.

  9. Acute and persistent iatrogenic Cushing's syndrome after a single dose of triamcinolone acetonide.

    Science.gov (United States)

    Iglesias, P; González, J; Díez, J J

    2005-12-01

    Iatrogenic Cushing's syndrome is a well-known adverse effect of glucocorticoids. It usually develops after prolonged exposure to excessive amounts of synthetic glucocorticolds. The development of iatrogenic Cushing's syndrome (ICS) after a single and low dose of synthetic glucocorticoid is an exceptional event. Up to now, only a few number of cases have been associated with triamcinolone acetonide and they have always been related to local administration. We report, for the first time, a patient who developed ICS after a single low dose of parenterally (im) administered triamcinolone acetonide. She was a 45-yr-old woman who referred to us because of cushingoid appearance, whose hormonal determinations were suggestive of secondary adrenal insufficiency. Clinical features were developed one month after the administration of a 40 mg single-dose of im triamcinolone acetonide because of acute laryngitis. Endocrinological evaluation confirmed the hypothalamic-pituitary-adrenal (HPA) axis suppression. Eight months later, cushingoid phenotype had completely disappeared and HPA function had spontaneously recovered. We review clinical features and comment on the possible pathogenic mechanisms of this particular and new form of ICS.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. Morbid obesity and outcome of ectopic pregnancy following capped single-dose regimen methotrexate.

    Science.gov (United States)

    Hoyos, Luis R; Malik, Mokerrum; Najjar, Marvin; Rodriguez-Kovacs, Javier; Abdallah, Mazen; Vilchez, Gustavo; Awonuga, Awoniyi O

    2017-02-01

    Evaluate whether morbid obesity influenced resolution, number of doses or ultimately surgical management of tubal ectopic pregnancy (TEP) when treated with single-dose regimen methotrexate (SDR-MTX) capped at 100 mg. Retrospective cohort study of patients with a diagnosis of TEP who underwent MTX treatment from 2000 to 2013. Patients were excluded if initial β-hCG ectopic size, embryonic heart tones, decrease of β-hCG, need for additional MTX doses and surgery despite treatment were recorded and compared among the groups. 151 women were included in the study, 89.4% (135/151) non-morbidly obese and 10.6% (16/151) morbidly obese. No differences in age distribution, ethnicity, pre-treatment presence of embryonic heart tones, maximum diameter of ectopic size ≥35 mm and β-hCG ≥5000 mIU/ml were found. Following treatment, the proportion of patients with at least an 80% decrease in their β-hCG levels or need for surgery were similar, however, morbidly obese patients were significantly more likely [11/134 vs. 5/16, OR 5.1 (1.5-17.3, p = 0.015)] to require an additional MTX dose. Among patients with TEP, morbidly obese patients were five times more likely to require an additional dose compared to non-morbidly obese when SDR-MTX capped at 100 mg was used for medical management.

  13. 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.

  14. Study on the therapeutic effect of small dose of estradiol and progesterone on post-menopausal osteoporosis

    International Nuclear Information System (INIS)

    Li Wenqi; Li Xin; Zhou Jiwen; Zhou Zhengli

    2004-01-01

    Objective: To explore the therapeutic effect and possible adverse side-effects of small dose of estradiol and progesterone on postmenopausal osteoporosis. Methods: Applying a GBD-928 mono-photon BMD radiometer, 68 women (past-menopausal over 3 years, age 52-59, body weight index 2 0.5 mg with MPA (medroxyprogesterone acetate) 0.5 mg daily. The medication laster for a whole years and BMD value was measured again. All subjects underwent gynecological physical examination, vaginal sonography, vaginal smear study and breast examination with infra-red ray both before and after the test period. Results: After one year medication, mean value of BMD in Group A was 0.49 ± 0.05, three percentage points higher than before. In Group B, this was 0.52 ± 0.06, another three percentage points higher. Ten Women with mild lobular hyperplasia and nine women with small uterine myoma ( 3 ) were all allocated to the hormone treated group. The lesions showed either little change or slight regression after the test period. Conclusion: Osteoporotic women receiving additional small doses of female hormones responded much better than those receiving calcium only. The WHI report which advised against HRT should be more critically studied

  15. Spectral signs of photochemical reactions when blood is exposed in vivo to therapeutic doses of ultraviolet radiation

    Science.gov (United States)

    Zalesskaya, G. A.; Ulashchik, V. S.; Mit'kovskaya, N. P.; Kuchinskii, A. V.; Laskina, O. V.

    2008-05-01

    We have used the absorption spectra of whole blood, erythrocytes, and plasma to study photochemical reactions initiated by exposure of blood in vivo to UV radiation (UV irradiation) in the UV-visible and IR regions of the spectrum. We have established that when blood is exposed to therapeutic doses of UV radiation (0.5 J/cm2), the absorption of blood proteins decreases as monitored using the UV absorption and luminescence bands of the proteins; photochemical reactions are initiated in the protein and heme components of the hemoglobin. For the studied doses, the reversible reaction of photodissociation of hemoglobin complexes with oxygen is one of the most likely primary reactions initiated by UV irradiation of blood. We conclude that changes in the position and relative intensities of the IR absorption bands of the peptide groups (stretching and bending vibrations of NH, CN, and CO bonds) may be due to conformational transitions in the blood protein macromolecules, induced with a change in the intermolecular hydrogen bonds on absorption of the UV radiation by the blood. The changes in the absorption spectra of blood initiated by UV irradiation are compared with the results of laboratory blood analyses.

  16. Single-dose pharmacokinetics and tolerability of oral delta-9- tetrahydrocannabinol in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Joerger, Markus; Wilkins, Justin; Fagagnini, Stefania; Baldinger, Reto; Brenneisen, Rudolf; Schneider, Ursula; Goldman, Bea; Weber, Markus

    2012-06-01

    Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS). We assessed the pharmacokinetics (PK) and tolerability of delta-9-tetrahydrocannabinol (THC) in ALS patients. Nine patients received THC single oral doses of 5mg and 10mg, separated by a wash-out period of two weeks. Blood samples for the determination of THC, 11-nor-9-carboxy-THC (THC-COOH) and hydroxy-THC (THC-OH) were taken up to 8 hours after intake. Adverse events were assessed by visual analogue scales (VAS). Plasma concentrations of the active metabolite THC-OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for THC's cardiovasculatory effects. Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in patients receiving 10mg compared to 5 mg THC. A marked interindividual variability was found for the absorption of oral THC (84%) and elimination of THC-COOH (45%). PK data did not support any clinically relevant deviation from linear PK in the investigated range of concentrations. Plasma concentrations of THC-OH were positively correlated with the individual heart rate. An E(max-model) was successfully fitted to individual heart rate, with a THC-OH plasma concentration of 3.2 x 10(-4) μmol/L for EC(50) and an E(max) of 93 bpm for heart rate. The higher 10mg dose of THC was dose-limiting in patients with ALS. High interindividual PK variability requires individuell titration of THC for potential therapeutic use in patients with ALS.

  17. 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.)

  18. 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.

  19. Single dose pharmacokinetics of the novel transdermal donepezil patch in healthy volunteers.

    Science.gov (United States)

    Kim, Yo Han; Choi, Hee Youn; Lim, Hyeong-Seok; Lee, Shi Hyang; Jeon, Hae Sun; Hong, Donghyun; Kim, Seong Su; Choi, Young Kweon; Bae, Kyun-Seop

    2015-01-01

    Donepezil is an acetylcholinesterase inhibitor indicated for Alzheimer's disease. The aim of this randomized, single-blind, placebo-controlled, single-dose, dose-escalation study was to investigate the safety, tolerability, and pharmacokinetics of the donepezil patch in healthy male subjects. Each healthy male subject received a single transdermal donepezil patch (72 hours patch-on periods) of 43.75 mg/12.5 cm(2), 87.5 mg/25 cm(2), or 175 mg/50 cm(2). Serial blood samples were collected up to 312 hours after patch application. The plasma concentrations of donepezil were determined by using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were obtained by noncompartmental analysis. Tolerability of the patches and performance of the patches (adhesion, skin irritation, residual donepezil content in the patch) were assessed throughout the study. The study was completed by 36 healthy subjects. After patch application, the maximal plasma donepezil concentration (Cmax) and the area under the curve (AUC) increased in a dose-proportional manner. Median time to Cmax was ~74-76 hours (~2-4 hours after patch removal), and mean t1/2β was ~63.77-93.07 hours. The average donepezil residue in the patch after 72 hours was ~73.9%-86.7% of the loading dose. There were neither serious adverse events nor adverse events that lead to discontinuation. Skin adhesion of the patch was good in 97.2% of the subjects. All skin irritations after patch removal were mild and were resolved during the study period. The donepezil patch appeared to be generally well tolerated and adhesive. Pharmacokinetic analysis of the donepezil patch demonstrated linear kinetics.

  20. Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission.

    Science.gov (United States)

    Chi, Benjamin H; Chintu, Namwinga; Cantrell, Ronald A; Kankasa, Chipepo; Kruse, Gina; Mbewe, Felistas; Sinkala, Moses; Smith, Peter J; Stringer, Elizabeth M; Stringer, Jeffrey S A

    2008-06-01

    To determine the impact of adjuvant single-dose peripartum tenofovir/emtricitabine (TDF/FTC) on intrapartum/early postpartum HIV transmission. In the setting of routine short-course zidovudine (ZDV) and peripartum nevirapine (NVP) for perinatal HIV prevention, participants were randomized to single-dose TDF (300 mg)/FTC (200 mg) or to no intervention in labor. Six-week infant HIV infection was compared according to actual-use drug regimens. Of 397 women randomized, 355 (89%) had infants who were alive and active at 6 weeks postpartum. Of these, 18 (5.1%) were infected in utero and 6 (1.8%) were infected intrapartum/early postpartum. Among the 243 who used ZDV and NVP, intrapartum/early postpartum transmission was not reduced among infants whose mothers received TDF/FTC compared with those who did not (2 of 123 [1.6%] vs. 3 of 109 [2.8%]; P = 0.67). Among the 49 infants whose mothers did not receive antenatal ZDV but who had confirmed NVP ingestion, transmission similarly did not differ (0 of 19 [0%] vs. 1 of 26 [3.4%]). TDF/FTC was not significantly associated with reduced overall transmission (odds ratio [OR] = 0.7, 95% confidence interval [CI]: 0.3 to 1.6), even when other antiretroviral drugs were considered (adjusted OR = 0.8, 95% CI: 0.3 to 1.8). Adjuvant peripartum single-dose TDF/FTC did not reduce perinatal transmission. Whether a higher dose might be effective remains unknown but should be studied in settings in which NVP is used without antenatal ZDV.

  1. Single-dose oral naproxen for acute postoperative pain: a quantitative systematic review

    Directory of Open Access Journals (Sweden)

    Moore R Andrew

    2003-09-01

    Full Text Available Abstract Background Naproxen and naproxen sodium are non-steroidal anti-inflammatory drugs used in a variety of painful conditions, including the treatment of postoperative pain. This review aims to assess the efficacy, safety and duration of action of a single oral dose of naproxen/naproxen sodium for moderate to severe acute postoperative pain in adults, compared with placebo. Methods The Cochrane Library (issue 4 2002, EMBASE, PubMed, MEDLINE and an in-house database were searched for randomised, double blind, placebo controlled trials of a single dose of orally administered naproxen or naproxen sodium in adults with acute postoperative pain. Pain relief or pain intensity data were extracted and converted into dichotomous information to give the number of patients with at least 50% pain relief over 4 to 6 hours. Relative benefit and number-needed-to-treat were then calculated. The percentage of patients with any adverse event, number-needed-to-harm, and time to remedication were also calculated. Results Ten trials with 996 patients in met the inclusion criteria. Six trials compared naproxen sodium 550 mg (252 patients with placebo (248 patients; the NNT for at least 50% pain relief over six hours was 2.6 (95% confidence interval 2.2 to 3.2. There was no significant difference between the number of patients experiencing any adverse event on treatment compared with placebo. Weighted mean time to remedication was 7.6 hours for naproxen sodium 550 mg (206 patients and 2.6 hours for placebo (205 patients. Four other trials used lower doses. Conclusion A single oral dose of naproxen sodium 550 mg is an effective analgesic in the treatment of acute postoperative pain. A low incidence of adverse events was found, although these were not reported consistently.

  2. Single low doses of MPTP decrease tyrosine hydroxylase expression in the absence of overt neuron loss.

    Science.gov (United States)

    Alam, Gelareh; Edler, Melissa; Burchfield, Shelbie; Richardson, Jason R

    2017-05-01

    Parkinson's disease (PD) is the second most common age-related neurodegenerative disease. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a prototypical neurotoxicant used in mice to mimic primary features of PD pathology including striatal dopamine depletion and dopamine neuron loss in the substantia nigra pars compacta (SNc). In the literature, there are several experimental paradigms involving multiple doses of MPTP that are used to elicit dopamine neuron loss. However, a recent study reported that a single low dose caused significant loss of dopamine neurons. Here, we determined the effect of a single intraperitoneal injection of one of three doses of MPTP (0.1, 2 and 20mg/kg) on dopamine neurons, labeled by tyrosine hydroxylase (TH + ), and total neuron number (Nissl + ) in the SNc using unbiased stereological counting. Data reveal a significant loss of neurons in the SNc (TH + and Nissl + ) only in the group treated with 20mg/kg MPTP. Groups treated with lower dose of MPTP (0.1 and 2mg/kg) only showed significant loss of TH + neurons rather than TH + and Nissl + neurons. Striatal dopamine levels were decreased in the groups treated with 2 and 20mg/kg MPTP and striatal terminal markers including, TH and the dopamine transporter (DAT), were only decreased in the groups treated with 20mg/kg MPTP. These data demonstrate that lower doses of MPTP likely result in loss of TH expression rather than actual dopamine neuron loss in the SN. This finding reinforces the need to measure both total neuron number along with TH + cells in determining dopamine neuron loss. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Single- and repeated-dose toxicities of aloe fermentation products in rats

    Science.gov (United States)

    Kim, Hyun-Kyoung; Baik, Soon-Ok; Choi, Soo-Young; Lee, Jae-Young

    2011-01-01

    In this study, aloe fermentation products were derived from mycelia from 3 mushrooms: Ganoderma lucidum (AG), Hericium erinaceum (AH), and Phellinus linteus (AP). Levels of aloin A and B increased with fermentation time. The highest levels were measured on the fifth day of fermentation. β-Glucan levels decreased with fermentation time. The safety of aloe fermentation products were examined in male and female Sprague-Dawley rats. Rats were orally administered the three aloe fermentation products at dose levels of 1, 2 or 5 g/kg for single-dose toxicity test and 0.5, 1, or 2 g/kg for repeated-dose toxicity test. There were no significant differences in body weight gain between vehicle control and AG-, AH- or AP-treated rats. Also, significant changes in daily feed intake and water consumption were not observed. In hematological analysis, none of the parameters were affected by aloe fermentation products with mushroom mycelia. This suggests that there are no negative effects on homeostasis and immunity. In blood biochemistry analysis, none of the markers were affected by feeding rats with AG, AH or AP. Similarly, there were no significant effects on markers for liver, kidney, skeletal and heart muscle functions. No remarkable lesions were observed in these organs at histopathology. Since there were no adverse effects of AG, AH and AP in single- or repeated-dose toxicity tests, even at higher doses than normal, we conclude that the aloe fermentation products with mushroom mycelia possess long-term safety and could be candidates as multifunctional nutrients for the improvement of intestinal function and immunity. PMID:21998613

  4. 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

  5. Single dose antibiotic therapy is not as effective as conventional regimens for management of acute urinary tract infections in children.

    Science.gov (United States)

    Madrigal, G; Odio, C M; Mohs, E; Guevara, J; McCracken, G H

    1988-05-01

    One hundred thirty-two children with acute urinary tract infection were randomly assigned to receive trimethoprim-sulfamethoxazole in one dose, two doses daily for 3 days or two doses daily for 7 days. The patient characteristics, etiologic agents and frequency of roentgenologic abnormalities were similar for the three treatment groups. There was no significant difference in bacteriologic cure rates for the single dose regimen (93%) and multidose regimens (96%). The difference in rates of recurrent urinary tract infection between the single dose (20.5%) and 3-day (5.6%) and 7-day (8%) regimens was statistically significant (P = 0.033). A single dose of trimethoprim-sulfamethoxazole is inadequate treatment for infants and children with acute urinary tract infection.

  6. Pharmacokinetics of Roflumilast and Its Active Metabolite Roflumilast N-Oxide in Healthy Chinese Subjects After Single and Multiple Oral Doses.

    Science.gov (United States)

    Li, Qian; Wang, Yiya; Liu, Lingye; Ma, Pengcheng; Ding, Li

    2017-06-01

    Roflumilast is a selective, oral phosphodiesterase 4 inhibitor approved for the treatment of severe chronic obstructive pulmonary disease. The aim of this study was to evaluate the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy Chinese subjects, and the effects of gender and food on their respective pharmacokinetic profiles. 36 healthy Chinese subjects were recruited in a randomized, single-center, open-label, parallel group study and assigned to 0.25-, 0.375-, and 0.5-mg dose groups. The single-dose pharmacokinetic studies in fasting condition were carried out in all groups. Moreover, the food effect study and multiple-dose study were conducted in 0.375-mg dose group. Serial blood samples were collected over 168 h after dosing, and plasma concentrations of roflumilast and roflumilast N-oxide were determined using a validated LC-MS/MS method. After oral administration of single doses of 0.25, 0.375 and 0.5 mg of roflumilast under fasting condition, the mean AUC 0-72h for roflumilast was 21.7 ± 8.3, 29.8 ± 8.3 and 54.2 ± 21.3 ng·h/mL, respectively. Meanwhile the mean AUC 0-168h for roflumilast N-oxide was 290 ± 103, 385 ± 107 and 673 ± 245 ng·h/mL, respectively. In the steady state after the multi-dose administration, the exposure to roflumilast in the subjects increased 20-40 %, and the exposure to roflumilast N-oxide increased about 169 %, compared to the single-dose administration. No statistically significant effect of gender on the disposition of roflumilast and roflumilast N-oxide was observed. Food had no effect on systemic exposure to roflumilast and roflumilast N-oxide in the subjects, but delayed the T max of roflumilast by 0.9 h and reduced the C max of roflumilast by approximately 20 %. Based upon between-study comparison, peak and systemic exposure of roflumilast and roflumilast N-oxide were higher in Chinese than that in Caucasian subjects after oral administration of the same dose (i.e., 0.25 and 0.5

  7. 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)

  8. Pharmacokinetics of a single subcutaneous dose of sustained release buprenorphine in northern elephant seals (Mirounga angustirostris).

    Science.gov (United States)

    Molter, Christine M; Barbosa, Lorraine; Johnson, Shawn; Knych, Heather K; Chinnadurai, Sathya K; Wack, Raymund F

    2015-03-01

    Information regarding analgesics in pinnipeds is limited. This study aimed to establish the pharmacokinetic parameters of a single subcutaneous dose of sustained release buprenorphine (Buprenorphine SR) in juvenile northern elephant seals (Mirounga angustirostris) with regard to its potential to provide long-lasting analgesia that requires infrequent dosing. Seals (n=26) were administered a single dose of sustained release buprenorphine at 0.12 mg/kg s.c. Blood samples were collected from the extradural intervertebral vein at 0 hr and at three or four of the following time points: 0.5, 1, 2, 6, 12, 24, 36, 48, 60, 96, 120, and 144 hr. Seals were examined daily for systemic and local adverse reactions. Plasma was analyzed by liquid chromatography tandem-mass spectrometry for buprenorphine and norbuprenorphine concentrations. A noncompartmental analysis for pharmacokinetic parameters was calculated using standard methods and equations. An average maximum concentration of 1.21 ng/ml (0.3-2.9 ng/ml) was detected 12 hr postadministration. Concentrations were quantifiable up to 144 hr postadministration but were below those expected to provide analgesia in some other species. No systemic adverse effects were noted in healthy seals receiving sustained release buprenorphine. Cellulitis or abscesses at the injection site were observed in 6/26 (23%) seals between 24 and 168 hr postadministration. Adverse local effects suggest that this drug should be used with caution in northern elephant seals.

  9. A study of the effects of therapeutic doses of ionizing radiation in vitro on Lactobacillus isolates originating from the vagina - a pilot study

    OpenAIRE

    Gosiewski, Tomasz; Mr?z, Tomasz; Ocho?ska, Dorota; Pabian, Wojciech; Bulanda, Malgorzata; Brzychczy-Wloch, Monika

    2016-01-01

    Background Ionizing radiation is used as a therapeutic option in the treatment of certain neoplastic lesions located, among others, in the pelvic region. The therapeutic doses of radiation employed often result in adverse effects manifesting themselves primarily in the form of genital tract infections in patients or diarrhea. The data available in the literature indicate disorders in the microbial ecosystem caused by ionizing radiation, which leads to the problems mentioned above. In the pres...

  10. Single Dose Trivalent Vesiculovax Vaccine Protects Macaques from Lethal Ebolavirus and Marburgvirus Challenge.

    Science.gov (United States)

    Matassov, Demetrius; Mire, Chad E; Latham, Theresa; Geisbert, Joan B; Xu, Rong; Ota-Setlik, Ayuko; Agans, Krystle N; Kobs, Dean J; Wendling, Morgan Q S; Burnaugh, Amanda; Rudge, Thomas L; Sabourin, Carol L; Egan, Michael A; Clarke, David K; Geisbert, Thomas W; Eldridge, John H

    2017-11-15

    Previous studies demonstrated that a single intramuscular (IM) dose of an attenuated vesicular stomatitis virus vector (Vesiculovax™, rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of Zaire ebolavirus (EBOV) protected nonhuman primates (NHP) from lethal challenge with EBOV Kikwit and Makona strains. Here we studied the immunogenicity of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies an optimal attenuated tri-valent rVSV vector formulation was identified which included rVSV vectors expressing EBOV , Sudan ebolavirus (SUDV) or Angola strain of Marburg marburgvirus (MARV) GPs. NHPs were then vaccinated with a single dose of the tri-valent formulation, followed by lethal challenge 28 days later with each of the three corresponding filoviruses. At day 14 post vaccination, a serum IgG response specific for all three GPs was detected in all vaccinated macaques. A modest and balanced cell-mediated immune response specific for each GP protein was also detected in a majority of vaccinated macaques. No matter the level of total GP-specific immune response detected post vaccination, all vaccinated macaques were protected from disease and death following lethal challenge with each of the three filoviruses. These findings indicate that vaccination with a single dose of attenuated rVSV-N4CT1 vectors each expressing a single filovirus GP may provide protection against those filoviruses most commonly responsible for outbreaks of hemorrhagic fever in sub-Saharan Africa. IMPORTANCE The West African Ebola Zaire outbreak in 2013 showed that this disease was not only a regional concern, but a worldwide problem and highlighted the need for a safe and efficacious vaccine to be administered to the populace. However, other endemic pathogens like Ebola Sudan and Marburg also pose an important health risk to the public and therefore require development of a vaccine prior to the occurrence of an outbreak

  11. Increased Excretion of C4-Carnitine Species after a Therapeutic Acetylsalicylic Acid Dose: Evidence for an Inhibitory Effect on Short-Chain Fatty Acid Metabolism

    Science.gov (United States)

    Mels, Catharina M. C.; Jansen van Rensburg, Peet; van der Westhuizen, Francois H.; Pretorius, Pieter J.; Erasmus, Elardus

    2011-01-01

    Acetylsalicylic acid and/or its metabolites are implicated to have various effects on metabolism and, especially, on mitochondrial function. These effects include both inhibitory and stimulatory effects. We investigated the effect of both combined and separate oral acetylsalicylic acid and acetaminophen administration at therapeutic doses on the urinary metabolite profile of human subjects. In this paper, we provided in vivo evidence, in human subjects, of a statistically significant increase in isobutyrylcarnitine after the administration of a therapeutic dose of acetylsalicylic acid. We, therefore, propose an inhibitory effect of acetylsalicylic acid on the short-chain fatty acid metabolism, possibly at the level of isobutyryl-CoA dehydrogenase. PMID:22084721

  12. Low-Dose Liver-Targeted Gene Therapy for Pompe Disease Enhances Therapeutic Efficacy of ERT via Immune Tolerance Induction

    Directory of Open Access Journals (Sweden)

    Sang-oh Han

    2017-03-01

    Full Text Available Pompe disease results from acid α-glucosidase (GAA deficiency, and enzyme replacement therapy (ERT with recombinant human (rh GAA has clinical benefits, although its limitations include the short half-life of GAA and the formation of antibody responses. The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV vector containing a liver-specific promoter. GAA knockout (KO mice were administered either a weekly injection of rhGAA (20 mg/kg or a single injection of AAV2/8-LSPhGAA (8 × 1011 vector genomes [vg]/kg. Both treatments significantly reduced glycogen content of the heart and diaphragm. Although ERT triggered anti-GAA antibody formation, there was no detectable antibody response following AAV vector administration. The efficacy of three lower dosages of AAV2/8-LSPhGAA was evaluated in GAA-KO mice, either alone or in combination with ERT. The minimum effective dose (MED identified was 8 × 1010 vg/kg to reduce glycogen content in the heart and diaphragm of GAA-KO mice. A 3-fold higher dose was required to suppress antibody responses to ERT. Efficacy from liver gene therapy was slightly greater in male mice than in female mice. Vector dose correlated inversely with anti-GAA antibody formation, whereas higher vector doses suppressed previously formed anti-GAA antibodies as late as 25 weeks after the start of ERT and achieved biochemical correction of glycogen accumulation. In conclusion, we identified the MED for effective AAV2/8-LSPhGAA-mediated tolerogenic gene therapy in Pompe disease mice.

  13. 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

  14. Thymic uptake after high dose I131 treatment in patients with differentiated thyroid carcinoma: interpretation and therapeutical management

    International Nuclear Information System (INIS)

    Borbon Arce, M.; Cambil Molina, T.; Martin Hernandez, T.; La Cinta Calvo Moron, M. de; La Riva Perez, P. de; Hernandez Herrero, C.; Castro Montano, J.

    2015-01-01

    Full text of publication follows. Aim: I 131 is a very important for initial staging, treatment and monitoring of differentiated thyroid carcinoma after a total thyroidectomy. Doubtful uptake foci may appear due to physiological tracer distribution or true concomitant pathology. Increased functional activity of the thymus may be physiological in children and adolescents. In adults is associated with thymic hyperplasia, primary neoplasms, metastases, inflammatory processes or even in normal parenchyma. Thymic uptake after high dose radioiodine treatment is frequent in young adults and deciding the need of additional therapy is difficult in some cases. Materials and methods: we present 5 cases of female patients with a mean age of 36.6 years(24-43), which were treated with a mean dose of 106 mCi of I 131 (100-150 mCi) that showed tracer uptake in the thymic area. A blind therapeutic dose of I 131 was administered to 3 patients due to high Tg levels. In the remaining two, one corresponds to a 131 I-WBS (Whole Body Scan) after remnants ablation treatment and the remaining one to a 131 I-WBS after a treatment dose given for lymph node metastases. The 131 I-WBS was performed 7 days after treatment. Conventional anterior and posterior planar images and SPECT / CT of head, neck and upper mediastinum were performed in all patients. Tg levels were measured with and without hormone replacement therapy in all cases. In every case thymic samples were sent to pathology for analysis. Results: in one patient an elective total thymectomy was performed due to the macroscopic appearance and the prominent tracer uptake. In a second one also a total thymectomy was decided due to the intense tracer uptake and because the patient was catalogued as high risk and had history of several bilateral lung metastases on a previous 131 I-WBS which disappeared. In the remaining three, non additional invasive procedure was considered due to the normal previous pathology reports of the thymus

  15. Blockade of leukotriene production by a single oral dose of MK-0591 in active ulcerative colitis

    DEFF Research Database (Denmark)

    Hillingsø, Jens; Kjeldsen, J; Laursen, L S

    1995-01-01

    -ethyl)thio)-5(quinolin+ ++-2ylmethyl-oxy)-1H-indol-2yl)-2,2-dimethyl-propanoate) exerts its effect by binding to the 5-lipoxygenase activating protein, thereby inhibiting the translocation and activation of 5-lipoxygenase. METHODS: Concentrations of leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) in rectal...... that a single oral 250 mg dose of MK-0591 results in nearly complete blockade of systemic leukotriene production and LTB4 formation in the target tissue of inflammation (the rectum). Controlled multiple-dose trials to assess the clinical efficacy of this novel 5-lipoxygenase-activating protein inhibitor seem......BACKGROUND: 5-Lipoxygenase products of arachidonic acid metabolism are thought to play a central role in the secondary amplification of the inflammatory response in a number of human inflammatory diseases, such as ulcerative colitis. MK-0591 (3-(1((4-chlorophenyl)methyl)-3((1,1-dimethyl...

  16. 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.

  17. Medical management of ectopic pregnancy with single-dose and 2-dose methotrexate protocols: human chorionic gonadotropin trends and patient outcomes.

    Science.gov (United States)

    Mergenthal, Michelle C; Senapati, Suneeta; Zee, Jarcy; Allen-Taylor, Lynne; Whittaker, Paul G; Takacs, Peter; Sammel, Mary D; Barnhart, Kurt T

    2016-11-01

    Ectopic pregnancy, although rare, is an important cause of female morbidity and mortality and early, effective treatment is critical. Systemic methotrexate has become widely accepted as a safe and effective alternative to surgery in the stable patient. As the number and timing of methotrexate doses differ in the 3 main medical treatment regimens, one might expect trends in serum human chorionic gonadotropin and time to resolution to vary depending on protocol. Furthermore, human chorionic gonadotropin trends and time to resolution may predict ultimate treatment success. This study hypothesized that the 2-dose methotrexate protocol would be associated with a faster initial decline in serum human chorionic gonadotropin levels and a shorter time to resolution compared to the single-dose protocol. A prospective multicenter cohort study included clinical data from women who received medical management for ectopic pregnancy. Rates of human chorionic gonadotropin change and successful pregnancy resolution were assessed. Propensity score modeling addressed confounding by indication, the potential for differential assignment of patients with better prognosis to the single-dose methotrexate protocol. In all, 162 ectopic pregnancies were in the final analysis; 114 (70%) were treated with the single-dose methotrexate and 48 (30%) with the 2-dose protocol. Site, race, ethnicity, and reported pain level were associated with differential protocol allocation (P ectopic rupture than those getting the 2-dose protocol. A prospective randomized controlled design is needed to remove confounding by indication. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Comparative assessment of single-dose and fractionated boron neutron capture therapy

    International Nuclear Information System (INIS)

    Coderre, J.A.; Micca, P.L.; Fisher, C.D.

    1995-01-01

    The effects of fractionating boron neutron capture therapy (BNCT) were evaluated in the intracerebral rat 9L gliosarcoma and rat spinal cord models using the Brookhaven Medical Research Reactor (BMRR) thermal neutron beam. The amino acid analog p-boronophenylalanine (BPA) was administered prior to each exposure to the thermal neutron beam. The total physical absorbed dose to the tumor during BNCT using BPA was 91% high-linear energy transfer (LET) radiation. Two tumor doses of 5.2 Gy spaced 48 h apart (n = 14) or three tumor doses of 5.2 Gy, each separated by 48 h (n = 10), produced 50 and 60% long-term (>1 year) survivors, respectively. The outcome of neither the two nor the three fractions of radiation was statistically different from that of the corresponding single-fraction group. In the rat spinal cord, the ED 50 for radiation myelopathy (as indicated by limb paralysis within 7 months) after exposure to the thermal beam alone was 13.6 ± 0.4 Gy. Dividing the beam-only irradiation into two or four consecutive daily fractions increased the ED 50 to 14.7 ± 0.2 Gy and 15.5 ± 0.4 Gy, respectively. Thermal neutron irradiation in the presence of BPA resulted in an ED 50 for myelopathy of 13.8 ± 0.6 Gy after a single fraction and 14.9 ± 0.9 Gy after two fractions. An increase in the number of fractions to four resulted in an ED 50 of 14.3 ± 0.6 Gy. The total physical absorbed dose to the blood in the vasculature of the spinal cord during BNCT using BPA was 80% high-LET radiation. It was observed that fractionation was of minor significance in the amelioration of damage to the normal central nervous system in the rat after boron neutron capture irradiation. 30 refs., 5 figs., 3 tabs

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

    Directory of Open Access Journals (Sweden)

    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.

  20. 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.)

  1. Efficacy of single-dose 500 mg mebendazole in soil-transmitted helminth infections: a review.

    Science.gov (United States)

    Mrus, J; Baeten, B; Engelen, M; Silber, S A

    2018-05-01

    Soil-transmitted helminthiasis (STH) is caused by Ascaris lumbricoides (roundworm), Trichuris trichiura (whipworm), and Ancylostoma duodenale and Necator americanus (hookworms). Mebendazole is one of the recommended preventive chemotherapy agents for STH. This review summarizes the efficacy data from 29 studies with single-dose 500 mg mebendazole in STH treatment and compares the results with those of a recently conducted phase 3 study of a 500 mg mebendazole chewable tablet against A. lumbricoides and T. trichiura infections. Studies that reported efficacy results against at least one STH infection were selected from the literature and efficacy data by each STH type were abstracted and pooled. Single-dose 500 mg mebendazole treatment resulted in a cure rate of 92.6% (range: 72.5-100%) for A. lumbricoides, 27.6% (range: 8.4-100%) for T. trichiura and 25.5% (range: 2.9-91.1%) for hookworms. Egg reduction rate for A. lumbricoides was 97.9% (range: 89.8-100%), for T. trichiura it was 72.9% (range: 31.6-93.0%) and for hookworms it was 72.0% (range: -6.5% (denoting an increase in egg count) to 98.3%). Similar results were observed in the studies that were placebo-controlled. In the phase 3 study, the cure rate and egg reduction rate reported was 83.7% and 97.9%, respectively, for A. lumbricoides and 33.9% and 59.7%, respectively, for T. trichiura. In conclusion, single-dose 500 mg mebendazole showed a high cure rate against A. lumbricoides and a substantial reduction in faecal egg count for all STH types. These results are consistent with the recently conducted phase 3 study of a new 500 mg chewable mebendazole tablet.

  2. Prolonged efficacy of a single dose of the bisphosphonate zoledronic acid.

    Science.gov (United States)

    Brown, Janet E; Ellis, Susan P; Lester, James E; Gutcher, Sandra; Khanna, Tina; Purohit, Om-Prakesh; McCloskey, Eugene; Coleman, Robert E

    2007-09-15

    Bisphosphonates play a central role in the management of bone loss due to a range of disorders, including metastatic bone disease, cancer treatment-induced bone loss, and postmenopausal osteoporosis. With potent bisphosphonates, such as zoledronic acid, it may be possible to maintain efficacy with relatively infrequent administration. Sixty-six patients who were osteopenic at >1 year following curative cancer therapy received a single i.v. 4 mg dose of the bisphosphonate zoledronic acid. Bone mineral density (BMD) was measured using double-beam X-ray absorptiometry scan and the bone resorption marker N-telopeptide of type II collagen was determined using a chemiluminescence ELISA assay. The single dose of zoledronic acid induced mean increases in bone BMD at the lumbar spine of 3.1%, 5.2%, and 5.3% and at the total hip of 2.7%, 3.5%, and 4.3% after 12, 24, and 36 months of follow-up, respectively (P < 0.001 at all time points). By 36 months, 84% of patients had achieved increase in BMD at the spine and 90% at the hip. The mean percentage decrease in the bone resorption marker N-telopeptide was approximately 58% at 6 weeks and 42%, 33%, and 31% at 12, 24, and 36 months, respectively (P < 0.001). A single dose of zoledronic acid in patients with low BMD results in a sustained increase in BMD and a corresponding decrease in bone resorption. Very infrequent administration of zoledronic acid may have clinical benefits in terms of convenience, reduced toxicity, improved compliance, and cost.

  3. Tiagabine adjunctive therapy in children with refractory epilepsy: a single-blind dose escalating study.

    Science.gov (United States)

    Uldall, P; Bulteau, C; Pedersen, S A; Dulac, O; Lyby, K

    2000-12-01

    Tiagabine, a specific gamma-aminobutyric acid-uptake inhibitor, has been shown to be reasonably well tolerated and efficacious as adjunctive treatment for partial seizures in adults and is now being investigated in children. This 4-month, single-blind study evaluated the tolerability, safety and preliminary efficacy of ascending doses (0.25-1.5 mg/kg/day) of tiagabine add-on therapy in 52 children over the age of 2 years with different syndromes of refractory epilepsy. Adverse events, mostly mild to moderate, were reported by 39% of children during the single-blind placebo period and by 83% of children during tiagabine treatment. The events predominantly affected the nervous system with asthenia (19%), nervousness (19%), dizziness (17%) and somnolence (17%) being the most common. Only three children (6%) withdrew because of adverse events. Tiagabine appeared to reduce seizures more in localisation-related epilepsy syndromes than in generalised epilepsy syndromes. Twenty-three patients with localisation-related epilepsy syndromes were included and 17 of these patients entered the fourth dosing period. The 17 patients had a median reduction of seizure rate in the fourth month of treatment of 33% compared with baseline. In comparison, 13 of 22 children with seven different generalised epilepsy syndromes entered the fourth dosing period with a median change of seizure rate of 0%. Two patients experienced single episodes of status epilepticus during treatment; both cases resolved. Tiagabine showed efficacy mainly in localisation-related syndromes and was well tolerated by most children in a group of very refractory patients and warrants further study in children with epilepsy.

  4. Economic analysis of the single-dose immunization strategy against hepatitis A in Argentina.

    Science.gov (United States)

    Vizzotti, C; Pippo, T; Urueña, A; Altuna, J; Palópoli, G; Hernández, M L; Artola, M F; Fernández, H; Orellano, P; Cañero-Velasco, M C; Ciocca, M; Ramonet, M; Diosque, M

    2015-05-07

    Vaccination against hepatitis A (HA) was carried out only as part of a limited outbreak control strategy in Argentina until June 2005, when universal immunization in infants was introduced into the national immunization calendar. A single-dose strategy was chosen instead of the standard two-dose schedule used elsewhere. This study aimed to estimate preventive, medical, and non-medical costs related to HA and to compare these costs in the periods before and after mass vaccination. A retrospective analysis estimated treatment costs of HA and unspecified hepatitis cases reported to the National Health Surveillance System from 2000 to 2010. Costs related to immunization, fulminant hepatitis (FH), liver transplantation, and death were projected as well. Using a social perspective and a healthcare system perspective, costs in two 5-year periods were compared: 2000-2004 versus 2006-2010. Finally, we evaluated the impact of different discount rates, FH risk, and exclusion of unspecified hepatitis cases in the sensitivity analysis. Total HA and unspecified hepatitis cases decreased from 157,871 in 2000-2004 to 17,784 in 2006-2010. Medical and non-medical costs decreased from US$11,811,600 and US$30,118,222 to US$1,252,694 and US$4,995,895 in those periods, respectively. Immunization costs increased from US$6,506,711 to US$40,912,132. Total preventive, medical, and non-medical costs decreased from US$48,436,534 to US$47,160,721, representing a 2.6% reduction in total costs between the two periods. When a healthcare system perspective was considered or unspecified hepatitis cases were excluded, total costs were 130.2% and 30.8% higher in 2006-2010 than in the previous period, respectively. After implementation of the universal single-dose vaccination against HA in infants in Argentina, an impressive decline was observed in HA cases, with a decrease in medical and non-medical costs in the first 5 years. The single-dose strategy, which is simpler and less expensive than the

  5. 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.

  6. 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

  7. 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...

  8. Carcinogenesis by a single dose of N-methyl-N-formylhydrazine.

    Science.gov (United States)

    Toth, B; Patil, K

    1980-05-01

    Single sc injections of N-methyl-N-formylhydrazine were given to randomly bred Swiss mice. The females received 180 micrograms per gram of body weight, while two groups of males were treated with either 120 or 100 micrograms per gram of body weight. The treatment resulted in induction of tumors of lungs with an incidence of 40% in the females. In males treated with the higher and lower doses, the incidences of preputial gland tumors were 12 and 12%, respectively. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of lungs, squamous cell papillomas, and carcinomas of preputial glands. N-Methyl-N-formylhydrazine is a constituent of the edible wild false morel mushroom Gyromitra esculenta, to which the human population is exposed in measurable quantities, sometimes at a single meal.

  9. 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.

  10. Transversus Abdominis Plane Blocks with Single-Dose Liposomal Bupivacaine in Conjunction with a Nonnarcotic Pain Regimen Help Reduce Length of Stay following Abdominally Based Microsurgical Breast Reconstruction.

    Science.gov (United States)

    Jablonka, Eric M; Lamelas, Andreas M; Kim, Julie N; Molina, Bianca; Molina, Nathan; Okwali, Michelle; Samson, William; Sultan, Mark R; Dayan, Joseph H; Smith, Mark L

    2017-08-01

    Side effects associated with use of postoperative narcotics for pain control can delay recovery after abdominally based microsurgical breast reconstruction. The authors evaluated a nonnarcotic pain control regimen in conjunction with bilateral transversus abdominis plane blocks on facilitating early hospital discharge. A retrospective analysis was performed of consecutive patients who underwent breast reconstruction using abdominally based free flaps, with or without being included in a nonnarcotic protocol using intraoperative transversus abdominis plane blockade. During this period, the use of locoregional analgesia evolved from none (control), to continuous bupivacaine infusion transversus abdominis plane and catheters, to single-dose transversus abdominis plane blockade with liposomal bupivacaine solution. Demographic factors, length of stay, inpatient opioid consumption, and complications were reported for all three groups. One hundred twenty-eight consecutive patients (182 flaps) were identified. Forty patients (62 flaps) were in the infusion-liposomal bupivacaine group, 48 (66 flaps) were in the single-dose blockade-catheter group, and 40 (54 flaps) were in the control group. The infusion-liposomal bupivacaine patients had a significantly shorter hospital stay compared with the single-dose blockade-catheter group (2.65 ± 0.66 versus 3.52 ± 0.92 days; p bupivacaine help facilitate early hospital discharge after abdominally based microsurgical breast reconstruction. A trend toward consistent discharge by postoperative day 2 was seen. This could result in significant cost savings for health care systems. Therapeutic, III.

  11. Wood creosote, the principal active ingredient of seirogan, an herbal antidiarrheal medicine: a single-dose, dose-escalation safety and pharmacokinetic study.

    Science.gov (United States)

    Kuge, Tomoo; Shibata, Takashi; Willett, Michael S

    2003-11-01

    To assess the safety, tolerability and pharmacokinetics of escalating single doses of wood creosote, an herbal antidiarrheal and antispasmodic agent. Randomized, double-blind, placebo-controlled study. Clinical research center. Forty (32 men, 8 women) healthy volunteers aged 19-42 years. By random assignment, 22 men and 8 women received escalating single doses of wood creosote (45, 90, 135, 180, and 225 mg) and 10 men received placebo (for each of the five dose levels, 6 subjects received active substance and 2 subjects received placebo). Vital signs, laboratory tests, and electrocardiograms were assessed; no dose-related or clinically significant changes were noted. Serial blood samples were obtained to determine the pharmacokinetics of four major active components of wood creosote: total (conjugated plus free) guaiacol, creosol, o-cresol, and 4-ethylguaiacol. The most common adverse events were mild headache and dizziness, with no dose-related trends being apparent. Area under the concentration-time curve from time zero to infinity increased in a dose-proportional manner for total guaiacol, creosol, and o-cresol and was not assessed for total 4-ethylguaiacol owing to lack of data at the low dose level. No apparent differences by sex were noted for any of the four active components. All four components were rapidly eliminated. Single oral doses of wood creosote up to 225 mg were safe and well tolerated in healthy men and women. Also, the doses of wood creosote were rapidly absorbed, conjugated, and eliminated. Such a rapid onset and short duration of action would appear desirable in the treatment of acute nonspecific diarrhea.

  12. Low and therapeutic doses of antidepressants are associated with similar response in the context of multimodal treatment of pain.

    Science.gov (United States)

    Bajwa, Zahid H; Simopoulos, Thomas T; Pal, Joshua; Kraemer, Jan J; Chopra, Pradeep; Nagda, Jyotsna V; Najib, Umer; Celestin, James; Sial, Khuram; Ahmad, Bilal; Warfield, Carol; Steinman, Theodore I; Wootton, Joshua

    2009-01-01

    . The data suggest that in the context of multimodal treatment for chronic pain, antidepressant therapy at both low and therapeutic doses demonstrates similar response rates. Tricyclic antidepressants (TCAs), which include secondary and tertiary amines, as well as SSRI/SNRIs and atypicals, all appear to show similar favorable response rates.

  13. The single dose pharmacokinetic profile of a novel oral human parathyroid hormone formulation in healthy postmenopausal women.

    Science.gov (United States)

    Hämmerle, Sibylle P; Mindeholm, Linda; Launonen, Aino; Kiese, Beate; Loeffler, Rolf; Harfst, Evita; Azria, Moise; Arnold, Michel; John, Markus R

    2012-04-01

    Parathyroid hormone (PTH), currently the only marketed anabolic treatment for osteoporosis, is available as the full-length hormone, human PTH1-84, or as the human PTH1-34 fragment (teriparatide). Both must be administered as a daily subcutaneous (sc) injection. A new oral formulation of human PTH1-34 (PTH134) is being developed as a more convenient option for patients. In this single-center, partially-blinded, incomplete cross-over study, the safety, tolerability, and exposure of oral PTH134 (teriparatide combined with 2 different quantities of the absorption enhancer 5-CNAC) were assessed in 32 healthy postmenopausal women. 16 subjects were randomized to receive 4 single doses out of 6 different treatments: placebo, teriparatide 20 μg sc, or 1, 2.5, 5 or 10 mg of oral PTH134 formulated with 200 mg 5-CNAC. Subsequently, another 16 subjects were randomized to receive 4 out of 6 different treatments: placebo, teriparatide 20 μg sc, or 2.5 or 5 mg of oral PTH134 formulated with either 100 or 200 mg 5-CNAC. Doses were given ≥6 days apart. All doses of PTH134 were rapidly absorbed, and showed robust blood concentrations in a dose-dependent manner. Interestingly, PTH1-34 disappeared from blood faster after oral than after sc administration. Specifically, 2.5 and 5 mg PTH134 (containing 200 mg 5-CNAC) demonstrated Cmax and AUC0-last values closest to those of sc teriparatide 20 μg (Forsteo®). Mean+/-SD hPTH134 Cmax values were, respectively, 74+/-59, 138+/-101, 717+/-496, and 1624+/-1579 pg/mL for 1, 2.5, 5, and 10 mg doses of this peptide administered with 200 mg 5-CNAC; while mean+/-SD AUC (0-last) values were, respectively, 30+/-40, 62+/-69, 320+/-269, and 627+/-633 h*pg/mL. The corresponding estimates for teriparatide 20 μg sc were 149+/-35 for Cmax and 236+/-58 for AUC (0-last) Ionized calcium remained within normal limits in all treatment groups except for 3 isolated events. Nine subjects withdrew due to treatment-related AEs. Of those, seven were taking PTH

  14. A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray.

    Science.gov (United States)

    Stott, C G; White, L; Wright, S; Wilbraham, D; Guy, G W

    2013-05-01

    A Phase I study to assess the single and multipledose pharmacokinetics (PKs) and safety and tolerability of oromucosally administered Δ(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, in healthy male subjects. Subjects received either single doses of THC/CBD spray as multiple sprays [2 (5.4 mg THC and 5.0 mg CBD), 4 (10.8 mg THC and 10.0 mg CBD) or 8 (21.6 mg THC and 20.0 mg CBD) daily sprays] or multiple doses of THC/CBD spray (2, 4 or 8 sprays once daily) for nine consecutive days, following fasting for a minimum of 10 h overnight prior to each dosing. Plasma samples were analyzed by gas chromatography-mass spectrometry for CBD, THC, and its primary metabolite 11-hydroxy-THC, and various PK parameters were investigated. Δ(9)-Tetrahydrocannabinol and CBD were rapidly absorbed following single-dose administration. With increasing single and multiple doses of THC/CBD spray, the mean peak plasma concentration (Cmax) increased for all analytes. There was evidence of dose-proportionality in the single but not the multiple dosing data sets. The bioavailability of THC was greater than CBD at single and multiple doses, and there was no evidence of accumulation for any analyte with multiple dosing. Inter-subject variability ranged from moderate to high for all PK parameters in this study. The time to peak plasma concentration (Tmax) was longest for all analytes in the eight spray group, but was similar in the two and four spray groups. THC/CBD spray was well-tolerated in this study and no serious adverse events were reported. The mean Cmax values (<12 ng/mL) recorded in this study were well below those reported in patients who smoked/inhaled cannabis, which is reassuring since elevated Cmax values are linked to significant psychoactivity. There was also no evidence of accumulation on repeated dosing.

  15. 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

  16. Compendium of Single-Event Latchup and Total Ionizing Dose Test Results of Commercial Analog to Digital Converters

    Science.gov (United States)

    Irom, Farokh; Agarwal, Shri G.

    2012-01-01

    This paper reports single-event latchup and total dose results for a variety of analog to digital converters targeted for possible use in NASA spacecraft's. The compendium covers devices tested over the last 15 years.

  17. Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

    Science.gov (United States)

    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.

  18. Effect of a simple two-step warfarin dosing algorithm on anticoagulant control as measured by time in therapeutic range : a pilot study

    NARCIS (Netherlands)

    Kim, Y. -K.; Nieuwlaat, R.; Connolly, S. J.; Schulman, S.; Meijer, K.; Raju, N.; Kaatz, S.; Eikelboom, J. W.

    Background: The efficacy and safety of vitamin K antagonists for the prevention of thromboembolism are dependent on the time for which the International Normalized Ratio (INR) is in the therapeutic range. The objective of our study was to determine the effect of introducing a simple two-step dosing

  19. Blood pressure and heart rate effects following a single dose of bitter orange.

    Science.gov (United States)

    Bui, Linda T; Nguyen, DiemThuy T; Ambrose, Peter J

    2006-01-01

    The ingredients of numerous "ephedra-free" dietary supplements used for weight loss include bitter orange, which contains sympathomimetic alkaloids such as synephrine. Due to the similarity in chemical structure to ephedrine and the potential sympathomimetic effects of synephrine, it is hypothesized that bitter orange may increase blood pressure (BP) and heart rate (HR). To determine the effects on BP and HR after a single dose of bitter orange in healthy adults. In a prospective, randomized, double-blind, placebo-controlled, crossover study, 15 young, healthy, adult subjects received either a single dose of Nature's Way Bitter Orange--a 900 mg dietary supplement extract standardized to 6% synephrine--or matching placebo, with a one week washout period. Systolic BP (SBP), diastolic BP (DBP), and HR were measured at baseline and every hour for 6 hours after administration. SBP after bitter orange was significantly increased versus placebo at hours 1-5 (p bitter orange, DBP after bitter orange was significantly increased versus placebo at hours 4 and 5 (p bitter orange versus placebo for hours 2-5 (p bitter orange versus placebo in young, healthy adults.

  20. The effect of a single dose of morphine on muscle fatigue indices in male rats

    Directory of Open Access Journals (Sweden)

    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.

  1. Single dose intravenous methyl prednisolone versus oral prednisolone in Bell's palsy: A randomized controlled trial

    Science.gov (United States)

    Giri, Prithvi; Garg, Ravindra Kumar; Singh, Maneesh Kumar; Verma, Rajesh; Malhotra, Hardeep Singh; Sharma, Praveen Kumar

    2015-01-01

    Objectives: Corticosteroids have been used in the treatment of Bell's palsy and several other postinfectious neurological conditions. We hypothesized that administration of a single dose of intravenous (IV) methylprednisolone might be an effective alternative to oral prednisolone. Materials and Methods: In this open label, randomized trial, patients with acute Bell's palsy were randomized into two groups. One group received single dose (500 mg) of IV methylprednisolone while the other group received 10 days of oral prednisone. Outcome was assessed at 1 and 3 months with House–Brackmann scale. Results: At 3 months, 93 (79.48%) patients had completely recovered. IV methylprednisolone and oral prednisolone groups had similar recovery rates (80% vs. 78.33%, P > 0.05). Patients with Grade 2 and 3 recovered completely. In patients with Grade 6, the recovery rate was 20%. A better outcome was observed if corticosteroids were administered within 3 days of onset of palsy. Conclusion: Intravenous methylprednisolone and oral prednisolone showed equivalent benefit in patients with acute Bell's palsy. PMID:25878371

  2. Successful comeback of the single-dose live oral cholera vaccine CVD 103-HgR.

    Science.gov (United States)

    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.

  3. Single dose of secnidazole treatment against naturally occuring Giardia duodenalis infection in Sakiz lambs

    Directory of Open Access Journals (Sweden)

    Kerem Ural

    2014-03-01

    Full Text Available Objective. The purposes of this study were to determine whether secnidazole administered at a single dose of 10 mg/kg, orally, lessens or eliminates Giardia cyst shedding, and to validate the benefit of secnidazole treatment on clinical signs and faecal consistency in lambs naturally infected with Giardia duodenalis. Materials and methods. To this extent weaned 12 weeks of age lambs were selected and randomly assigned into two groups based on placebo (group C, n=7 untreated control group or treatment (group S, n=10 lambs treated with a single dose of secnidazole at 10 mg/kg. Results. On days 0 and 10, before and after treatment, respectively, reduction in cyst excretion was determined. The faecal consistency and general health were recorded at each sampling day. Conclusions. During the study there was a high (99.98% reduction in cyst excretion in the secnidazol treatment group compared to the positive control group on day 10, resulting in a significant (p<0.001 reduction, making secnidazole highly effective treatment option.

  4. Effect of single oral dose of tramadol on gastric secretions pH

    Directory of Open Access Journals (Sweden)

    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.

  5. The Success of the Single-Dose Methotrexate Treatment in an Atypical Heterotopic Pregnancy

    Directory of Open Access Journals (Sweden)

    Serdar Başaranoğlu

    2016-06-01

    Full Text Available Heterotopic pregnancy refers to simultaneous presence of intrauterine and ectopic gestational sacs. Its incidence ex­hibits a rising trend due to the increased use of assisted reproductive technology (ART. This paper aims to present a rare case of tubal and cesarean scar heterotopic pregnancy that occurred following a spontaneous pregnancy. The pa­tient presenting with delayed menstruation and abdominal-inguinal pain was evaluated. Transvaginal ultrasonography revealed a gestational sac located in the scar of a previous cesarean section and in the left tubal region corresponding to a gestational age of 4 weeks and 5 days. The patient was hospitalized and informed about conservative and surgi­cal methods. Then, she was administered a single dose of methotrexate 75 mg intramuscularly. Post-operative period included ultrasonographic and laboratory follow-up. In conclusion, it should be remembered that single-dose systemic methotrexate therapy might constitute an alternative to surgery in unruptured hemodynamically stable cases. J Clin Exp Invest 2016; 7 (2: 200-202

  6. 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

  7. Variation with depth of dose distributions in single grains of quartz extracted from an irradiated concrete block

    DEFF Research Database (Denmark)

    Thomsen, Kristina Jørkov; Jain, M.; Bøtter-Jensen, L.

    2003-01-01

    irradiated normal to one face in the laboratory using Cs-137 gamma photons. The OSL dose-depth profile for the irradiated block was determined by measuring the dose distributions from single quartz grains extracted from slices taken across the block and compared with that predicted using Monte Carlo...

  8. Radioeffects on the advanced breast cancer treated preoperatively by a single large dose irradiation method

    International Nuclear Information System (INIS)

    Mikuriya, Shuichi; Konoeda, Koichi; Mikami, Akihiko

    1981-01-01

    A single irradiation with a large electron dose was applied on 26 cases of advanced breast cancer in National Medical Center Hospital. Pertinent voltage from 6 to 20 MeV betatron electron was selected in accordance with tumor sizes. In eight patients, 30 Gy were given at once and other patients were irradiated with fractionated dose from 10 to 20 Gy, two or three times within 2 or 3 weeks (total 28 - 38 Gy). The radioresponse in primary and metastatic lesions was macroscopically, histopathologically and immunologically examined. Direct effects of preoperative irradiation of the primary lesions in 18 out of 24 cases (75%) were relatively remarkable by histopathological examinations. Remarkable cellular infiltrations into tumor nests of primary lesions were observed in 14 out of 24 cases (58%). Abscopal effects on metastatic lymph nodes were observed macroscopically in 7 of 20 cases (35%) and microscopic abscopal effects were seen in 10 of 20 cases (50%). In 6 cases among these ten cases macroscopic abscopal effects were associated with microscopic ones. In tests for cellular immunity, blastoid formation rates of lymphocytes induced by PHA in vitro, lymphocytes and absolute numbers of T-cells in peripheral blood slightly decreased after the irradiation. However, in four kinds of skin tests, enhancements of the response were confirmed. The crude survival rate for 3 years of Stage III cases revealed 83.3% and relative survival rate of these cases was 85.5%. A single large electron dose for the treatment of advanced breast cancer may inhibit the depression of immunoreaction in hosts. (J.P.N.)

  9. Comparison of single-dose and multiple-dose pharmacokinetics between two formulations of hydrocodone bitartrate/acetaminophen: immediate-release versus biphasic immediate- release/extended release

    Directory of Open Access Journals (Sweden)

    Devarakonda K

    2015-09-01

    Full Text Available Krishna Devarakonda,1 Kenneth Kostenbader,2 Michael J Giuliani,3 Jim L Young4 1Department of Clinical Pharmacology, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 2Independent Pharmaceuticals Professional, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA; 3Research and Development, 4Clinical Affairs and Program Management, Mallinckrodt Pharmaceuticals, Hazelwood, MO, USA Objective: This study aimed to compare the single-dose and steady-state pharmacokinetics (PK of biphasic immediate-release (IR/extended-release (ER hydrocodone bitartrate (HB/acetaminophen (APAP and IR HB/APAP. Setting: The study was conducted in a contract research center. Participants: The study included healthy adults. Interventions: In a three-way crossover study, Study 1, participants received the following treatments: (A1 a single dose of IR/ER HB/APAP 7.5/325 mg one tablet, followed by one tablet every 12 hours (q12h; (B1 a single dose of IR/ER HB/APAP 7.5/325 mg two tablets, followed by two tablets q12h; (C1 a single dose of IR HB/APAP 7.5/325 mg two tablets (one tablet at hours 0 and 6, followed by one tablet q6h. In a two-way crossover study, Study 2, participants received the following treatments: (A2 an initial dose of IR/ER HB/APAP 7.5/325 mg three tablets, followed by two tablets q12h; (B2 three doses of IR HB/APAP 7.5/325 mg one tablet q4h, followed by one tablet q6h. Main outcome measures: PK values were compared, and adverse events were assessed. Results: Single-dose and steady-state area under the concentration–time curves for hydrocodone and APAP were similar for IR/ER and IR HB/APAP; the steady-state peak plasma concentrations (Cmax at steady state were also similar, but single-dose Cmax for hydrocodone was lower for IR/ER HB/APAP. For most PK parameters, 90% confidence intervals for geometric least squares mean ratios were not meaningfully different (80%–125%. Steady state was achieved in 2-3 days for IR/ER HB/APAP and in 2 days for IR HB/APAP. Median

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

    Science.gov (United States)

    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.

  11. Single dose oral ibuprofen plus caffeine for acute postoperative pain in adults.

    Science.gov (United States)

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

    2015-07-14

    There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone, and that the drug-specific benefits are essentially additive. This appears to be broadly true in postoperative pain and migraine headache across a range of different drug combinations, and when tested in the same and different trials. Adding caffeine to analgesics also increases the number of people obtaining good pain relief. Combinations of ibuprofen and caffeine are available without prescription in some parts of the world. To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus caffeine for moderate to severe 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), MEDLINE, EMBASE, the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of articles. The date of the most recent search was 1 February 2015. Randomised, double-blind, placebo- or active-controlled clinical trials of single dose oral ibuprofen plus caffeine for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants with at least 50% pain relief over six hours prescribed either ibuprofen plus caffeine or placebo. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the 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 effects. We identified five randomised, double-blind studies with 1501 participants, but

  12. Dose painting to treat single-lobe prostate cancer with hypofractionated high-dose radiation using targeted external beam radiation: Is it feasible?

    International Nuclear Information System (INIS)

    Amini, Arya; Westerly, David C.; Waxweiler, Timothy V.; Ryan, Nicole; Raben, David

    2015-01-01

    Targeted focal therapy strategies for treating single-lobe prostate cancer are under investigation. In this planning study, we investigate the feasibility of treating a portion of the prostate to full-dose external beam radiation with reduced dose to the opposite lobe, compared with full-dose radiation delivered to the entire gland using hypofractionated radiation. For 10 consecutive patients with low- to intermediate-risk prostate cancer, 2 hypofractionated, single-arc volumetric-modulated arc therapy (VMAT) plans were designed. The first plan (standard hypofractionation regimen [STD]) included the entire prostate gland, treated to 70 Gy delivered in 28 fractions. The second dose painting plan (DP) encompassed the involved lobe treated to 70 Gy delivered in 28 fractions, whereas the opposing, uninvolved lobe received 50.4 Gy in 28 fractions. Mean dose to the opposing neurovascular bundle (NVB) was considerably lower for DP vs STD, with a mean dose of 53.9 vs 72.3 Gy (p < 0.001). Mean penile bulb dose was 18.6 Gy for DP vs 19.2 Gy for STD (p = 0.880). Mean rectal dose was 21.0 Gy for DP vs 22.8 Gy for STD (p = 0.356). Rectum V 70 (the volume receiving ≥70 Gy) was 2.01% for DP vs 2.74% for STD (p = 0.328). Bladder V 70 was 1.69% for DP vs 2.78% for STD (p = 0.232). Planning target volume (PTV) maximum dose points were 76.5 and 76.3 Gy for DP and STD, respectively (p = 0.760). This study demonstrates the feasibility of using VMAT for partial-lobe prostate radiation in patients with prostate cancer involving 1 lobe. Partial-lobe prostate plans appeared to spare adjacent critical structures including the opposite NVB

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

    Science.gov (United States)

    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.

  14. 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.

  15. Pharmacokinetics of tedizolid following oral administration: single and multiple dose, effect of food, and comparison of two solid forms of the prodrug.

    Science.gov (United States)

    Flanagan, Shawn D; Bien, Paul A; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

    2014-03-01

    The single- and multiple-dose pharmacokinetics (PK) of tedizolid were examined after oral administration of tedizolid phosphate disodium (TPD), including the effect of food on PK. The relative bioavailability of TPD to the free acid tedizolid phosphate was determined to bridge the results of these and other studies to the solid form of the prodrug selected for further development. Randomized placebo-controlled, double-blind single- and multiple-ascending dose studies and randomized open-label, crossover food effect and relative bioavailability studies. Clinical Research Units. Healthy subjects. Study TR701-101 enrolled 40 subjects in single-ascending dose (200-1200 mg TPD or placebo) and 40 subjects in 21-day multiple-ascending dose (200, 300, or 400 mg TPD once/day; 600 mg linezolid twice/day; or placebo) arms. Study TR701-103 was a food-effect study in 12 subjects administered 600 mg TPD. Study TR701-108 was a relative bioavailability study in 12 subjects administered 150-mg tedizolid equivalents as TPD or tedizolid phosphate. Plasma concentrations of the prodrug tedizolid phosphate, its active moiety tedizolid, and/or linezolid were collected. After administration of 200 to 600 mg TPD, tedizolid values increased approximately dose proportionally in area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax ). Tedizolid half-life values were approximately 2-fold greater compared with linezolid. TPD administration with food delayed tedizolid absorption and reduced Cmax relative to the fasted state but did not alter AUC. Minimal accumulation was predicted and observed for tedizolid, whereas observed accumulation of linezolid exceeded predictions based on single-dose PK. Comparable PK of tedizolid was observed following oral administration of either TPD or tedizolid phosphate. In the multiple-ascending dose study, 3 of 24 tedizolid subjects were withdrawn under prespecified stopping rules (one each of elevated alanine

  16. PROSPECTIVE STUDY COMPARING EFFECTIVENESS OF SINGLE AND MULTIPLE DOSE 25 MICROGRAMS INTRAVAGINAL MISOPROSTOL FOR INDUCTION OF LABOUR AT TERM

    Directory of Open Access Journals (Sweden)

    Arati Achamma

    2016-06-01

    Full Text Available OBJECTIVES/PURPOSE To compare two dosing regimens of the same 25 mcg misoprostol with respect to Induction delivery interval, successful vaginal delivery and its associated maternal and neonatal outcomes. METHODS Prospective study was conducted among 300 low risk pregnant patients at 40 weeks’ gestation, attending labour room in the Dept. of OBG, Amala Institute of Medical sciences, comparing, A-single dose 25 mcg misoprostol in 24 hours Vs. B-multiple dose 25 mcg misoprostol (4 hourly up to 3 doses intravaginally for its effectiveness. RESULTS Statistically significant difference was obtained in the number of deliveries within 24 hours in group A and B (36.6% Vs. 63.4% with p value 0.002. The induction delivery interval between primigravidae and multigravidae were statistically significant (12.5 =/-3.9 Vs 11.08=/-4.3 with p value 0.035 but not significant between groups A and B. There was no statistical difference in other maternal and neonatal outcomes. Incidence of MSL and foetal distress were higher in primigravidae after single dose itself. Serious adverse outcomes like MAS, NND, APGAR<7 at one minute and uterine rupture were not encountered in this study. CONCLUSION Around 65% of women delivered with a single dose of misoprostol in 24 hours. Most multigravidae delivered vaginally with a single dose in 24 hours. It appears that in multigravidae a single dose induction is adequate; however, in primigravidae multiple doses of 25 mcg misoprostol is best to achieve delivery within 24 hours.

  17. Comparison of image quality and radiation dose between split-filter dual-energy images and single-energy images in single-source abdominal CT.

    Science.gov (United States)

    Euler, André; Obmann, Markus M; Szucs-Farkas, Zsolt; Mileto, Achille; Zaehringer, Caroline; Falkowski, Anna L; Winkel, David J; Marin, Daniele; Stieltjes, Bram; Krauss, Bernhard; Schindera, Sebastian T

    2018-02-19

    To compare image quality and radiation dose of abdominal split-filter dual-energy CT (SF-DECT) combined with monoenergetic imaging to single-energy CT (SECT) with automatic tube voltage selection (ATVS). Two-hundred single-source abdominal CT scans were performed as SECT with ATVS (n = 100) and SF-DECT (n = 100). SF-DECT scans were reconstructed and subdivided into composed images (SF-CI) and monoenergetic images at 55 keV (SF-MI). Objective and subjective image quality were compared among single-energy images (SEI), SF-CI and SF-MI. CNR and FOM were separately calculated for the liver (e.g. CNR liv ) and the portal vein (CNR pv ). Radiation dose was compared using size-specific dose estimate (SSDE). Results of the three groups were compared using non-parametric tests. Image noise of SF-CI was 18% lower compared to SEI and 48% lower compared to SF-MI (p 0.628). Subjective sharpness was equal between single-energy and monoenergetic images and diagnostic confidence was equal between single-energy and composed images. FOM liv was highest for SF-CI. FOM pv was equal for SEI and SF-MI (p = 0.78). SSDE was significant lower for SF-DECT compared to SECT (p quality at lower radiation dose compared to single-energy CT with ATVS. • Split-filter dual-energy results in 18% lower noise compared to single-energy with ATVS. • Split-filter dual-energy results in 11% lower SSDE compared to single-energy with ATVS. • Spectral shaping of split-filter dual-energy leads to an increased dose-efficiency.

  18. Acute dosing of latrepirdine (Dimebon™, a possible Alzheimer therapeutic, elevates extracellular amyloid-β levels in vitro and in vivo

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    Sano Mary

    2009-12-01

    Full Text Available Abstract Background Recent reports suggest that latrepirdine (Dimebon™, dimebolin, a retired Russian antihistamine, improves cognitive function in aged rodents and in patients with mild to moderate Alzheimer's disease (AD. However, the mechanism(s underlying this benefit remain elusive. AD is characterized by extracellular accumulation of the amyloid-β (Aβ peptide in the brain, and Aβ-lowering drugs are currently among the most popular anti-amyloid agents under development for the treatment of AD. In the current study, we assessed the effect of acute dosing of latrepirdine on levels of extracellular Aβ using in vitro and in vivo experimental systems. Results We evaluated extracellular levels of Aβ in three experimental systems, under basal conditions and after treatment with latrepirdine. Mouse N2a neuroblastoma cells overexpressing Swedish APP were incubated for 6 hr in the presence of either vehicle or vehicle + latrepirdine (500pM-5 μM. Synaptoneurosomes were isolated from TgCRND8 mutant APP-overexpressing transgenic mice and incubated for 0 to 10 min in the absence or presence of latrepirdine (1 μM or 10 μM. Drug-naïve Tg2576 Swedish mutant APP overexpressing transgenic mice received a single intraperitoneal injection of either vehicle or vehicle + latrepirdine (3.5 mg/kg. Picomolar to nanomolar concentrations of acutely administered latrepirdine increased the extracellular concentration of Aβ in the conditioned media from Swedish mutant APP-overexpressing N2a cells by up to 64% (p = 0.01, while a clinically relevant acute dose of latrepirdine administered i.p. led to an increase in the interstitial fluid of freely moving APP transgenic mice by up to 40% (p = 0.01. Reconstitution of membrane protein trafficking and processing is frequently inefficient, and, consistent with this interpretation, latrepirdine treatment of isolated TgCRND8 synaptoneurosomes involved higher concentrations of drug (1-10 μM and led to more modest

  19. Chemoprophylaxis of coccidiosis in lambs with a single oral dose of toltrazuril.

    Science.gov (United States)

    Gjerde, B; Helle, O

    1991-03-01

    The prophylactic efficacy of a single oral dose of toltrazuril against coccidiosis (mixed Eimeria infections) in naturally infected lambs was evaluated in two experiments. Toltrazuril at 20 mg kg-1, given on Day 7 or Day 10 after turnout on pasture, proved to be highly efficacious in preventing clinical coccidiosis under Norwegian conditions. Toltrazuril reduced the oocyst output to very low levels, prevented the development of diarrhoea and improved weight gain during the first 4-5 weeks after treatment. Treatment on Day 7 was superior to treatment on Day 10 with respect to improving weight gain and preventing the development of soft faeces. Lambs treated with toltrazuril on Day 7 seemed to be as immune as untreated lambs to natural reinfections with coccidia later in the grazing season. In one of the experiments, natural infections with the nematode Nematodirus battus produced a coccidiosis-like disease in some lambs simultaneously with the outbreak of coccidiosis.

  20. Pharmacokinetics and Placental Transfer of Single-Dose Tenofovir 1% Vaginal Gel in Term Pregnancy

    Science.gov (United States)

    Noguchi, Lisa; Parsons, Teresa; Macio, Ingrid; Kunjara Na Ayudhya, Ratiya P.; Chen, Jianmeng; Hendrix, Craig W.; Mâsse, Benoît; Valentine, Megan; Piper, Jeanna; Watts, D. Heather

    2011-01-01

    Tenofovir (TFV) 1% vaginal gel has been found to decrease sexual transmission of human immunodeficiency virus. To initiate investigations during pregnancy, 16 healthy pregnant women scheduled for cesarean delivery received a single application of TFV gel preoperatively. Maternal serum drug concentrations were determined and fetal cord blood, amniotic fluid, placental tissue, and endometrial tissue specimens were collected. The median maternal peak concentration and cord blood TFV concentrations were 4.3 and 1.9 ng/mL, respectively (∼100- and 40-fold lower than after TFV oral dosing, respectively). No adverse events were related to the use of TFV gel. These findings support ongoing and future investigations of TFV gel in pregnancy. Clinical Trial Registration: NCT00572273. http://www.clinicaltrials.gov/ct2/show/NCT00540605?term=mtn-002&rank=1. PMID:21930612

  1. 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

  2. Single-dose Toxicity of ShinYangHur Herbal Acupuncture

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    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.

  3. 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.

  4. Response of CEDIA amphetamines assay after a single dose of bitter orange.

    Science.gov (United States)

    Nguyen, DiemThuy T; Bui, Linda T; Ambrose, Peter J

    2006-04-01

    Bitter orange has recently been substituted as an ingredient in many "ephedra-free" dietary supplements used for weight loss. The primary active ingredient in bitter orange is synephrine. Previous reports have documented false-positive results from ephedrine with urine amphetamine assays. Because of the similarity in chemical structure of ephedrine and synephrine, it is hypothesized that ingestion of a bitter orange supplement may have the potential to cause false-positive results with urine amphetamine assays. The purpose of this study was to determine the response of the CEDIA Amphetamines Assay after ingestion of bitter orange. Six healthy adult male volunteers were administered a single oral dose of Nature's Way Bitter Orange, a 900-mg dietary supplement extract standardized to 6% synephrine. Urine specimens were collected at baseline and 3 and 6 hours post-administration. Additional urine specimens were collected from 1 subject at 9, 12, and 15 hours after administration. All specimens were analyzed by the CEDIA Amphetamines Assay. Urine specific gravity and pH also were measured. All urine specimens demonstrated a negative response to the CEDIA Amphetamines Assay. Urine specific gravity ranged from 1.007 to 1.028, and pH ranged from 5.0 to 7.0; thus, reducing the possibility that the negative results were caused by diluted specimens or reduced excretion of synephrine into alkaline urine. This information will be of value when health care providers or those who interpret drug screens are asked to provide consultation regarding the interference of bitter orange supplements with the CEDIA Amphetamines Assay. A single-dose of Nature's Way Bitter Orange was not found to cause a false-positive response to the CEDIA Amphetamines Assay in 6 healthy adult male volunteers.

  5. Deposition of diazepam and its metabolites in hair following a single dose of diazepam.

    Science.gov (United States)

    Wang, Xin; Johansen, Sys Stybe; Zhang, Yurong; Jia, Jingying; Rao, Yulan; Jiang, Fengli; Linnet, Kristian

    2017-01-01

    Only sporadic data are available on hair concentrations of diazepam and some of its metabolites (nordazepam, oxazepam, and temazepam) following a single controlled dose. The aim of this study was to investigate the deposition of diazepam and its metabolites in human hair after eight healthy volunteers (four women and four men, ages 24-26, East Asian) consumed 10 mg of diazepam. Hair was collected from all volunteers 1 month after exposure, and also 2 months post-exposure from men and 10 months post-exposure from women. Diazepam and the complete metabolite profile, including oxazepam glucuronide and temazepam glucuronide, were measured by ultra-high pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) with limits of quantifications (LOQs) of 0.5-2.5 pg/mg for diazepam, nordazepam, oxazepam, and temazepam, and of 10 pg/mg for oxazepam glucuronide and temazepam glucuronide. There were no differences by gender in the amounts of diazepam or metabolites found. The concentration of the main metabolite nordazepam was consistently higher than that of diazepam at both 1 and 2 months after consumption. Oxazepam and temazepam traces were found in some volunteers' hair, but the glucuronides were not detected. Diazepam and nordazepam levels at 10 months post-exposure were extremely low (near the LOQ), indicating drug loss by personal hygiene and physical handling. To our knowledge, this is the first single-dose diazepam study using black hair and the first study to include measurements of oxazepam glucuronide and temazepam glucuronide in human hair.

  6. Can Preoperative Intramuscular Single-Dose Dexamethasone Improve Patient-Centered Outcomes Following Third Molar Surgery?

    Science.gov (United States)

    Al-Dajani, Mahmoud

    2017-08-01

    Because of increased attention focused on administering dexamethasone to treat third molar surgical complications, this study investigated the efficacy of single-dose dexamethasone in managing postoperative complications after impacted third molar surgery. Pain intensity and analgesic intake, patients' discomfort, limitation of oral function, and limitation of daily activities were assessed. This triple-blinded split-mouth randomized controlled clinical trial included patients 18 to 30 years old who underwent randomized bilateral extractions of impacted mandibular third molars during 2 consecutive sessions. Each patient was given a single-dose intramuscular injection of dexamethasone (0.1 mg/kg) preoperatively in 1 session and a placebo in the other session. Data were collected daily for 7 postoperative days, and 14 patient-centered outcomes were interpreted. A 2-tailed P value less than .05 was considered significant. All 32 patients (100%) enrolled completed the study. When administered dexamethasone, patients reported less pain (P ≤ .007), took fewer analgesics (P ≤ .002), reported less swelling (P ≤ .007), had less difficulty in eating (P ≤ .024), had less difficulty in enjoying food (P ≤ .005), had less difficulty in speech (P = .043), had less trismus (P = .005), were absent less from school or work (P ≤ .016), and had less disruption of daily activity (P ≤ .042). The differences between the 2 conditions in bleeding, malaise, and sleep disturbance were not significant (P > .05). Prophylactic dexamethasone administered intramuscularly before third molar surgery should be recommended as a safe and effective strategy for decreasing pain and discomfort and enhancing oral functions and daily activities, unless contraindicated. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Detection of HIV drug resistance mutations in pregnant women receiving single dose Nevirapine in south India

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    Mini S Jacob

    2011-01-01

    Full Text Available Background: Single dose of Nevirapine to prevent mother to child transmission of HIV is the commonest preventive regimen in resource-limited countries. Objectives: The objective of this study was to detect drug-resistant virus after single dose of Nevirapine (sdNVP provided to delivering HIV seropositive (HIV+ve women and to evaluate the time taken for its decay. Results: Of the 36 consenting HIV+ve pregnant women enrolled into the study, the mean hemoglobin and total lymphocyte counts were 10.8 g/dl and 1843 cells/mm 3 , respectively. Mean CD4 counts in 64% of women was 363 cells/mm 3 and mean viral load for 16/36 women was 28,143 copies/ml of plasma. Nevirapine-resistance mutations were detected in 28% of women at delivery; using OLA (Oligonucleotide Ligation Assay. K103N mutations were seen in 19.4% of women while the Y181C mutation was seen in 5%. Both the mutations were detected in 2.7% of women. Sequential blood samples collected at delivery, 7-10 days, 6 weeks, 4 months, 6 months and one year postpartum showed that 81% of K103N mutations and 66.7% of Y181C mutations were detected at 6 weeks postpartum . Wild-type virus had replaced the mutants by one year postpartum in all women except one. Conclusion : These observations are relevant for future treatment with antiretroviral therapy in these women for their HIV disease.

  8. Alteration of the systemic and microcirculation by a single oral dose of flavan-3-ols.

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    Kodai Ingawa

    Full Text Available Several systematic reviews have reported that flow mediated dilatation (FMD was significantly increased in subjects after ingestion of chocolate that contains flavan-3-ols; however, the mechanisms responsible for this effect are not clear. In this study, we evaluated the effects of a single oral dose of flavan-3-ols on the systemic circulation and microcirculation in the cremaster muscle using intravital video microscopy in vivo. The cremaster muscle in rats was spread over a plastic chamber and a gastric tube was placed into the stomach. Blood flow in the cremasteric artery was determined using a laser Doppler flowmeter, while blood pressure and heart rate were measured by the tail-cuff method. Red blood cell velocity in arterioles and blood flow in the artery were significantly increased 5 min after the administration of 10 mg/kg flavan-3-ols compared with distilled water treatment. The number of capillaries recruited in the cremaster muscle was also significantly increased 15 min after treatment. Microscopic observation confirmed that increased shear stress on endothelial cells was maintained during the measurement period. The mean arterial blood pressure and heart rate were also significantly elevated soon after administration and returned to baseline before the end of the observation period. Plasma nitrate and nitrite levels, and NO phosphorylation of aortic tissue were significantly increased at 60 min after administration of flavan-3-ols. According to these results, a single oral dose of flavan-3-ols elevates blood pressure and flow transiently, and these effects induce NO production through increased shear stress on endothelial cells.

  9. 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.)

  10. Single intravenous and oral dose pharmacokinetics of florfenicol in the channel catfish (Ictalurus punctatus).

    Science.gov (United States)

    Gaunt, P S; Langston, C; Wrzesinski, C; Gao, D; Adams, P; Crouch, L; Sweeney, D; Endris, R

    2012-10-01

    Plasma distribution and elimination of florfenicol in channel catfish were investigated after a single dose (10 mg/kg) of intravenous (i.v.) or oral administration in freshwater at a mean water temperature of 25.4 °C. Florfenicol concentrations in plasma were analyzed by means of liquid chromatography with MS/MS detection. After i.v. florfenicol injection, the terminal half-life (t(1/2)), volume of distribution at steady state (V(ss)), and central volume of distribution (V(c)) were 8.25 h, 0.9 and 0.381 L/kg, respectively. After oral administration of florfenicol, the terminal t(1/2), C(max), T(max), and oral bioavailability (F) were 9.11 h, 7.6 μg/mL, 9.2 h, and 1.09, respectively. There was a lag absorption time of 1.67 h in oral dosing. Results from these studies support that 10 mg florfenicol/kg body weight in channel catfish is an efficacious dosage following oral administration. © 2011 Blackwell Publishing Ltd.

  11. Segmental hair analysis after a single dose of zolpidem: comparison with a previous study.

    Science.gov (United States)

    Cui, Xiaopei; Xiang, Ping; Zhang, Jingshuo; Shi, Yan; Shen, Baohua; Shen, Min

    2013-01-01

    Hair is a useful aid and sometimes even the only matrix in the analytical strategy in drug-facilitated crime (DFC) investigations. In this novel study, segmental hair analysis was performed after a single 10 mg dose of zolpidem was given to 20 Chinese volunteers. Hair was collected 1 month after administration and was analyzed using ultra-high-pressure liquid chromatography/electrospray ionization tandem mass spectrometry. Zolpidem concentrations were found to be in the range of 135.0-554.6 pg/mg in the proximal 0-2 cm segments. These results were markedly different from those reported by Villain et al., who used volunteers administered equal doses of zolpidem. The analytical method used, as well as the volunteers' hair color, inter-individual variations such as metabolic capacity, hair growth rate, drug incorporation rates, physical state of the hair, age, gender, body weight, etc. and diffusion from sweat or other secretions are all factors that should be considered when interpreting the DFC results.

  12. Dynamics of the general factor of personality in response to a single dose of caffeine.

    Science.gov (United States)

    Caselles, Antonio; Micó, Joan C; Amigó, Salvador

    2011-11-01

    General Factor of Personality (GFP) research is an emergent field in personality research. This paper uses a theoretical mathematical model to predict the short-term effects of a dose of a stimulant drug on GFP and reports the results of an experiment showing how caffeine achieves this. This study considers the General Factor of Personality Questionnaire (GFPQ) a good psychometric approach to assess GFP. The GFP dynamic mechanism of change is based on the Unique Trait Personality Theory (UTPT). This theory proposes the existence of GFP which occupies the apex of the hierarchy of personality, and extends from an impulsiveness-and-aggressiveness pole (approach tendency) to an anxiety-and-introversion pole (avoidance tendency). An experiment with 25 volunteers was performed. All the participants completed the GFPQ and the Sensation-Seeking Scale list of adjectives from the trait version of MAACL-R (Multiple Affect Adjective Checklist Revised) on an empty stomach. The participants in the experimental group (20) received 330 mg of caffeine. All the participants filled in a state version form with the sensation-seeking adjectives every 4.5 minutes. This study considers that the Sensation-Seeking Scale list of adjectives from the MAACL-R, available in both trait and state versions, is a good psychometric approach to assess GFP. The results show that GFP is modified by a single dose of caffeine in the direction predicted by the UTPT.

  13. Tissue distribution and elimination of BDE 47 in mice following a single oral dose

    Energy Technology Data Exchange (ETDEWEB)

    Staskal, D. [Curriculum in Toxicology, Chapel Hill, NC (United States); Diliberto, J.; DeVito, M.; Birnbaum, L. [US EPA, ORD, NHEERL, ETD, RTP (United States)

    2004-09-15

    2,2',4,4'-Tetrabromodiphenyl ether (BDE 47) is a polybrominated diphenyl ether (PBDE) congener which is part of a class of brominated flame retardants (BFRs) commonly used in a variety of highly flammable consumer goods. Concern for the effects of PBDEs has increased significantly in recent years as their presence has been detected in environmental samples and in human tissues at steadily increasing concentrations. Despite its small contribution to the PBDE global production and usage, BDE 47 is the major congener found in environmental samples and human tissue. Limited toxicology studies suggest that BDE 47 is a developmental neurotoxicant and an endocrine disruptor however, several data gaps exist and must be investigated in order to evaluate the human health risk of BDE 47. This study investigated basic toxicokinetic properties of BDE 47 in female C57BL/6J mice. Here we report the effect of time on the absorption, distribution, and excretion following a single, oral dose of 14C-labeled BDE 47. Animals were administered 1.0mg BDE 47/kg bw, a dose chosen based on previous studies. Distribution and elimination were monitored at several time points ranging from 1 hour to 21 days following exposure. Data from these basic toxicokinetic studies will be applied to studies investigating the toxicokinetics of BDE 47 in a developmental model as well as in the development of a physiologically-based pharmacokinetic (PBPK) model.

  14. 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 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.

  15. Results of single and repeat dose studies of the oral matrix metalloproteinase inhibitor marimastat in healthy male volunteers

    Science.gov (United States)

    Millar, Andrew W; Brown, Peter D; Moore, Jeff; Galloway, W Alan; Cornish, Alan G; Lenehan, Terence J; Lynch, Kevin P

    1998-01-01

    Aims To assess the tolerability and pharmacokinetic profile of single and repeat doses of the oral matrix metalloproteinase inhibitor marimastat in healthy male volunteers. Methods A total of 31 subjects participated in two placebo-controlled, rising-dose studies. The first study assessed the pharmacokinetics and tolerability of single doses of marimastat of 25, 50, 100, 200, 400 and 800 mg. In the second study, continuous dosing over 6.5 days with three incremental dose levels of 50, 100 and 200 mg twice daily was assessed. Full pharmacokinetic profiles were obtained on days 0 and 6, and trough concentrations were measured on all days. For each pharmacokinetic profile in the studies, summary measures including Cmax, tmax, elimination half-life and AUC were calculated. Urinary drug weights were also measured. All adverse events were documented, and haematological and biochemical variables, vital signs and ECGs were monitored throughout the study. Results Peak plasma concentrations were observed at 1.5–3 h for all subjects at all doses. Peak levels were approximately proportional to dose, as was drug exposure as calculated by AUC. Data from both studies indicate that the terminal elimination half-life is of the order of 8–10 h, and that there is no unexpected drug accumulation. Marimastat was well-tolerated, with adverse effects being mild and occurring with similar frequency to placebo. Small but reversible elevations in liver transaminases were noted with repeat dosing of marimastat, the most significant of these occurring at a dose of 200 mg twice daily. Conclusion Single and repeat oral doses of marimastat in healthy male subjects appear to be well-tolerated. The drug is rapidly absorbed with high peak levels achieved. It has a terminal elimination half-life of 8–10 h which would support twice daily dosing in further clinical trials. PMID:9489589

  16. Genetic injury in hybrid male mice exposed to low doses of /sup 60/CO. gamma. -rays or fission neutrons. 1. Response to single doses

    Energy Technology Data Exchange (ETDEWEB)

    Grahn, D.; Carnes, B.A.; Farrington, B.H.; Lee, C.H. (Argonne National Lab., IL (USA))

    1984-11-01

    Young adult male B6CF/sub 1/ mice were exposed to single whole body doses of fission neutrons or /sup 60/Co ..gamma.. rays. Postspermatogonial dominant lethal injury, incidence of reciprocal chromosome translocations induced in spermatogonia, incidence of abnormal epididymal sperm 4-6 weeks after exposure, and testis weight loss 3-6 weeks after exposure were all measured. Significant effects were seen at 1 and 2.5 rad of neutrons consistent with extrapolation from higher doses, with the exception of dominant lethal mutations, which occurred in significant excess of expectation. Dose-response functions were linear or linear-quadratic, depending upon end point, radiation quality, and dose range. For translocation frequencies, the D/sup 2/ term was negative for neutron and positive for ..gamma..-ray irradiations. RBE values varied with dose and end point. For testis weight loss and abnormal sperm over the full dose range, the RBEs were between 5 and 6. They were between 7 and 9 at lower doses (< 10 rad) for translocations. RBEs for postimplantation and total dominant lethal rates were 5-6 above 10 rad and 10-14 below 10 rad. The RBEs for preimplant losses were between 15 and 25 above 10 rad and possibly higher below 10 rad, although the data are statistically 'noisy'.

  17. Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options

    Directory of Open Access Journals (Sweden)

    Daniela Rodrigues

    2016-01-01

    Full Text Available Colorectal cancer (CRC is one of the most frequent cancers and is a leading cause of cancer death worldwide. Treatments used for CRC may include some combination of surgery, radiation therapy, chemotherapy, and targeted therapy. The current standard drugs used in chemotherapy are 5-fluorouracil and leucovorin in combination with irinotecan and/or oxaliplatin. Most recently, biologic agents have been proven to have therapeutic benefits in metastatic CRC alone or in association with standard chemotherapy. However, patients present different treatment responses, in terms of efficacy and toxicity; therefore, it is important to identify biological markers that can predict the response to therapy and help select patients that would benefit from specific regimens. In this paper, authors review CRC genetic markers that could be useful in predicting the sensitivity/resistance to chemotherapy.

  18. Pharmacokinetics of single-dose sildenafil administered orally in clinically healthy dogs: Effect of feeding and dose proportionality.

    Science.gov (United States)

    Akabane, R; Sato, T; Sakatani, A; Miyagawa, Y; Tazaki, H; Takemura, N

    2018-01-19

    Basic information related to the pharmacokinetics of sildenafil in dogs is scarce. This study aimed to describe the pharmacokinetic properties of oral sildenafil and determine the effect of feeding and dose proportionality. The effect of feeding on pharmacokinetics of sildenafil (1 mg/kg) was investigated using a crossover study with six dogs. In addition, the dose proportionality of sildenafil ranging 1-4 mg/kg was evaluated using five dogs in the fasted states. The plasma concentrations of sildenafil were determined using high-performance liquid chromatography, and pharmacokinetic parameters were calculated using a noncompartmental analysis. Sildenafil administrations were well tolerated in all studies. Feeding reduced the area under the curve extrapolated to infinity (AUC inf ) and the maximum plasma concentration (C max ) significantly. The elimination half-life (T 1/2 ) did not differ between the fasted and the fed states. For dose proportionality, nonproportional increases in AUC inf and C max at 1-4 mg/kg doses were detected by a power model analysis. © 2018 John Wiley & Sons Ltd.

  19. A single acute hepatotoxic dose of CCl4 causes oxidative stress in the rat brain

    Directory of Open Access Journals (Sweden)

    K.R. Ritesh

    2015-01-01

    Full Text Available Carbon tetrachloride (CCl4, a hepatotoxic agent is widely used to study the toxic mechanisms in experimental animals. We have investigated whether oxidative stress is induced in the brain at a single hepatotoxic dosage (1 ml/kg bw of CCl4. Increased lipid peroxidation (LPO, protein carbonyls (PC content and glutathione (GSH depletion were observed in the brain regions of rats treated with CCl4 which was higher than that of liver. A drastic reduction in the activity of glutathione-S-transferase (GST was seen in the brain regions which was higher than that of liver. Similarly, activities of glutathione peroxidase (GPx, glutathione reductase (GR, superoxide dismutase (SOD, catalase (CAT, NADH- and NADPH-dehydrogenase were reduced in the brain regions similar to that of liver. Higher induction of oxidative stress in the brain compared to that of liver implies vulnerability of the brain for CCl4 neurotoxicity. Our study shows that a single hepatotoxic dose of CCl4 is equally neurotoxic to rats.

  20. 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

  1. 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.

  2. A simple and fast physics-based analytical method to calculate therapeutic and stray doses from external beam, megavoltage x-ray therapy.

    Science.gov (United States)

    Jagetic, Lydia J; Newhauser, Wayne D

    2015-06-21

    State-of-the-art radiotherapy treatment planning systems provide reliable estimates of the therapeutic radiation but are known to underestimate or neglect the stray radiation exposures. Most commonly, stray radiation exposures are reconstructed using empirical formulas or lookup tables. The purpose of this study was to develop the basic physics of a model capable of calculating the total absorbed dose both inside and outside of the therapeutic radiation beam for external beam photon therapy. The model was developed using measurements of total absorbed dose in a water-box phantom from a 6 MV medical linear accelerator to calculate dose profiles in both the in-plane and cross-plane direction for a variety of square field sizes and depths in water. The water-box phantom facilitated development of the basic physical aspects of the model. RMS discrepancies between measured and calculated total absorbed dose values in water were less than 9.3% for all fields studied. Computation times for 10 million dose points within a homogeneous phantom were approximately 4 min. These results suggest that the basic physics of the model are sufficiently simple, fast, and accurate to serve as a foundation for a variety of clinical and research applications, some of which may require that the model be extended or simplified based on the needs of the user. A potentially important advantage of a physics-based approach is that the model is more readily adaptable to a wide variety of treatment units and treatment techniques than with empirical models.

  3. Single dose intratympanic mesna application inhibits propylene glycol induced cholesteatoma formation.

    Science.gov (United States)

    Ismi, O; Karabulut, Y Y; Bal, K K; Vayisoglu, Y; Unal, M

    2017-03-01

    Mesna (i.e. sodium 2-mercaptoethanesulfonate; C2H5NaO3S2) has been used in otological surgery such as cholesteatoma dissection and tympanic membrane lateralisation in atelectatic ears. However, this study aimed to investigate its effect on cholesteatoma formation. A total of 20 Wistar rats were divided into two groups of 10 animals. The right and left ears of control animals were treated with saline (saline control group; n = 10 ears) and propylene glycol plus saline (propylene glycol control group; n = 10 ears), respectively. In the mesna group, both ears were treated with propylene glycol plus mesna (n = 20 ears). On days 1, 8 and 15, the saline control group had intratympanic injections of 0.2 ml saline and the propylene glycol control and mesna groups had intratympanic injections of 0.2 ml 100 per cent propylene glycol. On day 22, the propylene glycol control group had a single intratympanic injection of 0.2 ml saline and the mesna group had a single intratympanic injection of 10 per cent mesna. Animals were killed 12 weeks after the last injection and the temporal bones were sent for histopathological evaluation. The cholesteatoma formation rate was 88 per cent in the propylene glycol control group, but was significantly lower in the mesna group (p = 0.01). There were no significant differences in granulation tissue formation (p = 0.498), cyst formation in the bulla (p = 0.381), fibrosis (p = 0.072) and epithelial hyperplasia (p = 0.081) among experimental groups. Intratympanic propylene glycol administration is an effective method of promoting experimental cholesteatoma formation. Administration of a single dose of intratympanic mesna inhibited cholesteatoma formation in an animal model.

  4. 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.

  5. Single induction dose of etomidate versus other induction agents for endotracheal intubation in critically ill patients.

    Science.gov (United States)

    Bruder, Eric A; Ball, Ian M; Ridi, Stacy; Pickett, William; Hohl, Corinne

    2015-01-08

    The use of etomidate for emergency airway interventions in critically ill patients is very common. In one large registry trial, etomidate was the most commonly used agent for this indication. Etomidate is known to suppress adrenal gland function, but it remains unclear whether or not this adrenal gland dysfunction affects mortality. The primary objective was to assess, in populations of critically ill patients, whether a single induction dose of etomidate for emergency airway intervention affects mortality.The secondary objectives were to address, in populations of critically ill patients, whether a single induction dose of etomidate for emergency airway intervention affects adrenal gland function, organ dysfunction, or health services utilization (as measured by intensive care unit (ICU) length of stay (LOS), duration of mechanical ventilation, or vasopressor requirements).We repeated analyses within subgroups defined by the aetiologies of critical illness, timing of adrenal gland function measurement, and the type of comparator drug used. We searched the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; CINAHL; EMBASE; LILACS; International Pharmaceutical Abstracts; Web of Science; the Database of Abstracts of Reviews of Effects (DARE); and ISI BIOSIS Citation index(SM) on 8 February 2013. We reran the searches in August 2014. We will deal with any studies of interest when we update the review.We also searched the Scopus database of dissertations and conference proceedings and the US Food and Drug Administration Database. We handsearched major emergency medicine, critical care, and anaesthesiology journals.We handsearched the conference proceedings of major emergency medicine, anaesthesia, and critical care conferences from 1990 to current, and performed a grey literature search of the following: Current Controlled Trials; National Health Service - The National Research Register; ClinicalTrials.gov; NEAR website. We included randomized controlled

  6. Single versus repeat doses of misoprostol for treatment of early pregnancy loss-a randomized clinical trial.

    Science.gov (United States)

    Mizrachi, Yossi; Dekalo, Ann; Gluck, Ohad; Miremberg, Hadas; Dafna, Lotem; Feldstein, Ohad; Weiner, Eran; Bar, Jacob; Sagiv, Ron

    2017-06-01

    Does repeat administration of misoprostol for early pregnancy loss increase the treatment success rate? Repeat administration of misoprostol does not increase the treatment success rate, and is associated with more analgesics use. Misoprostol reduces the need for surgical evacuation and shortens the time to complete expulsion in patients with early pregnancy loss. However, the impact of repeat doses of misoprostol is not clear. A randomized clinical trial was conducted in a single tertiary hospital, recruiting women with early pregnancy loss (misoprostol vaginally on Day 1, and were then randomly assigned into two groups: Patients in the single-dose group were evaluated on Day 8. Patients in the repeat-dose group were evaluated on Day 4, when they were given a repeat dose if required, and scheduled for re-evaluation on Day 8. If complete expulsion was not achieved on Day 8 (endometrial thickness >15 mm or the presence of gestational sac on transvaginal sonography), participants underwent surgical evacuation. The primary outcome was treatment success, defined as no need for surgical intervention up to Day 8. Final analysis included 87 participants in the single-dose group and 84 participants in the repeat-dose group, out of whom 41 (48.8%) received a second dose. Treatment succeeded in 67 (77%) patients in the single-dose group and 64 (76%) patients in the repeat-dose group (RR 0.98; 95% CI 0.83-1.16; P = 0.89). Patients in the repeat-dose group reported more use of over the counter analgesics (82.1% versus 69.0%, P = 0.04). The study was not blinded and our definition of complete expulsion may be debated. Follow-up time was not equal in all participants, since some had a complete expulsion on Day 4 and some underwent emergent D&C before Day 8. This, however, should not affect the primary outcome. Our results suggest that a single-dose protocol is superior to a repeat-dose protocol due to a comparable success rate and more favorable outcomes regarding the need for

  7. Pre-therapeutic factors for predicting survival after radioembolization: a single-center experience in 389 patients

    International Nuclear Information System (INIS)

    Paprottka, K.J.; Schoeppe, F.; Ingrisch, M.; Ruebenthaler, J.; Sommer, N.N.; Paprottka, P.M.; Toni, E. de; Ilhan, H.; Zacherl, M.; Todica, A.

    2017-01-01

    To determine pre-therapeutic predictive factors for overall survival (OS) after yttrium (Y)-90 radioembolization (RE). We retrospectively analyzed the pre-therapeutic characteristics (sex, age, tumor entity, hepatic tumor burden, extrahepatic disease [EHD] and liver function [with focus on bilirubin and cholinesterase level]) of 389 consecutive patients with various refractory liver-dominant tumors (hepatocellular carcinoma [HCC], cholangiocarcinoma [CCC], neuroendocrine tumor [NET], colorectal cancer [CRC] and metastatic breast cancer [MBC]), who received Y-90 radioembolization for predicting survival. Predictive factors were selected by univariate Cox regression analysis and subsequently tested by multivariate analysis for predicting patient survival. The median OS was 356 days (95% CI 285-427 days). Stable disease was observed in 132 patients, an objective response in 71 (one of which was complete remission) and progressive disease in 122. The best survival rate was observed in patients with NET, and the worst in patients with MBC. In the univariate analyses, extrahepatic disease (P < 0.001), large tumor burden (P = 0.001), high bilirubin levels (>1.9 mg/dL, P < 0.001) and low cholinesterase levels (CHE <4.62 U/I, P < 0.001) at baseline were significantly associated with poor survival. Tumor entity, tumor burden, extrahepatic disease and CHE were confirmed in the multivariate analysis as independent predictors of survival. Sex, applied RE dose and age had no significant influence on OS. Pre-therapeutic baseline bilirubin and CHE levels, extrahepatic disease and hepatic tumor burden are associated with patient survival after RE. Such parameters may be used to improve patient selection for RE of primary or metastatic liver tumors. (orig.)

  8. Pre-therapeutic factors for predicting survival after radioembolization: a single-center experience in 389 patients

    Energy Technology Data Exchange (ETDEWEB)

    Paprottka, K.J.; Schoeppe, F.; Ingrisch, M.; Ruebenthaler, J.; Sommer, N.N.; Paprottka, P.M. [LMU - University of Munich, Department of Clinical Radiology, Munich (Germany); Toni, E. de [LMU - University of Munich, Department of Hepatology, Munich (Germany); Ilhan, H.; Zacherl, M.; Todica, A. [LMU - University of Munich, Department of Nuclear Medicine, Munich (Germany)

    2017-07-15

    To determine pre-therapeutic predictive factors for overall survival (OS) after yttrium (Y)-90 radioembolization (RE). We retrospectively analyzed the pre-therapeutic characteristics (sex, age, tumor entity, hepatic tumor burden, extrahepatic disease [EHD] and liver function [with focus on bilirubin and cholinesterase level]) of 389 consecutive patients with various refractory liver-dominant tumors (hepatocellular carcinoma [HCC], cholangiocarcinoma [CCC], neuroendocrine tumor [NET], colorectal cancer [CRC] and metastatic breast cancer [MBC]), who received Y-90 radioembolization for predicting survival. Predictive factors were selected by univariate Cox regression analysis and subsequently tested by multivariate analysis for predicting patient survival. The median OS was 356 days (95% CI 285-427 days). Stable disease was observed in 132 patients, an objective response in 71 (one of which was complete remission) and progressive disease in 122. The best survival rate was observed in patients with NET, and the worst in patients with MBC. In the univariate analyses, extrahepatic disease (P < 0.001), large tumor burden (P = 0.001), high bilirubin levels (>1.9 mg/dL, P < 0.001) and low cholinesterase levels (CHE <4.62 U/I, P < 0.001) at baseline were significantly associated with poor survival. Tumor entity, tumor burden, extrahepatic disease and CHE were confirmed in the multivariate analysis as independent predictors of survival. Sex, applied RE dose and age had no significant influence on OS. Pre-therapeutic baseline bilirubin and CHE levels, extrahepatic disease and hepatic tumor burden are associated with patient survival after RE. Such parameters may be used to improve patient selection for RE of primary or metastatic liver tumors. (orig.)

  9. Importance of therapeutic patient education in ichthyosis: results of a prospective single reference center study.

    Science.gov (United States)

    Dufresne, Helene; Hadj-Rabia, Smail; Taïeb, Charles; Bodemer, Christine

    2013-08-01

    Ichthyoses are a heterogeneous group of rare genodermatoses. Patients and their families face difficulties related to daily care and management that may be aggravated by social isolation. To evaluate the impact of therapeutic educational programs in improving the knowledge of ichthyosis patients, and their relatives, about their disease. We organized a two sessions-program of "know-how" dedicated to the overall management of ichthyoses. These sessions were conducted based on a tool specifically designed for the study, which addressed our various areas of expertise through a collective game. The participants (patients and their parents and siblings) were divided into groups, and the questions were tailored according to the participants' age. The program was conceived as a knowledge reinforcement program that took place during a weekend of education and rest, organized away from healthcare structures. Our aim was to facilitate the program in a neutral place to encourage respite care and to ensure the availability of a multidisciplinary healthcare team. After the reinforcement session, children aged from 6 to 12 years and their families acquired the targeted know-how and social skills. Benefits of TPE in the management of ichthyoses are the following: (1) the trust between patients their families and the caregivers was strengthened; (2) the context of the program encouraged self-expression, answered questions and provided mutual aid; and (3) the more self-sufficient families could better manage emergencies.

  10. Therapeutic Effect of Novel Single-Stranded RNAi Agent Targeting Periostin in Eyes with Retinal Neovascularization

    Directory of Open Access Journals (Sweden)

    Takahito Nakama

    2017-03-01

    Full Text Available Retinal neovascularization (NV due to retinal ischemia remains one of the principal causes of vision impairment in patients with ischemic retinal diseases. We recently reported that periostin (POSTN may play a role in the development of preretinal fibrovascular membranes, but its role in retinal NV has not been determined. The purpose of this study was to examine the expression of POSTN in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of POSTN on retinal NV using Postn KO mice and human retinal endothelial cells (HRECs in culture. In addition, we used a novel RNAi agent, NK0144, which targets POSTN to determine its effect on the development of retinal NV. Our results showed that the expression of POSTN was increased in the vascular endothelial cells, pericytes, and M2 macrophages in ischemic retinas. POSTN promoted the ischemia-induced retinal NV by Akt phosphorylation through integrin αvβ3. NK0144 had a greater inhibitory effect than canonical double-stranded siRNA on preretinal pathological NV in vivo and in vitro. These findings suggest a causal relationship between POSTN and retinal NV, and indicate a potential therapeutic role of intravitreal injection of NK0144 for retinal neovascular diseases.

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

    Science.gov (United States)

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

    2014-12-01

    The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl(®) ). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4-16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  12. Single-dose methotrexate treatment for ectopic pregnancy and pregnancy of unknown location and progesterone as a predictor of success.

    Science.gov (United States)

    Wu, Joyce; Ludlow, Joanne P; De Vries, Bradley; Black, Kirsten; Beale, Philip

    2014-10-01

    The use of single-dose intramuscular administration of methotrexate in the treatment of ectopic pregnancies (EP) is a well-established practice. This study evaluates its use at a novel dose of 40 mg/m(2) body surface area (BSA). To evaluate the efficacy and safety of single-dose methotrexate treatment 40 mg/m(2) for tubal EP and persistent pregnancies of unknown location (PUL) and determine whether serum progesterone is a predictor of treatment success. Retrospective cohort study of patients receiving intramuscular methotrexate 40 mg/m(2) for the treatment of EP or PUL at Royal Prince Alfred Hospital over five years. One hundred and eighteen women received single-dose methotrexate with an overall success of 84%. Surgical intervention was needed in 16.6%. Pretreatment beta-hCG level and ectopic diagnosis were independent variables predictive of the need for surgery (P = 0.003 and 0.02, respectively). Serum progesterone level was not predictive of the need for a second dose or surgery. The sensitivity and specificity at pretreatment beta-hCG of 1202 IU/L were 84% and 74%, respectively. Commonly reported side effects included nausea, abdominal pain and heavy vaginal bleeding. Significant treatment-related adverse effects were rare. Single-dose IM methotrexate at a novel dose of 40 mg/m(2) is a safe and effective treatment for selected EP and persistent PUL. The risk of surgery was positively correlated to serum beta-hCG level and the diagnosis of EP. Progesterone was not a risk factor for surgery. Further studies are required to confirm the efficacy of this dose regimen and explore the safety of expectant management as an alternative to methotrexate treatment. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  13. Impact of β-lactam antibiotic therapeutic drug monitoring on dose adjustments in critically ill patients undergoing continuous renal replacement therapy.

    Science.gov (United States)

    Economou, Caleb J P; Wong, Gloria; McWhinney, Brett; Ungerer, Jacobus P J; Lipman, Jeffrey; Roberts, Jason A

    2017-05-01

    The objective of this study was to describe the effect of therapeutic drug monitoring (TDM) and dose adjustments of β-lactam antibiotics administered to critically ill patients undergoing continuous renal replacement therapy (CRRT) in a 30-bed tertiary intensive care unit (ICU). β-Lactam TDM data in our tertiary referral ICU were retrospectively reviewed. Clinical, demographic and dosing data were collected for patients administered β-lactam antibiotics while undergoing CRRT. The target trough concentration range was 1-10× the minimum inhibitory concentration (MIC). A total of 111 TDM samples from 76 patients (46 male) with a mean ± standard deviation age of 56.6 ± 15.9 years and weight of 89.1 ± 25.8 kg were identified. The duration of antibiotic therapy was between 2 days and 42 days. TDM identified a need for dose modification of β-lactam antibiotics in 39 (35%) instances; in 27 (24%) samples, TDM values resulted in decreasing the prescribed dose of β-lactam antibiotic whereas an increase in the prescribed dose occurred in 12 (11%) cases. In patients treated for hospital-acquired pneumonia and primary or secondary bacteraemia, the dose was required to be decreased in 10/25 (40%) and 7/46 (15%) cases, respectively, to attain target concentrations. β-Lactam TDM is a useful tool for guiding drug dosing in complex patients such as those receiving CRRT. Although over one-third of patients manifested concentrations outside the therapeutic range, most of these CRRT patients had excessive β-lactam concentrations. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  14. PHARMACOKINETICS OF A SINGLE DOSE OF METRONIDAZOLE AFTER RECTAL ADMINISTRATION IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

    Science.gov (United States)

    Sander, Samantha J; Siegal-Willott, Jessica L; Ziegler, Jessie; Lee, Elizabeth; Tell, Lisa; Murray, Suzan

    2016-03-01

    Metronidazole is a nitroimidazole antibacterial and antiprotozoal drug with bacteriocidal activity against a broad range of anaerobic bacteria. It is a recognized treatment for elephants diagnosed with anaerobic bacterial infection or protozoal disease or exhibiting signs of colonic impaction, diarrhea, and colic. This study evaluated the pharmacokinetics of rectally administered metronidazole (15 mg/kg) in five adult female Asian elephants (Elephas maximus). Serum samples were collected from each animal for 96 hr after rectal administration of metronidazole. Serum concentrations of metronidazole and its primary metabolite, hydroxymetronidazole, were measured via ultraperformance liquid chromatography. Data were analyzed via a noncompartmental pharmacokinetic approach. Results indicated that serum levels of metronidazole were quantifiable at the 0.25 hr time point and absent in all elephants by the 96 hr time point. The serum peak concentration (mean ± SD, 13.15 ± 2.59 μg/ml) and area under the curve from time 0 to infinity (mean ± SD, 108.79 ± 24.77 hr × μg/ml) were higher than that reported in domestic horses after similar usage. Concurrently, the time of maximum serum concentration (mean ± SD, 1.2 ± 0.45 hr) and terminal elimination half-life (harmonic mean ± pseudo-SD, 7.85 ± 0.93 hr) were longer when compared to equine reports. Rectal administration of metronidazole was well tolerated and rapidly absorbed in all study elephants. Based on the findings in this study, metronidazole administered at a single dose of 15 mg/kg per rectum in the Asian elephant is likely to result in serum concentrations above 4 μg/ml for 8 hr and above 2 μg/ml for 24 hr after treatment is administered. Dosing recommendations should reflect the mean inhibitory concentration of metronidazole for each pathogen.

  15. Comparative biodisponibility of a single dose captopril Formulations - doi:10.5020/18061230.2006.p5

    Directory of Open Access Journals (Sweden)

    Aline Kércia Alves Soares

    2012-01-01

    Full Text Available The aim of this study was to evaluate, on human volunteers, the performance of one captopril tablet formulation (Neo-Química Comércio Indústria Ltda against one standard tablet formulation (Capoten® 50mg Bristol-Myers Squibb Brasil S.A.Twenty-four healthy volunteers, as assessed by clinical and laboratory test evaluations, were enrolled in the study. The study was of a two way randomised crossover design comparing both captopril formulations. Plasma samples for determination of captopril were obtained by pre-dose and at frequent intervals for up to 24h post to one of the single dose formulations and were quantified by a validated method employing high-pressure liquid chromatography coupled to mass spectrometry (LCMSMS. The subjects were monitored through-out the study and the formulations were considered to be well tolerated. The maximum reached concentration (Cmax and areas under the curve (AUC0-24h were compared. Captopril Cmax geometric mean ratio was 108.5% (90% IC=101.8-115.7 of Capoten® values. Captopril AUC(0-24h geometric mean ratio was 109.3% (90% CI=102.7-116.3 of Capoten®. Since 90% CI for both Cmax and ratio AUC(0-24h for captopril were within the 80 to 125% interval proposed by both the Food and Drug Administration (FDA and the National Sanitary Surveillance Agency (ANVISA, it is concluded that Captopril Neo- Química was bioequivalent to Capoten® for both the rate and extent of absorption.

  16. Intravenous Single Dose Toxicity of Sweet Bee Venom in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Kwang-Ho Lee

    2015-09-01

    Full Text Available Objectives: Anaphylactic shock can be fatal to people who become hypersensitive when bee venom pharmacopuncture (BVP is used. Thus, sweet bee venom (SBV was developed to reduce these allergic responses. SBV is almost pure melittin, and SBV has been reported to have fewer allergic responses than BVP. BVP has been administered only into acupoints or intramuscularly, but we thought that intravenous injection might be possible if SBV were shown to be a safe medium. The aim of this study is to evaluate the intravenous injection toxicity of SBV through a single-dose test in Sprague-Dawley (SD rats. Methods: Male and female 6-week-old SD rats were injected intravenously with SBV (high dosage: 1.0 mL/animal; medium dosage: 0.5 mL/animal; low dosage: 0.1 mL/animal. Normal saline was injected into the control group in a similar method. We conducted clinical observations, body weight measurements, and hematology, biochemistry, and histological observations. Results: No death was observed in any of the experimental groups. Hyperemia was observed in the high and the medium dosage groups on the injection day, but from next day, no general symptoms were observed in any of the experimental groups. No significant changes due to intravenous SBV injection were observed in the weights, in the hematology, biochemistry, and histological observations, and in the local tolerance tests. Conclusion: The results of this study confirm that the lethal dose of SBV is over 1.0 mL/animal in SD rats and that the intravenous injection of SBV is safe in SD rats.

  17. Single-dose rofecoxib for acute postoperative pain in adults: a quantitative systematic review

    Directory of Open Access Journals (Sweden)

    McQuay Henry J

    2002-06-01

    Full Text Available Abstract Background Rofecoxib is a cyclo-oxygenase 2 selective inhibitor. This systematic review of rofecoxib in acute pain examined studies in adults of analgesic efficacy over six hours, the amount and quality of the evidence on extended duration of analgesia, and the quality and quantity of evidence on adverse events. Methods Cochrane Library (issue 4, 2001, Biological Abstracts (March 2002, MEDLINE (March 2002 and PubMed (March 2002 were searched using rofecoxib as a free text term. The area under the pain relief versus time curve was dichotomized using validated equations to derive the proportion of patients on rofecoxib 50 mg or placebo with at least 50% pain relief over six hours. This was used to calculate the number needed to treat for at least 50% pain relief over six hours for rofecoxib compared with placebo. Information on duration of analgesia and adverse events was also collected. Results Five included trials investigated 1,118 patients, of whom 211 received placebo and 464 received rofecoxib 50 mg. The NNT for rofecoxib 50 mg was 2.3 (95% confidence interval 2.0 to 2.6. The weighted mean remedication time was 1.9 hours for placebo (126 patients, 7.4 hours for ibuprofen 400 mg (97 patients and 13.6 hours for rofecoxib 50 mg (322 patients. Conclusion Rofecoxib at 2–4 times the standard daily dose for chronic pain is an effective single dose oral analgesic in acute pain. Limitations in trial reporting constrain conclusions about longer duration of analgesia and adverse event profile.

  18. A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose.

    Science.gov (United States)

    Velez de Mendizabal, Nieves; Jimenez-Mendez, Ricardo; Cooke, Erin; Montgomery, Carolyne J; Dawes, Joy; Rieder, Michael J; Aleksa, Katarina; Koren, Gideon; Jacobo-Cabral, Carlos O; Gonzalez-Ramirez, Rodrigo; Castañeda-Hernandez, Gilberto; Carleton, Bruce C

    2015-10-01

    Currently, the majority of the surgical procedures performed in paediatric hospitals are done on a day care basis, with post-operative pain being managed by caregivers at home. Pain after discharge of these post-operative children has historically been managed with oral codeine in combination with paracetamol (acetaminophen). Codeine is an opioid, which elicits its analgesic effects via metabolism to morphine and codeine-6-glucuronide. Oral morphine is a feasible alternative for outpatient analgesia; however, the pharmacokinetics of morphine after oral administration have been previously described only sparsely, and there is little information in healthy children. The clinical trial included 40 children from 2 to 6 years of age, with an American Society of Anaesthesiologists physical status classification of 1 or 2, who were undergoing surgical procedures requiring opioid analgesia. Morphine was orally administered prior to surgery in one of three doses: 0.1 mg/kg, 0.2 mg/kg and 0.3 mg/kg. Blood samples were collected for plasma morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations at 30, 60, 90, 120, 180 and 240 min after administration. All analyses were performed with the non-linear mixed-effect modelling software NONMEM version 7.2, using the first-order conditional estimation (FOCE) method. A pharmacokinetic model was developed to simultaneously describe the plasma profiles of morphine and its metabolites M3G and M6G after a single dose of oral morphine in young children (2-6 years of age). The disposition of morphine, M3G and M6G in plasma was best described by a one-compartment model. M3G and M6G metabolite formation was best described by a delay transit compartment, indicating a delay in the appearance of these two major metabolites. This model provides a foundation on which to further evaluate the use of oral morphine and its safety in young children. Longer follow-up time for morphine oral doses and incorporation of

  19. Oral contraception does not alter single dose saquinavir pharmacokinetics in women

    Science.gov (United States)

    Fröhlich, Margit; Burhenne, Jürgen; Martin-Facklam, Meret; Weiss, Johanna; von Wolff, Michael; Strowitzki, Thomas; Walter-Sack, Ingeborg; Haefeli, Walter E

    2004-01-01

    Aims Women experience more adverse drug reactions (ADR) to antiretroviral therapy than men. This may be attributed to higher plasma concentrations of protease inhibitors due to pharmacokinetic interactions with hormonal preparations. Thus, in the present study we aimed to investigate the influence of oral contraceptives (OC) on the pharmacokinetics of the protease inhibitor saquinavir. Methods Saquinavir was administered in a hard gelatin capsule formulation (Invirase®) to rule out confounding by pharmaceutical aids of the more frequently used soft gelatin capsule. After an overnight fast, eight healthy female participants ingested a single oral dose of 600 mg saquinavir immediately before and after the 19th dose of a combined, low dose OC (0.03 mg ethinylestradiol, 0.075 mg gestodene) in a prospective, fixed sequence study design. The first saquinavir application was scheduled on day 1, 2, or 3 of the individual menstrual cycle. Plasma concentrations of saquinavir and relative concentrations of its M2&M3-hydroxy metabolites were determined by LC/MS/MS for 48 h. Results Intake of OC resulted in a significant decrease in morning serum concentrations (before intake of OC, compared to day 19 of OC therapy) of 17β-estradiol by −23.4 pg ml−1 (57%, 95%CI: −76% to −37.4%); progesterone by −0.25 ng ml−1 (33%, 95%CI: −45.3% to −21.5%); follicle-stimulating hormone by −4.06 U l−1 (82%, 95%CI: −96.5% to −67.7%); and luteinizing hormone by −3.49 U l−1 (74%, 95%CI: −93 to −54.6%). Conversely, sexual hormone binding globulin serum concentrations increased by 83.6 nmol l−1 (205%, 95%CI: 32.2% to 377%). Pharmacokinetic parameters of saquinavir (AUC, Cmax, tmax, t1/2, CLR) were not affected by OC, nor was the relative metabolic ratio of saquinavir/M2&M3-hydroxy saquinavir. Furthermore, there was no association of serum hormone concentrations or MDR1-polymorphisms (C3435T and G2677T) with pharmacokinetic parameters of saquinavir. Conclusions There

  20. Therapeutic outcome of nasopharyngeal carcinoma with cranial nerve palsy: a single institution experience of 104 patients

    Directory of Open Access Journals (Sweden)

    Huang CC

    2017-04-01

    Full Text Available Chun-Chieh Huang,1,2 Fu-Min Fang,1 Hui-Chun Chen,1 Hsuan-Chih Hsu,1 Tai-Lin Huang,3 Yu-Li Su,3 Ya-Chun Chang4 1Department of Radiation Oncology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, 3Department of Hematology and Oncology, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China Purpose: Cranial nerve (CN palsy is the main symptom in patients with locally advanced nasopharyngeal carcinoma (NPC. This study aimed to evaluate the therapeutic outcome of NPC with CN palsy and to analyze the prognostic factors.Patients and methods: A total of 104 NPC patients with CN palsy curatively treated by conventional (n=44 or conformal (n=60 radiotherapy (RT were enrolled. Upper CN palsy was present in 81 patients, lower CN palsy in four patients, and both upper and lower CN palsy in 19 patients. Forty-one patients had CN palsy for >2 months before diagnosis.Results: Complete recovery of CN palsy was observed in 74 patients. The actuarial 5-year locoregional control (LRC, distant metastasis-free survival (DMFS, and overall survival (OS rates were 58.2%, 62.2%, and 38.4%, respectively. No significant difference was observed in CN recovery, LRC, DMFS, or OS for patients treated by conventional versus conformal technique. However, significant reduction of grade 3 or greater toxicities was found in those treated by the conformal technique (odds ratio =0.28.Conclusion: Patients with CN palsy presenting >2 months before diagnosis were hard to recover from palsy. The LRC, OS, and recovery from CN palsy did not significantly change with the treatment evolution. Patients with complete recovery from CN palsy had longer OS. Keywords: nasopharyngeal carcinoma, cranial nerve palsy, radiotherapy

  1. Dialysis dose in acute kidney injury: no time for therapeutic nihilism – a critical appraisal of the Acute Renal Failure Trial Network study

    Science.gov (United States)

    Ronco, Claudio; Cruz, Dinna; van Straaten, Helen Oudemans; Honore, Patrick; House, Andrew; Bin, Du; Gibney, Noel

    2008-01-01

    The optimal dialysis dose for acute kidney injury is a matter of great controversy. Clinical trials, predominantly single-center studies, have shown conflicting results. The Acute Renal Failure Trial Network (ATN) Study was designed to compare clinical outcomes between patients allocated to an intensive dose versus a less-intensive dose of renal replacement therapy. Recently, the results of this large randomized controlled multicenter study were published. The present article will discuss certain aspects of this trial: the overall design, the baseline patient characteristics, and comparison of the results with earlier studies. Finally, the article will address the implications of the ATN Study results for clinical practice. PMID:18983695

  2. Dialysis dose in acute kidney injury: no time for therapeutic nihilism--a critical appraisal of the Acute Renal Failure Trial Network study.

    Science.gov (United States)

    Ronco, Claudio; Cruz, Dinna; Oudemans van Straaten, Helen; Honore, Patrick; House, Andrew; Bin, Du; Gibney, Noel

    2008-01-01

    The optimal dialysis dose for acute kidney injury is a matter of great controversy. Clinical trials, predominantly single-center studies, have shown conflicting results. The Acute Renal Failure Trial Network (ATN) Study was designed to compare clinical outcomes between patients allocated to an intensive dose versus a less-intensive dose of renal replacement therapy. Recently, the results of this large randomized controlled multicenter study were published. The present article will discuss certain aspects of this trial: the overall design, the baseline patient characteristics, and comparison of the results with earlier studies. Finally, the article will address the implications of the ATN Study results for clinical practice.

  3. Efficacy of single dose of gentamicin in combination with metronidazole versus multiple doses for prevention of post-caesarean infection: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Lyimo Fadhili M

    2012-06-01

    Full Text Available Abstract Background Caesarean section is a commonly performed operation worldwide. It has been found to increase rates of maternal infectious morbidities more than five times when compared to vaginal delivery. Provision of intravenous prophylactic antibiotics 30 to 60 minutes prior to caesarean section has been found to reduce post-caesarean infection tremendously. Many centers recommend provision of a single dose of antibiotics, as repeated doses offer no benefit over a single dose. At Bugando Medical Centre post caesarean infection is among the top five causes of admission at the post-natal ward. Unfortunately, there is no consistent protocol for the administration of antibiotic prophylaxis to patients who are designated for caesarean section. Common practice and generally the clinician’s preference are to provide repeated dosages of antibiotic prophylaxis after caesarean section to most of the patients. This study aims to determine the comparative efficacy of a single dose of gentamicin in combination with metronidazole versus multiple doses for prevention of post caesarean infection. Methods/Design The study is an interventional, open-label, two-armed, randomized, single-center study conducted at Bugando Medical Centre Mwanza, Tanzania. It is an ongoing trial for the period of seven months; 490 eligible candidates will be enrolled in the study. Study subjects will be randomly allocated into two study arms; “A” and “B”. Candidates in “A” will receive a single dose of gentamicin in combination with metronidazole 30 to 60 minutes prior to the operation and candidates in “B” will receive the same drugs prior to the operation and continue with gentamicin and metronidazole for 24 hours. The two groups will be followed up for a period of one month and assessed for signs and symptoms of surgical site infection. Data will be extracted from a case record form and entered into Epi data3.1 software before being transferred to SPSS

  4. 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)

  5. A Multicenter Phase I/II Dose Escalation Study of Single-Dose Cidofovir Gel for Treatment of Recurrent Genital Herpes

    OpenAIRE

    Sacks, Stephen L.; Shafran, Stephen D.; Diaz-Mitoma, Francisco; Trottier, Sylvie; Sibbald, R. Gary; Hughes, April; Safrin, Sharon; Rudy, Jeff; McGuire, Brian; Jaffe, Howard S.

    1998-01-01

    A randomized, double-blind, clinic-initiated, sequential dose-escalation pilot study was performed to compare the safety and efficacy of single applications of 1, 3, and 5% cidofovir gel with placebo in the treatment of early, lesional, recurrent genital herpes at five Canadian outpatient sites. Ninety-six patients began treatment within 12 h of lesion appearance and were evaluated twice daily until healing of the lesion occurred. Cidofovir gel at all strengths significantly decreased the med...

  6. 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)

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

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Lulin, E-mail: lulin.yuan@duke.edu; Wu, Q. Jackie; Yin, Fang-Fang; Yoo, David [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Jiang, Yuliang [Department of Radiation Oncology, Peking University Third Hospital, Beijing, China, 100191 (China); Ge, Yaorong [Department of Software and Information Systems, University of North Carolina at Charlotte, Charlotte, North Carolina 28223 (United States)

    2014-02-15

    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

  8. Single coating of zinc ferrite renders magnetic nanomotors therapeutic and stable against agglomeration.

    Science.gov (United States)

    Venugopalan, Pooyath Lekshmy; Jain, Shilpee; Shivashankar, Srinivasrao; Ghosh, Ambarish

    2018-02-01

    Magnetic nanomotors with integrated theranostic capabilities can revolutionize biomedicine of the future. Typically, these nanomotors contain ferromagnetic materials, such that small magnetic fields can be used to maneuver and localize them in fluidic or gel-like environments. Motors with large permanent magnetic moments tend to agglomerate, which limits the scalability of this otherwise promising technology. Here, we demonstrate the application of a microwave-synthesized ferrite layer to reduce the agglomeration of helical ferromagnetic nanomotors by an order of magnitude, which allows them to be stored in a colloidal suspension for longer than six months and subsequently be manoeuvred with undiminished performance. The ferrite layer also rendered the nanomotors suitable as magnetic hyperthermia agents, as demonstrated by their cytotoxic effects on cancer cells. The two functionalities were inter-related since higher hyperthermia efficiency required a denser suspension, both of which were achieved in a single microwave-synthesized ferrite coating.

  9. Single-species versus dual-species probiotic supplementation as an emerging therapeutic strategy for obesity.

    Science.gov (United States)

    Karimi, G; Jamaluddin, R; Mohtarrudin, N; Ahmad, Z; Khazaai, H; Parvaneh, M

    2017-10-01

    Recent studies have reported beneficial effects of specific probiotics on obesity. However, the difference in the anti-obesity effects of probiotics as single species and dual species is still uncertain. Therefore, we aimed to compare the efficacy of single and dual species of bacteria on markers of obesity in high-fat diet-induced obese rats. A total of 40 male Sprague-Dawley rats were assigned to one of five groups of varying diets as follows: standard diet, high fat diet (HFD), HFD supplemented with Lactobacillus casei strain Shirota, HFD supplemented with Bifidobacterium longum and HFD supplemented with a mixture of these two bacterial species. After 15 weeks of supplementation, the animals were examined for changes in body weight, body fat, total count of bacteria in fecal, blood serum lipid profile, leptin, adiponectin and inflammatory biomarkers. Histological analysis of the liver and adipose tissue was performed and the hepatic mRNA expression levels of genes related to lipid metabolism were measured. It was found that probiotic supplementation of either B. longum or a mixture of B. longum and LcS bacteria significantly reduced weight and triglycerides in the HFD groups. Supplementation of B. longum bacteria showed better results in terms of modulating leptin level, fat mass, adipocyte size and lipoprotein lipase expression, as well as increasing adiponectin and peroxisome proliferator-activated receptors-γ expression compared to dual species of bacteria. No significant differences were observed in the total count of fecal bacteria, glucose and inflammatory biomarker levels between supplemented groups. B. longum supplementation in obesity was more beneficial in metabolic profile changes than the mixture species. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B

  10. Synovial fluid pharmacokinetics of tulathromycin, gamithromycin and florfenicol after a single subcutaneous dose in cattle.

    Science.gov (United States)

    Jones, Meredyth L; Washburn, Kevin E; Fajt, Virginia R; Rice, Somchai; Coetzee, Johann F

    2015-02-07

    Deep digital septic conditions represent some of the most refractory causes of severe lameness in cattle. The objective of this study was to determine the distribution of tulathromycin, gamithromycin and florfenicol into the synovial fluid of the metatarsophalangeal (MTP) joint of cattle after single subcutaneous administration of drug to evaluate the potential usefulness of these single-dose, long-acting antimicrobials for treating bacterial infections of the joints in cattle. Twelve cross-bred beef cows were randomly assigned to one of the drugs. Following subcutaneous administration, arthrocentesis of the left metatarsophalangeal joint was performed at various time points up to 240 hours post-injection, and samples were analyzed for drug concentration. In synovial fluid, florfenicol pharmacokinetic parameters estimates were: mean Tmax 7 +/- 2 hours, mean t½ 64.9 +/- 20.1 hours and mean AUC0-inf 154.0 +/- 26.2 ug*h/mL. Gamithromycin synovial fluid pharmacokinetic parameters estimates were: mean Tmax 8 hours, mean t½ 77.9 +/- 30.0 hours, and AUC0-inf 6.5 +/- 2.9 ug*h/mL. Tulathromycin pharmacokinetic parameters estimates in synovial fluid were: Tmax 19 +/- 10 hours, t½ 109 +/- 53.9 hours, and AUC0-inf 57.6 +/- 28.2 ug h/mL. In conclusion, synovial fluid concentrations of all three antimicrobials were higher for a longer duration than that of previously reported plasma values. Although clinical data are needed to confirm microbiological efficacy, florfenicol achieved a synovial fluid concentration greater than the MIC90 for F. necrophorum for at least 6 days.

  11. Pharmacokinetics and bioequivalence study of aniracetam after single-dose administration in healthy Chinese male volunteers.

    Science.gov (United States)

    Tian, Yuan; Zhang, Jing-Jing; Feng, Shu-Dan; Zhang, Zun-Jian; Chen, Yun

    2008-01-01

    The pharmacokinetics of aniracetam (CAS 72432-10-1) in Chinese healthy male volunteers was investigated for the first time. Twenty male volunteers were enrolled into this open, randomized, single blind two-sequence, two-period crossover study. Under fasting conditions, each subject received a single oral dose of 400 mg (2 x 200 mg/capsule) aniracetam as a test or reference formulation with a 3-day washout period between the two preparations. The plasma concentrations of aniracetam were analyzed by a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The pharmacokinetic parameters of the test and reference formulations were estimated as follows: The maximum plasma concentrations (Cmax) were 8.75 +/- 7.82 and 8.65 +/- 8.70 ng/mL, Tmax were 0.4 +/- 0.1 and 0.4 +/- 0.1 h, and plasma elimination half-lives (t(1/2)) were 0.47 +/- 0.16 and 0.49 +/- 0.24 h, respectively. The AUC(0-t) values demonstrated nearly identical bioavailability of aniracetam from the examined formulations. AUC(0-2.5) values were 4.53 +/- 6.62 and 4.76 +/- 6.65 ng h/mL, the areas under the plasma concentration-time curve (AUC(0-infinity) were 4.62 +/- 6.66 and 4.85 +/- 6.71 ng h/mL for the test and reference formulation, respectively. No statistical differences were observed for Cmax, and AUC(0-infinity) for aniracetam. The 90% confidence limits calculated for AUC and Cmax of aniracetam were within the standard bioequivalence range (80%-125% for AUC and Cmax). Therefore, the aniracetam test formulation can be regarded as bioequivalent to the aniracetam reference formulation.

  12. A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil.

    Science.gov (United States)

    An, Li-Jun; Zhang, Yang; Su, Zheng; Zhang, Xian-Long; Liu, Hai-Lin; Zhang, Zhi-Jie; Hu, Jian-Lin; Li, Shi-Tong

    2017-11-22

    Emergence agitation (EA) is a common phenomenon in preschool children during emergence from general anesthesia. This study evaluated the safety and efficacy of dezocine for emergence agitation in preschool children anesthetized with sevoflurane-remifentanil. A total of 100 preschool children, scheduled for elective laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia were randomized into two groups: Group C (n = 50) received Ringer's lactate 10 mL and Group D received Ringer's lactate 10 mL containing dezocine 0.1 mg/kg, postoperatively. Incidence of EA, defined as a score ≥ 3 on Aono's four point scale or Pediatric Anesthesia Emergence Delirium (PAED) score ≥ 10 in the PACU (10% vs. 76%) and the percentage of patients with severe EA (PAED score ≥ 13) (12% vs. 76%) were significantly lower in Group D compared to Group C (P preschool children that had undergone laparoscopic repair of an inguinal hernia by high ligation of the hernia sac under sevoflurane-remifentanil anesthesia. A single dose of dezocine suppresses emergence agitation in preschool children anesthetized with sevoflurane-remifentanil effectively: A double-blind, prospective, randomized, controlled study, Chinese Clinical Trial Registry (ID: ChiCTR-IOR-16010033), retrospectively registered on November 21, 2016.

  13. Single dose oral ranitidine improves MRCP image quality: a double-blind study

    Energy Technology Data Exchange (ETDEWEB)

    Bowes, M.T. [South Manchester University Hospitals NHS Trust, Wythenshawe, Manchester (United Kingdom); Martin, D.F. [South Manchester University Hospitals NHS Trust, Wythenshawe, Manchester (United Kingdom)]. E-mail: derrick.martin@smtr.nhs.uk; Melling, A. [South Manchester University Hospitals NHS Trust, Wythenshawe, Manchester (United Kingdom); Roberts, D. [South Manchester University Hospitals NHS Trust, Wythenshawe, Manchester (United Kingdom); Laasch, H.-U. [South Manchester University Hospitals NHS Trust, Wythenshawe, Manchester (United Kingdom); Sukumar, S. [South Manchester University Hospitals NHS Trust, Wythenshawe, Manchester (United Kingdom); Morris, J. [South Manchester University Hospitals NHS Trust, Wythenshawe, Manchester (United Kingdom)

    2007-01-15

    Aim: To investigate the possibility of whether a single 300 mg dose of ranitidine given orally 2-3 h before magnetic resonance cholangiopancreatography (MRCP) could reduce the signal from the stomach and duodenum, and thus increase the conspicuousness of the biliary tree. Materials and methods: Thirty-five volunteers (22 female, 13 male), (age range 21-50) were underwent MRCP in a double-blind, placebo-controlled, randomized, crossover trial on a Philips Intera 1.5 T machine using a phased array surface coil. Imaging was carried out in the coronal oblique plane. Six 40 mm sections were acquired at varying angles to delineate the biliary tree and pancreatic duct. The 70 examinations were blindly scored by three consultants experienced in cholangiography. Results: After ranitidine administration there was a significant decrease in signal from the stomach (mean = 17.7, p = 0.0005, CI 10, 25.3) and duodenum (mean = 18.4, p = 0.0005, 95%CI 9.6, 27.1) with a significant increase in conspicuousness of the distal common duct (mean = 7.7, p = 0.033, 95%CI 0.7, 14.7) and proximal common duct (mean = 8.7, p = 0.010 CI 2.2, 15.2). There were no adverse effects. Conclusion: Oral ranitidine is a cheap and effective agent to decrease signal from the upper gastrointestinal tract and to improve visibility of the biliary tree.

  14. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report

    Directory of Open Access Journals (Sweden)

    Flávia de L. Osório

    2015-03-01

    Full Text Available Objectives: Ayahuasca (AYA, a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Methods: Open-label trial conducted in an inpatient psychiatric unit. Results: Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D, the Montgomery-Åsberg Depression Rating Scale (MADRS, and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS. AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. Conclusions: These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

  15. Antidepressant effects of a single dose of ayahuasca in patients with recurrent depression: a preliminary report.

    Science.gov (United States)

    Osório, Flávia de L; Sanches, Rafael F; Macedo, Ligia R; Santos, Rafael G dos; Maia-de-Oliveira, João P; Wichert-Ana, Lauro; Araujo, Draulio B de; Riba, Jordi; Crippa, José A; Hallak, Jaime E

    2015-01-01

    Ayahuasca (AYA), a natural psychedelic brew prepared from Amazonian plants and rich in dimethyltryptamine (DMT) and harmine, causes effects of subjective well-being and may therefore have antidepressant actions. This study sought to evaluate the effects of a single dose of AYA in six volunteers with a current depressive episode. Open-label trial conducted in an inpatient psychiatric unit. Statistically significant reductions of up to 82% in depressive scores were observed between baseline and 1, 7, and 21 days after AYA administration, as measured on the Hamilton Rating Scale for Depression (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Anxious-Depression subscale of the Brief Psychiatric Rating Scale (BPRS). AYA administration resulted in nonsignificant changes in Young Mania Rating Scale (YMRS) scores and in the thinking disorder subscale of the BPRS, suggesting that AYA does not induce episodes of mania and/or hypomania in patients with mood disorders and that modifications in thought content, which could indicate psychedelic effects, are not essential for mood improvement. These results suggest that AYA has fast-acting anxiolytic and antidepressant effects in patients with a depressive disorder.

  16. Single dose oral ranitidine improves MRCP image quality: a double-blind study

    International Nuclear Information System (INIS)

    Bowes, M.T.; Martin, D.F.; Melling, A.; Roberts, D.; Laasch, H.-U.; Sukumar, S.; Morris, J.

    2007-01-01

    Aim: To investigate the possibility of whether a single 300 mg dose of ranitidine given orally 2-3 h before magnetic resonance cholangiopancreatography (MRCP) could reduce the signal from the stomach and duodenum, and thus increase the conspicuousness of the biliary tree. Materials and methods: Thirty-five volunteers (22 female, 13 male), (age range 21-50) were underwent MRCP in a double-blind, placebo-controlled, randomized, crossover trial on a Philips Intera 1.5 T machine using a phased array surface coil. Imaging was carried out in the coronal oblique plane. Six 40 mm sections were acquired at varying angles to delineate the biliary tree and pancreatic duct. The 70 examinations were blindly scored by three consultants experienced in cholangiography. Results: After ranitidine administration there was a significant decrease in signal from the stomach (mean = 17.7, p = 0.0005, CI 10, 25.3) and duodenum (mean = 18.4, p = 0.0005, 95%CI 9.6, 27.1) with a significant increase in conspicuousness of the distal common duct (mean = 7.7, p = 0.033, 95%CI 0.7, 14.7) and proximal common duct (mean = 8.7, p = 0.010 CI 2.2, 15.2). There were no adverse effects. Conclusion: Oral ranitidine is a cheap and effective agent to decrease signal from the upper gastrointestinal tract and to improve visibility of the biliary tree

  17. Topiramate modulates trigeminal pain processing in thalamo-cortical networks in humans after single dose administration.

    Science.gov (United States)

    Hebestreit, Julia M; May, Arne

    2017-01-01

    Migraine is the sixth most common cause of disability in the world. Preventive migraine treatment is used to reduce frequency, severity and duration of attacks and therefore lightens the burden on the patients' quality of life and reduces disability. Topiramate is one of the preventive migraine treatments of proven efficacy. The mechanism of action underlying the preventive effect of topiramate in migraine remains largely unknown. Using functional magnetic resonance imaging (fMRI) we examined the central effects of a single dose of topiramate (100mg) on trigeminal pain in humans, compared to placebo (mannitol). In this prospective, within subject, randomized, placebo-controlled and double-blind study, 23 healthy participants received a standardized nociceptive trigeminal stimulation and control stimuli whilst being in the scanner. No differences in the subjective intensity ratings of the painful stimuli were observed between topiramate and placebo sessions. In contrast, topiramate significantly decreased the activity in the thalamus and other pain processing areas. Additionally, topiramate increased functional coupling between the thalamus and several brain regions such as the bilateral precuneus, posterior cingulate cortex and secondary somatosensory cortex. These data suggest that topiramate exhibits modulating effects on nociceptive processing in thalamo-cortical networks during trigeminal pain and that the preventive effect of topiramate on frequent migraine is probably mediated by an effect on thalamo-cortical networks.

  18. Therapeutic response to single intravenous bolus administration of formate dehydrogenase in methanol-intoxicated rats.

    Science.gov (United States)

    Muthuvel, Arumugham; Rajamani, Rathinam; Sheeladevi, Rathinasamy

    2006-02-20

    Methanol remains to be a major public and environmental health hazard. Formic acid is the toxic metabolite responsible for the metabolic acidosis observed in methanol poisoning in humans, in non-human primates and in folate-depleted rodents. Cytochrome oxidase inhibition by formate leads to lactic acid accumulation, which contributes significantly to metabolic acidosis. Toxic effects in human beings are characterized by formic acidemia, metabolic acidosis, ocular toxicity, nervous system depression, blindness, coma and death. Elimination of formate is one of the principles of management in methanol poisoning. Hemodialysis facility is not readily available in all the places, in developing countries like India. Formate dehydrogenase (EC 1.2.1.2) acts directly over formate and converts formate into CO(2) in the presence of NAD. Effect of single intravenous bolus infusion of formate dehydrogenase, obtained from Candida boidinii; in methanol-intoxicated folate deficient rat model was evaluated. Folate depletion induced by methotrexate (MTX) treatment. Carbicarb (Carb) (equimolar solution of sodium carbonate and sodium bicarbonate) was used to treat metabolic acidosis. Experimental design consists of seven groups, namely Saline control, methanol control, MTX control, Enzyme control, MTX-methanol control, MTX-methanol-Carb and MTX-methanol-Carb-Enz group. Male wistar rats treated with MTX (0.3mg/kg) for a week, were injected (i.p.) with methanol (4 gm/kg), 12h latter, Carbicarb solution was infused, following this enzyme was infused (i.v.) in bolus. Blood samples were collected every 15 min for an hour from the cannulated left jugular vein and blood methanol, formate were estimated, respectively, with HPLC and fluorimetric assay. Blood pH, blood gases pO(2), pCO(2) and bicarbonate were monitored with blood gas analyzer in order to evaluate acid base status of the animal. Results obtained show that there is significant elimination of formate within 15 min. It may be

  19. Study on radiation dose in single-source and triple-source helical cone-beam scanning

    International Nuclear Information System (INIS)

    Lv Yang; Zhao Jun; Zhuang Tiange; Chen Kemin

    2008-01-01

    In this work we discuss the radiation area of helical cone-beam scanning and present the formulae to calculate the radiation dosage of single-source and triple-source helical cone-beam scanning. The results reveal that the radiation dose of triple-source helical cone-beam scanning is equal to that of single-source helical cone-beam scanning. (authors)

  20. Comparison between Single-Dose Esomeprazole- and Pantoprazole-Based Triple Therapy on the Effectiveness for Helicobacter pylori Eradication in Taiwanese Population

    Directory of Open Access Journals (Sweden)

    Hsiang-Yao Shih

    2012-01-01

    Full Text Available Background and Study Aims. To compare the effectiveness of two regimens, single-dose esomeprazole- and pantoprazole-based triple therapy, for Helicobacter pylori (H. pylori eradication. Patients and Methods. A total of 453 patients were enrolled for H. pylori eradication. They were randomly assigned to either EAC group (Esomeprazole 40 mg once daily, Amoxicillin 1 g twice daily, Clarithromycin 500 mg twice daily for 7 days or PAC group (Pantoprazole 40 mg twice daily, Amoxicillin 1 g twice daily, Clarithromycin 500 mg twice daily for 7 days. Follow-up endoscopy or urea breath test was scheduled 12–16 weeks after the eradication to evaluate the therapeutic response. Results. Higher eradication rate in EAC group than PAC group was shown by intention-to-treat analysis (EAC 72% versus PAC 55%, P<0.05 and per-protocol analysis (EAC 91% versus PAC 72%, P<0.05. The incidence of adverse effects (EAC 19% versus PAC 17%, P=0.712 and the compliance (EAC 87% versus PAC 91%, P=0.083 were comparable between these 2 groups. Conclusions. Single-dose esomeprazole-based triple therapy is effective for H. pylori eradication.

  1. Pharmacokinetics, pharmacodynamics and safety of CEP-26401, a high-affinity histamine-3 receptor antagonist, following single and multiple dosing in healthy subjects.

    Science.gov (United States)

    Spiegelstein, Ofer; Stevens, Jasper; Van Gerven, Joop; Nathan, Pradeep J; Maynard, James P; Mayleben, David W; Hellriegel, Edward; Yang, Ronghua

    2016-10-01

    CEP-26401 is a novel orally active, brain-penetrant, high-affinity histamine H3 receptor (H3R) antagonist, with potential therapeutic utility in cognition enhancement. Two randomized, double-blind, placebo-controlled dose escalation studies with single (0.02 to 5 mg) or multiple administration (0.02 to 0.5 mg once daily) of CEP-26401 were conducted in healthy subjects. Plasma and urine samples were collected to investigate CEP-26401 pharmacokinetics. Pharmacodynamic endpoints included a subset of tasks from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and nocturnal polysomnography. Population pharmacokinetic-pharmacodynamic modeling was conducted on one CANTAB and one polysomnography parameter of interest. CEP-26401 was slowly absorbed (median tmax range 3-6 hours) and the mean terminal elimination half-life ranged from 24-60 hours. Steady-state plasma concentrations were achieved within six days of dosing. CEP-26401 exhibits dose- and time-independent pharmacokinetics, and renal excretion is a major elimination pathway. CEP-26401 had a dose-dependent negative effect on sleep, with some positive effects on certain CANTAB cognitive parameters seen at lower concentrations. The derived three compartment population pharmacokinetic model, with first-order absorption and elimination, accurately described the available pharmacokinetic data. CEP-26401 was generally well tolerated up to 0.5 mg/day with most common treatment related adverse events being headache and insomnia. Further clinical studies are required to establish the potential of low-dose CEP-26401 in cognition enhancement. © The Author(s) 2016.

  2. Development of a fibre-optic dosemeter to measure the skin dose and percentage depth dose in the build-up region of therapeutic photon beams

    International Nuclear Information System (INIS)

    Kim, K. A.; Yoo, W. J.; Jang, K. W.; Moon, J.; Han, K. T.; Jeon, D.; Park, J. Y.; Cha, E. J.; Lee, B.

    2013-01-01

    In this study, a fibre-optic dosemeter (FOD) using an organic scintillator with a diameter of 0.5 mm for photon-beam therapy dosimetry was fabricated. The fabricated dosemeter has many advantages, including water equivalence, high spatial resolution, remote sensing and real-time measurement. The scintillating light generated from an organic-dosemeter probe embedded in a solid-water stack phantom is guided to a photomultiplier tube and an electrometer via 20 m of plastic optical fibre. Using this FOD, the skin dose and the percentage depth dose in the build-up region according to the depths of a solid-water stack phantom are measured with 6- and 15-MV photon-beam energies with field sizes of 10310 and 20320 cm 2 , respectively. The results are compared with those measured using conventional dosimetry films. It is expected that the proposed FOD can be effectively used in radiotherapy dosimetry for accurate measurement of the skin dose and the depth dose distribution in the build-up region due to its high spatial resolution. (authors)

  3. Tumor response and toxicity after single high-dose versus standard five-day divided-dose dactinomycin in childhood rhabdomyosarcoma.

    Science.gov (United States)

    Carli, M; Pastore, G; Perilongo, G; Grotto, P; De Bernardi, B; Ceci, A; Di Tullio, M; Madon, E; Pianca, C; Paolucci, G

    1988-04-01

    This report deals with a randomized prospective multicentric clinical trial in childhood rhabdomyosarcoma (RMS) conducted to evaluate the toxicity and the effectiveness of dactinomycin (ACT-D) administered as high, single doses v five-day, divided doses administered in combination with vincristine (VCR) and cyclophosphamide (CYC). Fifty-five group III evaluable patients (pts) less than 15 years of age with tumor size greater than 5 cm in diameter, without high-risk features of CNS involvement, and 15 group IV RMS pts were randomized to receive VAC as primary chemotherapy (CT): VCR, 1.5 mg/m2 intravenously (IV) days 1 and 8; CYC, 275 mg/m2 IV days 1 through 5; and ACT-D, 0.45 mg/m2 IV days 1 through 5 every 28 days for three cycles (33 pts), or VAC-M: CYC, 150 mg/m2 intramuscularly (IM) days 1 through 7; VCR, 2.0 mg/m2 IV day 8; and ACT-D, 1.7 mg/m2 IV day 8 every 21 days for four cycles (37 pts). Major responses (complete plus partial responses [PR]) were obtained in 67% of the VAC pts and in 70% of the VAC-M pts. Toxic effects were low, and no increased toxicity was observed in pts treated with high, single-dose ACT-D. These results confirm the effectiveness and feasibility of single, high doses of ACT-D with the advantage of requiring less pt hospitalization.

  4. [Single dose toxicity studies of calcipotriol (MC903) in rats and dogs].

    Science.gov (United States)

    Imaizumi, T; Tsuruta, M; Kitagaki, T; Ono, M; Shirakawa, K; Nagata, M; Konishi, R

    1996-07-01

    A single dose toxicity of calcipotriol (MC903), an anti-psoriasic agent, administered subcutaneously (s.c.) and percutaneously (p.c.) was studied in Slc:SD rats (s.c. and p.c.) and beagle dogs (s.c.). The LD50 values of MC903 were as follows: rats, 2.19 mg/kg in males and 2.51 mg/kg in females by s.c., and more than 15 mg/kg in both sexes by p.c.; dogs, more than 1.5 mg/kg in males by p.c. No sexual difference was noted in LD50 values of rats. Death of rats was observed from 1 to 3 days after administration by both routes. Dead animals showed decreases in body weight and locomotor activity, reddish tear, abnormal gait and dirty hair by both routes. Furthermore, dead animals administered by s.c. showed salivation, nasal discharge, piloerection, ptosis, diarrhea, urorrhea, nasal and vaginal bleeding, subnormal temperature, loose stool, cyanosis, irregular and deep respirations, clonic and tonic convulsions. Survival of rats showed similar signs to those of dead animals except for nasal discharge, nasal and vaginal bleeding, cyanosis, agonal respiration and convulsion. Discoloration of the kidney, white patch of the heart and a dilatation of the stomach wall were observed on macroscopic examinations. No mortalities were observed in dogs which showed vomiting, conjunctival congestion, circumoral and auricular reddenings, periblepharal purplish reddening, decreases in locomotor activity and defecation, emaciation, eye discharge, skin desquamation of treated area and an increase in respiration. On macroscopic examination, desquamation of the skin, reddening of the circumoral mucosa, pale gray yellow striations in renal tubules of the cortex and discoloration of the thyroid were observed. Histopathological findings revealed epidermal thickening with parakeratosis, fibrocytes, hypertrophy and hypersecretion of the sebaceous and sweat glands, formation of epitheloid glanulomas and infiltration of neutrophils in the subcutaneous tissues. Furthermore, moderate calcium

  5. Quality of life after palliative treatment for oesophageal carcinoma -- a prospective comparison between stent placement and single dose brachytherapy

    NARCIS (Netherlands)

    Homs, Marjolein Y. V.; Essink-Bot, Marie-Louise; Borsboom, Gerard J. J. M.; Steyerberg, Ewout W.; Siersema, Peter D.

    2004-01-01

    Metal stent placement and single dose brachytherapy are commonly used treatment modalities for the palliation of inoperable oesophageal carcinoma. We investigated generic and disease-specific health-related quality of life (HRQoL) after these palliative treatments. Patients with dysphagia from

  6. Brief report: enzyme inducers reduce elimination half-life after a single dose of nevirapine in healthy women.

    NARCIS (Netherlands)

    L'homme, R.F.A.; Dijkema, T.; Ven, A.J.A.M. van der; Burger, D.M.

    2006-01-01

    OBJECTIVE: Single-dose nevirapine (SD-NVP) to prevent mother-to-child transmission (MTCT) of HIV is associated with development of NVP resistance, probably because of its long half-life in combination with a low genetic barrier to resistance. The objective of this study was to find enzyme inducers

  7. Negligible risk of inducing resistance in Mycobacterium tuberculosis with single-dose rifampicin as post-exposure prophylaxis for leprosy

    NARCIS (Netherlands)

    Mieras, L. (Liesbeth); R. Anthony (Richard); W.H. van Brakel (Wim); Bratschi, M.W. (Martin W.); van den Broek, J. (Jacques); Cambau, E. (Emmanuelle); Cavaliero, A. (Arielle); Kasang, C. (Christa); Perera, G. (Geethal); Reichman, L. (Lee); J.H. Richardus (Jan Hendrik); P. Saunderson (Paul); Steinmann, P. (Peter); Yew, W.W. (Wing Wai)

    2016-01-01

    textabstractPost-exposure prophylaxis (PEP) for leprosy is administered as one single dose of rifampicin (SDR) to the contacts of newly diagnosed leprosy patients. SDR reduces the risk of developing leprosy among contacts by around 60 % in the first 2-3 years after receiving SDR. In countries where

  8. 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

  9. 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...

  10. Effects of a Single Dose of Parecoxib on Inflammatory Response and Ischemic Tubular Injury Caused by Hemorrhagic Shock in Rats

    Directory of Open Access Journals (Sweden)

    Mariana Takaku

    2018-01-01

    Full Text Available Parecoxib, a selective COX-2 inhibitor, is used to improve analgesia in postoperative procedures. Here we evaluated whether pretreatment with a single dose of parecoxib affects the function, cell injury, and inflammatory response of the kidney of rats subjected to acute hemorrhage. Inflammatory response was determined according to serum and renal tissue cytokine levels (IL-1α, IL-1β, IL-6, IL-10, and TNF-α. Forty-four adult Wistar rats anesthetized with sevoflurane were randomized into four groups: placebo/no hemorrhage (Plc/NH; parecoxib/no hemorrhage (Pcx/NH; placebo/hemorrhage (Plc/H; and parecoxib/hemorrhage (Pcx/H. Pcx groups received a single dose of intravenous parecoxib while Plc groups received a single dose of placebo (isotonic saline. Animals in hemorrhage groups underwent bleeding of 30% of blood volume. Renal function and renal histology were then evaluated. Plc/H showed the highest serum levels of cytokines, suggesting that pretreatment with parecoxib reduced the inflammatory response in rats subjected to hemorrhage. No difference in tissue cytokine levels between groups was observed. Plc/H showed higher percentage of tubular dilation and degeneration, indicating that parecoxib inhibited tubular injury resulting from renal hypoperfusion. Our findings indicate that pretreatment with a single dose of parecoxib reduced the inflammatory response and tubular renal injury without altering renal function in rats undergoing acute hemorrhage.

  11. 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

  12. Pharmacokinetic profile of nomegestrol acetate and 17β-estradiol after multiple and single dosing in healthy women.

    Science.gov (United States)

    Gerrits, Mireille G F; Schnabel, Peter G; Post, Teun M; Peeters, Pierre A M

    2013-02-01

    The pharmacokinetics of the monophasic oral contraceptive nomegestrol acetate (NOMAC) plus 17β-estradiol (E(2)) were investigated after a single dose and multiple dosing. NOMAC/E2 (2.5 mg/1.5 mg) was administered daily to healthy women (18-50 years, n=23) for 24 days; blood samples for pharmacokinetic analysis were obtained on Day 24 and again, after a 10-day pill-free interval, on Day 35 after a single dose. NOMAC reached steady state after 5 days with mean ±standard deviation (SD) trough NOMAC concentration (C(av)) of 4.4±1.4 ng/mL. On Day 24, mean±SD peak NOMAC concentration (Cmax, 12.3±3.5 ng/mL) was reached in mean 1.5 h (t(max)); the mean±SD elimination half-life (t(½)) was 45.9±15.3 h. After a single dose, NOMAC mean±SD C(max) was 7.2±2.0 ng/mL and mean±SD t(½) was 41.9±16.2 h. On Day 24, E2 mean±SD C(av) was 50.3±25.7 pg/mL; mean±SD Cmax was 86.0±51.3 pg/mL. After a single dose, mean±SD E2 Cmax was 253±179 pg/mL. These data demonstrate that NOMAC/E2 has a pharmacokinetic profile consistent with once-daily dosing. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. 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

  14. jConsequences of two different doses to the lungs during a single dose of total body irradiation: Results of a radomized study on 85 patients

    International Nuclear Information System (INIS)

    Girinsky, T.; Socie, G.; Ammarguellat, H.

    1994-01-01

    To evaluate the incidence of lung complications and leukemia recurrences after two different doses to the lungs during total body irradiation. Seventy-nine patients with acute leukemia (AML or ALL) in first complete remission or chronic myeloid leukemia in the chronic phase, five patients with high grade lymphoma, and one with chronic lymphocytic leukemia were entered in the study. They were given a single dose of total body irradiation (10 Gy over 4 h) with two different doses to the lungs (6 Gy or 8 Gy) prior to bone marrow transplantation. The median dose rate was 0.04 Gy/min. The median follow-up for both groups of patients was 24 months. The actuarial 5-year overall survival rate was similar in both groups, 59% and 43% for patients given 8 Gy and 6 Gy to the lungs, respectively. The lung complication rate was similar in the two groups (28% vs. 22% for the 8 Gy and 6 Gy group, respectively). The actuarial leukemia recurrence rate was significantly higher in the group of patients given 6 Gy to the lungs (25%) vs. 0% in the 8 Gy group. Interestingly, fall recurrences occurred in the group of patients who were given 6 Gy to the lungs, who had acute leukemia, and no chromic graft vs. host disease (GVHD). Although the number of patients was not very large and the follow-up relatively short, these findings suggest that a lower dose to the lungs could lead to an increased incidence of leukemia recurrences due to a lower dose to the thoracic wall or to a lower incidence of chronic GVHD. 9 refs., 4 figs., 1 tab

  15. 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)

  16. Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study.

    Science.gov (United States)

    Sanches, Rafael Faria; de Lima Osório, Flávia; Dos Santos, Rafael G; Macedo, Ligia R H; Maia-de-Oliveira, João Paulo; Wichert-Ana, Lauro; de Araujo, Draulio Barros; Riba, Jordi; Crippa, José Alexandre S; Hallak, Jaime E C

    2016-02-01

    Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Åsberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.

  17. SINGLE-DOSE CEFAZOLIN PROPHYLAXIS IN ELECTIVE LSCS- A PROSPECTIVE OBSERVATIONAL STUDY

    Directory of Open Access Journals (Sweden)

    Mannasseril Antony Kunjamma

    2017-10-01

    Full Text Available BACKGROUND Surgical site infections are the most common nosocomial infections. Postoperative complications, especially surgical site infections can double the length of time a patient stays in hospital and increase the cost of healthcare. Antibiotic prophylaxis before surgery has evolved over last twenty years and is definitely valuable to reduce postoperative wound infection. Obstetric surgeries are considered as clean contaminated wounds where antibiotic prophylaxis has proven beneficial in preventing postoperative complications, antibiotic resistance and economic burden. But, in countries like India, even a large group of obstetricians are reluctant to follow it. Hence, this study was conducted. The aim of the study is to study the effectiveness of single-dose cefazolin prophylaxis in preventing postoperative complications in patients undergoing elective cesarean compared to postoperative antibiotics. MATERIALS AND METHODS This was a prospective observational study conducted in the Department of Obstetrics and Gynaecology, Medical College, Kottayam, from January 2014-December 2014. After obtaining permission from the hospital ethical committee for research, hundred patients undergoing elective cesarean in our hospital were selected for the study using strict inclusion and exclusion criteria of which fifty patients received injection cefazolin 2g intravenously one hour before surgery. Remaining fifty patients who were matched for age, parity and body mass index were given cefotaxime and metronidazole pre and postoperatively. All these patients were followed up postoperatively for complications, antibiotic change and duration of hospital stay. Statistical analysis done using suitable software. RESULTS Complications were comparable in those receiving prophylactic cefazolin and those receiving postoperative antibiotics. Both groups required antibiotic change for complications. Patients requiring prolonged hospital stay was comparable in both the

  18. Effects of Single Dose Energy Drink on QT and P-Wave Dispersion

    Directory of Open Access Journals (Sweden)

    Huseyin Arinc

    2013-12-01

    Full Text Available INTRODUCTION: Aim of this study is to evaluate the cardiac electrophysiological effects of energy drink (Red Bull on QT and P duration and dispersion on surface electrocardiogram. METHODS: Twenty healthy volunteers older than 17 years of age were included the study. Subjects with a cardiac rhythm except sinus rhythm, history of atrial or ventricular arrhythmia, family history of premature sudden cardiac death, palpitations, T-wave abnormalities, QTc interval greater than 440 milliseconds, or those P-waves and QT intervals unavailable in at least eight ECG leads were excluded. Subjects having insomnia, lactose intolerance, caffeine allergy, recurrent headaches, depression, any psychiatric condition, and history of alcohol or drug abuse, pregnant or lactating women were also excluded from participation. 12 lead ECG was obtained before and after consumption of 250 cc enegry drink. QT and P-wave dispersion was calculated. RESULTS: No significant difference have occurred in heart rate (79 ± 14 vs.81 ±13, p=0.68, systolic pressure (114 ± 14 vs.118 ± 16,p=0.38, diastolic blood pressure (74 ± 12 vs.76 ± 14, p=0.64, QT dispersion (58 ± 12 vs. 57 ± 22, p= 0.785 and P-wave dispersion (37 ± 7 vs. 36 ± 13, p= 0.755 between before and 2 hours after consumption of energy drink. DISCUSSION AND CONCLUSION: Consumption of single dose energy drink doesn't affect QT dispersion and P-wave dispersion, heart rate and blood pressure in healthy adults.

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

    Science.gov (United States)

    De Luna-Bertos, E.; Ramos-Torrecillas, J.; García-Martínez, O.; Guildford, A.; Santin, M.; Ruiz, C.

    2013-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to reduce pain and inflammation. However, their effect on bone metabolisms is not well known, and results in the literature are contradictory. The present study focusses on the effect of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid, at therapeutic doses, on different biochemical and phenotypic pathways in human osteoblast-like cells. Osteoblasts (MG-63 cell line) were incubated in culture medium with 1–10 μM of dexketoprofen, ketorolac, metamizole, and acetylsalicylic acid. Flow cytometry was used to study antigenic profile and phagocytic activity. The osteoblastic differentiation was evaluated by mineralization and synthesis of collagen fibers by microscopy and alkaline phosphatase activity (ALP) by spectrophotometric assay. Short-term treatment with therapeutic doses of NSAIDs modulated differentiation, antigenic profile, and phagocyte activity of osteoblast-like cells. The treatment reduced ALP synthesis and matrix mineralization. However, nonsignificant differences were observed on collagen syntheses after treatments. The percentage of CD54 expression was increased with all treatments. CD80, CD86, and HLA-DR showed a decreased expression, which depended on NSAID and the dose applied. The treatments also decreased phagocyte activity in this cellular population. The results of this paper provide evidences that NSAIDs inhibit the osteoblast differentiation process thus reducing their ability to produce new bone mineralized extracellular matrix. PMID:24170983

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

    Directory of Open Access Journals (Sweden)

    E. De Luna-Bertos

    2013-01-01

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

  1. The different biological effects of single, fractioned and continuous low dose rate radiation on CL187 colorectal cancer cell line

    International Nuclear Information System (INIS)

    Wang Hao; Wang Junjie; Qu Ang; Li Jin'na; Liu Jingjia

    2012-01-01

    Objective: To investigate the effect and underlying mechanism of single, fractioned and continuous low dose rate radiation on CL187 colorectal cancer cell line. Methods: CL187 cells were exposed to 6 MV X-rays at a high dose rate of 4 Gy/min and 125 I seed at a low dose rate of 2.77 cGy/h with three groups:single dose radiation group (SDR), fractioned dose radiation group (FDR) by 2 Gy/f, and continuous low dose rate radiation group (CLDR). The radiation doses were 0, 2, 4 and 8 Gy. Total cell number and cell viability were determined by trypan blue. Clone forming assay was used to evaluate the cell proliferation ability. The percentage of apoptosis cells was analyzed by flow cytometry. Western blot was used to detect the protein expression levels of PHLPP2, PTEN and Bax. Results: Compared with SDR and FDR groups, the total cell number and survival fraction of CLDR group decreased. The relative biological effect (RBE) for 125 I seeds compared with 6 MV X-rays was 1.41. The percentage of apoptosis cells of CLDR group was significantly increased (t=-15.08, -11.99, P<0.05). The expression level of Bax increased in CLDR group, while no obvious changes were observed on PHLPP2 and PTEN among three groups. Conclusions: The expression level of PHLPP2 increases in SDR, FDR and CLDR group, while it seems that it was not influenced by dose rate. The expression level of Bax increased in three groups, while more colorectal CL187 cells in CLDR group may be killed due to the increase of Bax expression. (authors)

  2. A single institution study of radiation dose received from CT imaging: A comparison to Malaysian NDRL

    International Nuclear Information System (INIS)

    Osman, N D; Shamsuri, S B M; Razali, M A S M; Isa, S M; Tan, Y W

    2017-01-01

    Advancement of CT technology has led to an increase in CT scanning as it improves the diagnosis. However, it is important to assess health risk of patients associated with ionising radiation received from CT. This study evaluated current dose distributions at Advanced Medical and Dental Institute (AMDI), Malaysia and was used to establish Local Diagnostic Reference Level (LDRL). Dose indicators such as CT Dose Index (CTDI vol and CTDI w ) and Dose-Length Product (DLP) were gathered for all routine CT examinations performed at the Imaging Unit, AMDI from January 2015 to June 2016. The first and third quartile values for each dose indicator were determined. A total of 364 CT studies were performed during that period with the highest number of cases being Thorax-Abdomen-Pelvis (TAP) study (57% of total study). The CTDI w ranged between 2.0 mGy to 23.4 mGy per procedure. DLP values were ranged between 94 mGy.cm to 1687 mGy.cm. The local dose data was compared with the national DRL to monitor the current CT practice at AMDI and LDRL will be established from the calculated third quartile values of dose distribution. From the results, some of the local dose values exceeded the Malaysian and further evaluation is important to ensure the dose optimisation for patients. (paper)

  3. A single institution study of radiation dose received from CT imaging: A comparison to Malaysian NDRL

    Science.gov (United States)

    Osman, N. D.; Shamsuri, S. B. M.; Tan, Y. W.; Razali, M. A. S. M.; Isa, S. M.

    2017-05-01

    Advancement of CT technology has led to an increase in CT scanning as it improves the diagnosis. However, it is important to assess health risk of patients associated with ionising radiation received from CT. This study evaluated current dose distributions at Advanced Medical and Dental Institute (AMDI), Malaysia and was used to establish Local Diagnostic Reference Level (LDRL). Dose indicators such as CT Dose Index (CTDIvol and CTDIw) and Dose-Length Product (DLP) were gathered for all routine CT examinations performed at the Imaging Unit, AMDI from January 2015 to June 2016. The first and third quartile values for each dose indicator were determined. A total of 364 CT studies were performed during that period with the highest number of cases being Thorax-Abdomen-Pelvis (TAP) study (57% of total study). The CTDIw ranged between 2.0 mGy to 23.4 mGy per procedure. DLP values were ranged between 94 mGy.cm to 1687 mGy.cm. The local dose data was compared with the national DRL to monitor the current CT practice at AMDI and LDRL will be established from the calculated third quartile values of dose distribution. From the results, some of the local dose values exceeded the Malaysian and further evaluation is important to ensure the dose optimisation for patients.

  4. 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

  5. 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)

  6. A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration.

    Science.gov (United States)

    Sun, Changling; Wang, Xueling; Zheng, Zhaozhu; Chen, Dongye; Wang, Xiaoqin; Shi, Fuxin; Yu, Dehong; Wu, Hao

    2015-01-01

    This study aimed to investigate the sustained drug release properties and hearing protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA) stealth nanoparticles loaded with dexamethasone (DEX). DEX was fabricated into PEG-PLA nanoparticles using an emulsion and evaporation technique, as previously reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs) had a hydrodynamic diameter of 130±4.78 nm, and a zeta potential of -26.13±3.28 mV. The in vitro release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4), 5 days in artificial perilymph (pH 7.4), and 1 day in rat plasma. Coumarin 6-labeled NPs placed onto the round window membrane (RWM) of guinea pigs penetrated RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto the RWM of guinea pigs by a single-dose administration continuously released DEX in 48 hours, which was significantly longer than the free DEX that was cleared out within 12 hours after administration at the same dose. Further functional studies showed that locally administrated single-dose DEX-NPs effectively preserved outer hair cells in guinea pigs after cisplatin insult and thus significantly attenuated hearing loss at 4 kHz and 8 kHz frequencies when compared to the control of free DEX formulation. Histological analyses indicated that the administration of DEX-NPs did not induce local inflammatory responses. Therefore, prolonged delivery of DEX by PEG-PLA nanoparticles through local RWM diffusion (administration) significantly protected the hair cells and auditory function in guinea pigs from cisplatin toxicity, as determined at both histological and functional levels, suggesting the potential therapeutic benefits in clinical applications.

  7. 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

    -bleached and gamma-irradiated samples. We show that there is a linear relationship between the over-dispersion and the mean dose. Knowing this uncertainty relationship enables us to estimate the burial dose by comparing the predicted uncertainty on the running mean with that calculated from actual dispersion. (c...

  8. Single-dose methotrexate injection for treatment of ectopic pregnancy in women with relatively low levels of human chorionic gonadotropin.

    Science.gov (United States)

    Krissi, Haim; Peled, Yoav; Eitan, Ram; Bishara, Amani; Goldchmit, Chen; Ben-Haroush, Avi

    2013-05-01

    To evaluate potential risk factors at admission for failed single-dose methotrexate injection in women with ectopic pregnancy. File review of a tertiary medical center in Israel yielded 102 consecutive patients with ectopic pregnancy initially treated with single-dose methotrexate. Overall successful treatment was defined as normalization of human chorionic gonadotropin (hCG) levels after the first or second injection. The mean pretreatment hCG level for the whole cohort was 2350 ± 2955 mIU/mL (median, 1187 mIU/mL; 90th percentile, 5000 mIU/mL). Resolution of ectopic pregnancy was achieved after a single injection in 76/102 (74.5%) women and after a second dose in 16/21 (76.2%) women. The remaining 10 (9.8%) patients were treated surgically after the first (5/76) or the second (5/26) dose. The overall success rate for methotrexate treatment was 90.2%. On multivariate stepwise logistic analysis, fetal cardiac activity was an independent predictor of a failed first methotrexate injection, and presence of a yolk sac and mass size were independent predictors of overall methotrexate failure and need for secondary surgery. In patients with ectopic pregnancy and relatively low levels of serum hCG, the most important predictors of overall failure of methotrexate injection were the presence of a yolk sac and mass size. Copyright © 2013 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    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.

  10. 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

  11. Effect of single and fractionated doses of gamma radiation on pupariation of housefly

    International Nuclear Information System (INIS)

    Srinivasan, A.; Kesavan, P.C.

    1979-01-01

    Larvae of different ages from 40 hr to 72 hr were exposed to γ-rays ranging between 500 R and 10000 R; all ages of the larvae showed dose-dependence pupariation delay up to 4000 R. The shape of the puparia were not normal in the larvae irradiated with higher doses. Sparing effect of dose fractionation (SDF) was demonstrated for the pupariation delay. Sparing effect was quite marked at low dose-rate (15 R/second) than at high dose-rate (80 R/second) and maximum SDF was found with 2 hr interfraction interval as compared to 4.5 and 6.5 hr. The magnitude of SDF was comparatively less at 15 0 C than at 35 0 C indicating the occurrence of repair. Furthermore, the metabolic requirement of repair processes was evidenced by the abolition of SDF by inhibitors of energy metabolism, DNA binding agents and protein synthesis inhibitors. (author)

  12. Association of the multidrug resistance-1 gene single-nucleotide polymorphisms with the tacrolimus dose requirements in renal transplant recipients.

    Science.gov (United States)

    Anglicheau, Dany; Verstuyft, Céline; Laurent-Puig, Pierre; Becquemont, Laurent; Schlageter, Marie-Hélène; Cassinat, Bruno; Beaune, Philippe; Legendre, Christophe; Thervet, Eric

    2003-07-01

    The immunosuppressive drug tacrolimus, whose pharmacokinetic characteristics display large interindividual variations, is a substrate for P-glycoprotein (P-gp), the product of the multidrug resistance-1 (MDR1) gene. Some of the single nucleotide polymorphisms (SNP) of MDR1 reported correlated with the in vivo activity of P-gp. Because P-gp is known to control tacrolimus intestinal absorption, it was postulated that these polymorphisms are associated with tacrolimus pharmacokinetic variations in renal transplant recipients. The objective of this study was to evaluate in a retrospective study of 81 renal transplant recipients the effect on tacrolimus dosages and concentration/dose ratio of four frequent MDR1 SNP possibly associated with P-gp function (T-129C in exon 1b, 1236C>T in exon 12, 2677G>T,A in exon 21, and 3435C>T in exon 26). As in the general population, the SNP in exons 12, 21, and 26 were frequent (16, 17.3, and 22.2% for the variant homozygous genotype, respectively) and exhibited incomplete linkage disequilibrium. One month after tacrolimus introduction, exon 21 SNP correlated significantly with the daily tacrolimus dose (P < or = 0.05) and the concentration/dose ratio (P < or = 0.02). Tacrolimus dose requirements were 40% higher in homozygous than wild-type patients for this SNP. The concentration/dose ratio was 36% lower in the wild-type patients, suggesting that, for a given dose, their tacrolimus blood concentration is lower. Haplotype analysis substantiated these results and suggested that exons 26 and 21 SNP may be associated with tacrolimus dose requirements. Genotype monitoring of the MDR1 gene reliably predicts the optimal dose of tacrolimus in renal transplant recipients and may predict the initial daily dose needed by individual patients to obtain adequate immunosuppression.

  13. COMPARISON BETWEEN ABSORBED DOSES IN TARGET ORGANS IN PANORAMIC RADIOGRAPHY, USING SINGLE EMULSION AND DOUBLE EMULSION FILMS

    Directory of Open Access Journals (Sweden)

    A. R. Talaeipour

    2007-07-01

    Full Text Available "nThe use of panoramic radiography, due to its numerous advantages, is increasing. Radiographic films used in this technique are of double emulsion (DE type which are used with intensifying screens. Single emulsion (SE films can also be used. The purpose of this study was to determine the exposure parameters to achieve an appropriate optical density in these two types of films, and to estimate under such parameters, radiation doses to mandibular bone marrow (MBM, thyroid gland and parotid gland. This study was performed through a tissue equivalent phantom. First, with various tube voltage and tube current, 128 radiographs were taken of phantom with these two types of films. After examining the optical densities, the exposure parameters under which both films have the same density, were determined. Then, phantom again was exposed and MBM, thyroid gland and parotid gland absorbed doses were measured, using TLDs. It was demonstrated that: 1 SE films, in order to provide appropriate optical density, require two times radiation in comparison with double emulsion film; 2 using SE films increases MBM dose, up to 2-2.5 times, thyroid gland dose up to 1.7-2 times and parotid gland dose up to 1.3 times, in comparison with DE films; 3 in DE films, under lower exposure parameters and desirable processing, MBM dose up to 3.5 times, thyroid gland dose up to 1.5 times and parotid gland dose up to 2.5 times will increase. Considering that the risk of radiation induced cancers increases with repeated radiation doses, using SE films is not recommended.

  14. The biological effect of large single doses: a possible role for non-targeted effects in cell inactivation.

    Directory of Open Access Journals (Sweden)

    Marlon R Veldwijk

    Full Text Available BACKGROUND AND PURPOSE: Novel radiotherapy techniques increasingly use very large dose fractions. It has been argued that the biological effect of large dose fractions may differ from that of conventional fraction sizes. The purpose was to study the biological effect of large single doses. MATERIAL AND METHODS: Clonogenic cell survival of MCF7 and MDA-MB-231 cells was determined after direct X-ray irradiation, irradiation of feeder cells, or transfer of conditioned medium (CM. Cell-cycle distributions and the apoptotic sub-G1 fraction were measured by flow cytometry. Cytokines in CM were quantified by a cytokine antibody array. γH2AX foci were detected by immunofluorescence microscopy. RESULTS: The surviving fraction of MCF7 cells irradiated in vitro with 12 Gy showed an 8.5-fold decrease (95% c.i.: 4.4-16.3; P<0.0001 when the density of irradiated cells was increased from 10 to 50×10(3 cells per flask. Part of this effect was due to a dose-dependent transferrable factor as shown in CM experiments in the dose range 5-15 Gy. While no effect on apoptosis and cell cycle distribution was observed, and no differentially expressed cytokine could be identified, the transferable factor induced prolonged expression of γH2AX DNA repair foci at 1-12 h. CONCLUSIONS: A dose-dependent non-targeted effect on clonogenic cell survival was found in the dose range 5-15 Gy. The dependence of SF on cell numbers at high doses would represent a "cohort effect" in vivo. These results support the hypothesis that non-targeted effects may contribute to the efficacy of very large dose fractions in radiotherapy.

  15. Response of single leukemic cells to peptidase inhibitor therapy across time and dose using a microfluidic device.

    Science.gov (United States)

    Kovarik, Michelle L; Dickinson, Alexandra J; Roy, Pourab; Poonnen, Ranjit A; Fine, Jason P; Allbritton, Nancy L

    2014-02-01

    Single-cell methodologies are revealing cellular heterogeneity in numerous biological processes and pathologies. For example, cancer cells are characterized by substantial heterogeneity in basal signaling and in response to perturbations, such as drug treatment. In this work, we examined the response of 678 individual U937 (human acute myeloid leukemia) cells to an aminopeptidase-inhibiting chemotherapeutic drug (Tosedostat) over the course of 95 days. Using a fluorescent reporter peptide and a microfluidic device, we quantified the rate of reporter degradation as a function of dose. While the single-cell measurements reflected ensemble results, they added a layer of detail by revealing unique degradation patterns and outliers within the larger population. Regression modeling of the data allowed us to quantitatively explore the relationships between reporter loading, incubation time, and drug dose on peptidase activity in individual cells. Incubation time was negatively correlated with the number of peptide fragment peaks observed, while peak area (which was proportional to reporter loading) was positively correlated with both the number of fragment peaks observed and the degradation rate. Notably, a statistically significant change in the number of peaks observed was identified as dose increased from 2 to 4 μM. Similarly, a significant difference in degradation rate as a function of reporter loading was observed for doses ≥2 μM compared to the 1 μM dose. These results suggest that additional enzymes may become inhibited at doses >1 μM and >2 μM, demonstrating the utility of single-cell data to yield novel biological hypotheses.

  16. 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.

  17. Safety, tolerability, and pharmacokinetic evaluation of single- and multiple-ascending doses of a novel kappa opioid receptor antagonist LY2456302 and drug interaction with ethanol in healthy subjects.

    Science.gov (United States)

    Lowe, Stephen L; Wong, Conrad J; Witcher, Jennifer; Gonzales, Celedon R; Dickinson, Gemma L; Bell, Robert L; Rorick-Kehn, Linda; Weller, MaryAnn; Stoltz, Randall R; Royalty, Jane; Tauscher-Wisniewski, Sitra

    2014-09-01

    Accumulating evidence indicates that selective antagonism of kappa opioid receptors may provide therapeutic benefit in the treatment of major depressive disorder, anxiety disorders, and substance use disorders. LY2456302 is a high-affinity, selective kappa opioid antagonist that demonstrates >30-fold functional selectivity over mu and delta opioid receptors. The safety, tolerability, and pharmacokinetics (PK) of LY2456302 were investigated following single oral doses (2-60 mg), multiple oral doses (2, 10, and 35 mg), and when co-administered with ethanol. Plasma concentrations of LY2456302 were measured by liquid chromatography-tandem mass spectrometry method. Safety analyses were conducted on all enrolled subjects. LY2456302 doses were well-tolerated with no clinically significant findings. No safety concerns were seen on co-administration with ethanol. No evidence for an interaction between LY2456302 and ethanol on cognitive-motor performance was detected. LY2456302 displayed rapid oral absorption and a terminal half-life of approximately 30-40 hours. Plasma exposure of LY2456302 increased proportionally with increasing doses and reached steady state after 6-8 days of once-daily dosing. Steady-state PK of LY2456302 were not affected by coadministration of a single dose of ethanol. No clinically important changes in maximum concentration (Cmax ) or AUC of ethanol (in the presence of LY2456302) were observed. © 2014, The American College of Clinical Pharmacology.

  18. Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human

    Directory of Open Access Journals (Sweden)

    Fen Yang

    2017-10-01

    Full Text Available Physiologically based pharmacokinetic (PBPK/pharmacodynamic (PD models can contribute to animal-to-human extrapolation and therapeutic dose predictions. Buagafuran is a novel anxiolytic agent and phase I clinical trials of buagafuran have been completed. In this paper, a potentially effective dose for buagafuran of 30 mg t.i.d. in human was estimated based on the human brain concentration predicted by a PBPK/PD modeling. The software GastroPlusTM was used to build the PBPK/PD model for buagafuran in rat which related the brain tissue concentrations of buagafuran and the times of animals entering the open arms in the pharmacological model of elevated plus-maze. Buagafuran concentrations in human plasma were fitted and brain tissue concentrations were predicted by using a human PBPK model in which the predicted plasma profiles were in good agreement with observations. The results provided supportive data for the rational use of buagafuran in clinic.

  19. Angiotensin Converting Enzyme Inhibitors Mitigate Collagen Synthesis Induced by a Single Dose of Radiation to the Whole Thorax

    OpenAIRE

    Kma, Lakhan; Gao, Feng; Fish, Brian L.; Moulder, John E.; Jacobs, Elizabeth R.; Medhora, Meetha

    2012-01-01

    Our long-term goal is to use angiotensin converting enzyme (ACE) inhibitors to mitigate the increase in lung collagen synthesis that is induced by irradiation to the lung, which could result from accidental exposure or radiological terrorism. Rats (WAG/RijCmcr) were given a single dose of 13 Gy (dose rate of 1.43 Gy/min) of X-irradiation to the thorax. Three structurally-different ACE inhibitors, captopril, enalapril and fosinopril were provided in drinking water beginning 1 week after irradi...

  20. A Pilot Study on Single-dose Toxicity Testing of Hominis placenta Pharmacopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Yoo-Hwan Lee

    2015-06-01

    Full Text Available Objectives: This study was performed to analyze the toxicity and to find the lethal dose of the test substance Hominis placenta pharmacopuncture when used as a single-dose in 6 week old, male and female Sprague-Dawley (SD rats. Methods: All experiments were conducted at Biotoxtech (Chungwon, Korea, 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 Hominis placenta pharmacopuncture extracts, 0.125, 0.25 and 0.5 mL, were administered to the experimental group, and 0.5 mL doses of normal saline solution were 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 groups. Also, no significant changes in body weights were observed among the groups, and no significant differences in hematology/biochemistry, necropsy, and histopathology results were noted. Hematologically, some changes in the male rats in two experimental groups were observed, but those changes had no clinical or toxicological meaning because they were not dose dependent. Histopathological tests on the injected parts showed cell infiltration in the male rats in one of the experimental groups; however, that result was due to spontaneous generation and had no toxicological meaning. Therefore, this study showed that Hominis placenta pharmacopuncture had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusion: As a result of single-dose tests of the test substance Hominis placenta pharmacopuncture in 4 groups of rats, the lethal dose for both males and females exceeded 0.5 mL/animal. Therefore, the above findings suggest that treatment with Hominis placenta pharmacopuncture is relatively safe. Further studies on this subject are needed.

  1. Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy: The influence of gender and comedication

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    Rančić Nemanja

    2015-01-01

    Full Text Available Background/Aim. A combination of tacrolimus and other drugs such as corticosteroids has been commonly used immunosuppresive regimens. On the other hand, there is a growing body of evidence that male and female may differ in their response to the equal drug treatment. The aim of the study was to estimated the use of tacrolimus concentration/dose (C/D ratio for the assessment of the influence of gender differences and comedication on tacrolimus exposure in renal transplant recipients. Methods. This prospective case series study included 54 patients, in which the unit of monitoring was outpatient examination (1,872 of the renal transplant patients. The patients were monitored in the period 2010-2014, starting one month after the transplantation. Tacrolimus trough concentrations (TTC were measured by chemiluminescence microparticles immunoassay. Results. TTC and the tacrolimus C/D ratio were significantly lower in the females comparing with the males. Contrary to the males, in the females a significant increase of the tacrolimus daily dose (TDD per body weight and TTC, along with the corticosteroid dose increase, was not accompanied by any significant changes in the tacrolimus C/D ratio; in different corticosteroid doses faster elimination of tacrolimus was found with the exception of the doses > 0.25 mg/kg. In the patients treated with proton pump inhibitors, mainly with pantoprazole TDD per body weight and TTC were significantly higher, while the tacrolimus C/D ratio was significantly lower compared to the patients without this treatment. In the patients treated with calcium channel blockers, TDD per body weight was significantly lower (particularly with amlodipine while the tacrolimus C/D ratio was higher compared to the patients who were not treated by them. Conclusion. A lower tacrolimus exposure was detected in females in comparison to males. When gender differences were considered in the context of different corticosteroid doses, faster

  2. Single oral dose pharmacokinetics of decursin and decursinol angelate in healthy adult men and women.

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    Jinhui Zhang

    Full Text Available The ethanol extract of Angelica gigas Nakai (AGN root has promising anti-cancer and other bioactivities in rodent models. It is currently believed that the pyranocoumarin isomers decursin (D and decursinol angelate (DA contribute to these activities. We and others have documented that D and DA were rapidly converted to decursinol (DOH in rodents. However, our in vitro metabolism studies suggested that D and DA might be metabolized differently in humans. To test this hypothesis and address a key question for human translatability of animal model studies of D and DA or AGN extract, we conducted a single oral dose human pharmacokinetic study of D and DA delivered through an AGN-based dietary supplement Cogni.Q (purchased from Quality of Life Labs, Purchase, NY in twenty healthy subjects, i.e., 10 men and 10 women, each consuming 119 mg D and 77 mg DA from 4 vegicaps. Analyses of plasma samples using UHPLC-MS/MS showed mean time to peak concentration (Tmax of 2.1, 2.4 and 3.3 h and mean peak concentration (Cmax of 5.3, 48.1 and 2,480 nmol/L for D, DA and DOH, respectively. The terminal elimination half-life (t1/2 for D and DA was similar (17.4 and 19.3 h and each was much longer than that of DOH (7.4 h. The mean area under the curve (AUC0-48h for D, DA and DOH was estimated as 37, 335 and 27,579 h∙nmol/L, respectively. Gender-wise, men absorbed the parent compounds faster and took shorter time to reach DOH peak concentration. The human data supported an extensive conversion of D and DA to DOH, even though they metabolized DA slightly slower than rodents. Therefore, the data generated in rodent models concerning anti-cancer efficacy, safety, tissue distribution and pharmacodynamic biomarkers will likely be relevant for human translation.ClinicalTrials.gov NCT02114957.

  3. Use and knowledge of single dose activated charcoal: A survey of Australian doctors.

    Science.gov (United States)

    Corcoran, Gabriela; Chan, Betty; Chiew, Angela

    2016-10-01

    The use of single dose activated charcoal (SDAC) as a means of gastric decontamination is declining. The present study examined the potential use of SDAC in common overdose scenarios by Australian emergency doctors, compared with clinical toxicologists and current guidelines. We conducted a cross-sectional survey of emergency doctors and toxicologists on the use of SDAC. The survey covered demographic data, education and previous use of SDAC and six clinical scenarios. The scenarios selected included agents not bound to SDAC, sustained-release preparations and ingestions at varying time points. Statistical calculations were performed using Fisher's exact test. There were 397 emergency doctors and 20 toxicologists who responded to the survey. Seventy-one per cent (n = 280/397) of emergency doctors indicated they had received some education on decontamination. Eighty-three per cent (n = 331/397) had administered SDAC during their medical career, 29% (n = 117/397) within the past year. There was a significant difference in responses between emergency doctors and toxicologists in two scenarios; a toxic paracetamol ingestion presenting within 1 h (P = 0.009) and verapamil ingestion in a 3 year old boy (P = 0.001). Toxicologists were more likely to administer SDAC in these scenarios, 89% (n = 16/18) and 88% (n = 15/17), respectively, compared with 52% (n = 197/381) and 43% (n = 158/371) of emergency doctors. Our study showed that there is a significant variation in the use of SDAC between toxicologists and emergency doctors in some scenarios. Clinical toxicologists are more likely to administer SDAC in certain overdose settings. It is essential to provide education on the benefits versus actual risks of SDAC in acute poisoning so that doctors will understand when to administer SDAC or seek further advice. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

  4. Comparative evaluation of prophylactic single-dose intravenous antibiotic with postoperative antibiotics in elective urologic surgery

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    Mohammad K Moslemi

    2010-11-01

    site infection rates of categories A and B in Group 1 were 0 and two (0.86%, respectively, while those in Group 2 were 0 and five (0.92%, respectively. There was no significant difference in infection rates in terms of remote infection and surgical site infection between Group 1 and Group 2 (P = 0.670. The amounts, as well as the prices, for intravenously administered antibiotics decreased to approximately one quarter.Conclusion: Our protocol effectively decreased the amount of antibiotics used without increasing perioperative infection rates. Thus, our protocol of prophylactic antibiotic therapy can be recommended as an appropriate method for preventing perioperative infection in urologic surgery. Keywords: surgical site infection, antibiotic prophylaxis, single dose, urologic surgery

  5. Out-of-Field Dose Equivalents Delivered by Passively Scattered Therapeutic Proton Beams for Clinically Relevant Field Configurations

    International Nuclear Information System (INIS)

    Wroe, Andrew; Clasie, Ben; Kooy, Hanne; Flanz, Jay; Schulte, Reinhard; Rosenfeld, Anatoly

    2009-01-01

    Purpose: Microdosimetric measurements were performed at Massachusetts General Hospital, Boston, MA, to assess the dose equivalent external to passively delivered proton fields for various clinical treatment scenarios. Methods and Materials: Treatment fields evaluated included a prostate cancer field, cranial and spinal medulloblastoma fields, ocular melanoma field, and a field for an intracranial stereotactic treatment. Measurements were completed with patient-specific configurations of clinically relevant treatment settings using a silicon-on-insulator microdosimeter placed on the surface of and at various depths within a homogeneous Lucite phantom. The dose equivalent and average quality factor were assessed as a function of both lateral displacement from the treatment field edge and distance downstream of the beam's distal edge. Results: Dose-equivalent value range was 8.3-0.3 mSv/Gy (2.5-60-cm lateral displacement) for a typical prostate cancer field, 10.8-0.58 mSv/Gy (2.5-40-cm lateral displacement) for the cranial medulloblastoma field, 2.5-0.58 mSv/Gy (5-20-cm lateral displacement) for the spinal medulloblastoma field, and 0.5-0.08 mSv/Gy (2.5-10-cm lateral displacement) for the ocular melanoma field. Measurements of external field dose equivalent for the stereotactic field case showed differences as high as 50% depending on the modality of beam collimation. Average quality factors derived from this work ranged from 2-7, with the value dependent on the position within the phantom in relation to the primary beam. Conclusions: This work provides a valuable and clinically relevant comparison of the external field dose equivalents for various passively scattered proton treatment fields

  6. Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Jiang Li

    2017-01-01

    Full Text Available No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A (BTXA injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic foot after stroke to optimize this treatment in these patients. Eligible patients (n = 104 were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses (200 U or 400 U and two concentrations (50 U/mL or 100 U/mL. The following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment: spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden's graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4–7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.

  7. 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.

    Science.gov (United States)

    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