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Sample records for improve therapeutic dose

  1. 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.

  2. Mesenteric ischemia-reperfusion injury: clearly improved hemodynamics but only minor protection of the rat small intestine by (sub)therapeutic heparin sodium and enoxaparin doses.

    Science.gov (United States)

    Walensi, Mikolaj; de Groot, Herbert; Schulz, Rainer; Hartmann, Matthias; Petrat, Frank

    2013-01-01

    Tissue protection against ischemia (I)/reperfusion (R) injury by heparins can be due to their anticoagulant and/or non-anticoagulant properties. Here we studied the protective potential of the anticoagulant and the non-anticoagulant features of heparin sodium (HepSo) and enoxaparin (Enox) against mesenteric I/R injury in a rat model. Mesenteric I/R was induced in rats (n = 6 per group) by superior mesenteric artery occlusion (SMAO; 90 min) and reopening (120 min). Therapeutic/clinical and subtherapeutic/non-anticoagulant doses of HepSo (0.25 mg/kg bolus + 0.25 mg/kg × h; 0.05 mg/kg bolus + 0.1 mg/kg × h) or Enox (0.5 mg/kg bolus + 0.5 mg/kg × h; 0.05 mg/kg bolus + 0.1 mg/kg × h) were administered intravenously starting 30 min before SMAO to the end of reperfusion. Systemic/vital and intestinal microcirculatory parameters were measured during the whole experimental procedure, those of small intestine injury at the end. During intestinal reperfusion, mean arterial blood pressure and heart rates were significantly increased by HepSo and, less effectively, by Enox, in a dose-dependent manner. Intestinal microcirculation was only affected by the therapeutic HepSo dose, which decreased the microvascular flow and S(O2) during reperfusion. The subtherapeutic Enox treatment, as opposed to any HepSo dose, most effectively diminished I/R-induced intestinal hemorrhages, myeloperoxidase activity (as a measure of neutrophil invasion), and histopathological changes. Therapeutic but, to a lesser extent, also the subtherapeutic doses of both HepSo and Enox clearly improve hemodynamics during mesenteric reperfusion, while intestinal protection is exclusively provided by Enox, especially at its subtherapeutic dose. Alterations in intestinal microcirculation are not responsible for these effects. Thus, non-anticoagulant Enox doses and, preferably, heparin(oid)s unable to affect coagulation, could diminish clinical risks of I/R-induced gastrointestinal complications. Copyright

  3. 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.

  4. 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.

  5. 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

  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. 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)

  8. Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing.

    Science.gov (United States)

    Heard, Kennon; Green, Jody L; Anderson, Victoria; Bucher-Bartelson, Becki; Dart, Richard C

    2016-03-01

    Paracetamol protein adducts (PPA) are a biomarker of paracetamol exposure. PPA are quantified as paracetamol-cysteine (APAP-CYS), and concentrations above 1.1 μmol l(-1) have been suggested as a marker of paracetamol-induced hepatotoxicity. However, there is little information on the range of concentrations observed during prolonged therapeutic dosing. The aim of the present study was to describe the concentration of PPA in the serum of subjects taking therapeutic doses of paracetamol for at least 16 days. Preplanned secondary aim of a prospective randomized controlled (placebo vs. 4g day(-1) paracetamol) trial. We measured subjects' serum PPA concentrations every 3 days for a minimum of 16 days. We also measured concentrations on study days 1-3 and 16-25 in subsets of patients. PPA were quantified as APAP-CYS after gel filtration and protein digestion using liquid chromatography/mass spectrometry. Ninety per cent of subjects had detectable PPA after five doses. Median APAP-CYS concentrations in paracetamol-treated subjects increased to a plateau of 0.1 μmol l(-1) on day 7, where they remained. The highest concentration measured was 1.1 μmol l(-1) and two subjects never had detectable PPA levels. PPA were detected in the serum of 78% of subjects 9 days after their final dose. PPA are detectable in the vast majority of subjects taking therapeutic doses of paracetamol. While most have concentrations well below the threshold associated with hepatotoxicity, concentrations may approach 1.1 μmol l(-1) in rare cases. Adducts are detectable after a few doses and can persist for over a week after dosing is stopped. © 2015 The British Pharmacological Society.

  9. Physical dose of therapeutic exercises in institutional neck rehabilitation.

    Science.gov (United States)

    Wasenius, Niko; Karapalo, Teppo; Sjögren, Tuulikki; Pekkonen, Mika; Mälkiä, Esko

    2013-03-01

    To determine the intensity and volume of therapeutic exercises during a standard 13-day inpatient neck rehabilitation course in relation to overall physical activity in rehabilitation and everyday life. Cross-sectional study. Subjects (n = 19; 16 women and 3 men; mean age 48.6 years, standard deviation (SD) 6.6) with chronic non-specific neck pain were recruited from two inpatient neck rehabilitation courses. Intensity and volume of therapeutic exercises and physical activity were measured in metabolic equivalents (METs) with an objective measurement device and all-time recall questionnaire. Maximum oxygen uptake was determined in METs (METc) by direct maximal cycle ergometer. Subjects' mean METc was 7.2 METs (SD 1.4) or 25.3 ml/kg/min (SD 4.8). Intensity of all therapeutic exercises was 1.9 METs or 27 %METc (SD 5.1) and volume 7.7 MET-hours/week. Intensity of specific neck and shoulder exercises was 2.0 METs or 28 %METc (SD 5.4) and volume 2.5 MET-hours/week. In addition, subjects were more active in everyday life than in inpatient rehabilitation. The therapeutic exercise dose failed to reach previously reported target values for pain relief. The dose of therapeutic exercises and confounding physical activity should be carefully controlled in pain rehabilitation programmes.

  10. 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)

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

    Directory of Open Access Journals (Sweden)

    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

  12. Sub-therapeutic doses of fluvastatin and valsartan are more effective than therapeutic doses in providing beneficial cardiovascular pleiotropic effects in rats: A proof of concept study.

    Science.gov (United States)

    Janić, Miodrag; Lunder, Mojca; France Štiglic, Alenka; Jerin, Aleš; Skitek, Milan; Černe, Darko; Marc, Janja; Drevenšek, Gorazd; Šabovič, Mišo

    2017-12-01

    Statins and sartans can, in therapeutic doses, induce pleiotropic cardiovascular effects. Similar has recently been shown also for sub-therapeutic doses. We thus explored and compared the cardiovascular pleiotropic efficacy of sub-therapeutic vs. therapeutic doses. Wistar rats were randomly divided into 7 groups receiving fluvastatin, valsartan and their combination in sub-therapeutic and therapeutic doses, or saline. After 6weeks, the animals were euthanised, their hearts and thoracic aortas isolated, and blood samples taken. Endothelium-dependent relaxation of the thoracic aortae and ischaemic-reperfusion injury of the isolated hearts were assessed along with the related serum parameters and genes expression. Fluvastatin and valsartan alone or in combination were significantly more effective in sub-therapeutic than therapeutic doses. The sub-therapeutic combination greatly increased thoracic aorta endothelium-dependent relaxation and maximally protected the isolated hearts against ischaemia-reperfusion injury and was thus most effective. Beneficial effects were accompanied by increased levels of nitric oxide (NO) and decreased levels of asymmetric dimethylarginine (ADMA) in the serum (again prominently induced by the sub-therapeutic combination). Furthermore, nitric oxide synthase 3 (NOS3) and endothelin receptor type A (EDNRA) genes expression increased, but only in both combination groups and without significant differences between them. In the therapeutic dose groups, fluvastatin and valsartan decreased cholesterol values and systolic blood pressure. Sub-therapeutic doses of fluvastatin and valsartan are more effective in expressing cardiovascular pleiotropic effects than therapeutic doses of fluvastatin and/or valsartan. These results could be of significant clinical relevance. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. [Directions for use of corticosteroids and calcineurin inhibitors against generalized myasthenia gravis: therapeutic strategies that can lead to early improvements and veer away from high-dose oral corticosteroids].

    Science.gov (United States)

    Utsugisawa, Kimiaki; Nagane, Yuriko; Suzuki, Shigeaki; Suzuki, Norihiro

    2012-01-01

    The advent of effective immune treatment has meant that myasthenia gravis (MG) is most often not lethal. However, many MG patients still find it difficult to maintain daily activities due to chronic residual fatigability and long-term side effects of medication, since full remission without immune treatment is not common. Our analysis demonstrated that disease severity, dose of oral corticosteroids, and depressive state are the major independent factors negatively associated with self-reported QOL (MG-QOL15-J score). It is noteworthy that oral corticosteroid, the first-line agent for MG, is negatively associated with patients' QOL. When the analysis took into account MGFA postintervention status and dose of oral prednisolne (PSL), the MG-QOL15-J score of MM status patients taking ≤ 5 mg PSL per day is identically low (i.e., just as good QOL) as that seen in CSR and is a target of treatment. In order to veer away from high-dose oral corticosteroids and to achieve early MM or better status with PSL ≤ 5 mg/day, we advocate the early aggressive treatment strategy that can achieve early improvement by performing an aggressive therapy using combined treatment with plasmapheresis and high-dose intravenous methylprednisolone and then maintain an improved clinical status using low-dose oral corticosteroids and calcineurin inhibitors (cyclosporine microemulsion and tacrolimus). The early stages of MG are susceptible to treatment with calcineurin inhibitors. When using cyclosporine microemulsion for MG, blood concentrations 2 h after administration (C2) correlate with clinical improvement and immediately before administration (C0) with side effects (increased serum creatinine and/or hypertension). Monitoring of C2 and C0 levels is useful to estimate efficacy and safety of the drug.

  14. Therapeutic strategies to improve control of hypertension.

    Science.gov (United States)

    Armario, Pedro; Waeber, Bernard

    2013-03-01

    Blood pressure is poorly controlled in most European countries and the control rate is even lower in high-risk patients such as patients with chronic kidney disease, diabetic patients or previous coronary heart disease. Several factors have been associated with poor control, some of which involve the characteristic of the patients themselves, such as socioeconomic factors, or unsuitable life-styles, other factors related to hypertension or to associated comorbidity, but there are also factors directly associated with antihypertensive therapy, mainly involving adherence problems, therapeutic inertia and therapeutic strategies unsuited to difficult-to-control hypertensive patients. It is common knowledge that only 30% of hypertensive patients can be controlled using monotherapy; all the rest require a combination of two or more antihypertensive drugs, and this can be a barrier to good adherence and log-term persistence in patients who also often need to use other drugs, such as antidiabetic agents, statins or antiplatelet agents. The fixed combinations of three antihypertensive agents currently available can facilitate long-term control of these patients in clinical practice. If well tolerated, a long-term therapeutic regimen that includes a diuretic, an ACE inhibitor or an angiotensin receptor blocker, and a calcium channel blocker is the recommended optimal triple therapy.

  15. Cone-beam computed tomography imaging: therapeutic staff dose during chemoembolisation procedure

    International Nuclear Information System (INIS)

    Paul, Jijo; Vogl, Thomas J; Chacko, Annamma; Mbalisike, Emmanuel C

    2014-01-01

    Cone-beam computed tomography (CBCT) imaging is an important requirement to perform real-time therapeutic image-guided procedures on patients. The purpose of this study is to estimate the personal-dose-equivalent and annual-personal-dose from CBCT imaging during transarterial chemoembolisation (TACE). Therapeutic staff doses (therapeutic and assistant physician) were collected during 200 patient (65  ±  15 years, range: 40–86) CBCT examinations over six months. Absorbed doses were assessed using thermo-luminescent dosimeters during patient hepatic TACE therapy. We estimated personal-dose-equivalent (PDE) and annual-personal-dose (APD) from absorbed dose based on international atomic energy agency protocol. APD for therapeutic procedure was calculated (therapeutic physician: 5.6 mSv; assistant physician: 5.08 mSv) based on institutional work load. Regarding PDE, the hands of the staff members received a greater dose compared to other anatomical locations (therapeutic physician: 56 mSv, 72 mSv; assistant physician: 12 mSv, 14 mSv). Annual radiation doses to the eyes and hands of the staff members were lower compared to the prescribed limits by the International Commission on Radiological Protection (ICRP). PDE and APD of both therapeutic staff members were within the recommended ICRP-103 annual limit. Dose to the assistant physician was lower than the dose to the therapeutic physician during imaging. Annual radiation doses to eye-lenses and hands of both staff members were lower than prescribed limits. (paper)

  16. 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)

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

    African Journals Online (AJOL)

    is thought to result from direct stimulation of post-synaptic receptors and inhibition ..... optimal effect could be extensive with the use of nutritional supplements; therefore ... These studies support the theory that higher doses of PSE may result in.

  18. Improved dose estimates for nuclear criticality accidents

    International Nuclear Information System (INIS)

    Wilkinson, A.D.; Basoglu, B.; Bentley, C.L.; Dunn, M.E.; Plaster, M.J.; Dodds, H.L.; Yamamoto, T.

    1995-01-01

    Slide rules are improved for estimating doses and dose rates resulting from nuclear criticality accidents. The original slide rules were created for highly enriched uranium solutions and metals using hand calculations along with the decades old Way-Wigner radioactive decay relationship and the inverse square law. This work uses state-of-the-art methods and better data to improve the original slide rules and also to extend the slide rule concept to three additional systems; i.e., highly enriched (93.2 wt%) uranium damp (H/ 235 U = 10) powder (U 3 O 8 ) and low-enriched (5 wt%) uranium mixtures (UO 2 F 2 ) with a H/ 235 U ratio of 200 and 500. Although the improved slide rules differ only slightly from the original slide rules, the improved slide rules and also the new slide rules can be used with greater confidence since they are based on more rigorous methods and better nuclear data

  19. [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.

  20. 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)

  1. Milrinone in advanced heart failure: dose and therapeutic monitor outside intensive care unit.

    Science.gov (United States)

    Charisopoulou, Dafni; Leaver, Neil; Banner, Nicholas R

    2014-04-01

    Advanced chronic heart failure (ACHF) patients often require inotropes before transplantation or ventricular assist device implantation. Milrinone, an inotrope and vasodilator, may accumulate in cardiorenal syndrome with serious adverse effects. We investigated the potential for therapeutic drug monitoring of milrinone levels using High Performance Liquid Chromatography Mass Spectrometry (HPLC-MS). 22 ACHF patients (15 males, 49±9 years) received milrinone 50 µg/kg intravenously (i.v.) during heart catheterization. Milrinone levels were 216±71 ng/ml (within the reported therapeutic range: 100-300 ng/ml), followed by improvements in cardiac index, pulmonary artery and wedge pressures (p milrinone (5-26 days) at 0.1-0.2 µg/kg/min, titrated according to plasma milrinone levels. No adverse events occurred. Therapeutic levels were achieved with doses of 0.2±0.06 µg/Kg/min, below those recommended in Summary of Product Characteristics. Milrinone therapy can be noninvasively monitored by HPLC-MS, while avoiding toxicity in ACHF.

  2. 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.

  3. 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

  4. An unusual case of hypothermia associated with therapeutic doses of olanzapine: a case report

    Directory of Open Access Journals (Sweden)

    Ratnayake Shiroma L

    2011-05-01

    Full Text Available Abstract Introduction We report a case of a 42-year-old man who had symptomatic hypothermia as a result of taking olanzapine for paranoid schizophrenia. According to published data, only a few cases of hypothermia associated with olanzapine have been reported since its introduction into clinical use. Case presentation A 42-year-old Sri Lankan man with schizophrenia who was being treated with a therapeutic dose of olanzapine presented with reduced level of consciousness. He had a core temperature of 32°C and was bradycardic. At the time of admission, the electrocardiogram showed sinus bradycardia with J waves. He did not have any risk factors for developing hypothermia except the use of olanzapine. There was improvement in his clinical condition with reversal of electrocardiogram changes following gradual rewarming and the omission of olanzapine. Conclusion Hypothermia induced by antipsychotic medications is not uncommon, but olanzapine-induced hypothermia is rare and occurrence has been reported during initiation or increasing the dose. But here the patient developed hypothermia without dose adjustment.

  5. Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer

    International Nuclear Information System (INIS)

    Martinez, Alvaro A.; Gustafson, Gary; Gonzalez, Jose; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

    2002-01-01

    Purpose: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Methods and Materials: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level ≥10.0 ng/mL, Gleason score ≥7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. Results: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p<0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p=0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Conclusion: Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause

  6. 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

  7. 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

  8. Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn's disease in rats.

    Science.gov (United States)

    Tawfik, Dina Ibrahim; Osman, Afaf Sayed; Tolba, Hedayat Mahmoud; Khattab, Aida; Abdel-Salam, Lubna O; Kamel, Mahmoud M

    2016-10-01

    Crohn's disease is a relapsing inflammatory condition afflicting the digestive tract. Drugs used for treatment of Crohn's disease may be associated with serious side effects. Endogenous opioid peptides modulate inflammatory cytokine production. Opioid antagonists have been shown to play a role in healing and repair of tissues. This work was designed to detect the possible beneficial effects of opioid antagonist naltrexone in indomethacin-induced Crohn's disease in rats. Enteritis was induced in male albino rats by two subcutaneous injection of indomethacin in a dose of 7.5mg/kg 24h apart started on day one. Salfasalazine, naltrexone and their combination were administered orally from day one of induction of enteritis to day 10. Disease activity index, serum levels of C-reactive protein and tumor necrosis factor-α, macroscopic and microscopic pathological scores and in vitro motility studies were evaluated. Induction of enteritis resulted in significant increase of disease activity index, significant elevation of serum levels of C-reactive protein and tumor necrosis factor-α, significant deterioration of pathological scores and significant increase in the mean contractility response of the isolated ileal segments compared with normal untreated rats. Treatment with sulfasalazine, low dose of natrexone or their combination resulted in significant improvement of all measured parameters compared with enteritis group. The current finding could provide new interesting opportunity for developing new therapeutic approaches for treatment of Crohn's disease. Use of naltrexone, especially in small dose, has little side effects making it of interest for treatment of Crohn's disease. Also, it provides the possibility of reduced doses of other drugs if it is used as combined therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Computerized clinical decision support systems for therapeutic drug monitoring and dosing: A decision-maker-researcher partnership systematic review

    Directory of Open Access Journals (Sweden)

    Weise-Kelly Lorraine

    2011-08-01

    Full Text Available Abstract Background Some drugs have a narrow therapeutic range and require monitoring and dose adjustments to optimize their efficacy and safety. Computerized clinical decision support systems (CCDSSs may improve the net benefit of these drugs. The objective of this review was to determine if CCDSSs improve processes of care or patient outcomes for therapeutic drug monitoring and dosing. Methods We conducted a decision-maker-researcher partnership systematic review. Studies from our previous review were included, and new studies were sought until January 2010 in MEDLINE, EMBASE, Evidence-Based Medicine Reviews, and Inspec databases. Randomized controlled trials assessing the effect of a CCDSS on process of care or patient outcomes were selected by pairs of independent reviewers. A study was considered to have a positive effect (i.e., CCDSS showed improvement if at least 50% of the relevant study outcomes were statistically significantly positive. Results Thirty-three randomized controlled trials were identified, assessing the effect of a CCDSS on management of vitamin K antagonists (14, insulin (6, theophylline/aminophylline (4, aminoglycosides (3, digoxin (2, lidocaine (1, or as part of a multifaceted approach (3. Cluster randomization was rarely used (18% and CCDSSs were usually stand-alone systems (76% primarily used by physicians (85%. Overall, 18 of 30 studies (60% showed an improvement in the process of care and 4 of 19 (21% an improvement in patient outcomes. All evaluable studies assessing insulin dosing for glycaemic control showed an improvement. In meta-analysis, CCDSSs for vitamin K antagonist dosing significantly improved time in therapeutic range. Conclusions CCDSSs have potential for improving process of care for therapeutic drug monitoring and dosing, specifically insulin and vitamin K antagonist dosing. However, studies were small and generally of modest quality, and effects on patient outcomes were uncertain, with no convincing

  10. Nonopioid substance use disorders and opioid dose predict therapeutic opioid addiction.

    Science.gov (United States)

    Huffman, Kelly L; Shella, Elizabeth R; Sweis, Giries; Griffith, Sandra D; Scheman, Judith; Covington, Edward C

    2015-02-01

    Limited research examines the risk of therapeutic opioid addiction (TOA) in patients with chronic noncancer pain. This study examined TOA among 199 patients undergoing long-term opioid therapy at the time of admission to a pain rehabilitation program. It was hypothesized that nonopioid substance use disorders and opioid dosage would predict TOA. Daily mean opioid dose was 132.85 mg ± 175.39. Patients with nonopioid substance use disorders had 28 times the odds (odds ratio [OR] = 28.58; 95% confidence interval [CI] = 10.86, 75.27) of having TOA. Each 50-mg increase in opioid dose nearly doubled the odds of TOA (OR = 1.73; 95% CI = 1.29, 2.32). A 100-mg increase was associated with a 3-fold increase in odds (OR = 3.00; 95% CI = 1.67, 5.41). Receiver operating characteristic analysis revealed that opioid dose was a moderately accurate predictor (area under the curve = .75; 95% CI = .68, .82) of TOA. The sensitivity (.70) and specificity (.68) of opioid dose in predicting TOA was maximized at 76.10 mg; in addition, 46.00 mg yielded 80% sensitivity in identifying TOA. These results underscore the importance of obtaining a substance use history prior to prescribing and suggest a low screening threshold for TOA in patients who use opioids in the absence of improvement in pain or functional impairment. This article examines TOA in patients with chronic noncancer pain undergoing long-term opioid therapy. Results suggest that patients should be screened for nonopioid substance use disorders prior to prescribing. In the absence of improvement in pain or function, there is a low threshold (∼50 mg daily opioid dose) for addiction screening. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

  11. 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

    progress. Analysis of heart rate frequency after exercise showed positive dynamics for the restoration of its values, which indicates an increase of adaptive capacity of cardiovascular system. Analysis of the dynamics of the mean values of systolic and diastolic blood pressure, measured before the training, and right after it, showed moderate increase in systolic blood pressure and gradual decrease in diastolic blood pressure after classes (р<0.05. We observed a significant reduction in the incidence of pathological types of reaction and increased frequency of eutonic type of reaction (p <0.05 after the sanatory-resort treatment which included classes of therapeutic dosed "Nordic" walking. As the main criterion of effectiveness of sanatorium stage of treatment in patients with combined cardiovascular abnormity we suggested physical performance degree of reduction indicator. Accurate positive dynamics of physical performance decrease was observed in the group of patients as it reduced in 1.6 times (p<0.05, which was accompanied by general health improvement and exercise tolerance of patients. Thus, medical rehabilitation with the use of classes of therapeutic dosed "Nordic" walking in patients with coronary heart disease and arterial hypertension promotes formation of adequate response of the cardiovascular system to physical activity and is well tolerated. Classes of therapeutic dosed "Nordic" walking have normalizing effect on the overall and peripheral hemodynamics, which is reflected in the normalization of systolic blood pressure (р < 0.05 and formation of its adequate dynamics in response to exercise, as well as the restoration of diastolic blood pressure (р<0.05 after exercise. Course application of classes of therapeutic dosed "Nordic" walking allows to correct pathologic types of reactions of cardiovascular system during exercise, in particular, the transition from the pathological types of reaction to eutonic, and significantly improves physical performance and

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

    Science.gov (United States)

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

    2012-01-01

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

  13. Single Enteral Loading Dose of Phenobarbital for Achieving Its Therapeutic Serum Levels in Neonates

    Science.gov (United States)

    Turhan, Ali H.; Atici, Aytug; Okuyaz, Cetin; Uysal, Sercan

    2010-01-01

    Aim To investigate whether therapeutic serum drug levels may be achieved with a single enteral loading dose of phenobarbital. Methods The study was performed at the Mersin University Hospital in Turkey between April 2004 and August 2006, and included 29 newborn babies with seizure. After the acute treatment of the seizure with midazolam at a dose of 0.1 mg/kg, phenobarbital was administered by orogastric route at a loading dose of 20 mg/kg. Serum phenobarbital concentrations were measured at 0.5, 3, 6, and 12 hours after the loading. Serum phenobarbital levels between 10-30 μg/mL were considered as the therapeutic range. Results The serum phenobarbital levels reached therapeutic values in 9 (31%), 19 (66%), 21 (72%), and 23 (79%) patients at 0.5, 3, 6, and 12 hours after loading, respectively, while they did not reach therapeutic values in 6 patients (21%) after 12 hours. Four of the patients in whom there was no increase in serum phenobarbital levels had hypoxic-ischemic encephalopathy. Conclusion Enteral loading of phenobarbital can achieve therapeutic serum levels in the large majority of newborn babies with seizure and may be safely used in babies with the intact gastrointestinal tract. PMID:20564764

  14. 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

  15. Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA

    International Nuclear Information System (INIS)

    Speight, E.L.; Farr, P.M.

    1994-01-01

    In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. This study demonstrates that psoriasis may clear rapidly, without burning, using high-dose UVA. Availability of a suitable irradiation apparatus would allow rapid and effective PUVA treatment to be used for localized, resistant disease. (author)

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

    Directory of Open Access Journals (Sweden)

    Zygmunt Warzecha

    2017-04-01

    Full Text Available 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. Results: 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. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

  17. 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.

  18. Achievement of Therapeutic Goals with Low-Dose Imiglucerase in Gaucher Disease: A Single-Center Experience

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    Irina Tukan

    2013-01-01

    Full Text Available Gaucher disease, a lysosomal storage disorder, is a multisystem disorder with variable and unpredictable onset and severity. Disease-specific enzyme replacement therapy (ERT has been shown to reverse or ameliorate disease-specific hepatosplenomegaly and anemia and thrombocytopenia. ERT also impacts bone manifestations, including bone crises, bone pain, and appearance of new osteonecrosis, and improves bone mineral density to varying degrees. The objective of this study was to assess achievement of predefined therapeutic goals based on international registry outcomes for Israeli patients with Gaucher disease receiving imiglucerase for four consecutive years on a low-dose regimen followed in a single center. All data were taken from patient files. The therapeutic goals were taken from standards published in the literature for disease-specific clinical parameters. Among 164 patients at baseline, values for spleen and liver volumes, hemoglobin and platelet counts, and Z-scores for lumbar spine and femoral were significantly different from the goal. After four years ERT, there was a significant improvement ( in each of the therapeutic goal parameters from baseline. 15.2% of these patients achieved all hematology-visceral goals. In children, there was achievement of linear growth and puberty. This survey highlights the good overall response in symptomatic patients receiving low-dose ERT with imiglucerase in Israel.

  19. Communication techniques for improved acceptance and adherence with therapeutic footwear.

    Science.gov (United States)

    van Netten, Jaap J; Francis, Anthony; Morphet, Ashley; Fortington, Lauren V; Postema, Klaas; Williams, Anita

    2017-04-01

    Clients' acceptance and adherence with orthoses can be influenced by a clinician's communication skills. In this clinical note, we describe two communication techniques, in the context of therapeutic footwear. Person-centred communication involves engaging with and listening to the attitudes of the client towards their condition, as well as discussing acceptance and expectations, in a structured consultation. Building a relationship is crucial and requires clients to feel heard and understood. An important influence on the acceptance and adherence is that a client makes a conscious decision to receive their device. This active receipt can be facilitated through shared decision making, wherein clinicians give clear, relevant and meaningful examples, based on clinical evidence, and ensure this is understood. Two communication techniques for clinicians providing therapeutic footwear are described. These can be adapted for use with provision of other assistive technologies to improve client acceptance and adherence. Clinical relevance Small changes in how clinicians communicate to their clients in daily practice can have a big influence on the subsequent acceptance and adherence with therapeutic footwear and indeed other prescribed assistive technologies.

  20. 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)

  1. 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.

  2. 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)

  3. Therapeutic Enzymes: Applications and Approaches to Pharmacological Improvement.

    Science.gov (United States)

    Yari, Maryam; Ghoshoon, Mohammad B; Vakili, Bahareh; Ghasemi, Younes

    2017-01-01

    Among therapeutic proteins, enzymes represent small and of course profitable market. They can be used to treat important, rare, and deadly diseases. Enzyme therapy is the only available treatment for certain disorders. Here, pharmaceutical enzymes are reviewed. They are categorized in four main groups, enzymes in replacement therapy, enzymes in cancer treatment, enzymes for fibrinolysis, and finally enzymes that are used topically for various treatments. Furthermore, enzyme gene therapy and future perspective of therapeutic enzymes are mentioned in brief. There are many important approved enzymes in pharmaceutical market. Several approaches such as point mutation, fusion protein designing, glycoengineering, and PEGylation were used to achieve improved enzymes. Although sometimes enzymes were engineered to facilitate production and purification process, appropriate delivery to target sites, extending half-life, and reducing immunogenicity are among the main goals of engineering approaches. Overall, enzymes play a critical role in treatment of common and rare diseases. Evaluation of new enzymes as well as improvement of approved enzymes are of the most important challenges in biotechnology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

    Science.gov (United States)

    Alam, Nausheen; Najam, Rahila

    2015-01-01

    Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

  5. 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

  6. The improvement of diagnostic and therapeutic imaging in Africa

    International Nuclear Information System (INIS)

    2015-02-01

    The 8. Pan-African Congress of Radiology and Imaging on the improvement of diagnostic and therapeutic imaging in Africa was hosted in Nairobi Kenya. The conference focusses on Review of Radiation Safety in Medical X-Ray Diagnosis, Medical Practitioners of Radiology & Imaging in the Dock. It also addresses issues Knowledge, Attitude, and Practice of Clinicians, Practicing at the Kenyatta National Hospital on Ionizing Radiation and Procurement in the Imaging Department. The Need for Understanding Technical Specifications,Students Experience in Radiography, Radioiodine Therapy for Graves’ Disease, Role of ultrasound in the diagnosis and management of gestational trophoblastic disease in Rural health facilities were areas interest. Diabetes Mellitus and the Musculoskeletal System, Imaging the Traumatized Spine ‘Clearing the Cervical Spine’, The Radiation Safety Culture: Image Gently and Radiation Protection of the Young Patient: Kenya perspective were discussed during the conference

  7. 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

  8. Three dimensional conformal radiation therapy may improve the therapeutic ratio of radiation therapy after pneumonectomy for lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Trouette, R; Causse, N; Elkhadri, M; Caudry, M; Maire, J P; Houlard, J P; Racaldini, L; Demeaux, H

    1995-12-01

    Three dimensional conformal radiation therapy would allow to decrease the normal tissue dose while maintaining the same target dose as standard treatment. To evaluate the feasibility of normal tissue dose reduction for ten patients with pneumonectomy for lung cancer, we determined the dose distribution to the normal tissue with 3-dimensional conformal radiation therapy (3-DCRT) and conventional treatment planning (CTP). Dose-volume histograms for target and normal tissue (lung, heart) were used for comparison of the different treatment planning. The mean percentages of lung and heart volumes which received 40 Gy with 3-DCRT were respectively 63% and 37% of the mean percentage of lung and volumes which received the same dose with CTP. These preliminary results suggest that conformal therapy may improve the therapeutic ratio by reducing risk to normal tissue.

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

    Science.gov (United States)

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

    2016-08-01

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

  10. Characteristics of therapeutic electron beams and their determination from depth dose curves

    Energy Technology Data Exchange (ETDEWEB)

    Novotny, J; Pernicka, F [Ceskoslovenska Akademie Ved, Prague. Ustav Dozimetrie Zareni

    1980-09-01

    The distribution of absorbed dose in the environment irradiated with broad beams of high-energy electrons is analyzed physically and therapeutically. A number of parameters are defined with the aid of which the beams of electrons may be characterized in great detail and compared. The theoretical calculations of individual parameters are compared with the values measured using the Ostron betatron in the central axis of the beam at a distance of 65 cm from the target; the differences found are ascribed to the spectrum of electrons, the scattering of electrons on the homogenizing foils, collimators, monitoring chambers, etc.

  11. An evaluation of high-dose jobs for ALARA improvement

    International Nuclear Information System (INIS)

    Mun, J. H.; Kim, H. S.

    1997-01-01

    It is well known that about 70 percent of occupational dose have incurred from maintenance jobs at outage period. To reduce occupational dose, first, the high-dose jobs at the outage period should be identified and evaluated. For this, the database program is used, which contains the ORE data of reference plants, Kori Units 3 and 4. As a result, it is found that the jobs related to steam generator are the highest dose jobs in terms of collective ORE dose. From the analysis of the job procedures of those jobs, the ALARA improvements are also derived

  12. An analysis of the dose and the therapeutic effect of 131I in treating youngsters with Graves disease

    International Nuclear Information System (INIS)

    Li Jia; Qin Lan; Ren Zhong; Zhang Youping

    2010-01-01

    Objective: To analyses the clinical data of 131 I in treating youngsters with Graves disease, and to explore the effective dose range which is appropriate for Chinese youngsters with Graves disease. Methods: Two hundred and thirty-four youngsters with Graves disease were selected in this study, their ages were between 8 and 17, the average quality of their thyroids was (59.0±16.5)g. According to the absorbed dose of 131 I per gram of thyroid gland, 234 patients were divided into five groups: A: 1.11- 2.59 MBq/g. The therapeutic effect was evaluated by observing after treatment. And calculate the recovery rate, the improvement rate and the incidence rate of hypothyroidism. Results: (1) One hundred and fifty-two (64.95%) patients were cured, 56 (23.93%) were much better than before and 26 (11.11%) were hypothyroid. The therapeutic effect of group B was the best in all groups. (2) The recovery rate: there was no significant difference between group B, group C and group D (χ 2 =2.68, P>0.05). The recovery rate of group B was better than group A and group E (χ 2 =10.20 and χ 2 =5.49, P 2 =1.94, P>0.05). The improvement rate of group A was the highest (χ 2 =8.74, χ 2 =6.68, χ 2 =7.01 and χ 2 =11.12, P 2 =2.71, P>0.05). Group E had the highest incidence rate of hypothyroidism (χ 2 =12.36, χ = 11.58, χ 2 =9.37 and χ 2 =4.36, P 131 I is a safe and effective therapeutic approach for youngsters with Graves disease. We suggest the absorbed dose range of 131 I per gram of thyroid gland is 1.48-2.59 MBq/g, which can obtain the better therapeutic effect and can't increase the incidence rate of hypothyroidism. (authors)

  13. 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

  14. Toward endobronchial Ir-192 high-dose-rate brachytherapy therapeutic optimization

    International Nuclear Information System (INIS)

    Gay, H A; Allison, R R; Downie, G H; Mota, H C; Austerlitz, C; Jenkins, T; Sibata, C H

    2007-01-01

    A number of patients with lung cancer receive either palliative or curative high-dose-rate (HDR) endobronchial brachytherapy. Up to a third of patients treated with endobronchial HDR die from hemoptysis. Rather than accept hemoptysis as an expected potential consequence of HDR, we have calculated the radial dose distribution for an Ir-192 HDR source, rigorously examined the dose and prescription points recommended by the American Brachytherapy Society (ABS), and performed a radiobiological-based analysis. The radial dose rate of a commercially available Ir-192 source was calculated with a Monte Carlo simulation. Based on the linear quadratic model, the estimated palliative, curative and blood vessel rupture radii from the center of an Ir-192 source were obtained for the ABS recommendations and a series of customized HDR prescriptions. The estimated radius at risk for blood vessel perforation for the ABS recommendations ranges from 7 to 9 mm. An optimized prescription may in some situations reduce this radius to 4 mm. The estimated blood perforation radius is generally smaller than the palliative radius. Optimized and individualized endobronchial HDR prescriptions are currently feasible based on our current understanding of tumor and normal tissue radiobiology. Individualized prescriptions could minimize complications such as fatal hemoptysis without sacrificing efficacy. Fiducial stents, HDR catheter centering or spacers and the use of CT imaging to better assess the relationship between the catheter and blood vessels promise to be useful strategies for increasing the therapeutic index of this treatment modality. Prospective trials employing treatment optimization algorithms are needed

  15. 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.

  16. Enrofloxacin in therapeutic doses alters cytokine production by porcine PBMCs induced by lipopolysaccharide.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Pejsak, Zygmunt

    2017-07-01

    The effect of enrofloxacin on cytokine secretion by porcine peripheral blood mononuclear cells (PBMCs) was studied. Twenty 8-20-week-old pigs were randomly divided into two groups: control (C, n = 10) and experimental (E, n = 10) were used. Pigs from group E received enrofloxacin at therapeutic dose for 5 consecutive days. Blood samples were collected at 0 (before antibiotic administration), 2, 4 (during antibiotic therapy) 6, 9, 14 21, 35, 49, and 63 d of study (after treatment). PBMCs of pigs from both groups were incubated with or without lipopolysaccharide (LPS). Ex vivo production on interleukin (IL)-4, IL-6, IL-10, INF-γ, and TNF-α were analyzed using ELISA assay. Intramuscular administration of enrofloxacin to healthy pigs for 5 consecutive days induced a transitory reduction of the ex vivo response of PBMCs to LPS in terms of IL-6 and TNF-α secretion. The level of IL-6 returned to day 0 level shortly after end of treatment, while the TNF-α production remained reduced 10 d after the end of treatment. Our results indicate that enrofloxacin given in vivo in therapeutic doses has an immunomodulatory effect through its capacity to inhibit ex vivo secretion of IL-6 and TNF-α by porcine PBMC after LPS stimulation.

  17. Comparative pharmacokinetics between a microdose and therapeutic dose for clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen), and phenobarbital in human volunteers.

    Science.gov (United States)

    Lappin, Graham; Shishikura, Yoko; Jochemsen, Roeline; Weaver, Richard John; Gesson, Charlotte; Brian Houston, J; Oosterhuis, Berend; Bjerrum, Ole J; Grynkiewicz, Grzegorz; Alder, Jane; Rowland, Malcolm; Garner, Colin

    2011-06-14

    A clinical study was conducted to assess the ability of a microdose (100 μg) to predict the human pharmacokinetics (PK) following a therapeutic dose of clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen) and phenobarbital, both within the study and by reference to the existing literature on these compounds and to explore the source of any nonlinearity if seen. For each drug, 6 healthy male volunteers were dosed with 100 μg (14)C-labelled compound. For clarithromycin, sumatriptan, and propafenone this labelled dose was administered alone, i.e. as a microdose, orally and intravenously (iv) and as an iv tracer dose concomitantly with an oral non-labelled therapeutic dose, in a 3-way cross over design. The oral therapeutic doses were 250, 50, and 150 mg, respectively. Paracetamol was given as the labelled microdose orally and iv using a 2-way cross over design, whereas phenobarbital was given only as the microdose orally. Plasma concentrations of total (14)C and parent drug were measured using accelerator mass spectrometry (AMS) or HPLC followed by AMS. Plasma concentrations following non-(14)C-labelled oral therapeutic doses were measured using either HPLC-electrochemical detection (clarithromycin) or HPLC-UV (sumatriptan, propafenone). For all five drugs an oral microdose predicted reasonably well the PK, including the shape of the plasma profile, following an oral therapeutic dose. For clarithromycin, sumatriptan, and propafenone, one parameter, oral bioavailability, was marginally outside of the normally acceptable 2-fold prediction interval around the mean therapeutic dose value. For clarithromycin, sumatriptan and propafenone, data obtained from an oral and iv microdose were compared within the same cohort of subjects used in the study, as well as those reported in the literature. For paracetamol (oral and iv) and phenobarbital (oral), microdose data were compared with those reported in the literature only. Where 100 μg iv (14)C-doses were

  18. Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

    Science.gov (United States)

    Martinez, Alvaro A; Gustafson, Gary; Gonzalez, José; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

    2002-06-01

    To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

  19. Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts.

    Science.gov (United States)

    Tseng, Chih-Wen; Trimble, Cornelia; Zeng, Qi; Monie, Archana; Alvarez, Ronald D; Huh, Warner K; Hoory, Talia; Wang, Mei-Cheng; Hung, Chien-Fu; Wu, T-C

    2009-05-01

    Current therapeutic approaches to treatment of patients with bulky cervical cancer are based on conventional in situ ablative modalities including cisplatin-based chemotherapy and radiation therapy. The 5-year survival of patients with nonresectable disease is dismal. Because over 99% of squamous cervical cancer is caused by persistent infection with an oncogenic strain of human papillomavirus (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally required for disease initiation and persistence, HPV-targeted immune strategies present a compelling opportunity in which to demonstrate proof of principle. Sublethal doses of radiation and chemotherapeutic agents have been shown to have synergistic effect in combination with either vaccination against cancer-specific antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes (CTLs). Here, we explored the combination of low-dose radiation therapy with DNA vaccination with calreticulin (CRT) linked to the mutated form of HPV-16 E7 antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors. We observed that TC-1 tumor-bearing mice treated with radiotherapy combined with CRT/E7(detox) DNA vaccination generated significant therapeutic antitumor effects and the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of treated mice. Furthermore, treatment with radiotherapy was shown to render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we observed that treatment with radiotherapy during the second DNA vaccination generated the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with the chemotherapy in combination with radiation and CRT/E7(detox) DNA vaccination generate significantly enhanced therapeutic antitumor effects. The clinical implications of the study are discussed.

  20. Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers

    Directory of Open Access Journals (Sweden)

    Stefano Salmaso

    2013-01-01

    Full Text Available Over the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. In particular, stealth nanocarriers can be obtained by polymeric coating. In this paper, the basic concept underlining the “stealth” properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed.

  1. 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)

  2. Predicted and observed therapeutic dose exceedances of ionizable pharmaceuticals in fish plasma from urban coastal systems.

    Science.gov (United States)

    Scott, W Casan; Du, Bowen; Haddad, Samuel P; Breed, Christopher S; Saari, Gavin N; Kelly, Martin; Broach, Linda; Chambliss, C Kevin; Brooks, Bryan W

    2016-04-01

    Instream flows of the rapidly urbanizing watersheds and estuaries of the Gulf of Mexico in Texas (USA) are increasingly dominated by reclaimed waters. Though ionizable pharmaceuticals have received increasing attention in freshwaters, many research questions remain unanswered, particularly in tidally influenced urban coastal systems, which experience significant spatiotemporal variability in pH that influences bioavailability and bioaccumulation. The authors coupled fish plasma modeling of therapeutic hazard values with field monitoring of water chemistry variability and pharmaceutical occurrence to examine whether therapeutic hazards to fish existed within these urban coastal ecosystems and whether therapeutic hazards differed within and among coastal locations and seasons. Spatial and temporal fluctuations in pH within study sites altered the probability of encountering pharmaceutical hazards to fish. Significant water quality differences were consistently observed among traditional parameters and pharmaceuticals collected from surface and bottom waters, which are rarely sampled during routine surface water quality assessments. The authors then compared modeling predictions of fish plasma concentrations of pharmaceuticals to measured plasma levels from various field-collected fish species. Diphenhydramine and diltiazem were observed in plasma of multiple species, and diltiazem exceeded human therapeutic doses in largemouth bass, catfish, and mullet inhabiting these urban estuaries. Though the present study only examined a small number of target analytes, which represent a microcosm of the exposome of these fish, coastal systems are anticipated to be more strongly influenced by continued urbanization, altered instream flows, and population growth in the future. Unfortunately, aquatic toxicology information for diltiazem and many other pharmaceuticals is not available for marine and estuarine organisms, but such field observations suggest that potential adverse

  3. Improvements to the Hunter Dose tracking system

    Energy Technology Data Exchange (ETDEWEB)

    Whiteside, T. S. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Aucott, T. J. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Brand, A. D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Diprete, D. P. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2017-07-01

    Since 1965, the Savannah River Site (SRS) has conducted deer hunts which are open to the general public. SRS performs field monitoring for cesium-137 (Cs-137) of each harvested animal to determine whether the animal may be released to the hunter. A new field system for measuring Cs-137 in the harvested animals has been developed. The system incorporates numerous enhancements compared to the original system. The original system was composed of two Ludlum Measurements scalar-driven 2 inch x 2 inch sodium iodide counters, while the new system is based on a single Ametek Ortec Digibase-driven 2 inch x 4 inch x 16 inch sodium iodide gamma spectrometer. The new system includes a series of easy-to-assemble stainless steel encapsulated lead shields. The combination of the larger detector size and lead shielding improved the detection limit of the new system by a factor of approximately three compared to the original system. This lower detection limit allows for a larger number of measurements to be directly compared to the laboratory results, in cases where animal portions have been sampled. The results from developing and using this system are presented as well as recommendations on improvements to the overall field monitoring of the SRS hunts.

  4. Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic doses on the fertility of female Wistar rats.

    Science.gov (United States)

    Figueiró-Filho, Ernesto Antonio; Aydos, Ricardo Dutra; Senefonte, Flávio Renato de Almeida; Ferreira, Cristiane Munaretto; Pereira, Erica Freire de Vasconcelos; Oliveira, Vanessa Marcon de; Menezes, Giovanna Pádoa de; Bósio, Marco Antonio Costa

    2014-07-01

    To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A peffect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats.

  5. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure

    Science.gov (United States)

    Montgomery, Rusty L.; Hullinger, Thomas G.; Semus, Hillary M.; Dickinson, Brent A.; Seto, Anita G.; Lynch, Joshua M.; Stack, Christianna; Latimer, Paul A.; Olson, Eric N.; van Rooij, Eva

    2012-01-01

    Background Diastolic dysfunction in response to hypertrophy is a major clinical syndrome with few therapeutic options. MicroRNAs act as negative regulators of gene expression by inhibiting translation or promoting degradation of target mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR-208a prevents pathological cardiac remodeling and upregulation of Myh7 in response to pressure overload. Whether this miRNA might contribute to diastolic dysfunction or other forms of heart disease is currently unknown. Methods and Results Here, we show that systemic delivery of an antisense oligonucleotide induces potent and sustained silencing of miR-208a in the heart. Therapeutic inhibition of miR-208a by subcutaneous delivery of antimiR-208a during hypertension-induced heart failure in Dahl hypertensive rats dose-dependently prevents pathological myosin switching and cardiac remodeling while improving cardiac function, overall health, and survival. Transcriptional profiling indicates that antimiR-208a evokes prominent effects on cardiac gene expression; plasma analysis indicates significant changes in circulating levels of miRNAs on antimiR-208a treatment. Conclusions These studies indicate the potential of oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR-208 as a potent therapeutic target for the modulation of cardiac function and remodeling during heart disease progression. PMID:21900086

  6. Work management practices that reduce dose and improve efficiency

    International Nuclear Information System (INIS)

    Miller, D.W.; Hulin, M.

    1998-01-01

    Work management practices at nuclear power plants can dramatically affect the outcome of annual site dose goals and outage costs. This presentation discusses global work management practices that contribute to dose reduction including work philosophy, work selection, work planning, work scheduling, worker training, work implementation and worker feedback. The presentation is based on a two-year international effort (sponsored by NEA/IAEA ISOE) to study effective work practices that reduce dose. Experts in this area believe that effective work selection and planning practices can substantially reduce occupational dose during refueling outages. For example, some plants represented in the expert group complete refueling outages in 12-18 days (Finland) with doses below 0,90 person-Sv. Other plants typically have 50-75 day outages with substantially higher site doses. The fundamental reasons for longer outages and higher occupational doses are examined. Good work management principles that have a proven track record of reducing occupational dose are summarized. Practical methods to reduce work duration and dose are explained. For example, scheduling at nuclear power plants can be improved by not only sequencing jobs on a time line but also including zone and resource-based considerations to avoid zone congestion and manpower delays. An ongoing, global, benchmarking effort is described which provides current duration and dose information for repetitive jobs to participating utilities world-wide. (author)

  7. Improvement of dose evaluation method for employees at severe accident

    International Nuclear Information System (INIS)

    Onda, Takashi; Yoshida, Yoshitaka; Kudo, Seiichi; Nishimura, Kazuya

    2003-01-01

    It is expected that the selection of access routes for employees who engage in emergency work at a severe accident in a nuclear power plant makes a difference in their radiation dose values. In order to examine how much difference arises in the dose by the selection of the access routes, in the case of a severe accident in a pressurized water reactor plant, we improved the method to obtain the dose for employees and expanded the analyzing system. By the expansion of the system and the improvement of the method, we have realized the followings: (1) in the whole plant area, the dose evaluation is possible, (2) the efficiency of calculation is increased by the reduction of the number of radiation sources, etc, and (3) the function is improved by introduction of the sky shine calculation into the highest floor, etc. The improved system clarifies the followings: (1) the doses change by selected access routes, and this system can give the difference in the doses quantitatively, and (2) in order to suppress the dose, it is effective to choose the most adequate access route for the employees. (author)

  8. Therapeutic improvement of colonic anastomotic healing under complicated conditions

    DEFF Research Database (Denmark)

    Nerstrøm, Malene; Krarup, Peter-Martin; Jørgensen, Lars Nannestad

    2016-01-01

    AIM: To identify therapeutic agents for the prophylaxis of gastrointestinal anastomotic leakage (AL) under complicated conditions. METHODS: The PubMed and EMBASE databases were searched for English articles published between January 1975 and September 2014. Studies with the primary purpose of imp...... controls in experimental chemotherapeutic models. CONCLUSION: This systematic review identified potential therapeutic agents, but more studies are needed before concluding that any of these are useful for AL prophylaxis....

  9. 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.

  10. Ozone dosing alters the biological potential and therapeutic outcomes of plasma rich in growth factors.

    Science.gov (United States)

    Anitua, E; Zalduendo, M M; Troya, M; Orive, G

    2015-04-01

    Until now, ozone has been used in a rather empirical way. This in-vitro study investigates, for the first time, whether different ozone treatments of plasma rich in growth factors (PRGF) alter the biological properties and outcomes of this autologous platelet-rich plasma. Human plasma rich in growth factors was treated with ozone using one of the following protocols: a continuous-flow method; or a syringe method in which constant volumes of ozone and PRGF were mixed. In both cases, ozone was added before, during and after the addition of calcium chloride. Three ozone concentrations, of the therapeutic range 20, 40 and 80 μg/mL, were tested. Fibrin clot properties, growth factor content and the proliferative effect on primary osteoblasts and gingival fibroblasts were evaluated. Ozone treatment of PRGF using the continuous flow protocol impaired formation of the fibrin scaffold, drastically reduced the levels of growth factors and significantly decreased the proliferative potential of PRGF on primary osteoblasts and gingival fibroblasts. In contrast, treatment of PRGF with ozone using the syringe method, before, during and after the coagulation process, did not alter the biological outcomes of the autologous therapy. These findings suggest that ozone dose and the way that ozone combines with PRGF may alter the biological potential and therapeutic outcomes of PRGF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. 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

  12. Improving lithium therapeutics by crystal engineering of novel ionic cocrystals.

    Science.gov (United States)

    Smith, Adam J; Kim, Seol-Hee; Duggirala, Naga K; Jin, Jingji; Wojtas, Lukasz; Ehrhart, Jared; Giunta, Brian; Tan, Jun; Zaworotko, Michael J; Shytle, R Douglas

    2013-12-02

    Current United States Food and Drug Administration (FDA)-approved lithium salts are plagued with a narrow therapeutic window. Recent attempts to find alternative drugs have identified new chemical entities, but lithium's polypharmacological mechanisms for treating neuropsychiatric disorders are highly debated and are not yet matched. Thus, re-engineering current lithium solid forms in order to optimize performance represents a low cost and low risk approach to the desired therapeutic outcome. In this contribution, we employed a crystal engineering strategy to synthesize the first ionic cocrystals (ICCs) of lithium salts with organic anions. We are unaware of any previous studies that have assessed the biological efficacy of any ICCs, and encouragingly we found that the new speciation did not negatively affect established bioactivities of lithium. We also observed that lithium ICCs exhibit modulated pharmacokinetics compared to lithium carbonate. Indeed, the studies detailed herein represent an important advancement in a crystal engineering approach to a new generation of lithium therapeutics.

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

    International Nuclear Information System (INIS)

    Lima, Fabiana Farias de

    2002-09-01

    organs, such as the narrow and gonads, of up to 78.4%.Possible benefits to the institution also include the use of less radioactive material and a reduction in radiation exposures to the staff during the manipulation and administration of the 131 I. To facilitate the calculations of the optimum therapeutic activity of 131 I for individual patients, a simple and fast dose planning program was created (PlanDose). The program has been set up to evaluate thryroid remant ablation, but it can also be used for the calculation of the activity to be administered for treatment of hyperthyroidism. This protocol of calculated optimal patient-specific 131 I. activities allows a better determination of the necessary ablative dose for patients with differentiated carcinoma of the thyroid, and is an example of optimizing the practice of radiation protection. (author)

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

    Science.gov (United States)

    Garner, Colin R; Park, Kevin B; French, Neil S; Earnshaw, Caroline; Schipani, Alessandro; Selby, Andrew M; Byrne, Lindsay; Siner, Sarah; Crawley, Francis P; Vaes, Wouter H J; van Duijn, Esther; deLigt, Rianne; Varendi, Heili; Lass, Jane; Grynkiewicz, Grzegorz; Maruszak, Wioletta; Turner, Mark 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. Methods [14C]-PARA concentrations in 10–15 µl plasma samples were measured after enteral or i.v. administration of a single [14C]-PARA microdose or mixed in with therapeutic dose in infants receiving PARA as part of their therapeutic regimen. Results Thirty-four infants were included in the PARA PK analysis for this study: oral microdose (n = 4), i.v. microdose (n = 6), oral therapeutic (n = 6) and i.v. therapeutic (n = 18). The respective mean clearance (CL) values (SDs in parentheses) for these dosed groups were 1.46 (1.00) l h–1, 1.76 (1.07) l h–1, 2.93 (2.08) l h–1 and 2.72 (3.10) l h–1, t1/2 values 2.65 h, 2.55 h, 8.36 h and 7.16 h and dose normalized AUC(0-t) (mg l–1 h) values were 0.90 (0.43), 0.84 (0.57), 0.7 (0.79) and 0.54 (0.26). Conclusions All necessary ethical, scientific, clinical and regulatory procedures were put in place to conduct PK studies using enteral and systemic microdosing in two European centres. The pharmacokinetics of a therapeutic dose (mg kg–1) and a microdose (ng kg–1) in babies between 35 to 127 weeks post-menstrual age. [14C]-PARA pharmacokinetic parameters were within a two-fold range after a therapeutic dose or a microdose. Exploratory studies using doses significantly less than therapeutic doses may offer ethical and safety advantages with increased bionalytical sensitivity in selected exploratory paediatric pharmacokinetic studies. PMID:25619398

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

    Science.gov (United States)

    Garner, Colin R; Park, Kevin B; French, Neil S; Earnshaw, Caroline; Schipani, Alessandro; Selby, Andrew M; Byrne, Lindsay; Siner, Sarah; Crawley, Francis P; Vaes, Wouter H J; van Duijn, Esther; deLigt, Rianne; Varendi, Heili; Lass, Jane; Grynkiewicz, Grzegorz; Maruszak, Wioletta; Turner, Mark A

    2015-07-01

    The aims of the study were to compare [(14)C]-paracetamol ([(14)C]-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. [(14)C]-PARA concentrations in 10-15 µl plasma samples were measured after enteral or i.v. administration of a single [(14)C]-PARA microdose or mixed in with therapeutic dose in infants receiving PARA as part of their therapeutic regimen. Thirty-four infants were included in the PARA PK analysis for this study: oral microdose (n = 4), i.v. microdose (n = 6), oral therapeutic (n = 6) and i.v. therapeutic (n = 18). The respective mean clearance (CL) values (SDs in parentheses) for these dosed groups were 1.46 (1.00) l h(-1), 1.76 (1.07) l h(-1), 2.93 (2.08) l h(-1) and 2.72 (3.10) l h(-1), t(1/2) values 2.65 h, 2.55 h, 8.36 h and 7.16 h and dose normalized AUC(0-t) (mg l(-1) h) values were 0.90 (0.43), 0.84 (0.57), 0.7 (0.79) and 0.54 (0.26). All necessary ethical, scientific, clinical and regulatory procedures were put in place to conduct PK studies using enteral and systemic microdosing in two European centres. The pharmacokinetics of a therapeutic dose (mg kg(-1)) and a microdose (ng kg(-1)) in babies between 35 to 127 weeks post-menstrual age. [(14)C]-PARA pharmacokinetic parameters were within a two-fold range after a therapeutic dose or a microdose. Exploratory studies using doses significantly less than therapeutic doses may offer ethical and safety advantages with increased bionalytical sensitivity in selected exploratory paediatric pharmacokinetic studies. © 2015 The British Pharmacological Society.

  16. Improved Dose Targeting for a Clinical Epithermal Neutron Capture Beam Using Optional 6Li Filtration

    International Nuclear Information System (INIS)

    Binns, Peter J.; Riley, Kent J.; Ostrovsky, Yakov; Gao Wei; Albritton, J. Raymond; Kiger, W.S.; Harling, Otto K.

    2007-01-01

    Purpose: The aim of this study was to construct a 6 Li filter and to improve penetration of thermal neutrons produced by the fission converter-based epithermal neutron beam (FCB) for brain irradiation during boron neutron capture therapy (BNCT). Methods and Materials: Design of the 6 Li filter was evaluated using Monte Carlo simulations of the existing beam line and radiation transport through an ellipsoidal water phantom. Changes in beam performance were determined using three figures of merit: (1) advantage depth (AD), the depth at which the total biologically weighted dose to tumor equals the maximum weighted dose to normal tissue; (2) advantage ratio (AR), the ratio of the integral tumor dose to that of normal tissue averaged from the surface to the AD; and (3) advantage depth dose rate (ADDR), the therapeutic dose rate at the AD. Dosimetry performed with the new filter installed provided calibration data for treatment planning. Past treatment plans were recalculated to illustrate the clinical potential of the filter. Results: The 8-mm-thick Li filter is more effective for smaller field sizes, increasing the AD from 9.3 to 9.9 cm, leaving the AR unchanged at 5.7 but decreasing the ADDR from 114 to 55 cGy min -1 for the 12 cm diameter aperture. Using the filter increases the minimum deliverable dose to deep seated tumors by up to 9% for the same maximum dose to normal tissue. Conclusions: Optional 6 Li filtration provides an incremental improvement in clinical beam performance of the FCB that could help to establish a therapeutic window in the future treatment of deep-seated tumors

  17. Effects of an acute therapeutic or rewarding dose of amphetamine on acquisition of Pavlovian autoshaping and ventral striatal dopamine signaling.

    Science.gov (United States)

    Schuweiler, D R; Athens, J M; Thompson, J M; Vazhayil, S T; Garris, P A

    2018-01-15

    Rewarding doses of amphetamine increase the amplitude, duration, and frequency of dopamine transients in the ventral striatum. Debate continues at the behavioral level about which component of reward, learning or incentive salience, is signaled by these dopamine transients and thus altered in addiction. The learning hypothesis proposes that rewarding drugs result in pathological overlearning of drug-predictive cues, while the incentive sensitization hypothesis suggests that rewarding drugs result in sensitized attribution of incentive salience to drug-predictive cues. Therapeutic doses of amphetamine, such as those used to treat attention-deficit hyperactivity disorder, are hypothesized to enhance the ventral striatal dopamine transients that are critical for reward-related learning and to enhance Pavlovian learning. However, the effects of therapeutic doses of amphetamine on Pavlovian learning are poorly understood, and the effects on dopamine transients are completely unknown. We determined the effects of an acute pre-training therapeutic or rewarding amphetamine injection on the acquisition of Pavlovian autoshaping in the intact rat. We also determined the effects of these doses on electrically evoked transient-like dopamine signals using fast-scan cyclic voltammetry in the anesthetized rat. The rewarding dose enhanced the amplitude and duration of DA signals, caused acute task disengagement, impaired learning for several days, and triggered incentive sensitization. The therapeutic dose produced smaller enhancements in DA signals but did not have similar behavioral effects. These results underscore the necessity of more studies using therapeutic doses, and suggest a hybrid learning/incentive sensitization model may be required to explain the development of addiction. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. 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

  19. Isolation time determination of patients with differentiated thyroid carcinoma treated with therapeutic doses of 131 radioiodine

    International Nuclear Information System (INIS)

    Sierralta, M.P.; Lillo, R.; Massardo, T.; Jofre, M.J.

    2002-01-01

    Isolation time determination of patients with differentiated thyroid carcinoma treated with therapeutic doses of 131 radioiodine. Introduction: The coadyuvant treatment with 131 I had proven to be useful in patients with differentiated thyroid carcinoma (DTC). Due to the physical characteristics of this radioisotope these patients must be absolutely isolated in order to reduce the radioactive exposure to other individuals. The aim of the study was to determine the time required to reach the maximum permissible radiation exposure level (0,25mR/h) to general public. Material between August 1999 and May 2000, 30 patients with DTC diagnosis in the University of Chile Clinical Hospital Nuclear Medicine Centre were studied, 25 women (83%) and 5 men (17%), mean age 45 years old (15-71 range). Tumoral histology was 86% papillary and 14% follicular types. Thirty one doses of 131 I were administered ( one patient received 2 doses): 24 of 100 mCi (77%), 5 of 150 mCi (16%) and 2 of 200 mCi (7%); afterwards the 1 m exposition rate in air was measured at neck level with a Geiger-Mueller detector. The procedure was repeated on day 4 and every day following until the predicted radiation exposure levels were reached. Results: The average exposure rate at day 0 ( after given the radiopharmaceutical) was 20,12 mR/h (4-32 range). At day 4 the average rate was 0,21 mR/h (0,08-0,34 ), and 61% (n=19) of the patients reached 0,25 mR/h within that day. On day 5 10% (n=3) reached 0,25 mR/h (0,25-0,26), on day 6 16% (n=5) reached 0,25 mR/h (0,2-0,28), on day 7 6% (n=2) reached 0,39 mR/h (0,25-0,48) and the remaining 7% on day 13 and day 17 (n=2). Conclusion After a treatment dose of 131 iodine over 60% of the cases can finish the isolation on day 4, and 90% on day 7. The measurement of 131 I uptake after 24 hours will help to determine the evolution of post treatment levels

  20. Isolation time determination of patients with differentiated thyroid carcinoma treated with therapeutic doses of 131 radioiodine

    Energy Technology Data Exchange (ETDEWEB)

    Sierralta, M P [University of Chile Clinical Hospital Nuclear Medicine Centre, Santiago (Chile); Military Hospital Nuclear Medicine Department , Santiago (Chile); Lillo, R; Massardo, T [University of Chile Clinical Hospital Nuclear Medicine Centre, Santiago (Chile); Jofre, M J [Military Hospital Nuclear Medicine Department, Santiago (Chile)

    2002-09-01

    Isolation time determination of patients with differentiated thyroid carcinoma treated with therapeutic doses of 131 radioiodine. Introduction: The coadyuvant treatment with 131 I had proven to be useful in patients with differentiated thyroid carcinoma (DTC). Due to the physical characteristics of this radioisotope these patients must be absolutely isolated in order to reduce the radioactive exposure to other individuals. The aim of the study was to determine the time required to reach the maximum permissible radiation exposure level (0,25mR/h) to general public. Material between August 1999 and May 2000, 30 patients with DTC diagnosis in the University of Chile Clinical Hospital Nuclear Medicine Centre were studied, 25 women (83%) and 5 men (17%), mean age 45 years old (15-71 range). Tumoral histology was 86% papillary and 14% follicular types. Thirty one doses of 131 I were administered ( one patient received 2 doses): 24 of 100 mCi (77%), 5 of 150 mCi (16%) and 2 of 200 mCi (7%); afterwards the 1 m exposition rate in air was measured at neck level with a Geiger-Mueller detector. The procedure was repeated on day 4 and every day following until the predicted radiation exposure levels were reached. Results: The average exposure rate at day 0 ( after given the radiopharmaceutical) was 20,12 mR/h (4-32 range). At day 4 the average rate was 0,21 mR/h (0,08-0,34 ), and 61% (n=19) of the patients reached 0,25 mR/h within that day. On day 5 10% (n=3) reached 0,25 mR/h (0,25-0,26), on day 6 16% (n=5) reached 0,25 mR/h (0,2-0,28), on day 7 6% (n=2) reached 0,39 mR/h (0,25-0,48) and the remaining 7% on day 13 and day 17 (n=2). Conclusion After a treatment dose of 131 iodine over 60% of the cases can finish the isolation on day 4, and 90% on day 7. The measurement of 131 I uptake after 24 hours will help to determine the evolution of post treatment levels.

  1. Low-dose radiation potentiates the therapeutic efficacy of folate receptor-targeted hapten therapy.

    Science.gov (United States)

    Sega, Emanuela I; Lu, Yingjuan; Ringor, Michael; Leamon, Christopher P; Low, Philip S

    2008-06-01

    Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm(3) before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Mice bearing 300-mm(3) subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon alpha) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm(3). More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.

  2. Low-Dose Radiation Potentiates the Therapeutic Efficacy of Folate Receptor-Targeted Hapten Therapy

    International Nuclear Information System (INIS)

    Sega, Emanuela I.; Lu Yingjuan; Ringor, Michael; Leamon, Christopher P.; Low, Philip S.

    2008-01-01

    Purpose: Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm 3 before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Methods and Materials: Mice bearing 300-mm 3 subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon α) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Results: Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm 3 . More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. Conclusions: These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice

  3. Pharmacokinetic and pharmacogenomic profiles of telmisartan after the oral microdose and therapeutic dose.

    Science.gov (United States)

    Ieiri, Ichiro; Nishimura, Chisa; Maeda, Kazuya; Sasaki, Tomohiro; Kimura, Miyuki; Chiyoda, Takeshi; Hirota, Tekeshi; Irie, Shin; Shimizu, Hitoshi; Noguchi, Takanori; Yoshida, Kenji; Sugiyama, Yuichi

    2011-08-01

    In this study, we evaluated (a) the contribution of SLCO1B3 and UGT1A polymorphisms to the pharmacokinetics of telmisartan in two forms, a microdose (MD) and a therapeutic dose (TD); (b) linkage disequilibrium (LD) between UGT1A1 and UGT1A3; and (c) linearity in the pharmacokinetics of telmisartan between the two forms. Telmisartan was orally administered at MD condition (100 μg), and then at TD condition (80 mg) to 33 healthy volunteers whose genotypes were prescreened by DMET Plus. Plasma concentrations of telmisartan and its glucuronide were measured by LC-MS/MS, and population pharmacokinetic analysis was performed. No obvious effect of SLCO1B3 polymorphisms (334T>G, 699G>A, and rs11045585) on the pharmacokinetics of telmisartan was observed. The strong LD between UGT1A1*6 and UGT1A3*4a, and between UGT1A1*28 and UGT1A3*2a were observed. After both MD and TD administration, the mean area under the curve0-24 (±standard deviation) of telmisartan was significantly lower and higher in individuals with the UGT1A3*2a (TD, 1701±970 ng hr/ml; MD, 978±537 pg hr/ml) and *4a variants (TD, 5340±1168; MD, 3145±1093), respectively, compared with those in individuals with UGT1A3*1/*1 (TD, 2969±1456; MD, 1669±726). These results were quantitatively confirmed by population pharmacokinetic analysis. Nonlinearity of the dose-exposure relationship was observed between the MD and TD. The haplotypes of UGT1A3 significantly influenced pharmacokinetics of telmisartan and a strong LD between UGT1A1 genotype and UGT1A3 haplotype was observed. These findings are potentially of pharmacological and toxicological importance to the development and clinical use of drugs.

  4. IMPROVING THE REPORTING OF THERAPEUTIC EXERCISE INTERVENTIONS IN REHABILITATION RESEARCH.

    Science.gov (United States)

    Page, Phil; Hoogenboom, Barb; Voight, Michael

    2017-04-01

    The foundation of evidence-based practice lies in clinical research, which is based on the utilization of the scientific method. The scientific method requires that all details of the experiment be provided in publications to support replication of the study in order to evaluate and validate the results. More importantly, clinical research can only be translated into practice when researchers provide explicit details of the study. Too often, rehabilitation exercise intervention studies lack the appropriate detail to allow clinicians to replicate the exercise protocol in their patient populations. Therefore, the purpose of this clinical commentary is to provide guidelines for optimal reporting of therapeutic exercise interventions in rehabilitation research. 5.

  5. Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

    International Nuclear Information System (INIS)

    Fossa, Anthony A.; Wisialowski, Todd A.; Cremers, Thomas; Hart, Marieke van der; Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q.

    2012-01-01

    Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular

  6. Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

    Energy Technology Data Exchange (ETDEWEB)

    Fossa, Anthony A., E-mail: anthony.fossa@icardiac.com [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Wisialowski, Todd A. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States); Cremers, Thomas; Hart, Marieke van der [Brains On-Line B.V., University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen (Netherlands); Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q. [Department of Global Safety Pharmacology, Department of Pharmacokinetics, Dynamics and Metabolism, and Neuroscience, Pfizer Global Research and Development Eastern Point Road, Groton, CT 06340 (United States)

    2012-11-01

    Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood pressure (BP) and heart rate (HR) due to enhanced sympathetic neurotransmission, chronic treatment changes the responsiveness of the central noradrenergic system and suppresses these effects via autonomic regulation. To better understand the relationship between NE increases and cardiovascular safety, we investigated acute and chronic effects of the NRI reboxetine on central NE release and on BP and HR and electrical alternans, a measure of arrhythmia liability, in guinea pigs. NE release was assessed by microdialysis in medial prefrontal cortex (mPFC) and hypothalamic paraventricular nucleus (PVN); BP and HR were measured by telemetry. Animals were treated for 28 days with 15 mg/kg/day of reboxetine or vehicle via an osmotic minipump and then challenged with acute intravenous doses of reboxetine. Animals chronically treated with reboxetine had 2-fold higher extracellular basal NE levels in mPFC and PVN compared to basal levels after chronic vehicle treatment. BP was significantly increased after the first day of treatment, and gradually returned to vehicle levels by day 21. These data indicate that chronic NRI treatment may lead to an increase in central NE levels and a concomitant reduction in BP based on exposure–response curves compared to vehicle treatment, suggesting a larger separation between preclinical estimates of efficacy vs. safety compared to acute NRI treatment. -- Highlights: ► Acute RBX produces blood pressure increases acutely that decrease with chronic RBX ► Chronic RBX increases brain NE levels, a preclinical surrogate of improved efficacy ► Short-term screening of NRI often underestimates the chronic therapeutic index ► Chronic cardiovascular

  7. Therapeutic drug monitoring: how to improve drug dosage and patient safety in tuberculosis treatment

    Directory of Open Access Journals (Sweden)

    Giovanni Sotgiu

    2015-03-01

    Full Text Available In this article we describe the key role of tuberculosis (TB treatment, the challenges (mainly the emergence of drug resistance, and the opportunities represented by the correct approach to drug dosage, based on the existing control and elimination strategies. In this context, the role and contribution of therapeutic drug monitoring (TDM is discussed in detail. Treatment success in multidrug-resistant (MDR TB cases is low (62%, with 7% failing or relapsing and 9% dying and in extensively drug-resistant (XDR TB cases is even lower (40%, with 22% failing or relapsing and 15% dying. The treatment of drug-resistant TB is also more expensive (exceeding €50 000 for MDR-TB and €160 000 for XDR-TB and more toxic if compared to that prescribed for drug-susceptible TB. Appropriate dosing of first- and second-line anti-TB drugs can improve the patient's prognosis and lower treatment costs. TDM is based on the measurement of drug concentrations in blood samples collected at appropriate times and subsequent dose adjustment according to the target concentration. The ‘dried blood spot’ technique offers additional advantages, providing the rationale for discussions regarding a possible future network of selected, quality-controlled reference laboratories for the processing of dried blood spots of difficult-to-treat patients from reference TB clinics around the world.

  8. The rabbit biodistribution of a therapeutic dose of zoledronic acid labeled with Tc-99m

    International Nuclear Information System (INIS)

    Asikoglu, Makbule; Gamze Durak, Funda

    2009-01-01

    The aim of the present study was to label a therapeutic dose of zoledronic acid (ZOL) with Tc-99m, evaluate its in vitro stability and compare its biodistribution to 99m Tc-methylene biphosphonate ( 99m Tc-MDP) in normal rabbits. Preparation of 0.50 mg of 99m Tc-ZOL was carried out by the reduction of 99m Tc-pertechnetate in the presence of stannous chloride. The radiolabeling efficiency was found to be greater than 99%. The labeled complex was stable at least up to 6 h at room temperature determined by paper chromatography. 99m Tc-ZOL and 99m Tc-MDP were administered intravenously to the rabbits for scintigraphic studies. Between 99m Tc-ZOL and 99m Tc-MDP, there were no significant differences in the ratios of femur/BG and lumbar vertebrae/BG, whereas epiphysis/BG and the kidney/BG ratios of 99m Tc-MDP were higher than 99m Tc-ZOL at the static studies.

  9. 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.

  10. [Relation between dose, plasma concentration and therapeutic effect of theophylline in children with sleep apnea].

    Science.gov (United States)

    Rodríguez-Palomares, C; Ugartechea, J C; Palma-Aguirre, J A; Juárez-Olguín, H; Calderón-Mandujano, B

    1989-12-01

    The plasma concentration of theophylline was determined in twelve children with infantile sleep apnea (average age 48.5 days). The purpose of the study was to correlate concentrations with the dosages given, the therapeutic response and any adverse effects which could arise. In addition, other pharmacokinetic values were found, half-life (t 1/2) and clearance concentrations (Clss). The oral maintenance dose used was 4 mg/kg/24 h. The serum concentration of theophylline was determined by a homogeneous immunoassay enzyme technique (EMIT). A bad correlation was found (r = 0.45) between the oral dosage given and the plasma concentrations found. This was probably due to variations in the clearance of the drug. Yet, plasma concentrations fell between 3.0 and 12.6 micrograms/mL, enough to satisfactorily control apneic episodes in all the children included in the study without undesirable side-effects. Only one patient had some trouble in falling asleep and showed signs of irritability. The half-life was 13.30 +/- 7.46 hours and Clss was 36.64 +/- 12.98 mL/h/kg. In general, our results correlate with those reported in the literature. The accuracy of the pharmacokinetic parameters with two samples is reliable, therefore avoiding the use of multiple sampling in this group of children.

  11. Therapeutic games to improve attachment capabilities and protect sexual health.

    Science.gov (United States)

    Beier, Klaus M; Rebensburg, Klaus; Behrmann, Malte

    2010-01-01

    From the very beginning of life, man's fundamental needs for acceptance, security, trust, warmth and closeness can only be satisfied in relationships [1]. During infancy this is accomplished by body contact and the emotional experience of being taken care of, for instance by the sheltering manner in which an infant is held during breast-feeding. Through this parental loving care the modus of satisfying psychosocial fundamental needs by skin contact is learned by the infant and reinforced on a neuronal level, the way all processes of learning elementary skills generally are. According to present knowledge, chronic lack of security transmitted by frustration of psychosocial fundamental needs increases the probability of developing psychological and physical disorders. Furthermore it hinders overcoming prevailing diseases [2]. In developing therapeutic computer games this phylogenetically established programming for attachment in order to fulfill fundamental psychosocial needs will be the focus of interaction, cognitive triggers and strategic as well as emotional rules to be applied in the games which are designed in a modular way for difficult developmental phases (e.g. adolescence) or various chronic diseases. This is a new approach transferring sexological clinical experience into therapeutic computer games for prevention purposes and protection of sexual health.

  12. 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.

  13. Clean focus, dose and CD metrology for CD uniformity improvement

    Science.gov (United States)

    Lee, Honggoo; Han, Sangjun; Hong, Minhyung; Kim, Seungyoung; Lee, Jieun; Lee, DongYoung; Oh, Eungryong; Choi, Ahlin; Kim, Nakyoon; Robinson, John C.; Mengel, Markus; Pablo, Rovira; Yoo, Sungchul; Getin, Raphael; Choi, Dongsub; Jeon, Sanghuck

    2018-03-01

    Lithography process control solutions require more exacting capabilities as the semiconductor industry goes forward to the 1x nm node DRAM device manufacturing. In order to continue scaling down the device feature sizes, critical dimension (CD) uniformity requires continuous improvement to meet the required CD error budget. In this study we investigate using optical measurement technology to improve over CD-SEM methods in focus, dose, and CD. One of the key challenges is measuring scanner focus of device patterns. There are focus measurement methods based on specially designed marks on scribe-line, however, one issue of this approach is that it will report focus of scribe line which is potentially different from that of the real device pattern. In addition, scribe-line marks require additional design and troubleshooting steps that add complexity. In this study, we investigated focus measurement directly on the device pattern. Dose control is typically based on using the linear correlation behavior between dose and CD. The noise of CD measurement, based on CD-SEM for example, will not only impact the accuracy, but also will make it difficult to monitor dose signature on product wafers. In this study we will report the direct dose metrology result using an optical metrology system which especially enhances the DUV spectral coverage to improve the signal to noise ratio. CD-SEM is often used to measure CD after the lithography step. This measurement approach has the advantage of easy recipe setup as well as the flexibility to measure critical feature dimensions, however, we observe that CD-SEM metrology has limitations. In this study, we demonstrate within-field CD uniformity improvement through the extraction of clean scanner slit and scan CD behavior by using optical metrology.

  14. Optimal treatment scheduling of ionizing radiation and sunitinib improves the antitumor activity and allows dose reduction

    International Nuclear Information System (INIS)

    Kleibeuker, Esther A; Hooven, Matthijs A ten; Castricum, Kitty C; Honeywell, Richard; Griffioen, Arjan W; Verheul, Henk M; Slotman, Ben J; Thijssen, Victor L

    2015-01-01

    The combination of radiotherapy with sunitinib is clinically hampered by rare but severe side effects and varying results with respect to clinical benefit. We studied different scheduling regimes and dose reduction in sunitinib and radiotherapy in preclinical tumor models to improve potential outcome of this combination treatment strategy. The chicken chorioallantoic membrane (CAM) was used as an angiogenesis in vivo model and as a xenograft model with human tumor cells (HT29 colorectal adenocarcinoma, OE19 esophageal adenocarcinoma). Treatment consisted of ionizing radiation (IR) and sunitinib as single therapy or in combination, using different dose-scheduling regimes. Sunitinib potentiated the inhibitory effect of IR (4 Gy) on angiogenesis. In addition, IR (4 Gy) and sunitinib (4 days of 32.5 mg/kg per day) inhibited tumor growth. Ionizing radiation induced tumor cell apoptosis and reduced proliferation, whereas sunitinib decreased tumor angiogenesis and reduced tumor cell proliferation. When IR was applied before sunitinib, this almost completely inhibited tumor growth, whereas concurrent IR was less effective and IR after sunitinib had no additional effect on tumor growth. Moreover, optimal scheduling allowed a 50% dose reduction in sunitinib while maintaining comparable antitumor effects. This study shows that the therapeutic efficacy of combination therapy improves when proper dose-scheduling is applied. More importantly, optimal treatment regimes permit dose reductions in the angiogenesis inhibitor, which will likely reduce the side effects of combination therapy in the clinical setting. Our study provides important leads to optimize combination treatment in the clinical setting

  15. Neuroprotective effect of STAZN, a novel azulenyl nitrone antioxidant, in focal cerebral ischemia in rats: dose-response and therapeutic window

    Science.gov (United States)

    Ley, James J.; Belayev, Ludmila; Saul, Isabel; Becker, David A.; Ginsberg., Myron D.

    2007-01-01

    Stilbazulenyl nitrone (STAZN) is a potent antioxidant that, in a rat model of transient focal cerebral ischemia, confers significant enduring functional and morphological neuroprotection. This study investigated the influence of dose and time of administration on the neuroprotective effects of STAZN in the intraluminal-suture model of middle cerebral artery occlusion (MCAo). Dose-Response At 2 and 4h after the onset of MCAo, animals received intravenously either STAZN (low dose=0.07 mg/kg, n=8), (medium dose=0.7 mg/kg, n=9), (high dose=3.5 mg/kg, n=9), an equivalent volume of vehicle (30% Solutol HS15 and 70% isotonic saline, 0.37 ml/kg, n=5), or saline (0.37 ml/kg, n=5). Only the medium dose improved scores (p<0.05) on a standardized neurobehavioral test at 1, 2 and 3d after MCAo. Only the medium dose reduced the total infarction (51%, p=0.014) compared to controls. These results indicate that STAZN exhibits maximal neuroprotection at the 0.7 mg/kg dose. Therapeutic Window STAZN (0.6 mg/kg) dissolved in dimethylsulfoxide was given intra-peritoneally at 2 and 4h (n=11), 3 and 5h (n=10), 4 and 6h (n=10), or 5 and 7h (n=7) after the onset of MCAo. Additional doses were given at 24 and 48h. Vehicle (dimethylsulfoxide, 2.0 ml/kg, n=6) was administered at 3, 5, 24 and 48h. STAZN treatment initiated at 2 or 3h after the onset of MCAo improved neurological scores (p<0.001) and reduced total infarction (42.2%, p<0.05) compared to controls. PMID:17945201

  16. Trials to optimize dosimetry for 153Sm-EDTMP therapy to improve therapeutic effects

    International Nuclear Information System (INIS)

    Riccabona, G.; Moncayo-Naveda, R.; Oberlandstaetter, M.; Donnemiller, E.; Kendler, D.

    2001-01-01

    In a trial to improve results of therapy with 153 Sm-EDTMP for pain control in patients with disseminated bone metastases dosimetric studies were performed. Out of 30 treated patients 8 were selected for the study at random (5 breast Ca., 3 prostate Ca.). Whole body retention (WBR) of 99m Tc-DPD and 99m Tc-EDTMP was compared with WBR of 153 Sm-EDTMP. Volume of metastases and regional 99 m Tc-phosphonate uptake were assessed by SPECT and conjugated whole body scan data after phantom studies. Effective half-life was estimated also. Clinically results of pain control, side effects and changes of in vitro parameters were followed after therapy for up to 8 months. Therapy was performed in these patients with 55,5 MBq/kg body weight. Results showed an identical pattern of radioactivity distribution on 99 Tc-phosphonate and 153 Sm-EDTMP posttherapy scans, WBR of tracers and therapeutic agent was similar. Tumour volumes were 151-652 mL, count ratios metastases/normal bone 1,72-2,41, so that 6-50% of applied 153 Sm-EDTMP were concentrated in bone lesions. This gave dose estimates of 2,8-13,7 Gy in metastases. Evaluation of clinical results showed that the majority of very good results were observed in patients receiving > 10 Gy (n=3) while with lower doses only 1/4 responded very well. 1 patient was lost to follow-up due to death in the first month after therapy. Moderate and transient myelodepression (platelets) was seen in 3/7 patients without relation to Gy applied. As obviously 153 Sm concentration is not homogenous in bone metastases it can be assumed, that in border zones between tumour and bone 30-40 Gy can be delivered when 10 Gy are calculated for the whole lesion, which would explain the satisfactory therapeutic effect in our study. The dosimetric approach to 153 Sm-EDTMP therapy could necessitate the application of higher amounts of 153 Sm-EDTMP to reach adequate radiation doses in lesions without necessarily increasing risk of myelodepression and with even

  17. Targeted nanoparticle delivery of therapeutic antisense microRNAs presensitizes glioblastoma cells to lower effective doses of temozolomide in vitro and in a mouse model.

    Science.gov (United States)

    Malhotra, Meenakshi; Sekar, Thillai Veerapazham; Ananta, Jeyarama S; Devulapally, Rammohan; Afjei, Rayhaneh; Babikir, Husam A; Paulmurugan, Ramasamy; Massoud, Tarik F

    2018-04-20

    Temozolomide (TMZ) chemotherapy for glioblastoma (GBM) is generally well tolerated at standard doses but it can cause side effects. GBMs overexpress microRNA-21 and microRNA-10b, two known oncomiRs that promote cancer development, progression and resistance to drug treatment. We hypothesized that systemic injection of antisense microRNAs (antagomiR-21 and antagomiR-10b) encapsulated in cRGD-tagged PEG-PLGA nanoparticles would result in high cellular delivery of intact functional antagomiRs, with consequent efficient therapeutic response and increased sensitivity of GBM cells to lower doses of TMZ. We synthesized both targeted and non-targeted nanoparticles, and characterized them for size, surface charge and encapsulation efficiency of antagomiRs. When using targeted nanoparticles in U87MG and Ln229 GBM cells, we showed higher uptake-associated improvement in sensitivity of these cells to lower concentrations of TMZ in medium. Co-inhibition of microRNA-21 and microRNA-10b reduced the number of viable cells and increased cell cycle arrest at G2/M phase upon TMZ treatment. We found a significant increase in expression of key target genes for microRNA-21 and microRNA-10b upon using targeted versus non-targeted nanoparticles. There was also significant reduction in tumor volume when using TMZ after pre-treatment with loaded nanoparticles in human GBM cell xenografts in mice. In vivo targeted nanoparticles plus different doses of TMZ showed a significant therapeutic response even at the lowest dose of TMZ, indicating that preloading cells with antagomiR-21 and antagomiR-10b increases cellular chemosensitivity towards lower TMZ doses. Future clinical applications of this combination therapy may result in improved GBM response by using lower doses of TMZ and reducing nonspecific treatment side effects.

  18. Pelvic interstitial brachytherapy - improving the therapeutic ratio with magnetic resonance imaging and optimization

    International Nuclear Information System (INIS)

    Swift, Patrick S.; Hricak, Hedvig; Forstner, Rosemary; Powell, C. Bethan; Purser, Phil; Weaver, Keith; Phillips, Theodore L.

    1996-01-01

    Introduction Interstitial brachytherapy in the pelvic region is often hampered by the radiation oncologist's inability to precisely differentiate tumor versus normal tissue during the planning and implantation procedures, often resulting in either excessive or incomplete coverage of tumor volume. The marked improvement in pelvic imaging seen with magnetic resonance, in conjunction with isodose optimization programs for remote-afterloading units, has created an opportunity to significantly improve the therapeutic ratio. Methods From 1992-1995, 23 interstitial perineal templates were performed in 22 patients with pelvic malignancies, using the pulsed low-dose-rate Selectron with dose optimization. MR imaging was performed immediately prior to the implant, with a MUPIT placed against the perineum and a vaginal obturator in place. These images were used for tumor volume measurements, determination of the number, depth and angle of needles required for the implant, and identification of position of normal tissues (rectum, small bowel, bladder) relative to the tumor. After implantation of stainless steel needles, orthogonal radiographs were obtained for isodose calculation, and planning carried out with isodose optimization. Patients were followed closely on a routine schedule, until time of last visit or until death. Every effort possible was made to assess local disease status at time of death. Results Sixteen patients with primary disease (14 cervix, 1 vulva, 1 vagina) and 6 with recurrent (2 with prior radiation) were implanted, all but 3 with curative intent. Nine patients with advanced cervix or vulvar cancer received concomitant chemotherapy (5FU + platinum or mitomycin-C) with the external beam therapy. At a median follow-up of 18.1 months for all cases, only three patients have failed locally for an actuarial local control of 85% at 1.5 years. Nine patients are alive and free of disease, 8 are alive with distant disease only (mean follow-up of 19.1 months), 2

  19. 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

  20. Improved late survival and disability after stroke with therapeutic anticoagulation for atrial fibrillation: a population study.

    LENUS (Irish Health Repository)

    Hannon, Niamh

    2011-09-01

    Although therapeutic anticoagulation improves early (within 1 month) outcomes after ischemic stroke in hospital-admitted patients with atrial fibrillation, no information exists on late outcomes in unselected population-based studies, including patients with all stroke (ischemic and hemorrhagic).

  1. 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

  2. 3D in radiotherapy - pushing the dose envelope to improve cure

    International Nuclear Information System (INIS)

    Leibel, Steven A.

    1996-01-01

    Approximately one in four newly diagnosed cancer patients receive radiation in the initial attempt to cure the tumor. In terms of the 1996 cancer incidence data, this comprises more than 350,000 patients. Inasmuch as 25% of these patients initially relapse at primary tumor sites, the issue of improving local control remains a major challenge to the profession. Recent improvements in treatment planning and delivery have enhanced the precision of radiotherapy, but radiation resistance remains a critical issue that confounds the potential for cure in many tumors. Chemical and biological modifiers of the radiation response have provided an approach with clinical promise, but their therapeutic impact remains to be established. Hence, tumor dose escalation continues to represent the most viable approach to improve local control. Recent experience with new conformal radiotherapy techniques has demonstrated that significant tumor dose escalation is feasible with concomitant reduction in normal tissue toxicity. This experience provides the best hope for immediate improvement in the rates of local tumor control. It remains, nonetheless, unclear how far the dose envelope can be pushed and whether this would be sufficient to overcome the problem of local failure. It may turn out that biological modification of the radiation response may still be necessary to provide a maximal control in certain types of tumors

  3. An improved Monte Carlo (MC) dose simulation for charged particle cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ying, C. K. [Advanced Medical and Dental Institute, AMDI, Universiti Sains Malaysia, Penang, Malaysia and School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu (Malaysia); Kamil, W. A. [Advanced Medical and Dental Institute, AMDI, Universiti Sains Malaysia, Penang, Malaysia and Radiology Department, Hospital USM, Kota Bharu (Malaysia); Shuaib, I. L. [Advanced Medical and Dental Institute, AMDI, Universiti Sains Malaysia, Penang (Malaysia); Matsufuji, Naruhiro [Research Centre of Charged Particle Therapy, National Institute of Radiological Sciences, NIRS, Chiba (Japan)

    2014-02-12

    Heavy-particle therapy such as carbon ion therapy are more popular nowadays because of the nature characteristics of charged particle and almost no side effect to patients. An effective treatment is achieved with high precision of dose calculation, in this research work, Geant4 based Monte Carlo simulation method has been used to calculate the radiation transport and dose distribution. The simulation have the same setting with the treatment room in Heavy Ion Medical Accelerator, HIMAC. The carbon ion beam at the isocentric gantry nozzle for the therapeutic energy of 290 MeV/u was simulated, experimental work was carried out in National Institute of Radiological Sciences, NIRS, Chiba, Japan by using the HIMAC to confirm the accuracy and qualities dose distribution by MC methods. The Geant4 based simulated dose distribution were verified with measurements for Bragg peak and spread out Bragg peak (SOBP) respectively. The verification of results shows that the Bragg peak depth-dose and SOBP distributions in simulation has good agreement with measurements. In overall, the study showed that Geant4 based can be fully applied in the heavy-ion therapy field for simulation, further works need to be carry on to refine and improve the Geant4 MC simulations.

  4. An improved Monte Carlo (MC) dose simulation for charged particle cancer therapy

    International Nuclear Information System (INIS)

    Ying, C. K.; Kamil, W. A.; Shuaib, I. L.; Matsufuji, Naruhiro

    2014-01-01

    Heavy-particle therapy such as carbon ion therapy are more popular nowadays because of the nature characteristics of charged particle and almost no side effect to patients. An effective treatment is achieved with high precision of dose calculation, in this research work, Geant4 based Monte Carlo simulation method has been used to calculate the radiation transport and dose distribution. The simulation have the same setting with the treatment room in Heavy Ion Medical Accelerator, HIMAC. The carbon ion beam at the isocentric gantry nozzle for the therapeutic energy of 290 MeV/u was simulated, experimental work was carried out in National Institute of Radiological Sciences, NIRS, Chiba, Japan by using the HIMAC to confirm the accuracy and qualities dose distribution by MC methods. The Geant4 based simulated dose distribution were verified with measurements for Bragg peak and spread out Bragg peak (SOBP) respectively. The verification of results shows that the Bragg peak depth-dose and SOBP distributions in simulation has good agreement with measurements. In overall, the study showed that Geant4 based can be fully applied in the heavy-ion therapy field for simulation, further works need to be carry on to refine and improve the Geant4 MC simulations

  5. An improved Monte Carlo (MC) dose simulation for charged particle cancer therapy

    International Nuclear Information System (INIS)

    Ying, C.K.; Kamil, W.A.; Shuaib, I.L.; Ying, C.K.; Kamil, W.A.

    2013-01-01

    Full-text: Heavy-particle therapy such as carbon ion therapy are more popular nowadays because of the nature characteristics of charged particle and almost no side effect to patients. An effective treatment is achieved with high precision of dose calculation, in this research work, Geant4 based Monte Carlo simulation method has been used to calculate the radiation transport and dose distribution. The simulation have the same setting with the treatment room in Heavy Ion Medical Accelerator, HIMAC. The carbon ion beam at the isocentric gantry nozzle for the therapeutic energy of 290 MeV/u was simulated, experimental work was carried out in National Institute of Radiological Sciences, NIRS, Chiba, Japan by using the HIMAC to confirm the accuracy and qualities dose distribution by MC methods. The Geant4 based simulated dose distribution were verified with measurements for Bragg peak and spread out Bragg peak (SOBP) respectively. The verification of results shows that the Bragg peak depth-dose and SOBP distributions in simulation has good agreement with measurements. In overall, the study showed that Geant4 based can be fully applied in the heavy ion therapy field for simulation, further works need to be carry on to refine and improve the Geant4 MC simulations. (author)

  6. 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....

  7. Therapeutic treatment plan optimization with probability density-based dose prescription

    International Nuclear Information System (INIS)

    Lian Jun; Cotrutz, Cristian; Xing Lei

    2003-01-01

    The dose optimization in inverse planning is realized under the guidance of an objective function. The prescription doses in a conventional approach are usually rigid values, defining in most instances an ill-conditioned optimization problem. In this work, we propose a more general dose optimization scheme based on a statistical formalism [Xing et al., Med. Phys. 21, 2348-2358 (1999)]. Instead of a rigid dose, the prescription to a structure is specified by a preference function, which describes the user's preference over other doses in case the most desired dose is not attainable. The variation range of the prescription dose and the shape of the preference function are predesigned by the user based on prior clinical experience. Consequently, during the iterative optimization process, the prescription dose is allowed to deviate, with a certain preference level, from the most desired dose. By not restricting the prescription dose to a fixed value, the optimization problem becomes less ill-defined. The conventional inverse planning algorithm represents a special case of the new formalism. An iterative dose optimization algorithm is used to optimize the system. The performance of the proposed technique is systematically studied using a hypothetical C-shaped tumor with an abutting circular critical structure and a prostate case. It is shown that the final dose distribution can be manipulated flexibly by tuning the shape of the preference function and that using a preference function can lead to optimized dose distributions in accordance with the planner's specification. The proposed framework offers an effective mechanism to formalize the planner's priorities over different possible clinical scenarios and incorporate them into dose optimization. The enhanced control over the final plan may greatly facilitate the IMRT treatment planning process

  8. Improvement of quantification of somatic radiation risks at low doses

    International Nuclear Information System (INIS)

    Jacobi, W.; Paretzke, H.G.; Henrichs, K.; Hettig, H.; Jacob, P.; Merkle, W.; Messerer, P.; Schindel, F.

    1985-10-01

    In this research contract several selected topics of basic relevancy for assessment models of radiological consequences of hypothetical reactor accidents have been considered. The investigations focussed on the following areas: 1) Age dependent dose conversion factors for members of the public and their variability for radioisotopes of iodine, strontium, and caesium, - improvement of the accuracy of dose calculations for external gamma irradiation from cloud- and ground-shine; 2) analysis of data and models relevant for the assessment of exposure-time-effect relationships for lethal somatic late effects of lung and breast cancer and of leukemia; 3) analysis of various health status indices (e.g. ''loss of healthy life span'') with respect to their usefulness in addition to incidence, mortality, etc. for the evaluation of the magnitude of a health detriment due to a previous radiation exposure. (orig./HP) [de

  9. Can prebiotics and probiotics improve therapeutic outcomes for undernourished individuals?

    Science.gov (United States)

    Sheridan, Paul O; Bindels, Laure B; Saulnier, Delphine M; Reid, Gregor; Nova, Esther; Holmgren, Kerstin; O'Toole, Paul W; Bunn, James; Delzenne, Nathalie; Scott, Karen P

    2014-01-01

    It has become clear in recent years that the human intestinal microbiota plays an important role in maintaining health and thus is an attractive target for clinical interventions. Scientists and clinicians have become increasingly interested in assessing the ability of probiotics and prebiotics to enhance the nutritional status of malnourished children, pregnant women, the elderly, and individuals with non-communicable disease-associated malnutrition. A workshop was held by the International Scientific Association for Probiotics and Prebiotics (ISAPP), drawing on the knowledge of experts from industry, medicine, and academia, with the objective to assess the status of our understanding of the link between the microbiome and under-nutrition, specifically in relation to probiotic and prebiotic treatments for under-nourished individuals. These discussions led to four recommendations:   (1) The categories of malnourished individuals need to be differentiated To improve treatment outcomes, subjects should first be categorized based on the cause of malnutrition, additional health-concerns, differences in the gut microbiota, and sociological considerations. (2) Define a baseline "healthy" gut microbiota for each category Altered nutrient requirement (for example, in pregnancy and old age) and individual variation may change what constitutes a healthy gut microbiota for the individual. (3) Perform studies using model systems to test the effectiveness of potential probiotics and prebiotics against these specific categories These should illustrate how certain microbiota profiles can be altered, as members of different categories may respond differently to the same treatment. (4) Perform robust well-designed human studies with probiotics and/or prebiotics, with appropriate, defined primary outcomes and sample size These are critical to show efficacy and understand responder and non-responder outcomes. It is hoped that these recommendations will lead to new approaches that

  10. An investigation of dose changes for therapeutic kilovoltage x-ray beams with underlying lead shielding

    International Nuclear Information System (INIS)

    Hill, Robin; Healy, Brendan; Holloway, Lois; Baldock, Clive

    2007-01-01

    Kilovoltage x-ray beams are used to treat cancer on or close to the skin surface. Many clinical cases use high atomic number materials as shielding to reduce dose to underlying healthy tissues. In this work, we have investigated the effect on both the surface dose and depth doses in a water phantom with lead shielding at depth in the phantom. The EGSnrc Monte Carlo code was used to simulate the water phantom and to calculate the surface doses and depth doses using primary x-ray beam spectra derived from an analytical model. The x-ray beams were in the energy range of 75-135 kVp with field sizes of 2, 5 and 8 cm diameter. The lead sheet was located beneath the water surface at depths ranging from 0.5-7.5 cm. The surface dose decreased as the lead was positioned closer to the water surface and as the field size was increased. The variation in surface dose as a function of x-ray beam energy was only small but the maximum reduction occurred for the 100 kVp x-ray beam. For the 8 cm diameter field with the lead at 1 cm depth and using the 100 kVp x-ray beam, the surface dose was reduced to 0.898 of the surface dose in the water phantom only. Measured surface dose changes, using a Farmer-type ionization chamber, agreed with the Monte Carlo calculated doses. Calculated depth doses in water with a lead sheet positioned below the surface showed that the dose fall-off increased as the lead was positioned closer to the water surface as compared to the depth dose in the water phantom only. Monte Carlo calculations of the total x-ray beam spectrum at the water surface showed that the total fluence decreased due to a reduction in backscatter from within the water and very little backscatter from the lead. The mean energy of the x-ray spectrum varied less than 1 keV, with the lead at 1 cm beneath the water phantom surface. As the Monte Carlo calculations showed good agreement with the measured results, this method can be used to verify surface dose changes in clinical situations

  11. 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

  12. Improving Therapeutic Relationships: Joint Crisis Planning for Individuals With Psychotic Disorders.

    Science.gov (United States)

    Farrelly, Simone; Lester, Helen; Rose, Diana; Birchwood, Max; Marshall, Max; Waheed, Waquas; Henderson, R Claire; Szmukler, George; Thornicroft, Graham

    2015-12-01

    Outcomes for individuals with psychosis remain far from acceptable. Recently, prominent psychiatrists have called for an improved understanding of the impact of social contexts, and how social contexts might influence the development and maintenance of mental health problems. A key social context for individuals with psychosis is the therapeutic relationship. As part of a trial of joint crisis planning in England, this qualitative study aimed to determine the mechanism through which joint crisis planning might affect the therapeutic relationship. Results suggest that routine processes in mental health care are affected by policy and organizational requirements for risk mitigation-aspects that undermine person-centered approaches. In contrast, strong therapeutic relationships are characterized by individualized care and reliable and respectful treatment. The Joint Crisis Plan intervention partially succeeded in reducing contextual influences on routine role enactments, facilitating the demonstration of respect and improving the therapeutic relationship. © The Author(s) 2015.

  13. 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.

  14. 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)

  15. Determination of the dose equivalents due to neutrons produced during therapeutic irradiations with a Varian CLINAC 2500

    International Nuclear Information System (INIS)

    Carrillo, Ricardo E.

    1991-01-01

    This experiment it was designed to quantify that so important it is the dose equivalent deposited by the neutron flow that is generated by photonuclear reactions during therapeutic irradiations with X rays of produced high-energy for an accelerator Varian CLINAC 2500. This accelerator type is routinely used in the Department of Radiotherapy of the Hospital of the University of Wisconsin, E.U. The equivalent dose was measured in diverse towns of the room of irradiations using the activation of thin sheets of gold put in the center of plastic recipients full with water. In general, the recipients were 1 m or more than the floor and at distances still bigger than the walls. The irradiations were made using photons with the highest energy that you can select with this team - 24 MeV. The due equivalent dose to neutrons taken place here by the energy photons used they were measured and reported. (author)

  16. Selections of appropriate regimen of high-dose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: reargument of such contentious therapeutic preferences.

    Science.gov (United States)

    Ren, Jun; Di, Lijun; Song, Guohong; Yu, Jing; Jia, Jun; Zhu, Yuling; Yan, Ying; Jiang, Hanfang; Liang, Xu; Che, Li; Zhang, Jie; Wan, Fengling; Wang, Xiaoli; Zhou, Xinna; Lyerly, Herbert Kim

    2013-10-01

    We hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients. Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m(2) docetaxel and 75 mg/m(2) thiotepa versus 87 patients of HDC + DC/CIK: 120 mg/m(2) docetaxel to mobilize peripheral CD34(+) progenitor cells, a sequence of HDC (120 mg/m(2) docetaxel, plus 175 mg/m(2) thiotepa) + DC/CIK, with or without 400 mg/m(2) carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS). Compared with SDC, PFS and OS were improved in HDC + DC/CIK (median PFS 10.2 vs. 3.7 months, P < 0.001; median OS 33.1 vs. 15.2 months, P < 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed prolonged PFS and OS. SDC group also achieved the similar response as previous reports. Our study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.

  17. Quantifying the importance of pMHC valency, total pMHC dose and frequency on nanoparticle therapeutic efficacy.

    Science.gov (United States)

    Sugarman, Jordan; Tsai, Sue; Santamaria, Pere; Khadra, Anmar

    2013-05-01

    Nanoparticles (NPs) coated with β-cell-specific peptide major histocompatibility complex (pMHC) class I molecules can effectively restore normoglycemia in spontaneously diabetic nonobese diabetic mice. They do so by expanding pools of cognate memory autoreactive regulatory CD8+ T cells that arise from naive low-avidity T-cell precursors to therapeutic levels. Here we develop our previously constructed mathematical model to explore the effects of compound design parameters (NP dose and pMHC valency) on therapeutic efficacy with the underlying hypothesis that the functional correlates of the therapeutic response (expansion of autoregulatory T cells and deletion of autoantigen-loaded antigen-presenting cells by these T cells) are biphasic. We show, using bifurcation analysis, that the model exhibits a 'resonance'-like behavior for a given range of NP dose in which bistability between the healthy state (possessing zero level of effector T-cell population) and autoimmune state (possessing elevated level of the same population) disappears. A heterogeneous population of model mice subjected to several treatment protocols under these new conditions is conducted to quantify both the average percentage of autoregulatory T cells in responsive and nonresponsive model mice, and the average valency-dependent minimal optimal dose needed for effective therapy. Our results reveal that a moderate increase (≥1.6-fold) in the NP-dependent expansion rate of autoregulatory T-cell population leads to a significant increase in the efficacy and the area corresponding to the effective treatment regimen, provided that NP dose ≥8 μg. We expect the model developed here to generalize to other autoimmune diseases and serve as a computational tool to understand and optimize pMHC-NP-based therapies.

  18. Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL.

    Science.gov (United States)

    Barr, Paul M; Brown, Jennifer R; Hillmen, Peter; O'Brien, Susan; Barrientos, Jacqueline C; Reddy, Nishitha M; Coutre, Steven; Mulligan, Stephen P; Jaeger, Ulrich; Furman, Richard R; Cymbalista, Florence; Montillo, Marco; Dearden, Claire; Robak, Tadeusz; Moreno, Carol; Pagel, John M; Burger, Jan A; Suzuki, Samuel; Sukbuntherng, Juthamas; Cole, George; James, Danelle F; Byrd, John C

    2017-05-11

    Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours. It is unknown if intermittent interruption of ibrutinib therapy contributes to altered clinical outcomes. We therefore evaluated the effect of ibrutinib dose adherence on patient outcomes in the phase 3 RESONATE trial. The overall mean dose intensity (DI) was 95% with median treatment duration of ∼9 months. Pharmacokinetic assessment of ibrutinib exposure at 420-mg dose suggested similar exposure regardless of patient weight or age. As assessed by independent review committee, patients with higher DI experienced longer median progression-free survival (PFS) compared with those with lower DI regardless of del17p and/or TP53 status. Of 79 patients requiring a drug hold, treatment was restarted at the original dose in 73 (92%) patients. Mean duration of a missed-dose event was 18.7 days (range, 8-56). Patients missing ≥8 consecutive days of ibrutinib had a shorter median PFS vs those missing ibrutinib dosing at 420 mg as clinically feasible to achieve optimal outcomes in patients with previously treated CLL. The trial was registered at www.clinicaltrials.gov as #NCT01578707. © 2017 by The American Society of Hematology.

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

    International Nuclear Information System (INIS)

    Thompson, Reid F.; Schneider, Ralf A.; Albertini, Francesca; Lomax, Antony J.; Ares, Carmen; Goitein, Gudrun; Hug, Eugen B.

    2013-01-01

    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

  20. 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.

  1. WE-FG-BRA-05: Potential Clinical Benefit of LINAC Flattening-Filter-Free (FFF) Mode - Improvement of Treatment Therapeutic Ratio

    International Nuclear Information System (INIS)

    Chang, S; Rivera, J; Tian, H; Price, A; Santos, C; Zhang, Y

    2016-01-01

    Purpose: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0.05Gy/s, and 2) the dose-rate effect’s potential working mechanism by studying the expression of the P53 gene, linked to tumor suppression and cell regulation after radiation damage. Methods: We used mouse model C57BL/6J, the same as that used in the ultrahigh dose-rate studies, and exposed them to total body irradiation (TBI) using the Elekta Versa accelerator 10MV photons. Mice (N=20) were given a total dose of 12Gy in both the high dose-rate group (n=10) using the FFF-mode and the conventional dose-rate group (n=10) using the conventional does rate mode. The FFF-mode treatment setup consisted of a 15cm×15cm field size setting at 53.2cm SSD while the conventional-mode set-up consisted of a 10cm×10cm field size at 100SSD. Post-radiation, animals were monitored daily for survival analysis and signs of moribundity requiring euthanasia. In addition, mouse spleens were harvested for P53 analysis at different time points. Results: For 12Gy TBI, the 1.3Gy/s FFF-mode high dose-rate produced a statistically significant (p=0.02) improvement in mouse survival compared to the 0.05Gy/s conventional dose-rate. An initial P53 study at the time of death time-point indicates that high dose-rate radiation induced a stronger expression of P53 than conventional dose-rate radiation. Conclusion: Our pilot study indicates that the FFF-mode high dose-rate radiation, which has been used largely to improve clinical throughput, may provide

  2. WE-FG-BRA-05: Potential Clinical Benefit of LINAC Flattening-Filter-Free (FFF) Mode - Improvement of Treatment Therapeutic Ratio

    Energy Technology Data Exchange (ETDEWEB)

    Chang, S [Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, NC (United States); Department of Biomedical Engineering, University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, North Carolina (United States); Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC (United States); Rivera, J [Department of Biomedical Engineering, University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, North Carolina (United States); Tian, H [Xuzhou Medical College, Xuzhou, Jiangsu (China); Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC (United States); Price, A [Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, NC (United States); Santos, C [Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC (United States); Zhang, Y [Department of Radiation Oncology, UNC School of Medicine, Chapel Hill, NC (United States); Xuzhou Medical College, Xuzhou, Jiangsu (China); Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC (United States)

    2016-06-15

    Purpose: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0.05Gy/s, and 2) the dose-rate effect’s potential working mechanism by studying the expression of the P53 gene, linked to tumor suppression and cell regulation after radiation damage. Methods: We used mouse model C57BL/6J, the same as that used in the ultrahigh dose-rate studies, and exposed them to total body irradiation (TBI) using the Elekta Versa accelerator 10MV photons. Mice (N=20) were given a total dose of 12Gy in both the high dose-rate group (n=10) using the FFF-mode and the conventional dose-rate group (n=10) using the conventional does rate mode. The FFF-mode treatment setup consisted of a 15cm×15cm field size setting at 53.2cm SSD while the conventional-mode set-up consisted of a 10cm×10cm field size at 100SSD. Post-radiation, animals were monitored daily for survival analysis and signs of moribundity requiring euthanasia. In addition, mouse spleens were harvested for P53 analysis at different time points. Results: For 12Gy TBI, the 1.3Gy/s FFF-mode high dose-rate produced a statistically significant (p=0.02) improvement in mouse survival compared to the 0.05Gy/s conventional dose-rate. An initial P53 study at the time of death time-point indicates that high dose-rate radiation induced a stronger expression of P53 than conventional dose-rate radiation. Conclusion: Our pilot study indicates that the FFF-mode high dose-rate radiation, which has been used largely to improve clinical throughput, may provide

  3. 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

  4. Study on dose distribution of therapeutic proton beams with prompt gamma measurement

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J. W. [National Cancer Center, Seoul (Korea, Republic of); Min, C. H.; Kim, C. H.; Kim, D. K.; Yoon, M. Y. [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2007-03-15

    The proton beam has an advantage of the sharp dose falloff in dose distribution called Bragg peak while conventional radiation therapy modalities such as photons exhibit considerable amount of exit dose. To take advantage of this property it is important to know the exact location of the distal dose falloff. An error can cause overdose to the normal tissue or underdose to the tumor volume. The only way of finding out the dose distribution in-situ in particle therapy is to measure the gammas produced by nuclear reactions with tissue materials. Two kinds of gammas can be used: one is prompt gamma and the other is coincident gamma from the positron-emission isotopes. We chose to detect prompt gammas, and developed a prompt gamma scanning system (PGS). The proton beams of the proton therapy facility at National Cancer Center were used. The gamma distribution was compared to the dose distribution measured by an ionization chamber at three different energies of 100, 150, 200 MeV's. The two distributions were well correlated within 1-2 mm. The effect of high-energy neutron appeared as blurred distribution near the distal dose falloff at the energy of 200 MeV. We then tested the PGS shielding design by adding additional layer of paraffin plates outside of the PGS, and found that fast neutrons significantly affect the background level. But the location of the dose fall-off was nearly coincident. The analysis of gamma energy spectrum showed that cut-off energy in gamma counting can be adjusted to enhance the signal to noise ratio. Further the ATOM phantom, which has similar tissue structure to human, was used to investigate the gamma distribution for the case of inhomogeneous matter. The location of dose falloff region was found to be well defined as for water phantom. Next an actual therapy beam, which was produced by the double scattering method, was used, for which the dose falloff by the gamma distribution was completely wiped out by background neutrons. It is not

  5. 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.

  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. Patient radiation doses in therapeutic endoscopic retrograde cholangiopancreatography in Patras and the key role of the operator

    International Nuclear Information System (INIS)

    Hadjiconstanti, Anastasia C.; Messaris, Gerasimos A. T.; Panayiotakis, George S.; Thomopoulos, Konstantinos C.

    2017-01-01

    The patient radiation doses, in conjunction with the operator experience, in therapeutic endoscopic retrograde cholangiopancreatography (ERCP) procedures, performed in our hospital, were obtained. Ninety-six patients participated in the study and were divided into 3 groups, based on the operator experience. The dosimetric indices, fluoroscopy time (FT), cumulative dose (K a,r ) and air kerma-area product (P KA ), were collected. For the total and weight banding group the third quartile values of the distribution of FT, K a,r and P KA were 2.90 and 2.92 min, 6.89 and 6.93 mGy and 1.84 and 1.85 Gycm 2 , respectively, and were comparative or significantly lower than the corresponding values previously reported. Taking as a criterion the operator, the differences in the patient radiation doses were statistically significant, with the highest dose recorded for the operator of the lowest experience degree. The values obtained could contribute in establishing local and national diagnostic reference levels and in optimising ERCP procedure. (authors)

  10. Pregnancy after high therapeutic doses of iodine-131 in differentiated thyroid cancer: potential risks and recommendations

    International Nuclear Information System (INIS)

    Casara, D.; Rubello, D.; Saladini, G.; Piotto, A.; Pelizzo, M.R.; Girelli, M.E.; Busnardo, B.

    1993-01-01

    Seventy female patients who had been treated with high doses of iodine-131 for differented thyroid cancer (DTC) and who had a subsequent pregnancy were evaluated. The global 131 I dose ranged from 1.85 to 16.55 GBq (mean±SD=4.39±25.20 GBq). Age at first therapy ranged from 15 to 36 years (mean±SD=24.3±5.0 years) and the interval from 131 I therapy to pregnancy varied from 2 to 10 years (mean±SD=5.3±2.8 years). The estimated radiation dose to the gonads ranged from 10 to 63 cGy (mean±SD=24.0±13.5 cGy). All patients were treated with L-thyroxine at doses capable of suppressing thyroid-stimulating hormone. Seventy-three children were followed-up and seven pregnancies are still in progress. One child was affected by Fallot's trilogy and three had a low birth weight though with subsequent regular growth; the others were healthy with subsequent regular growth. No newborn with clinical or biochemical thyroid dysfunctions was found. Two spontaneous abortions during the second month of pregnancy were recorded. One of two patients in question subsequently had two healthy children. On the basis of these data, previous administration of high 131 I doses does not appear to be a valid reason for dissuading young female DTC patients from considering pregnancy. However, patients should be advised to avoid pregnancy after 131 I administration for a period sufficient to ensure complete elimination of the radionuclide and to permit confirmation of complete disease remission, i.e. at least 1 year in our opinion. (orig.)

  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. Administration of BMSCs with muscone in rats with gentamicin-induced AKI improves their therapeutic efficacy.

    Directory of Open Access Journals (Sweden)

    Pengfei Liu

    Full Text Available The therapeutic action of bone marrow-derived mesenchymal stem cells (BMSCs in acute kidney injury (AKI has been reported by several groups. However, recent studies indicated that BMSCs homed to kidney tissues at very low levels after transplantation. The lack of specific homing of exogenously infused cells limited the effective implementation of BMSC-based therapies. In this study, we provided evidence that the administration of BMSCs combined with muscone in rats with gentamicin-induced AKI intravenously, was a feasible strategy to drive BMSCs to damaged tissues and improve the BMSC-based therapeutic effect. The effect of muscone on BMSC bioactivity was analyzed in vitro and in vivo. The results indicated that muscone could promote BMSC migration and proliferation. Some secretory capacity of BMSC still could be improved in some degree. The BMSC-based therapeutic action was ameliorated by promoting the recovery of biochemical variables in urine or blood, as well as the inhibition of cell apoptosis and inflammation. In addition, the up-regulation of CXCR4 and CXCR7 expression in BMSCs could be the possible mechanism of muscone amelioration. Thus, our study indicated that enhancement of BMSCs bioactivities with muscone could increase the BMSC therapeutic potential and further developed a new therapeutic strategy for the treatment of AKI.

  13. Interpersonal problems as predictors of therapeutic alliance and symptom improvement in cognitive therapy for depression.

    Science.gov (United States)

    Renner, Fritz; Jarrett, Robin B; Vittengl, Jeffrey R; Barrett, Marna S; Clark, Lee Anna; Thase, Michael E

    2012-05-01

    The degree to which interpersonal problems of depressed patients improve over the course of cognitive therapy (CT) and relate to the quality of the therapeutic alliance and to symptom improvement, remains unclear. We analyzed data of adult outpatients (N=523) with major depressive disorder participating in a clinical trial to determine the factor structure of the Inventory of Interpersonal Problems-Circumplex (IIP-C) and to relate the observed factor scores to the quality of the therapeutic alliance and symptom improvement over the course of CT. Patients received 16-20 sessions protocol (50-60 min each) of individual CT according to the treatment manual by Beck et al. (1979). We found a three-factor structure (interpersonal distress, agency, and communion) of interpersonal problems. Interpersonal distress decreased (d=.90), but interpersonal style did not change substantively during CT (communion d=.03; agency d=.14). High initial agency scores related negatively to the therapeutic alliance (β=-.12), whereas high initial communion scores related positively to the therapeutic alliance (β=.15). Elevated pre-treatment interpersonal distress scores were related to both weaker therapeutic alliances (β=.13) and higher symptom levels throughout treatment (β=.10). All patients in this study had recurrent MDD and it is therefore uncertain whether the results would generalize to patients with other psychiatric disorders. This study supports the use of the IIP-C as a comprehensive measure of patients' interpersonal style and interpersonal distress. The IIP-C measured before CT showed some predictive validity with respect to therapeutic alliance measured at the midpoint and therapy outcome. The clinical importance of these findings is discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Interpersonal problems as predictors of therapeutic alliance and symptom improvement in cognitive therapy for depression

    Science.gov (United States)

    Renner, Fritz; Jarrett, Robin B.; Vittengl, Jeffrey R.; Barrett, Marna S.; Clark, Lee Anna; Thase, Michael E.

    2012-01-01

    Background The degree to which interpersonal problems of depressed patients improve over the course of cognitive therapy (CT) and relate to the quality of the therapeutic alliance and to symptom improvement, remain unclear. Methods We analyzed data of adult outpatients (N = 523) with major depressive disorder participating in a clinical trial to determine the factor structure of the Inventory of Interpersonal Problems-Circumplex (IIP-C) and to relate the observed factor scores to the quality of the therapeutic alliance and symptom improvement over the course of CT. Patients received 16–20 sessions protocol (50–60 minutes each) of individual CT according to the treatment manual by Beck et al. (1979). Results We found a three-factor structure (interpersonal distress, agency, and communion) of interpersonal problems. Interpersonal distress decreased (d = .90), but interpersonal style did not change substantively during CT (communion d = .03; agency d = .14). High initial agency scores related negatively to the therapeutic alliance (β = −.12), whereas high initial communion scores related positively to the therapeutic alliance (β = .15). Elevated pre-treatment interpersonal distress scores were related to both weaker therapeutic alliances (β = .13) and higher symptom levels throughout treatment (β = .10). Limitations All patients in this study had recurrent MDD and it is therefore uncertain whether the results would generalize to patients with other psychiatric disorders. Conclusions This study supports the use of the IIP-C as a comprehensive measure of patients' interpersonal style and interpersonal distress. The IIP-C measured before CT showed some predictive validity with respect to therapeutic alliance measured at the midpoint and therapy outcome. The clinical importance of these findings is discussed. PMID:22306232

  15. Dose Measurement and Calculation of Asymmetric X-Ray Fields from Therapeutic Linac

    International Nuclear Information System (INIS)

    El-Attar, A. L.; Abdel-Wanees, M. E.; Hashem, M. A.

    2011-01-01

    Linear accelerators with x-ray collimators that move independently are becoming increasingly common for treatment with asymmetric fields. In this paper we present a simplified approach to the calculation of dose for asymmetric fields. A method is described for calculating the beam profiles, depth doses and output factors for asymmetric fields of radiation produced by linear accelerators (siemens mevatron M2) with independent jaws. Values are calculated from data measured for symmetric fields. Symmetric field data are modified using opened off-axis factors (OAFs) and primary off-centre ratios (POCRs) which are obtained from in air measurements of the largest possible opened field. Beam hardening occurring within the flattening filter is taken into account using of attenuation coefficients for opened field and used to generate the opened POCR at different depths. A full investigation to compare measured and calculated profiles demonstrates favorable agreement.

  16. Predictor factors in the effectiveness of the therapeutic dose in the Graves diseases

    International Nuclear Information System (INIS)

    Puscar, Ana

    2006-01-01

    The treatment of the Graves diseases includes different options, between which are the antithyroid drugs, 131 I and/or the surgery. Of all of them, the 131 I, it has been increasing the use through the years, going to constitute the treatment of election for many authors, due to the big effectiveness to obtain a rapid healing of this illness. On the other hand, controversies exist about this use, related about the administration doses of 131 I [es

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

    International Nuclear Information System (INIS)

    Lin, S.-Y.; Chu, T.-C.; Lin, J.-P.; Liu, M.-T.

    2002-01-01

    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 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 Bone , PDD Ti and PDD 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 Bone , PDD Ti and 4-5% in PDD 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 Bone at any depth. Profile Ti reveals that MC slightly exceeds ADAC at off-axis position 1.0-2.0 cm. Profile Co reveals this more obviously. This finding means that scatter radiation from these denser materials is significant and cannot be predicted precisely in ADAC

  18. 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.

  19. 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.

  20. Incidence of postpartum haemorrhage in women receiving therapeutic doses of low-molecular-weight heparin: results of a retrospective cohort study

    NARCIS (Netherlands)

    Roshani, Sara; Cohn, Danny M.; Stehouwer, Alexander C.; Wolf, Hans; van der Post, Joris A. M.; Büller, Harry R.; Kamphuisen, Pieter W.; Middeldorp, Saskia

    2011-01-01

    Background Low-molecular-weight heparin (LMWH) is the drug of choice to prevent venous thrombosis in pregnancy, but the optimal dose for prevention while avoiding bleeding is unclear. This study investigated whether therapeutic doses of LMWH increase the incidence of postpartum haemorrhage (PPH) in

  1. Incidence of postpartum haemorrhage in women receiving therapeutic doses of low-molecular-weight heparin : results of a retrospective cohort study

    NARCIS (Netherlands)

    Roshani, Sara; Cohn, Danny M; Stehouwer, Alexander C; Wolf, Hans; van der Post, Joris A M; Büller, Harry R; Kamphuisen, Pieter W; Middeldorp, Saskia

    2011-01-01

    Background Low-molecular-weight heparin (LMWH) is the drug of choice to prevent venous thrombosis in pregnancy, but the optimal dose for prevention while avoiding bleeding is unclear. This study investigated whether therapeutic doses of LMWH increase the incidence of postpartum haemorrhage (PPH) in

  2. 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

  3. Quantification of rabbit bone metabolism (BM) before (B) and after (A) sub-therapeutic doses of (89 Sr) -Initial results

    International Nuclear Information System (INIS)

    Braga, F.J.H.N.; Kinoshita, A.; Turco, F.P.; Moraes, F.A.; Iazigi, N.; Souza, J.F.; Trad, C.S.

    1997-01-01

    Full text. Some beta emitters, such as 89 Sr, 153 Sm and 186 Re are in current use worldwide for the palliation of bone pain caused by metastases, mainly in cases of disseminated bone metastases when conventional radiotherapy has already been used to maximum dose and when pain relief does not occur with the use of current drugs. In order to quantifying the reduction of RBM after such procedures, we have studied 10 young rabbits (2.5 months old, 1.5 kg), 2 h after the intravenous injection with 150 MBq of 99 m Tc - M D P. Rabbits were counted for 30 seconds in a scintillation camera. A region of interest (ROI) was drawn in the left knee joint. The knee joint was chosen because of its high BM in young animals. Each rabbit received 1.5 MBq per kilo of 89 Sr intravenously immediately after this initial evaluation (therapeutic doses for humans are 2.0 MBq per kg). One month after, rabbits were evaluated again with 99 M T C- MDP as described before and a second ROI was drawn in the same knee joint.The means of counts observed B and A 89 Sr injection were 11, 222 and 4, 399 respectively. These means are significantly different (p <0.05) and represent a reduction of over 60% in the knee joint BM after the 89 Sr dose

  4. Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas D.; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-01-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling either medium dose (3.53%), low dose (1.29%), or placebo cannabis with the primary outcome being VAS pain intensity. Psychoactive side-effects, and neuropsychological performance were also evaluated. Mixed effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the two active dose groups’ results (p>0.7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo vs. low dose, 2.9 for placebo vs. medium dose, and 25 for medium vs. low dose. As these NNT are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being, for all intents and purposes, as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well-tolerated, and neuropsychological effects were of limited duration and readily reversible within 1–2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. PMID:23237736

  5. Weathering the storm: Improving therapeutic interventions for cytokine storm syndromes by targeting disease pathogenesis.

    Science.gov (United States)

    Weaver, Lehn K; Behrens, Edward M

    2017-03-01

    Cytokine storm syndromes require rapid diagnosis and treatment to limit the morbidity and mortality caused by the hyperinflammatory state that characterizes these devastating conditions. Herein, we discuss the current knowledge that guides our therapeutic decision-making and personalization of treatment for patients with cytokine storm syndromes. Firstly, ICU-level supportive care is often required to stabilize patients with fulminant disease while additional diagnostic evaluations proceed to determine the underlying cause of cytokine storm. Pharmacologic interventions should be focused on removing the inciting trigger of inflammation and initiation of an individualized immunosuppressive regimen when immune activation is central to the underlying disease pathophysiology. Monitoring for a clinical response is required to ensure that changes in the therapeutic regimen can be made as clinically warranted. Escalation of immunosuppression may be required if patients respond poorly to the initial therapeutic interventions, while a slow wean of immunosuppression in patients who improve can limit medication-related toxicities. In certain scenarios, a decision must be made whether an individual patient requires hematopoietic cell transplantation to prevent recurrence of disease. Despite these interventions, significant morbidity and mortality remains for cytokine storm patients. Therefore, we use this review to propose a clinical schema to guide current and future attempts to design rational therapeutic interventions for patients suffering from these devastating conditions, which we believe speeds the diagnosis of disease, limits medication-related toxicities, and improves clinical outcomes by targeting the heterogeneous and dynamic mechanisms driving disease in each individual patient.

  6. 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

  7. 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

  8. Morphine and clonidine combination therapy improves therapeutic window in mice: synergy in antinociceptive but not in sedative or cardiovascular effects.

    Directory of Open Access Journals (Sweden)

    Laura S Stone

    Full Text Available Opioids are used to manage all types of pain including acute, cancer, chronic neuropathic and inflammatory pain. Unfortunately, opioid-related adverse effects such as respiratory depression, tolerance, physical dependence and addiction have led to an underutilization of these compounds for adequate pain relief. One strategy to improve the therapeutic utility of opioids is to co-administer them with other analgesic agents such as agonists acting at α2-adrenergic receptors (α2ARs. Analgesics acting at α2ARs and opioid receptors (ORs frequently synergize when co-administered in vivo. Multimodal analgesic techniques offer advantages over single drug treatments as synergistic combination therapies produce analgesia at lower doses, thus reducing undesired side effects. This inference presumes, however, that the synergistic interaction is limited to the analgesic effects. In order to test this hypothesis, we examined the effects of α2AR/OR combination therapy in acute antinociception and in the often-undesired side effects of sedation and cardiovascular depression in awake unrestrained mice. Morphine, clonidine or their combination was administered by spinal or systemic injection in awake mice. Antinociception was determined using the warm water tail flick assay (52.5°C. Sedation/motor impairment was evaluated using the accelerating rotarod assay and cardiovascular function was monitored by pulse oximetry. Data were converted to percent maximum possible effect and isobolographic analysis was performed to determine if an interaction was subadditive, additive or synergistic. Synergistic interactions between morphine and clonidine were observed in the antinociceptive but not in the sedative/motor or cardiovascular effects. As a result, the therapeutic window was improved ∼200-fold and antinociception was achieved at non-sedating doses with little to no cardiovascular depression. In addition, combination therapy resulted in greater maximum analgesic

  9. Low-dose vaporized cannabis significantly improves neuropathic pain.

    Science.gov (United States)

    Wilsey, Barth; Marcotte, Thomas; Deutsch, Reena; Gouaux, Ben; Sakai, Staci; Donaghe, Haylee

    2013-02-01

    We conducted a double-blind, placebo-controlled, crossover study evaluating the analgesic efficacy of vaporized cannabis in subjects, the majority of whom were experiencing neuropathic pain despite traditional treatment. Thirty-nine patients with central and peripheral neuropathic pain underwent a standardized procedure for inhaling medium-dose (3.53%), low-dose (1.29%), or placebo cannabis with the primary outcome being visual analog scale pain intensity. Psychoactive side effects and neuropsychological performance were also evaluated. Mixed-effects regression models demonstrated an analgesic response to vaporized cannabis. There was no significant difference between the 2 active dose groups' results (P > .7). The number needed to treat (NNT) to achieve 30% pain reduction was 3.2 for placebo versus low-dose, 2.9 for placebo versus medium-dose, and 25 for medium- versus low-dose. As these NNTs are comparable to those of traditional neuropathic pain medications, cannabis has analgesic efficacy with the low dose being as effective a pain reliever as the medium dose. Psychoactive effects were minimal and well tolerated, and neuropsychological effects were of limited duration and readily reversible within 1 to 2 hours. Vaporized cannabis, even at low doses, may present an effective option for patients with treatment-resistant neuropathic pain. The analgesia obtained from a low dose of delta-9-tetrahydrocannabinol (1.29%) in patients, most of whom were experiencing neuropathic pain despite conventional treatments, is a clinically significant outcome. In general, the effect sizes on cognitive testing were consistent with this minimal dose. As a result, one might not anticipate a significant impact on daily functioning. Published by Elsevier Inc.

  10. Urinary biomarkers of trimethoprim bioactivation in vivo following therapeutic dosing in children.

    Science.gov (United States)

    van Haandel, Leon; Goldman, Jennifer L; Pearce, Robin E; Leeder, J Steven

    2014-02-17

    The antimicrobial trimethoprim-sulfamethoxazole (TMP-SMX) is widely used for the treatment of skin and soft-tissue infections in the outpatient setting. Despite its therapeutic benefits, TMP-SMX has been associated with a number of adverse drug reactions, which have been primarily attributed to the formation of reactive metabolites from SMX. Recently, in vitro experiments have demonstrated that TMP may form reactive intermediates as well. However, evidence of TMP bioactivation in patients has not yet been demonstrated. In this study, we performed in vitro trapping experiments with N-acetyl-l-cysteine (NAC) to determine stable markers of reactive TMP intermediates, focusing on eight potential markers (NAC-TMP adducts), some of which were previously identified in vitro. We developed a specific and sensitive assay involving liquid chromatography followed by tandem mass spectrometry for measurement of these adducts in human liver microsomal samples and expanded the methodology toward the detection of these analytes in human urine. Urine samples from four patients receiving TMP-SMX treatment were analyzed, and all samples demonstrated the presence of six NAC-TMP adducts, which were also detected in vitro. These adducts are consistent with the formation of imino-quinone-methide and para-quinone-methide reactive intermediates in vivo. As a result, the TMP component of TMP-SMX should be considered as well when evaluating adverse drug reactions to TMP-SMX.

  11. 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.

  12. Determination of crossed gamma doses for garlic improvement (Allium Sativum)

    International Nuclear Information System (INIS)

    Perez Talavera, S.; Labrada, A.; Savin, V.

    1991-01-01

    The determination of four Cuban varieties of garlic was made so as to optimized the use of ionizing radiations in Cuba to breed vegetatively propagated crops such as garlic. The dose-effect regresion equation characterizing the radioinhibition zone of each crop was presented. We used a criteria to select the irradiation dose to be used in mutation breeding techniques based on obtaining height variability in the productive indicators, a survival and a number of garlic cloves high enough to allow and adequate reproduction of M1 plants. It was verified that this small inhibitor doses of radiations produced a higher percentage of good variability than the medium and high doses. With the use of small inhibitor doses (GR10-GR20) on the Guadalupe-15 garlic variety, 65 variety plants were obtained., 93.7% out of this number is higher than the control in the indicators considered

  13. Improved Therapeutic Regimens for Treatment of Post-Traumatic Ocular Infections

    Science.gov (United States)

    2011-05-01

    cystoid macular oedema in uveitis . Clin. Exp. Ophthalmol. 29, 2–6 (2001). 36 Campochiaro PA, Lim JI. Aminoglycoside toxicity in the treatment of...TELEPHONE NUMBER (include area code) Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 Improved Therapeutic Regimens for Treatment of...injury and adequate treatment . This proposal was designed to analyze the effectiveness of antibiotics, anti-inflammatory drugs, and non-conventional

  14. 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.

  15. Drug persistence and need for dose intensification to adalimumab therapy; the importance of therapeutic drug monitoring in inflammatory bowel diseases.

    Science.gov (United States)

    Gonczi, Lorant; Kurti, Zsuzsanna; Rutka, Mariann; Vegh, Zsuzsanna; Farkas, Klaudia; Lovasz, Barbara D; Golovics, Petra A; Gecse, Krisztina B; Szalay, Balazs; Molnar, Tamas; Lakatos, Peter L

    2017-08-08

    Therapeutic drug monitoring (TDM) aid therapeutic decision making in patients with inflammatory bowel disease (IBD) who lose response to anti-TNF therapy. Our aim was to evaluate the frequency and predictive factors of loss of response (LOR) to adalimumab using TDM in IBD patients. One hundred twelve IBD patients (with 214 TDM measurements, CD/UC 84/28, male/female 50/62, mean age CD/UC: 36/35 years) were enrolled in this consecutive cohort from two referral centres in Hungary. Demographic data were comprehensively collected and harmonized monitoring strategy was applied. Previous and current therapy, laboratory data and clinical activity were recorded at the time of TDM. Patients were evaluated either at the time of suspected LOR or during follow-up. TDM measurements were determined by commercial ELISA (LISA TRACKER, Theradiag, France). Among 112 IBD patients, LOR/drug persistence was 25.9%/74.1%. The cumulative ADA positivity (>10 ng/mL) and low TL (<5.0 μg/mL) was 12.1% and 17.8% after 1 year and 17.3% and 29.5% after 2 years of adalimumab therapy. Dose intensification was needed in 29.5% of the patients. Female gender and ADA positivity were associated with LOR (female gender: p < 0.001, OR:7.8 CI 95%: 2.5-24.3, ADA positivity: p = 0.007 OR:3.6 CI 95%: 1.4-9.5). ADA development, low TL and need for dose intensification were frequent during adalimumab therapy and support the selective use of TDM in IBD patients treated with adalimumab. ADA positivity and gender were predictors of LOR.

  16. Providing Quality Therapeutics in Switzerland: Role of the Stakeholders and Recent Incentives for Further Improvements.

    Science.gov (United States)

    Besson, Marie; Samer, Caroline; Rollason, Victoria; Dayer, Pierre; Desmeules, Jules

    2015-07-01

    Quality therapeutics play an important role in Switzerland's health care and economy. Switzerland holds a key position in the world of research and development, as well as in drug production. Recently, new emphasis has been placed on promoting clinical research and maintaining Switzerland's position as a center of excellence in the field. Recent revisions to the law regarding medical trials in human research allow for better allocation of regulatory resources and simplified procedures for drugs already authorized in Switzerland. The country has its own regulatory agency, the Swiss Agency for Therapeutic Products (Swissmedic), which is a public institution of the Swiss government. Swissmedic is responsible for ensuring safety in medicines, particularly regarding authorizations and market surveillance in the sector of medicinal products and medical devices. Although the centralized authorization procedure of the European Union for medicines does not apply to Switzerland, there are mutual recognition mechanisms between the Swiss medicine regulatory authority and the European Medicines Agency. Swissmedic is also in charge of postmarketing safety and oversees the national pharmacovigilance center, which collaborates closely with the World Health Organization center in Uppsala. In addition, university hospital-based clinical pharmacologists, who are involved in basic science and clinical research, regulatory affairs, ethics committees, and pharmacovigilance, promote quality therapeutics. This article discusses the role of the various stakeholders and the recent efforts made to provide a better allocation of resources aimed at further improving quality therapeutics in Switzerland. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  17. 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.

  18. 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

  19. 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...

  20. Time improvement of photoelectric effect calculation for absorbed dose estimation

    International Nuclear Information System (INIS)

    Massa, J M; Wainschenker, R S; Doorn, J H; Caselli, E E

    2007-01-01

    Ionizing radiation therapy is a very useful tool in cancer treatment. It is very important to determine absorbed dose in human tissue to accomplish an effective treatment. A mathematical model based on affected areas is the most suitable tool to estimate the absorbed dose. Lately, Monte Carlo based techniques have become the most reliable, but they are time expensive. Absorbed dose calculating programs using different strategies have to choose between estimation quality and calculating time. This paper describes an optimized method for the photoelectron polar angle calculation in photoelectric effect, which is significant to estimate deposited energy in human tissue. In the case studies, time cost reduction nearly reached 86%, meaning that the time needed to do the calculation is approximately 1/7 th of the non optimized approach. This has been done keeping precision invariant

  1. Improvement of the following accident dose assessment system

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Enn Han; Han, Moon Hee; Suh, Kyung Suk; Hwang, Won Tae; Choi, Young Gil [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1999-12-15

    The FADAS has been updates for calculating the real-time wind fields continuously at the nuclear sites in Korea. The system has been constructed to compute the wind fields using its own process for the dummy meteorological data, and dose not effect on the overall wind field module. If the radioactive materials are released into the atmosphere in real situation, the calculations of wind fields and exposure dose in the previous FADAS are performed in the case of the recognition of the above situation in the source term evaluation module. The current version of FADAS includes the program for evaluating the effect of the predicted accident and the assumed scenario together. The dose assessment module is separated into the real-time and the supposed accident respectively.

  2. Novel high dose rate lip brachytherapy technique to improve dose homogeneity and reduce toxicity by customized mold

    International Nuclear Information System (INIS)

    Feldman, Jon; Appelbaum, Limor; Sela, Mordechay; Voskoboinik, Ninel; Kadouri, Sarit; Weinberger, Jeffrey; Orion, Itzhak; Meirovitz, Amichay

    2014-01-01

    The purpose of this study is to describe a novel brachytherapy technique for lip Squamous Cell Carcinoma, utilizing a customized mold with embedded brachytherapy sleeves, which separates the lip from the mandible, and improves dose homogeneity. Seven patients with T2 lip cancer treated with a “sandwich” technique of High Dose Rate (HDR) brachytherapy to the lip, consisting of interstitial catheters and a customized mold with embedded catheters, were reviewed for dosimetry and outcome using 3D planning. Dosimetric comparison was made between the “sandwich” technique to “classic” – interstitial catheters only plan. We compared dose volume histograms for Clinical Tumor Volume (CTV), normal tissue “hot spots” and mandible dose. We are reporting according to the ICRU 58 and calculated the Conformal Index (COIN) to show the advantage of our technique. The seven patients (ages 36–81 years, male) had median follow-up of 47 months. Four patients received Brachytherapy and External Beam Radiation Therapy, 3 patients received brachytherapy alone. All achieved local control, with excellent esthetic and functional results. All patients are disease free. The Customized Mold Sandwich technique (CMS) reduced the high dose region receiving 150% (V150) by an average of 20% (range 1–47%), The low dose region (les then 90% of the prescribed dose) improved by 73% in average by using the CMS technique. The COIN value for the CMS was in average 0.92 as opposed to 0.88 for the interstitial catheter only. All differences (excluding the low dose region) were statistically significant. The CMS technique significantly reduces the high dose volume and increases treatment homogeneity. This may reduce the potential toxicity to the lip and adjacent mandible, and results in excellent tumor control, cosmetic and functionality

  3. 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

    reduction for many organs, such as the narrow and gonads, of up to 78.4%.Possible benefits to the institution also include the use of less radioactive material and a reduction in radiation exposures to the staff during the manipulation and administration of the {sup 131} I. To facilitate the calculations of the optimum therapeutic activity of {sup 131} I for individual patients, a simple and fast dose planning program was created (PlanDose). The program has been set up to evaluate thryroid remant ablation, but it can also be used for the calculation of the activity to be administered for treatment of hyperthyroidism. This protocol of calculated optimal patient-specific {sup 131} I. activities allows a better determination of the necessary ablative dose for patients with differentiated carcinoma of the thyroid, and is an example of optimizing the practice of radiation protection. (author)

  4. ACDOS2: an improved neutron-induced dose rate code

    International Nuclear Information System (INIS)

    Lagache, J.C.

    1981-06-01

    To calculate the expected dose rate from fusion reactors as a function of geometry, composition, and time after shutdown a computer code, ACDOS2, was written, which utilizes up-to-date libraries of cross-sections and radioisotope decay data. ACDOS2 is in ANSI FORTRAN IV, in order to make it readily adaptable elsewhere

  5. ACDOS2: an improved neutron-induced dose rate code

    Energy Technology Data Exchange (ETDEWEB)

    Lagache, J.C.

    1981-06-01

    To calculate the expected dose rate from fusion reactors as a function of geometry, composition, and time after shutdown a computer code, ACDOS2, was written, which utilizes up-to-date libraries of cross-sections and radioisotope decay data. ACDOS2 is in ANSI FORTRAN IV, in order to make it readily adaptable elsewhere.

  6. Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of Quantitative Pharmacology Towards First Registration and Expanding Therapeutic Use.

    Science.gov (United States)

    Nayak, Satyaprakash; Sander, Oliver; Al-Huniti, Nidal; de Alwis, Dinesh; Chain, Anne; Chenel, Marylore; Sunkaraneni, Soujanya; Agrawal, Shruti; Gupta, Neeraj; Visser, Sandra A G

    2018-03-01

    Quantitative pharmacology (QP) applications in translational medicine, drug-development, and therapeutic use were crowd-sourced by the ASCPT Impact and Influence initiative. Highlighted QP case studies demonstrated faster access to innovative therapies for patients through 1) rational dose selection for pivotal trials; 2) reduced trial-burden for vulnerable populations; or 3) simplified posology. Critical success factors were proactive stakeholder engagement, alignment on the value of model-informed approaches, and utilizing foundational clinical pharmacology understanding of the therapy. © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  7. Development of a methodology to determine optimized therapeutic doses of {sup 131}I for the treatment of hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, Francisco de; Santas, Bernardo Maranhao; Dantas, Ana Leticia Almeida; Lucena, Eder Augusto [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)]. E-mail: faraujo@ird.gov.br; Melo, Rossana Corbo de; Rebelo, Ana Maria de Oliveira [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina

    2007-07-01

    Several methods can be used to determine the activity of {sup 131}I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology to evaluate therapeutic doses through the determination of biokinetic parameters and the activity of {sup 131}I deposited in the thyroid of patients submitted to the treatment of hyperthyroidism with {sup 131}I. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of {sup 131}I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The calculation of the calibration factor of the scintillation camera allows the determination of activities in the thyroid of patients in pre-established time periods through a 48-hours uptake curve. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were 39.3 {+-} 0.8 and 4.3 {+-} 0.2 respectively. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use

  8. Hydroxychloroquine Blood Levels in SLE: Clarifying dosing controversies and improving adherence

    Science.gov (United States)

    Durcan, Laura; Clarke, William A; Magder, Laurence S.; Petri, Michelle

    2015-01-01

    OBJECTIVES Hydroxychloroquine is used for its effect on systemic lupus erythematosus (SLE) disease activity and long-term benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is dosing controversy; rheumatologists recommend weight-based, while ophthalmologists advocate height-based ‘ideal body weight’ dosing. METHODS Patients were prescribed hydroxychloroquine not to exceed 6.5mg/kg (max400mg/day). In hemodialysis, the dose was 200mg after each session, in renal insufficiency it was 200mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the impact of measurement and counseling on adherence, we compared the proportion of patients with a level of 500ng/ml or higher based on how many prior assessments the patient had. RESULTS The proportion of patients with hydroxychloroquine levels in the therapeutic range differed significantly by age, gender and vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, sub-therapeutic and therapeutic levels, disease activity decreased (SLEDAI 2.92, 2.36 and 2.20)(P=0.04, for trend). At first, 56% were therapeutic and by the third measurement this increased to 80% (p =hydroxychloroquine levels. Renal failure dosing led to sub-optimum levels. We show that weight-based dosing (max 400mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling and repeated testing can increase adherences rates. PMID:26428205

  9. An improved standard total dose test for CMOS space electronics

    International Nuclear Information System (INIS)

    Fleetwood, D.M.; Winokur, P.S.; Riewe, L.C.; Pease, R.L.

    1989-01-01

    The postirradiation response of hardened and commercial CMOS devices is investigated as a function of total dose, dose rate, and annealing time and temperature. Cobalt-60 irradiation at ≅ 200 rad(SiO 2 )/s followed by a 1-week 100 degrees C biased anneal and testing is shown to be an effective screen of hardened devices for space use. However, a similar screen and single-point test performed after Co-60 irradiation and elevated temperature anneal cannot be generally defined for commercial devices. In the absence of detailed knowledge about device and circuit radiation response, a two-point standard test is proposed to ensure space surviability of CMOS circuits: a Co-60 irradiation and test to screen against oxide-trapped charge related failures, and an additional rebound test to screen against interface-trap related failures. Testing implications for bipolar technologies are also discussed

  10. Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence.

    Science.gov (United States)

    Durcan, Laura; Clarke, William A; Magder, Laurence S; Petri, Michelle

    2015-11-01

    Hydroxychloroquine (HCQ) is used for its effect on systemic lupus erythematosus (SLE) disease activity and longterm benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is disagreement about dosing; rheumatologists recommend weight-based dosing while some other specialists advocate height-based "ideal body weight" dosing. Patients were prescribed HCQ not exceeding 6.5 mg/kg (max 400 mg/day). In hemodialysis, the dose was 200 mg after each session, and in renal insufficiency it was 200 mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the effect of measurement and counseling on adherence, we compared the proportion of patients with a level of 500 ng/ml or higher based on the number of prior assessments. The proportion of patients with HCQ levels in the therapeutic range differed significantly by age, sex, and Vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, subtherapeutic, and therapeutic levels, disease activity decreased (SLE Disease Activity Index 2.92, 2.36, and 2.20, p = 0.04 for trend). At first, 56% were therapeutic, and by the third measurement this increased to 80% (p ≤ 0.0001). There was a trend toward higher disease activity with lower HCQ levels. Renal failure dosing led to suboptimum levels. We show that weight-based dosing (max 400 mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling, and repeated testing can increase adherence rates.

  11. Efficacy and safety of a multifactor intervention to improve therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD: protocol for the ICEPOC study

    Directory of Open Access Journals (Sweden)

    Prados-Torres Daniel

    2011-02-01

    Full Text Available Abstract Background Low therapeutic adherence to medication is very common. Clinical effectiveness is related to dose rate and route of administration and so poor therapeutic adherence can reduce the clinical benefit of treatment. The therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD is extremely poor according to most studies. The research about COPD adherence has mainly focussed on quantifying its effect, and few studies have researched factors that affect non-adherence. Our study will evaluate the effectiveness of a multifactor intervention to improve the therapeutic adherence of COPD patients. Methods/Design A randomized controlled clinical trial with 140 COPD diagnosed patients selected by a non-probabilistic method of sampling. Subjects will be randomly allocated into two groups, using the block randomization technique. Every patient in each group will be visited four times during the year of the study. Intervention: Motivational aspects related to adherence (beliefs and behaviour: group and individual interviews; cognitive aspects: information about illness; skills: inhaled technique training. Reinforcement of the cognitive-emotional aspects and inhaled technique training will be carried out in all visits of the intervention group. Discussion Adherence to a prescribed treatment involves a behavioural change. Cognitive, emotional and motivational aspects influence this change and so we consider the best intervention procedure to improve adherence would be a cognitive and emotional strategy which could be applied in daily clinical practice. Our hypothesis is that the application of a multifactor intervention (COPD information, dose reminders and reinforcing audiovisual material, motivational aspects and inhalation technique training to COPD patients taking inhaled treatment will give a 25% increase in the number of patients showing therapeutic adherence in this group compared to the control group. We will

  12. Sleep disturbance as detected by actigraphy in pre-pubertal juvenile monkeys receiving therapeutic doses of fluoxetine.

    Science.gov (United States)

    Golub, Mari S; Hogrefe, Casey E

    2016-01-01

    Sleep disturbance is a reported side effect of antidepressant drugs in children. Using a nonhuman primate model of childhood selective serotonin reuptake inhibitor (SSRI) therapy, sleep was studied quantitatively with actigraphy. Two 48-h sessions were recorded in the home cage environment of juvenile male rhesus monkeys at two and three years of age, after one and two years of treatment with a therapeutic dose of the SSRI fluoxetine, and compared to vehicle treated controls. A third session was conducted one year after discontinuation of treatment at four years of age. During treatment, the fluoxetine group demonstrated sleep fragmentation as indexed by a greater number of rest-activity transitions compared to controls. In addition fluoxetine led to more inactivity during the day as indexed by longer duration of rest periods and the reduced activity during these periods. The fluoxetine effect on sleep fragmentation, but not on daytime rest, was modified by the monkey's genotype for polymorphisms of monoamine oxidase A (MAOA), an enzyme that metabolizes serotonin. After treatment, the fluoxetine effect on nighttime rest-activity transitions persisted, but daytime activity was not affected. The demonstration in this nonhuman primate model of sleep disturbance in connection with fluoxetine treatment and specific genetic polymorphisms, and in the absence of diagnosed psychopathology, can help inform use of this drug in children. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Cosolvent-free polymer gel dosimeters with improved dose sensitivity and resolution for x-ray CT dose response

    Energy Technology Data Exchange (ETDEWEB)

    Chain, J N M; McAuley, K B [Department of Chemical Engineering, Queen' s University, Kingston, K7L 3N6 (Canada); Jirasek, A [Department of Physics and Astronomy, University of Victoria, Victoria, V8W 3P6 (Canada); Schreiner, L J, E-mail: kim.mcauley@chee.queensu.ca [Cancer Centre of Southeastern Ontario, Kingston, K7L 5P9 (Canada)

    2011-04-07

    This study reports new N-isopropylacrylamide (NIPAM) polymer gel recipes with increased dose sensitivity and improved dose resolution for x-ray CT readout. NIPAM can be used to increase the solubility of N, N'-methylenebisacrylamide (Bis) in aqueous solutions from approximately 3% to 5.5% by weight, enabling the manufacture of dosimeters containing up to 19.5%T, which is the total concentration of NIPAM and Bis by weight. Gelatin is shown to have a mild influence on dose sensitivity when gels are imaged using x-ray CT, and a stronger influence when gels are imaged optically. Phantoms that contain only 3% gelatin and 5 mM tetrakis hydroxymethyl phosphonium chloride are sufficiently stiff for dosimetry applications. The best cosolvent-free gel formulation has a dose sensitivity in the linear range ({approx}0.88 H Gy{sup -1}) that is a small improvement compared to the best NIPAM-based gels that incorporate isopropanol as a cosolvent ({approx}0.80 H Gy{sup -1}). This new gel formulation results in enhanced dose resolution ({approx}0.052 Gy) for x-ray CT readout, making clinical applications of this imaging modality more feasible.

  14. Cosolvent-free polymer gel dosimeters with improved dose sensitivity and resolution for x-ray CT dose response

    International Nuclear Information System (INIS)

    Chain, J N M; McAuley, K B; Jirasek, A; Schreiner, L J

    2011-01-01

    This study reports new N-isopropylacrylamide (NIPAM) polymer gel recipes with increased dose sensitivity and improved dose resolution for x-ray CT readout. NIPAM can be used to increase the solubility of N, N'-methylenebisacrylamide (Bis) in aqueous solutions from approximately 3% to 5.5% by weight, enabling the manufacture of dosimeters containing up to 19.5%T, which is the total concentration of NIPAM and Bis by weight. Gelatin is shown to have a mild influence on dose sensitivity when gels are imaged using x-ray CT, and a stronger influence when gels are imaged optically. Phantoms that contain only 3% gelatin and 5 mM tetrakis hydroxymethyl phosphonium chloride are sufficiently stiff for dosimetry applications. The best cosolvent-free gel formulation has a dose sensitivity in the linear range (∼0.88 H Gy -1 ) that is a small improvement compared to the best NIPAM-based gels that incorporate isopropanol as a cosolvent (∼0.80 H Gy -1 ). This new gel formulation results in enhanced dose resolution (∼0.052 Gy) for x-ray CT readout, making clinical applications of this imaging modality more feasible.

  15. High-dose estradiol improves cognition for women with AD: results of a randomized study.

    Science.gov (United States)

    Asthana, S; Baker, L D; Craft, S; Stanczyk, F Z; Veith, R C; Raskind, M A; Plymate, S R

    2001-08-28

    To characterize the cognitive and neuroendocrine response to treatment with a high dose of estrogen for postmenopausal women with AD. Twenty postmenopausal women with AD were randomized to receive either 0.10 mg/day of 17 beta-estradiol by skin patch or a placebo patch for 8 weeks. Subjects were evaluated at baseline, at weeks 3, 5, and 8 during treatment, and again 8 weeks after treatment termination. During each visit, cognition was assessed with a battery of neuropsychological tests, and blood samples were collected to measure plasma estradiol as well as several other neuroendocrine markers of interest. Significant effects of estrogen treatment were observed on attention (Stroop Color Word Interference Test), verbal memory (Buschke Selective Reminding Test), and visual memory (Figure Copy/Memory). In addition, women treated with estrogen demonstrated improved performance on a test of semantic memory (Boston Naming Test) compared with subjects who received a placebo. Estrogen appeared to have a suppressive effect on the insulin-like growth factor (IGF) system such that plasma concentration of IGF binding protein-3 was significantly reduced and plasma levels of estradiol and IGF-I were negatively correlated during estrogen treatment. Administration of a higher dose of estrogen may enhance attention and memory for postmenopausal women with AD. Although these findings provide further clinical evidence to support a cognitive benefit of estrogen for women with AD, studies evaluating the effect of estradiol administration, in particular, using larger sample sizes and for longer treatment durations are warranted before the therapeutic potential of estrogen replacement for women with AD can be firmly established.

  16. 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

  17. Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension.

    Science.gov (United States)

    Hilleman, D E; Reyes, A P; Wurdeman, R L; Faulkner, M

    2001-08-01

    Recent hypertension trials have demonstrated the importance of achieving goal blood pressures to reduce the risk of target organ damage. In patients with moderate to severe hypertension, the use of high-dose monotherapy and/or combinations of drugs are necessary to achieve these goals. Fixed-dose combination products may be useful in these patients by reducing the number of daily doses required to control blood pressure. The objective of the present study was to evaluate the efficacy and safety of a therapeutic interchange between high-dose calcium channel blocker therapy and a fixed-dose combination of amlodipine/ benazepril (Lotrel; Novartis Pharmaceuticals, USA) in patients with moderate to severe hypertension. A total of 75 patients were switched from amlodipine (n = 25), felodipine (n = 25), and nifedipine-GITS (n = 25) to amlodipine/benazepril. Twenty-eight of the 75 patients (37%) were taking either a beta-blocker or a diuretic in addition to the high-dose calcium channel blocker prior to the switch. Blood pressure control, side effects and the cost of the therapeutic interchange were evaluated in the year following the therapeutic interchange. Sixty-six of the 75 (88%) patients were successfully switched with maintenance of blood pressure control and without the development of new dose-limiting side effects. Reasons for treatment failure after the therapeutic interchange included loss of blood pressure control in five patients and the development of new dose-limiting side effects in four patients. These side effects included cough in three patients and rash in one patient. After accounting for differences in drug acquisition cost and costs related to the switch (clinic and emergency room and laboratory tests), a cost savings of $16030 for all 75 patients was realised in the first year. The per patient-per year cost savings was $214. Our data indicate that a therapeutic interchange from selected high-dose calcium channel blockers to a fixed-dose combination

  18. An improved analytical model for CT dose simulation with a new look at the theory of CT dose

    International Nuclear Information System (INIS)

    Dixon, Robert L.; Munley, Michael T.; Bayram, Ersin

    2005-01-01

    Gagne [Med. Phys. 16, 29-37 (1989)] has previously described a model for predicting the sensitivity and dose profiles in the slice-width (z) direction for CT scanners. The model, developed prior to the advent of multidetector CT scanners, is still widely used; however, it does not account for the effect of anode tilt on the penumbra or include the heel effect, both of which are increasingly important for the wider beams (up to 40 mm) of contemporary, multidetector scanners. Additionally, it applied only on (or near) the axis of rotation, and did not incorporate the photon energy spectrum. The improved model described herein transcends all of the aforementioned limitations of the Gagne model, including extension to the peripheral phantom axes. Comparison of simulated and measured dose data provides experimental validation of the model, including verification of the superior match to the penumbra provided by the tilted-anode model, as well as the observable effects on the cumulative dose distribution. The initial motivation for the model was to simulate the quasiperiodic dose distribution on the peripheral, phantom axes resulting from a helical scan series in order to facilitate the implementation of an improved method of CT dose measurement utilizing a short ion chamber, as proposed by Dixon [Med. Phys. 30, 1272-1280 (2003)]. A more detailed set of guidelines for implementing such measurements is also presented in this paper. In addition, some fundamental principles governing CT dose which have not previously been clearly enunciated follow from the model, and a fundamental (energy-based) quantity dubbed 'CTDI-aperture' is introduced

  19. Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

    Directory of Open Access Journals (Sweden)

    Aloísio Sales da Cunha

    1987-10-01

    Full Text Available A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ and the quantitative Kato-Katz (K-K methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28% and K-K (80% became significative. When this number dropped to less than 2,000 the percentage of false negative

  20. Team-based learning to improve learning outcomes in a therapeutics course sequence.

    Science.gov (United States)

    Bleske, Barry E; Remington, Tami L; Wells, Trisha D; Dorsch, Michael P; Guthrie, Sally K; Stumpf, Janice L; Alaniz, Marissa C; Ellingrod, Vicki L; Tingen, Jeffrey M

    2014-02-12

    To compare the effectiveness of team-based learning (TBL) to that of traditional lectures on learning outcomes in a therapeutics course sequence. A revised TBL curriculum was implemented in a therapeutic course sequence. Multiple choice and essay questions identical to those used to test third-year students (P3) taught using a traditional lecture format were administered to the second-year pharmacy students (P2) taught using the new TBL format. One hundred thirty-one multiple-choice questions were evaluated; 79 tested recall of knowledge and 52 tested higher level, application of knowledge. For the recall questions, students taught through traditional lectures scored significantly higher compared to the TBL students (88%±12% vs. 82%±16%, p=0.01). For the questions assessing application of knowledge, no differences were seen between teaching pedagogies (81%±16% vs. 77%±20%, p=0.24). Scores on essay questions and the number of students who achieved 100% were also similar between groups. Transition to a TBL format from a traditional lecture-based pedagogy allowed P2 students to perform at a similar level as students with an additional year of pharmacy education on application of knowledge type questions. However, P3 students outperformed P2 students regarding recall type questions and overall. Further assessment of long-term learning outcomes is needed to determine if TBL produces more persistent learning and improved application in clinical settings.

  1. A therapeutic dose of zolpidem reduces thalamic GABA in healthy volunteers: a proton MRS study at 4 T.

    Science.gov (United States)

    Licata, Stephanie C; Jensen, J Eric; Penetar, David M; Prescot, Andrew P; Lukas, Scott E; Renshaw, Perry F

    2009-05-01

    Zolpidem is a nonbenzodiazepine sedative/hypnotic that acts at GABA(A) receptors to influence inhibitory neurotransmission throughout the central nervous system. A great deal is known about the behavioral effects of this drug in humans and laboratory animals, but little is known about zolpidem's specific effects on neurochemistry in vivo. We evaluated how acute administration of zolpidem affected levels of GABA, glutamate, glutamine, and other brain metabolites. Proton magnetic resonance spectroscopy ((1)H MRS) at 4 T was employed to measure the effects of zolpidem on brain chemistry in 19 healthy volunteers. Participants underwent scanning following acute oral administration of a therapeutic dose of zolpidem (10 mg) in a within-subject, single-blind, placebo-controlled, single-visit study. In addition to neurochemical measurements from single voxels within the anterior cingulate (ACC) and thalamus, a series of questionnaires were administered periodically throughout the experimental session to assess subjective mood states. Zolpidem reduced GABA levels in the thalamus, but not the ACC. There were no treatment effects with respect to other metabolite levels. Self-reported ratings of "dizzy," "nauseous," "confused," and "bad effects" were increased relative to placebo, as were ratings on the sedation/intoxication (PCAG) and psychotomimetic/dysphoria (LSD) scales of the Addiction Research Center Inventory. Moreover, there was a significant correlation between the decrease in GABA and "dizzy." Zolpidem engendered primarily dysphoric-like effects and the correlation between reduced thalamic GABA and "dizzy" may be a function of zolpidem's interaction with alpha1GABA(A) receptors in the cerebellum, projecting through the vestibular system to the thalamus.

  2. A therapeutic dose of zolpidem reduces thalamic GABA in healthy volunteers: A proton MRS study at 4 Tesla

    Science.gov (United States)

    Licata, Stephanie C.; Jensen, J. Eric; Penetar, David M.; Prescot, Andrew P.; Lukas, scott E.; Renshaw, Perry F.

    2009-01-01

    Background Zolpidem is a non-benzodiazepine sedative/hypnotic that acts at GABAA receptors to influence inhibitory neurotransmission throughout the central nervous system. A great deal is known about the behavioral effects of this drug in humans and laboratory animals, but little is known about zolpidem’s specific effects on neurochemistry in vivo. Objectives We evaluated how acute administration of zolpidem affected levels of GABA, glutamate, glutamine, and other brain metabolites. Methods Proton magnetic resonance spectroscopy (1H MRS) at 4 Tesla was employed to measure the effects of zolpidem on brain chemistry in 19 healthy volunteers. Participants underwent scanning following acute oral administration of a therapeutic dose of zolpidem (10 mg) in a within-subject, single-blind, placebo-controlled, single-visit study. In addition to neurochemical measurements from single voxels within the anterior cingulate (ACC) and thalamus, a series of questionnaires were administered periodically throughout the experimental session to assess subjective mood states. Results Zolpidem reduced GABA levels in the thalamus, but not the ACC. There were no treatment effects with respect to other metabolite levels. Self-reported ratings of “dizzy”, “nauseous”, “confused”, and “bad effects” were increased relative to placebo, as were ratings on the sedation/intoxication (PCAG) and psychotomimetic/dysphoria (LSD) scales of the Addiction Research Center Inventory. Moreover, there was a significant correlation between the decrease in GABA and “dizzy”. Conclusions Zolpidem engendered primarily dysphoric-like effects and the correlation between reduced thalamic GABA and “dizzy” may be a function of zolpidem’s interaction with α1GABAA receptors in the cerebellum, projecting through the vestibular system to the thalamus. PMID:19125238

  3. 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.

  4. SU-F-T-174: Patient-Specific Point Dose Measurement Using Fiber Optic Radiation Sensor Using Cerenkov Radiation for Proton Therapeutic Beam

    Energy Technology Data Exchange (ETDEWEB)

    Son, J [Korea University, Seoul, Seoul (Korea, Republic of); National Cancer Center, Goyang-si (Korea, Republic of); Kim, M [Dongnam Institute of Radiological & Medical Sciences, Busan, Busan (Korea, Republic of); Yoon, M [Korea University, Seoul (Korea, Republic of); Shin, D [National Cancer Center, Goyang-si (Korea, Republic of)

    2016-06-15

    Purpose: A fiber-optic radiation sensor using Cerenkov radiation (FOCR) has been widely studied for use as a dosimeter for proton therapeutic beam. We developed the FOCR, and it applied to patient-specific point dose measurement in order to evaluate the effectiveness of the FOCR system for proton therapy QA. Methods: Calibration of FOCR was performed with an ionization chamber whose absolute doses were determined according to the IAEA TRS-398 protocol. To determine the calibration curve, the FOCR was irradiated perpendicularly to the proton beam at the 13 dose levels steps. We selected five actual patient treatment plans performed at proton therapy center and compared the resulting FOCR measurements with the ionization chamber measurements. Results: The Cerenkov light yield of the FOCR increases linearly with as the dose measured using the ionization chamber increases from 0 cGy to 500 cGy. The results indicate that the fitting curve is linear, suggesting that dose measurement based on the light yield of the FOCR is possible. The results of proton radiation dose QA performed using the FOCR for 10 proton fields and five patients are good agreement with an ionization chamber. Conclusion: We carried out the patient QA using the FOCR for proton therapeutic beam and evaluated the effectiveness of the FOCR as a proton therapy QA tool. Our results indicate that the FOCR is suitable for use in patient QA of clinical proton beams.

  5. Therapeutic cranial nerve irradiation: results from a multi-center dose response study of radiosurgery for trigeminal neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Kondziolka, D; Flickinger, J; Lunsford, L D; Young, R; Vermeulen, S; Duma, C; Jacques, D B; Rand, R; Regis, J; Peragut, J C; Epstein, M H; Lindquist, C

    1995-07-01

    Purpose/Objective: We performed a multi-institution study to evaluate the technique, dose-selection parameters, and results of gamma knife stereotactic radiosurgery in the management of trigeminal neuralgia. We hypothesized that MRI-stereotactic targeting of the trigeminal nerve and irradiation with a single 4 mm isocenter, 2-4 mm anterior to the brainstem, could be a safe and effective treatment for this disorder. Materials and Methods: Fifty patients at five centers had radiosurgery using a single 4 mm isocenter targeted at the root entry zone. All patients had typical trigeminal neuralgia. The mean patient age was 70 years, (range, 40-87). Thirty-two patients had undergone prior surgery, and the mean number of procedures performed was 2.8 (range, 1-7). Eighteen patients (36%) had not had prior surgery before radiosurgery. Maximum radiosurgery doses included 60 Gy (n=8), 65 Gy (n=3), 70 Gy (n=27), 75 Gy (n=2), 80 Gy (n=6) and 90 Gy (n=4). All patients were discharged within 24 hours and were studied in regard to the degree of pain relief, latency interval to pain relief, sensory loss, and the need for further therapy. Mean follow-up after radiosurgery was 9.2 months (range, 2-26 months). Results: At last follow-up, 25 patients (50%) had excellent control (pain-free), 17 (34%) had good control (50-90% relief), and 8 (16%) had failed (see Figure). The median time to pain relief was one month. We identified an actuarial response rate of 53% for complete pain relief at seven months, and 93% for pain reduction (50-100% relief). At 18 months, these results declined to 48% and 77% respectively. A significantly greater proportion of patients receiving a radiosurgery maximum dose of {>=} 70 Gy achieved complete pain relief (63% vs. 18%) and >50% pain reduction (96% vs. 80%) than those with doses <70 Gy. Patients without prior surgery had significantly better outcomes in univariate testing. Three patients (6%) developed increased facial paresthesiae after radiosurgery

  6. Therapeutic cranial nerve irradiation: results from a multi-center dose response study of radiosurgery for trigeminal neuralgia

    International Nuclear Information System (INIS)

    Kondziolka, D.; Flickinger, J.; Lunsford, L.D.; Young, R.; Vermeulen, S.; Duma, C.; Jacques, D.B.; Rand, R.; Regis, J.; Peragut, J.C.; Epstein, M.H.; Lindquist, C.

    1995-01-01

    Purpose/Objective: We performed a multi-institution study to evaluate the technique, dose-selection parameters, and results of gamma knife stereotactic radiosurgery in the management of trigeminal neuralgia. We hypothesized that MRI-stereotactic targeting of the trigeminal nerve and irradiation with a single 4 mm isocenter, 2-4 mm anterior to the brainstem, could be a safe and effective treatment for this disorder. Materials and Methods: Fifty patients at five centers had radiosurgery using a single 4 mm isocenter targeted at the root entry zone. All patients had typical trigeminal neuralgia. The mean patient age was 70 years, (range, 40-87). Thirty-two patients had undergone prior surgery, and the mean number of procedures performed was 2.8 (range, 1-7). Eighteen patients (36%) had not had prior surgery before radiosurgery. Maximum radiosurgery doses included 60 Gy (n=8), 65 Gy (n=3), 70 Gy (n=27), 75 Gy (n=2), 80 Gy (n=6) and 90 Gy (n=4). All patients were discharged within 24 hours and were studied in regard to the degree of pain relief, latency interval to pain relief, sensory loss, and the need for further therapy. Mean follow-up after radiosurgery was 9.2 months (range, 2-26 months). Results: At last follow-up, 25 patients (50%) had excellent control (pain-free), 17 (34%) had good control (50-90% relief), and 8 (16%) had failed (see Figure). The median time to pain relief was one month. We identified an actuarial response rate of 53% for complete pain relief at seven months, and 93% for pain reduction (50-100% relief). At 18 months, these results declined to 48% and 77% respectively. A significantly greater proportion of patients receiving a radiosurgery maximum dose of ≥ 70 Gy achieved complete pain relief (63% vs. 18%) and >50% pain reduction (96% vs. 80%) than those with doses <70 Gy. Patients without prior surgery had significantly better outcomes in univariate testing. Three patients (6%) developed increased facial paresthesiae after radiosurgery

  7. Novel approaches to improve the therapeutic index of head and neck radiotherapy: An analysis of data from the PARSPORT randomised phase III trial

    International Nuclear Information System (INIS)

    Buettner, Florian; Miah, Aisha B.; Gulliford, Sarah L.; Hall, Emma; Harrington, Kevin J.; Webb, Steve; Partridge, Mike; Nutting, Christopher M.

    2012-01-01

    Purpose: Subjective xerostomia is a common side-effect following radiotherapy for the treatment of head-and-neck cancer. Standard mean dose models previously used to model xerostomia only that partially predict the occurrence of xerostomia. Studies in animal models have suggested that there are regional variations in the radiosensitivity of the parotid glands. In this work we tested the hypothesis that this is also true for the human parotid gland. Methods: We present novel dose–response models explicitly taking the spatial distribution of the radiation dose into account. We considered dose to the submandibular gland and other clinical factors and used a variable-selection algorithm to select the best dose–response model. This methodology was applied to 63 head and neck cancer patients and validated using two independent patient cohorts of 19 and 29 patients, respectively. Results: The predictive accuracy of dose–response models improved significantly when including regional variations of radiosensitivity of the parotid glands compared to standard mean-dose models (p = 0.001, t-test). Beneficial dose-pattern analysis demonstrated the importance of minimising dose to the lateral and cranial component of the human parotid gland in order to avoid xerostomia. Furthermore we found an evidence that surgical removal of the sub-mandibular gland significantly increases the risk of radiation-induced xerostomia. Conclusion: Dose–response models which take the shape of the dose-distribution into account predicted xerostomia significantly better than standard mean-dose models. Our novel model could be used to rank potential treatment plans more reliably according to their therapeutic index and may be useful to generate better treatment plans.

  8. Patient-Centered Prescription Model to improve therapeutic adherence in patients with multimorbidity

    Directory of Open Access Journals (Sweden)

    Javier González-Bueno

    2018-05-01

    Full Text Available To date, interventions to improve medication adherence in patients with multimorbidity have shown modest and inconsistent efficacy among available studies. Thereby, we should define new approaches aimed at improving medication adherence tailored to effective prescribing, with a multidisciplinary approach and patient-centered. In this regard, the Patient-Centered Prescription Model has shown its usefulness on improving appropriateness of drug treatments in patients with clinical complexity. For that, this strategy addresses the following four steps: 1 Patient-Centered assessment; 2 Diagnosis-Centered assessment; 3 Medication-Centered assessment; and 4 Therapeutic Plan. We propose through a clinical case an adaptation of the Patient-Centered Prescription Model to enhance both appropriateness and medication adherence in patients with multimorbidity. To this end, we have included on its first step the Spanish version of a cross-culturally adapted scale for the multidimensional assessment of medication adherence. Furthermore, we suggest a set of interventions to be applied in the three remaining steps of the model. These interventions were firstly identified by an overview of systematic reviews and then selected by a panel of experts based on Delphi methodology. All of these elements have been considered appropriate in patients with multimorbidity according to three criteria: strength of their supporting evidence, usefulness in the target population and feasibility of implementation in clinical practice. The proposed approach intends to lay the foundations for an innovative way in tackling medication adherence in patients with multimorbidity.

  9. A new therapeutic effect of simvastatin revealed by functional improvement in muscular dystrophy.

    Science.gov (United States)

    Whitehead, Nicholas P; Kim, Min Jeong; Bible, Kenneth L; Adams, Marvin E; Froehner, Stanley C

    2015-10-13

    Duchenne muscular dystrophy (DMD) is a lethal, degenerative muscle disease with no effective treatment. DMD muscle pathogenesis is characterized by chronic inflammation, oxidative stress, and fibrosis. Statins, cholesterol-lowering drugs, inhibit these deleterious processes in ischemic diseases affecting skeletal muscle, and therefore have potential to improve DMD. However, statins have not been considered for DMD, or other muscular dystrophies, principally because skeletal-muscle-related symptoms are rare, but widely publicized, side effects of these drugs. Here we show positive effects of statins in dystrophic skeletal muscle. Simvastatin dramatically reduced damage and enhanced muscle function in dystrophic (mdx) mice. Long-term simvastatin treatment vastly improved overall muscle health in mdx mice, reducing plasma creatine kinase activity, an established measure of muscle damage, to near-normal levels. This reduction was accompanied by reduced inflammation, more oxidative muscle fibers, and improved strength of the weak diaphragm muscle. Shorter-term treatment protected against muscle fatigue and increased mdx hindlimb muscle force by 40%, a value comparable to current dystrophin gene-based therapies. Increased force correlated with reduced NADPH Oxidase 2 protein expression, the major source of oxidative stress in dystrophic muscle. Finally, in old mdx mice with severe muscle degeneration, simvastatin enhanced diaphragm force and halved fibrosis, a major cause of functional decline in DMD. These improvements were accompanied by autophagy activation, a recent therapeutic target for DMD, and less oxidative stress. Together, our findings highlight that simvastatin substantially improves the overall health and function of dystrophic skeletal muscles and may provide an unexpected, novel therapy for DMD and related neuromuscular diseases.

  10. 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.

  11. Improved walking ability and reduced therapeutic stress with an electromechanical gait device.

    Science.gov (United States)

    Freivogel, Susanna; Schmalohr, Dieter; Mehrholz, Jan

    2009-09-01

    To evaluate the effectiveness of repetitive locomotor training using a newly developed electromechanical gait device compared with treadmill training/gait training with respect to patient's ambulatory motor outcome, necessary personnel resources, and discomfort experienced by therapists and patients. Randomized, controlled, cross-over trial. Sixteen non-ambulatory patients after stroke, severe brain or spinal cord injury sequentially received 2 kinds of gait training. Study intervention A: 20 treatments of locomotor training with an electromechanical gait device; control intervention B: 20 treatments of locomotor training with treadmill or task-oriented gait training. The primary variable was walking ability (Functional Ambulation Category). Secondary variables included gait velocity, Motricity-Index, Rivermead-Mobility-Index, number of therapists needed, and discomfort and effort of patients and therapists during training. Gait ability and the other motor outcome related parameters improved for all patients, but without significant difference between intervention types. However, during intervention A, significantly fewer therapists were needed, and they reported less discomfort and a lower level of effort during training sessions. Locomotor training with or without an electromechanical gait trainer leads to improved gait ability; however, using the electromechanical gait trainer requires less therapeutic assistance, and therapist discomfort is reduced.

  12. Breviscapine Injection Improves the Therapeutic Effect of Western Medicine on Angina Pectoris Patients.

    Science.gov (United States)

    Wang, Chuan; Li, Yafeng; Gao, Shoucui; Cheng, Daxin; Zhao, Sihai; Liu, Enqi

    2015-01-01

    To evaluate the beneficial and adverse effects of breviscapine injection in combination with Western medicine on the treatment of patients with angina pectoris. The Cochrane Central Register of Controlled Trials, Medline, Science Citation Index, EMBASE, the China National Knowledge Infrastructure, the Wanfang Database, the Chongqing VIP Information Database and the China Biomedical Database were searched to identify randomized clinical trials (RCTs) that evaluated the effects of Western medicine compared to breviscapine injection plus Western medicine on angina pectoris patients. The included studies were analyzed using RevMan 5.1.0 software. The literature search yielded 460 studies, wherein 16 studies matched the selection criteria. The results showed that combined therapy using Breviscapine plus Western medicine was superior to Western medicine alone for improving angina pectoris symptoms (OR=3.77, 95% Cl: 2.76~5.15) and also resulted in increased electrocardiogram (ECG) improvement (OR=2.77, 95% Cl: 2.16~3.53). The current evidence suggests that Breviscapine plus Western medicine achieved a superior therapeutic effect compared to Western medicine alone.

  13. Biological dose estimation for charged-particle therapy using an improved PHITS code coupled with a microdosimetric kinetic model

    International Nuclear Information System (INIS)

    Sato, Tatsuhiko; Watanabe, Ritsuko; Kase, Yuki; Niita, Koji; Sihver, Lembit

    2009-01-01

    -particle therapy was established using the improved PHITS coupled with a microdosimetric kinetic (MK) model. The detailed procedures for improving the PHITS code and establishing the biological-dose-estimation method were presented elsewhere. Hence, this report focuses on describing their capabilities to optimize the treatment planning of charged particle therapy, thereby maximizing the therapeutic effect on tumor while minimizing unintended harmful effects on surrounding normal tissues. (author)

  14. Dose-rate and the reciprocity law: TL response of Ge-doped SiO2 optical fibers at therapeutic radiation doses

    International Nuclear Information System (INIS)

    Abdul Rahman, A.T.; Nisbet, A.; Bradley, D.A.

    2011-01-01

    An investigation has been made on commercially available Ge-doped SiO 2 optical fibers as a novel thermoluminescence system for radiotherapy dosimetry. This dosimeter has previously been shown by the group to provide sensitive dosimetry over a wide range of electron and photon dose, suitable for the needs of radiotherapy. In addition the optical fiber offers small physical size (125 μm diameter) and hence high spatial resolution. The reciprocity between thermoluminescence (TL) yield of Ge-doped SiO 2 optical fibers and dose has been investigated for fixed radiation dose for a range of photon and electron dose rates. For electron beams of nominal energies in the range of 9-20 MeV, we have investigated the TL response of these fibers for dose rates between 100 and 1000 cGy min -1 . For photon beams of nominal energies in the range of 6-15 MV, we have used dose rates of 100-600 cGy min -1 . Reproducibility and fading at fixed absorbed dose (3 Gy) and dose rate for the optical fibers were also investigated. At fixed dose rates, the TL optical fibers were found to produce a flat TL yield within 4% (1σ) and 3% (1σ) for electron and photon beams, respectively. The optical fibers demonstrated good reproducibility (±1.5%), low residual signal for a readout temperature of 300 o C and negligible fading. A weak dependence on dose-rate has been observed in the range of 3.4-3.9% for electrons (with an associated uncertainty of 4%) and 2.4-2.9% for photons (with an associated uncertainty of <4%). For electron and photon energies we note a consistent trend towards lower response in the TL yield of between 3.4-3.9% and 2.4-2.7%, respectively, at the higher dose rates in comparison with the response at lower dose rates. In addition we note an appreciable systematic energy dependence for both electron and photon beams. It is important to take such factors into account for providing precise and accurate radiotherapy dosimetry. It is also apparent that the optical fibers can be re

  15. Dose-rate and the reciprocity law: TL response of Ge-doped SiO{sub 2} optical fibers at therapeutic radiation doses

    Energy Technology Data Exchange (ETDEWEB)

    Abdul Rahman, A.T., E-mail: a.t.abdulrahman@surrey.ac.uk [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH, Surrey (United Kingdom); School of Physics and Material Studies, Faculty of Applied Sciences, Universiti Teknologi MARA Malaysia (UiTM), Campus of Negeri Sembilan, 72000 Kuala Pilah (Malaysia); Nisbet, A. [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH, Surrey (United Kingdom); Departments of Medical Physics, the Royal Surrey County Hospital (RSCH) NHS Trust, Edgerton Road, Guildford GU2 7XX, Surrey (United Kingdom); Bradley, D.A. [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH, Surrey (United Kingdom)

    2011-10-01

    An investigation has been made on commercially available Ge-doped SiO{sub 2} optical fibers as a novel thermoluminescence system for radiotherapy dosimetry. This dosimeter has previously been shown by the group to provide sensitive dosimetry over a wide range of electron and photon dose, suitable for the needs of radiotherapy. In addition the optical fiber offers small physical size (125 {mu}m diameter) and hence high spatial resolution. The reciprocity between thermoluminescence (TL) yield of Ge-doped SiO{sub 2} optical fibers and dose has been investigated for fixed radiation dose for a range of photon and electron dose rates. For electron beams of nominal energies in the range of 9-20 MeV, we have investigated the TL response of these fibers for dose rates between 100 and 1000 cGy min{sup -1}. For photon beams of nominal energies in the range of 6-15 MV, we have used dose rates of 100-600 cGy min{sup -1}. Reproducibility and fading at fixed absorbed dose (3 Gy) and dose rate for the optical fibers were also investigated. At fixed dose rates, the TL optical fibers were found to produce a flat TL yield within 4% (1{sigma}) and 3% (1{sigma}) for electron and photon beams, respectively. The optical fibers demonstrated good reproducibility ({+-}1.5%), low residual signal for a readout temperature of 300 {sup o}C and negligible fading. A weak dependence on dose-rate has been observed in the range of 3.4-3.9% for electrons (with an associated uncertainty of 4%) and 2.4-2.9% for photons (with an associated uncertainty of <4%). For electron and photon energies we note a consistent trend towards lower response in the TL yield of between 3.4-3.9% and 2.4-2.7%, respectively, at the higher dose rates in comparison with the response at lower dose rates. In addition we note an appreciable systematic energy dependence for both electron and photon beams. It is important to take such factors into account for providing precise and accurate radiotherapy dosimetry. It is also

  16. Improvement of Off-site Dose Assessment Code for Operating Nuclear Power Plant

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Juyub; Kim, Juyoul; Shin, Kwangyoung [FNC Technology Co. Ltd., Yongin (Korea, Republic of); You, Songjae; Moon, Jongyi [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2014-05-15

    XOQDOQ code which calculates atmospheric Dispersion factor was included into INDAC also. A research on the improvement of off-site dose assessment system for an operating nuclear power plant was performed by KINS in 2011. As a result, following improvements were derived: - Separation of dose assessment for new and existing facilities - Update of food ingestion data - Consideration of multi-unit operation and so on In order to reflect the results, INDAC is under modification. INDAC is an integrated dose assessment code for an operating nuclear power plant and consists of three main modules: XOQDOQ, GASDOS and LIQDOS. The modules are under modification in order to improve the accuracy of assessment and usability. Assessment points for multi-unit release can be calculated through the improved code and the method on dose assessment for multi-unit release has been modified, so that the dose assessment result of multi-unit site becomes more realistic by relieving excessive conservatism. Finally, as the accuracy of calculation modules has been improved, the reliability of dose assessment result has been strengthened.

  17. Monte Carlo dose calculation improvements for low energy electron beams using eMC

    International Nuclear Information System (INIS)

    Fix, Michael K; Frei, Daniel; Volken, Werner; Born, Ernst J; Manser, Peter; Neuenschwander, Hans

    2010-01-01

    The electron Monte Carlo (eMC) dose calculation algorithm in Eclipse (Varian Medical Systems) is based on the macro MC method and is able to predict dose distributions for high energy electron beams with high accuracy. However, there are limitations for low energy electron beams. This work aims to improve the accuracy of the dose calculation using eMC for 4 and 6 MeV electron beams of Varian linear accelerators. Improvements implemented into the eMC include (1) improved determination of the initial electron energy spectrum by increased resolution of mono-energetic depth dose curves used during beam configuration; (2) inclusion of all the scrapers of the applicator in the beam model; (3) reduction of the maximum size of the sphere to be selected within the macro MC transport when the energy of the incident electron is below certain thresholds. The impact of these changes in eMC is investigated by comparing calculated dose distributions for 4 and 6 MeV electron beams at source to surface distance (SSD) of 100 and 110 cm with applicators ranging from 6 x 6 to 25 x 25 cm 2 of a Varian Clinac 2300C/D with the corresponding measurements. Dose differences between calculated and measured absolute depth dose curves are reduced from 6% to less than 1.5% for both energies and all applicators considered at SSD of 100 cm. Using the original eMC implementation, absolute dose profiles at depths of 1 cm, d max and R50 in water lead to dose differences of up to 8% for applicators larger than 15 x 15 cm 2 at SSD 100 cm. Those differences are now reduced to less than 2% for all dose profiles investigated when the improved version of eMC is used. At SSD of 110 cm the dose difference for the original eMC version is even more pronounced and can be larger than 10%. Those differences are reduced to within 2% or 2 mm with the improved version of eMC. In this work several enhancements were made in the eMC algorithm leading to significant improvements in the accuracy of the dose calculation

  18. Monte Carlo dose calculation improvements for low energy electron beams using eMC.

    Science.gov (United States)

    Fix, Michael K; Frei, Daniel; Volken, Werner; Neuenschwander, Hans; Born, Ernst J; Manser, Peter

    2010-08-21

    The electron Monte Carlo (eMC) dose calculation algorithm in Eclipse (Varian Medical Systems) is based on the macro MC method and is able to predict dose distributions for high energy electron beams with high accuracy. However, there are limitations for low energy electron beams. This work aims to improve the accuracy of the dose calculation using eMC for 4 and 6 MeV electron beams of Varian linear accelerators. Improvements implemented into the eMC include (1) improved determination of the initial electron energy spectrum by increased resolution of mono-energetic depth dose curves used during beam configuration; (2) inclusion of all the scrapers of the applicator in the beam model; (3) reduction of the maximum size of the sphere to be selected within the macro MC transport when the energy of the incident electron is below certain thresholds. The impact of these changes in eMC is investigated by comparing calculated dose distributions for 4 and 6 MeV electron beams at source to surface distance (SSD) of 100 and 110 cm with applicators ranging from 6 x 6 to 25 x 25 cm(2) of a Varian Clinac 2300C/D with the corresponding measurements. Dose differences between calculated and measured absolute depth dose curves are reduced from 6% to less than 1.5% for both energies and all applicators considered at SSD of 100 cm. Using the original eMC implementation, absolute dose profiles at depths of 1 cm, d(max) and R50 in water lead to dose differences of up to 8% for applicators larger than 15 x 15 cm(2) at SSD 100 cm. Those differences are now reduced to less than 2% for all dose profiles investigated when the improved version of eMC is used. At SSD of 110 cm the dose difference for the original eMC version is even more pronounced and can be larger than 10%. Those differences are reduced to within 2% or 2 mm with the improved version of eMC. In this work several enhancements were made in the eMC algorithm leading to significant improvements in the accuracy of the dose

  19. Improvement of dose distribution of esophageal irradiation using the field-within-a-field technique

    International Nuclear Information System (INIS)

    Iwai, Tsugunori; Okabe, Keigo; Yamato, Hidetada; Murakami, Jyunji; Nakazawa, Yasuo; Kato, Mitsuyoshi

    2002-01-01

    The wide radiation field for mediastinal dose distribution should be inhomogeneous with the usual simple opposed beam irradiation. The purpose of this study was to improve the dose distribution of the mediastinum using a conventional planning system with a dose-volume histogram (DVH) and the field-in-field technique. Three-dimensional (3D) dose distribution is obtained in bilateral opposed-field irradiation. An overdose area obtained from the 3D dose distribution is defined and reprojected into the irradiation field. A new reduced field is created by removing the reprojected overdose area. A 3D dose distribution is again obtained and compared with the results from first one. Procedures were repeated until each of the target volumes was within ±5% of the prescribed dose and the irradiation volume within 107% or less of the prescribed dose. From the DVH analysis, our field-within-a-field technique resulted in a more uniform dose distribution within the conventional planning. The field-within-a-field technique involves many parameters, and an inverse planning algorithm is suitable for computation. However, with our method, the forward planning system is adequate for planning, at least in a relatively straightforward planning system such as bilateral opposed fields therapy. (author)

  20. Improving dose homogeneity in head and neck radiotherapy with custom 3-D compensation

    International Nuclear Information System (INIS)

    Brock, Linda K.; Harari, Paul M.; Sharda, Navneet N.; Paliwal, Bhudatt R.; Kinsella, Timothy J.

    1996-01-01

    Purpose/Objective: Anatomic contour irregularities and tissue inhomogeneities can lead to significant radiation dose variation across complex treatment volumes. Such dose non-uniformity occurs routinely in radiation of the head and neck (H and N) despite beam shaping with blocks or beam modification with wedges. Small dose variations are amplified by the high total doses delivered (often >70 Gy) which can thereby influence late normal tissue complications as well as tumor control. We have therefore implemented the routine use of 3-D custom tissue compensators for our H and N cancer patients fabricated directly from CT scan contour data obtained in the treatment position. The capacity of such compensators to improve dose uniformity in patients with tumors of the H and N is herein reported. Materials and Methods: Between July 1992 and March 1995, 80 patients receiving H and N radiotherapy had 3-D custom compensators fabricated for their treatment course. Detailed dosimetric records have been reviewed for thirty cases to date (60 custom compensators). Dose uniformity across the treatment volume, peak dose delivery and maximum doses to selected, clinically relevant, anatomic subsites were analyzed and compared with uncompensated and wedged plans. Dose-volume histograms were generated and volumes receiving greater than 5% and 10% of the prescribed dose noted. Phantom dose measurements were performed for compensated fields using a water chamber and were compared to calculated doses in order to evaluate the accuracy of isodoses generated by the Theraplan treatment planning system. Accuracy of the fabrication and positioning of the custom compensators was verified by direct measurement. Results: Custom compensators resulted in an average reduction of dose variance across the treatment volume from 13.8% (7-20%) for the uncompensated plans to 4.5% (2-7%) with the compensators. Wedged plans were variable but on average an 8% (3-15%) dose variance was noted. Maximum doses

  1. Keeping an eye on the ring: COMS plaque loading optimization for improved dose conformity and homogeneity.

    Science.gov (United States)

    Gagne, Nolan L; Cutright, Daniel R; Rivard, Mark J

    2012-09-01

    To improve tumor dose conformity and homogeneity for COMS plaque brachytherapy by investigating the dosimetric effects of varying component source ring radionuclides and source strengths. The MCNP5 Monte Carlo (MC) radiation transport code was used to simulate plaque heterogeneity-corrected dose distributions for individually-activated source rings of 14, 16 and 18 mm diameter COMS plaques, populated with (103)Pd, (125)I and (131)Cs sources. Ellipsoidal tumors were contoured for each plaque size and MATLAB programming was developed to generate tumor dose distributions for all possible ring weighting and radionuclide permutations for a given plaque size and source strength resolution, assuming a 75 Gy apical prescription dose. These dose distributions were analyzed for conformity and homogeneity and compared to reference dose distributions from uniformly-loaded (125)I plaques. The most conformal and homogeneous dose distributions were reproduced within a reference eye environment to assess organ-at-risk (OAR) doses in the Pinnacle(3) treatment planning system (TPS). The gamma-index analysis method was used to quantitatively compare MC and TPS-generated dose distributions. Concentrating > 97% of the total source strength in a single or pair of central (103)Pd seeds produced the most conformal dose distributions, with tumor basal doses a factor of 2-3 higher and OAR doses a factor of 2-3 lower than those of corresponding uniformly-loaded (125)I plaques. Concentrating 82-86% of the total source strength in peripherally-loaded (131)Cs seeds produced the most homogeneous dose distributions, with tumor basal doses 17-25% lower and OAR doses typically 20% higher than those of corresponding uniformly-loaded (125)I plaques. Gamma-index analysis found > 99% agreement between MC and TPS dose distributions. A method was developed to select intra-plaque ring radionuclide compositions and source strengths to deliver more conformal and homogeneous tumor dose distributions than

  2. Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose-Response Curves in Worsening Refractory Congestive Heart Failure.

    Science.gov (United States)

    Paterna, Salvatore; Di Gaudio, Francesca; La Rocca, Vincenzo; Balistreri, Fabio; Greco, Massimiliano; Torres, Daniele; Lupo, Umberto; Rizzo, Giuseppina; di Pasquale, Pietro; Indelicato, Sergio; Cuttitta, Francesco; Butler, Javed; Parrinello, Gaspare

    2015-10-01

    14% for urine output; 29, 24, and 16% for total sodium excretion; 45, 34, and 20% for urinary osmolarity; and 27, 36, and 32% for total furosemide excretion in groups 1, 2, and 3, respectively. These findings were translated in an improvement in the furosemide dose-response curves in these patients. These results may serve as new pathophysiological basis for HSS use in the treatment of refractory CHF.

  3. Asymmetric fan beams (AFB) for improvement of the craniocaudal dose distribution in helical tomotherapy delivery

    International Nuclear Information System (INIS)

    Gladwish, Adam; Kron, Tomas; McNiven, Andrea; Bauman, Glenn; Van Dyk, Jake

    2004-01-01

    Helical tomotherapy (HT) is a novel radiotherapy technique that utilizes intensity modulated fan beams that deliver highly conformal dose distributions in a helical beam trajectory. The most significant limitation in dose delivery with a constant fan beam thickness (FBT) is the penumbra width of the dose distribution in the craniocaudal direction, which is equivalent to the FBT. We propose to employ a half-blocked fan beam at start and stop location to reduce the penumbra width by half. By opening the jaw slowly during the helical delivery until the desired FBT is achieved it is possible to create a sharper edge in the superior and inferior direction from the target. The technique was studied using a tomotherapy beam model implemented on a commercial treatment planning system (Theraplan Plus V3.0). It was demonstrated that the dose distribution delivered using a 25 mm fan beam can be improved significantly, to reduce the dose to normal structures located superiorly and inferiorly of the target. Dosimetry for this technique is straightforward down to a FBT of 15 mm and implementation should be simple as no changes in couch movement are required compared to a standard HT delivery. We conclude that the use of asymmetric collimated fan beams for the start and stop of the helical tomotherapeutic dose delivery has the potential of significantly improving the dose distribution in helical tomotherapy

  4. Improving dose homogeneity in routine head and neck radiotherapy with custom 3-D compensation

    International Nuclear Information System (INIS)

    Harari, P.M.; Sharda, N.N.; Brock, L.K.; Paliwal, B.R.

    1998-01-01

    Background and purpose: Anatomic contour irregularity and tissue inhomogeneity can lead to significant radiation dose variation across the complex treatment volumes found in the head and neck (HandN) region. This dose inhomogeneity can routinely create focal hot or cold spots of 10-20% despite beam shaping with blocks or beam modification with wedges. Since 1992, we have implemented the routine use of 3-D custom tissue compensators fabricated directly from CT scan contour data obtained in the treatment position in order to improve dose uniformity in patients with tumors of the HandN. Materials and methods: Between July 1992 and January 1997, 160 patients receiving comprehensive HandN radiotherapy had 3-D custom compensators fabricated for their treatment course. Detailed dosimetric records have been analyzed for 30 cases. Dose uniformity across the treatment volume and clinically relevant maximum doses to selected anatomic sub-sites were examined with custom-compensated, uncompensated and optimally-wedged plans. Results: The use of 3-D custom compensators resulted in an average reduction of dose variance across the treatment volume from 19±4% for the uncompensated plans to 5±2% with the use of 3-D compensators. Optimally-wedged plans were variable, but on average a 10±3% dose variance was noted. For comprehensive HandN treatment which encompassed the larynx within the primary field design, the peak doses delivered were reduced by 5-15% with 3-D custom compensation as compared to optimal wedging. Conclusions: The use of 3-D custom tissue compensation can improve dose homogeneity within the treatment volume for HandN cancer patients. Maximum doses to clinically important structures which often receive greater than 105-110% of the prescribed dose are routinely reduced with the use of 3-D custom compensators. Improved dose uniformity across the treatment volume can reduce normal tissue complication profiles and potentially allow for delivery of higher total doses in

  5. On the impact of improved dosimetric accuracy on head and neck high dose rate brachytherapy.

    Science.gov (United States)

    Peppa, Vasiliki; Pappas, Eleftherios; Major, Tibor; Takácsi-Nagy, Zoltán; Pantelis, Evaggelos; Papagiannis, Panagiotis

    2016-07-01

    To study the effect of finite patient dimensions and tissue heterogeneities in head and neck high dose rate brachytherapy. The current practice of TG-43 dosimetry was compared to patient specific dosimetry obtained using Monte Carlo simulation for a sample of 22 patient plans. The dose distributions were compared in terms of percentage dose differences as well as differences in dose volume histogram and radiobiological indices for the target and organs at risk (mandible, parotids, skin, and spinal cord). Noticeable percentage differences exist between TG-43 and patient specific dosimetry, mainly at low dose points. Expressed as fractions of the planning aim dose, percentage differences are within 2% with a general TG-43 overestimation except for the spine. These differences are consistent resulting in statistically significant differences of dose volume histogram and radiobiology indices. Absolute differences of these indices are however small to warrant clinical importance in terms of tumor control or complication probabilities. The introduction of dosimetry methods characterized by improved accuracy is a valuable advancement. It does not appear however to influence dose prescription or call for amendment of clinical recommendations for the mobile tongue, base of tongue, and floor of mouth patient cohort of this study. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Multi-dose drug dispensing as a tool to improve medication adherence: A study in patients using vitamin K antagonists.

    Science.gov (United States)

    van Rein, Nienke; de Geus, Kristel S; Cannegieter, Suzanne C; Reitsma, Pieter H; van der Meer, Felix J M; Lijfering, Willem M

    2018-01-01

    Multi-dose drug dispensing (MDD) is a dosing aid that provides patients with disposable bags containing all drugs intended for 1 dosing moment. MDD is believed to increase medication adherence, but studies are based on self-reported data, and results may depend on socially desirable answers. Therefore, our purpose was to determine the effect of MDD on medication adherence in non-adherent patients taking vitamin K antagonists (VKAs), and to compare with instructing patients on medication use. We conducted a before-after study in non-adherent patients where MDD was the exposure and change in adherence after MDD initiation was the outcome (within patient comparison). Time in therapeutic range (TTR) was selected as a measure for adherence, as this reflects stability of VKA treatment. To analyze whether MDD improved adherence as compared with standard care (ie, letters or calls from nurses of the anticoagulation clinic), non-adherent patients without MDD were also followed to estimate their TTR change over time (between patient comparison). Eighty-three non-adherent VKA patients started using MDD. The median TTR was 63% before MDD and 73% 6 months after MDD. The within patient TTR increased on average by 13% (95%CI 6% to 21%) within 1 month after starting MDD and remained stable during the next 5 months. The TTR of MDD-patients increased 10% (95%CI 2% to 19%) higher as compared with non-MDD patients within 1 month but was similar after 4 months (TTR difference 3%, 95%CI -2% to 9%). Adherence improved after initiation of MDD. Compared with instructing patients, MDD was associated with better adherence within 1 month but was associated with similar improvement after 4 months. Copyright © 2017 John Wiley & Sons, Ltd.

  7. 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)

  8. Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases.

    Science.gov (United States)

    Oh, Doo-Byoung

    2015-08-01

    Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently, enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic enzymes for Gaucher disease have N-glycans with terminal mannose residues for targeting to macrophages, the others require N-glycans containing mannose-6-phosphates that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic enzymes is essential for the clearance of accumulated compounds, the suitable glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic enzymes with improved efficacy.

  9. Maternal Depression Mediates the Link Between Therapeutic Alliance and Improvements in Adolescent Externalizing Behavior

    NARCIS (Netherlands)

    Granic, I.; Otten, R.; Blokland, K.; Solomon, T.; Engels, R.C.M.E.; Ferguson, B.

    2012-01-01

    The current study: (1) examined the relation between therapeutic alliance and changes in adolescent externalizing behavior in Multisystemic Therapy; (2) tested whether maternal depression mediates this relation; and (3) determined whether mothers' and clinicians' perceptions of the alliance

  10. Improved preclinical cardiovascular therapeutic indices with long-term inhibition of norepinephrine reuptake using reboxetine

    NARCIS (Netherlands)

    Fossa, Anthony A.; Wisialowski, Todd A.; Cremers, Thomas; van der Hart, Marieke; Tseng, Elaine; Deng, Shibing; Rollema, Hans; Wang, Ellen Q.

    2012-01-01

    Norepinephrine reuptake inhibitors (NRIs) acutely increase norepinephrine (NE) levels, but therapeutic antidepressant activity is only observed after weeks of treatment because central NE levels progressively increase during continued drug exposure. Similarly, while NRIs acutely increase blood

  11. Clonazepam as a therapeutic adjunct to improve the management of depression: a brief review.

    Science.gov (United States)

    Morishita, Shigeru

    2009-04-01

    Clonazepam, first used for seizure disorders, is now increasingly used to treat affective disorders. We summarize the use of clonazepam to improve the management of depression. Clonazepam is useful for treatment-resistant and/or protracted depression, as well as for acceleration of response to conventional antidepressants. Clonazepam is at this time recommended for use in combination with SSRIs (fluoxetine, fluvoxamine, sertraline) as an antidepressant, and should be used at a dosage of 2.5-6.0 mg/day. If clonazepam is effective, a response should be observed within 2-4 weeks. It is significantly more effective for unipolar than for bipolar depression. Low-dose, long-term treatment with clonazepam exhibits a prophylactic effect against recurrence of depression. Although the mechanism of action of clonazepam has not yet been established, some investigators have been suggested that it involves enhancement of anti-anxiety effects, anticonvulsant effects on subclinical epilepsy, increase in 5-HT/monoamine synthesis or decrease in 5-HT receptor sensitivity mediated through the GABA system, and regulate in GABA activity.

  12. 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

  13. 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.

  14. Improvement of Dose Homogeneity in a 3-Dimensional Conformal Radiotherapy for Head and Neck Cancer

    International Nuclear Information System (INIS)

    Kim, Yong Nam; Lee, Chang Geol; Chung, Kyeong Keun; Kim, Joo Young; Seong, Jin Sil

    2007-01-01

    When an electron field is abutted at the surface with a photon field for head-and-neck cancer (HNC) treatment, the traditional method using bilateral field gives rise to an extreme inhomogeneity of dose distribution with both very hot and very cold regions. When we consider clinically only tumor doses of primary concern regardless of dose to normal tissues, the hot spots can be accepted, depending on their magnitude, extent, and location. However, an extreme inhomogeneity inside the radiation field is generally undesirable. An overdose to normal tissues around a target region or an underdosage in the tumor may be problematic. This study intends to develop a novel approach to improve the dose distribution inside the photon-electron abutting fields for HNC treatment

  15. Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans.

    Science.gov (United States)

    Gottlieb, Assaf; Daneshjou, Roxana; DeGorter, Marianne; Bourgeois, Stephane; Svensson, Peter J; Wadelius, Mia; Deloukas, Panos; Montgomery, Stephen B; Altman, Russ B

    2017-11-24

    Genome-wide association studies are useful for discovering genotype-phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into "gene level" effects. Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression-on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort.

  16. Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans

    Directory of Open Access Journals (Sweden)

    Assaf Gottlieb

    2017-11-01

    Full Text Available Abstract Background Genome-wide association studies are useful for discovering genotype–phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into “gene level” effects. Methods Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression—on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. Results We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Conclusions Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort

  17. Improving abdomen tumor low-dose CT images using a fast dictionary learning based processing

    International Nuclear Information System (INIS)

    Chen Yang; Shi Luyao; Shu Huazhong; Luo Limin; Coatrieux, Jean-Louis; Yin Xindao; Toumoulin, Christine

    2013-01-01

    In abdomen computed tomography (CT), repeated radiation exposures are often inevitable for cancer patients who receive surgery or radiotherapy guided by CT images. Low-dose scans should thus be considered in order to avoid the harm of accumulative x-ray radiation. This work is aimed at improving abdomen tumor CT images from low-dose scans by using a fast dictionary learning (DL) based processing. Stemming from sparse representation theory, the proposed patch-based DL approach allows effective suppression of both mottled noise and streak artifacts. The experiments carried out on clinical data show that the proposed method brings encouraging improvements in abdomen low-dose CT images with tumors. (paper)

  18. Implementation of the systems approach to improve a pharmacist-managed vancomycin dosing service.

    Science.gov (United States)

    Gagnon, David J; Roberts, Russel; Sylvia, Lynne

    2014-12-01

    Quality improvements achieved by applying the systems approach to assess the clinical effectiveness, operational efficiency, and financial feasibility of a pharmacist-managed vancomycin dosing service are described. Faced with increased patient volumes and resource demands, the pharmacy department at Tufts Medical Center conducted an evaluation of its adult inpatient vancomycin dosing service using the systems approach, which emphasizes multidisciplinary assessment of system inputs, processes, and outcomes and consensus-building methods to identify needed changes and recommended action steps. A multidisciplinary committee composed of representatives of the medical center's pharmacy, internal medicine, infectious diseases, nursing, phlebotomy, and clinical laboratory services was assembled; in a series of three moderated monthly sessions, committee members deliberated and ultimately reached consensus on a list of action items. Relative to a concurrent intradepartmental assessment of the vancomycin dosing service based solely on pharmacist feedback, the systems approach identified a greater number and wider array of needed improvements in key program areas. Quality improvements implemented as a direct result of the systems-based analysis included a policy change authorizing pharmacists to order serum vancomycin determinations without physician cosignature and inclusion of a vancomycin dosing algorithm in the institutional antibiotic dosing guide. Future changes based on deliverable action items will result in a structured process to help direct program resources toward the patients most in need of pharmacist-managed vancomycin dosing services. The systems approach allowed for a comprehensive multidisciplinary evaluation of the service, as indicated by the identification of process improvements not identified by the department of pharmacy alone. Copyright © 2014 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  19. 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.

  20. Daily high doses of fluoxetine for weight loss and improvement in lifestyle before bariatric surgery

    NARCIS (Netherlands)

    Dolfing, JG; Wolffenbuttel, BHR; Oei, HI; ten Hoor-Aukerna, NM; Schweitzer, DH

    Background: The number of gastric restrictive bariatric operations is increasing each year, but about one-fifth of patients will become disappointed due to unsatisfactory weight reduction or annoying complications. We questioned whether weight reduction by taking high doses of fluoxetine improves

  1. Toward an organ based dose prescription method for the improved accuracy of murine dose in orthovoltage x-ray irradiators

    International Nuclear Information System (INIS)

    Belley, Matthew D.; Wang, Chu; Nguyen, Giao; Gunasingha, Rathnayaka; Chao, Nelson J.; Chen, Benny J.; Dewhirst, Mark W.; Yoshizumi, Terry T.

    2014-01-01

    Purpose: Accurate dosimetry is essential when irradiating mice to ensure that functional and molecular endpoints are well understood for the radiation dose delivered. Conventional methods of prescribing dose in mice involve the use of a single dose rate measurement and assume a uniform average dose throughout all organs of the entire mouse. Here, the authors report the individual average organ dose values for the irradiation of a 12, 23, and 33 g mouse on a 320 kVp x-ray irradiator and calculate the resulting error from using conventional dose prescription methods. Methods: Organ doses were simulated in the Geant4 application for tomographic emission toolkit using the MOBY mouse whole-body phantom. Dosimetry was performed for three beams utilizing filters A (1.65 mm Al), B (2.0 mm Al), and C (0.1 mm Cu + 2.5 mm Al), respectively. In addition, simulated x-ray spectra were validated with physical half-value layer measurements. Results: Average doses in soft-tissue organs were found to vary by as much as 23%–32% depending on the filter. Compared to filters A and B, filter C provided the hardest beam and had the lowest variation in soft-tissue average organ doses across all mouse sizes, with a difference of 23% for the median mouse size of 23 g. Conclusions: This work suggests a new dose prescription method in small animal dosimetry: it presents a departure from the conventional approach of assigninga single dose value for irradiation of mice to a more comprehensive approach of characterizing individual organ doses to minimize the error and uncertainty. In human radiation therapy, clinical treatment planning establishes the target dose as well as the dose distribution, however, this has generally not been done in small animal research. These results suggest that organ dose errors will be minimized by calibrating the dose rates for all filters, and using different dose rates for different organs

  2. Disrupting the Scaffold to Improve Focal Adhesion Kinase–Targeted Cancer Therapeutics

    Science.gov (United States)

    Cance, William G.; Kurenova, Elena; Marlowe, Timothy; Golubovskaya, Vita

    2013-01-01

    Focal adhesion kinase (FAK) is emerging as a promising cancer target because it is highly expressed at both the transcriptional and translational level in cancer and is involved in many aspects of tumor growth, invasion, and metastasis. Existing FAK-based therapeutics focus on inhibiting the kinase's catalytic function and not the large scaffold it creates that includes many oncogenic receptor tyrosine kinases and tumor suppressor proteins. Targeting the FAK scaffold is a feasible and promising approach for developing highly specific therapeutics that disrupt FAK signaling pathways in cancer. PMID:23532331

  3. Disrupting the scaffold to improve focal adhesion kinase-targeted cancer therapeutics.

    Science.gov (United States)

    Cance, William G; Kurenova, Elena; Marlowe, Timothy; Golubovskaya, Vita

    2013-03-26

    Focal adhesion kinase (FAK) is emerging as a promising cancer target because it is highly expressed at both the transcriptional and translational level in cancer and is involved in many aspects of tumor growth, invasion, and metastasis. Existing FAK-based therapeutics focus on inhibiting the kinase's catalytic function and not the large scaffold it creates that includes many oncogenic receptor tyrosine kinases and tumor suppressor proteins. Targeting the FAK scaffold is a feasible and promising approach for developing highly specific therapeutics that disrupt FAK signaling pathways in cancer.

  4. Verification of the absorbed dose values determined with plane parallel ionization chambers in therapeutic electron beams using ferrous sulfate dosimetry

    International Nuclear Information System (INIS)

    Plaetsen, A. van der; Thierens, H.; Palmans, H.

    2000-01-01

    Absolute and relative dosimetry measurements in clinical electron beams using different detectors were performed at a Philips SL18 accelerator. For absolute dosimetry, ionization chamber measurements with the PTW Markus and PTW Roos plane parallel chambers were performed in water following the recommendations of the TRS-381 Code of Practice, using different options for chamber calibration. The dose results obtained with these ionization chambers using the electron beam calibration method were compared with the dose response of the ferrous sulphate (Fricke) chemical dosimeter. The influence of the choice of detector type on the determination of physical quantities necessary for absolute dose determination was investigated and discussed. Results for d max , R 50 and R p were in agreement within statistical uncertainties when using a diode, diamond or plane parallel chamber. The effective point of measurement for the Markus chamber is found to be shifted 0.5 mm from the front surface of the cavity. Fluence correction factors, h m , for dose determination in electron beams using a PMMA phantom were determined experimentally for both plane parallel chamber types. (author)

  5. Is dosing of therapeutic immunoglobulins optimal? A review of a three-decade long debate in europe

    NARCIS (Netherlands)

    Kerr, Jacqueline; Quinti, Isabella; Eibl, Martha; Chapel, Helen; Späth, Peter J.; Sewell, W. A. Carrock; Salama, Abdulgabar; van Schaik, Ivo N.; Kuijpers, Taco W.; Peter, Hans-Hartmut

    2014-01-01

    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

  6. Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy: The influence of gender and comedication

    Directory of Open Access Journals (Sweden)

    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

  7. A rational quantitative approach to determine the best dosing regimen for a target therapeutic effect: a unified formalism for antibiotic evaluation.

    Science.gov (United States)

    Li, Jun; Nekka, Fahima

    2013-02-21

    The determination of an optimal dosing regimen is a critical step to enhance the drug efficacy and avoid toxicity. Rational dosing recommendations based on mathematical considerations are increasingly being adopted in the process of drug development and use. In this paper, we propose a quantitative approach to evaluate the efficacy of antibiotic agents. By integrating both pharmacokinetic (PK) and pharmacodynamic (PD) information, this approach gives rise to a unified formalism able to measure the cause-effect of dosing regimens. This new pharmaco-metric allows to cover a whole range of antibiotics, including the two well known concentration and time dependent classes, through the introduction of the Hill-dependency concept. As a direct fallout, our formalism opens a new path toward the bioequivalence evaluation in terms of PK and PD, which associates the in vivo drug concentration and the in vitro drug effect. Using this new approach, we succeeded to reveal unexpected, but relevant behaviors of drug performance when different drug regimens and drug classes are considered. Of particular notice, we found that the doses required to reach the same therapeutic effect, when scheduled differently, exhibit completely different tendencies for concentration and time dependent drugs. Moreover, we theoretically confirmed the previous experimental results of the superiority of the once daily regimen of aminoglycosides. The proposed methodology is appealing for its computational features and can easily be applicable to design fair clinical protocols or rationalize prescription decisions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Microdosing clinical study: pharmacokinetic, pharmacogenomic (SLCO2B1), and interaction (grapefruit juice) profiles of celiprolol following the oral microdose and therapeutic dose.

    Science.gov (United States)

    Ieiri, Ichiro; Doi, Yohei; Maeda, Kazuya; Sasaki, Tomohiro; Kimura, Miyuki; Hirota, Takeshi; Chiyoda, Takeshi; Miyagawa, Mayuko; Irie, Shin; Iwasaki, Kazuhide; Sugiyama, Yuichi

    2012-07-01

    The authors evaluated the contribution of the SLCO2B1 polymorphism to the pharmacokinetics of celiprolol at a microdose (MD) and therapeutic dose (TD) and compared pharmacokinetic proportionality between the 2 dose forms in 30 SLCO2B1 genotype-matched healthy volunteers. Three drugs (celiprolol, fexofenadine, and atenolol) were orally administered as a cassette dosing following the MD (totally 97.5 µg) and then a TD (100 mg) of celiprolol, with and without grapefruit juice. The mean AUC(0-24) of celiprolol was lower in SLCO2B1*3/*3 individuals (775 ng·h/mL) than in *1/*3 (1097 ng·h/mL) and *1/*1 (1547 ng·h/mL) individuals following the TD, and this was confirmed in population pharmacokinetic analysis with statistical significances; however, SLCO2B1 genotype-dependent differences disappeared following the MD. Dose-normalized AUC of celiprolol at the MD was much lower than that at the TD, explained by the saturation of the efflux transporter. Thus, the effect of SLCO2B1 polymorphism on the AUC of celiprolol clearly observed only at the TD may be due to the saturation of the efflux transport systems.

  9. 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

  10. Improved estimates of external gamma dose rates in the environs of Hinkley Point Power Station

    International Nuclear Information System (INIS)

    Macdonald, H.F.; Thompson, I.M.G.

    1988-07-01

    The dominant source of external gamma dose rates at centres of population within a few kilometres of Hinkley Point Power Station is the routine discharge of 41-Ar from the 'A' station magnox reactors. Earlier estimates of the 41-Ar radiation dose rates were based upon measured discharge rates, combined with calculations using standard plume dispersion and cloud-gamma integration models. This report presents improved dose estimates derived from environmental gamma dose rate measurements made at distances up to about 1 km from the site, thus minimising the degree of extrapolation introduced in estimating dose rates at locations up to a few kilometres from the site. In addition, results from associated chemical tracer measurements and wind tunnel simulations covering distances up to about 4 km from the station are outlined. These provide information on the spatial distribution of the 41-Ar plume during the initial stages of its dispersion, including effects due to plume buoyancy and momentum and behaviour under light wind conditions. In addition to supporting the methodology used for the 41-Ar dose calculations, this information is also of generic interest in the treatment of a range of operational and accidental releases from nuclear power station sites and will assist in the development and validation of existing environmental models. (author)

  11. Improvement of dose determination using glass display of mobile phones for accident dosimetry

    International Nuclear Information System (INIS)

    Discher, M.; Woda, C.; Fiedler, I.

    2013-01-01

    Previous studies have demonstrated that mobile phones can be used as suitable emergency dosimeters in case of an accidental radiation overexposure. Glass samples extracted from displays of mobile phones are sensitive to ionizing radiation and can be measured using the thermoluminescence (TL) method. A non-radiation induced background signal (so-called zero dose signal) was observed which overlaps with the radiation induced signal and consequently limits the minimum detectable dose. Investigations of several glasses from different displays showed that it is possible to reduce the zero dose signal up to 90% by etching the glass surface with concentrated hydrofluoric acid. With this approach a reduction of the detection limit of a factor of four, corresponding to approximately 80 mGy, was achieved. Dosimetric properties of etched samples are presented and developed protocols validated by dose recovery tests under realistic conditions. With the improvements in sample preparation the proposed method of dose determination is a competitive alternative to OSL/TL measurements of electronic components and chip cards and provides a useful option for retrospective accident dosimetry. -- Highlights: ► Glass displays from mobile phones have good potential for emergency dosimetry. ► The background signal can be reduced by etching glass samples with hydrofluoric acid. ► The minimum detectable dose can be lowered to approximately 80 mGy

  12. Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics

    Science.gov (United States)

    Banerjee, Subhamoy; Sahoo, Amaresh Kumar; Chattopadhyay, Arun; Sankar Ghosh, Siddhartha

    2014-08-01

    The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a ‘green synthesis’ method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV-vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells.

  13. Recombinant IκBα-loaded curcumin nanoparticles for improved cancer therapeutics

    International Nuclear Information System (INIS)

    Banerjee, Subhamoy; Ghosh, Siddhartha Sankar; Sahoo, Amaresh Kumar; Chattopadhyay, Arun

    2014-01-01

    The field of recombinant protein therapeutics has been evolving rapidly, making significant impact on clinical applications for several diseases, including cancer. However, the functional aspects of proteins rely exclusively on their structural integrity, in which nanoparticle mediated delivery offers unique advantages over free proteins. In the present work, a novel strategy has been developed where the nanoparticles (NPs) used for the delivery of the recombinant protein could contribute to enhancing the therapeutic efficacy of the recombinant protein. The transcription factor, NFκB, involved in cell growth and its inhibitor, IκBα, regulates its proliferation. Another similar naturally available molecule, which inhibits the function of NFκB, is curcumin. Hence, we have developed a ‘green synthesis’ method for preparing water-soluble curcumin nanoparticles to stabilize recombinant IκBα protein. The NPs were characterized by UV–vis and fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering before administration into human cervical carcinoma (HeLa) and glioblastoma (U87MG) cells. Experimental results demonstrated that this combined module had enhanced therapeutic efficacy, causing apoptotic cell death, which was confirmed by cytotoxicity assay and flowcytometry analyses. The expression of apoptotic genes studied by semi-quantitative reverse transcription PCR delineated the molecular pathways involved in cell death. Thus, our study revealed that the functional delivery of recombinant IκBα-loaded curcumin NPs has promise as a natural-product-based protein therapeutics against cancer cells. (paper)

  14. Image guided adaptive brachytherapy with combined intracavitary and interstitial technique improves the therapeutic ratio in locally advanced cervical cancer: Analysis from the retroEMBRACE study

    DEFF Research Database (Denmark)

    LU, Fokdal; Sturdza, Alina; Mazeron, Renaud

    2016-01-01

    Background and purpose Image guided adaptive brachytherapy (IGABT) using intracavitary applicators (IC) has led to a significant improvement of local control in locally advanced cervical cancer (LACC). Further improvement has been obtained with combined intracavitary/interstitial (IC/IS) applicat...... IC/IS brachytherapy improves the therapeutic ratio in LACC by enabling a tumour specific dose escalation resulting in significantly higher local control in large tumours without adding treatment related late morbidity.......Background and purpose Image guided adaptive brachytherapy (IGABT) using intracavitary applicators (IC) has led to a significant improvement of local control in locally advanced cervical cancer (LACC). Further improvement has been obtained with combined intracavitary/interstitial (IC....../IS) applicators. The aim of this analysis was to evaluate the impact on local control and late morbidity of application of combined IS/IC brachytherapy in a large multicentre population. Material/methods 610 patients with LACC from the retroEMBRACE study were included. Patients were divided into an IC group (N...

  15. Two-dimensional pencil beam scaling: an improved proton dose algorithm for heterogeneous media

    International Nuclear Information System (INIS)

    Szymanowski, Hanitra; Oelfke, Uwe

    2002-01-01

    New dose delivery techniques with proton beams, such as beam spot scanning or raster scanning, require fast and accurate dose algorithms which can be applied for treatment plan optimization in clinically acceptable timescales. The clinically required accuracy is particularly difficult to achieve for the irradiation of complex, heterogeneous regions of the patient's anatomy. Currently applied fast pencil beam dose calculations based on the standard inhomogeneity correction of pathlength scaling often cannot provide the accuracy required for clinically acceptable dose distributions. This could be achieved with sophisticated Monte Carlo simulations which are still unacceptably time consuming for use as dose engines in optimization calculations. We therefore present a new algorithm for proton dose calculations which aims to resolve the inherent problem between calculation speed and required clinical accuracy. First, a detailed derivation of the new concept, which is based on an additional scaling of the lateral proton fluence is provided. Then, the newly devised two-dimensional (2D) scaling method is tested for various geometries of different phantom materials. These include standard biological tissues such as bone, muscle and fat as well as air. A detailed comparison of the new 2D pencil beam scaling with the current standard pencil beam approach and Monte Carlo simulations, performed with GEANT, is presented. It was found that the new concept proposed allows calculation of absorbed dose with an accuracy almost equal to that achievable with Monte Carlo simulations while requiring only modestly increased calculation times in comparison to the standard pencil beam approach. It is believed that this new proton dose algorithm has the potential to significantly improve the treatment planning outcome for many clinical cases encountered in highly conformal proton therapy. (author)

  16. 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

  17. Immune response in pigs treated with therapeutic doses of enrofloxacin at the time of vaccination against Aujeszky's disease.

    Science.gov (United States)

    Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Rachubik, Jarosław; Lipowski, Andrzej; Pejsak, Zygmunt

    2015-06-01

    The effect of treatment with enrofloxacin was studied on the postvaccinal immune response in pigs. Forty pigs were used (control not vaccinated (C), control vaccinated (CV), vaccinated, received enrofloxacin (ENRO)). From day -1 to day 3 pigs from ENRO group received enrofloxacin at the recommended dose. Pigs from ENRO and CV groups were vaccinated twice against Aujeszky's disease virus (ADV). There was a significant delay in the production of humoral response of enrofloxacin dosed pigs when compared with CV group. Moreover, in ENRO group the significant decrease in IFN-γ production and significantly lower values of stimulation index after ADV restimulation was noted, as compared with CV group. The secretion of IL-6, IL-10 and TNF-α by PBMC after recall stimulation was also affected in ENRO group. The results indicate that enrofloxacin, in addition to its antimicrobial properties, possess significant immunomodulatory effects and may alter the immune response to vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Therapeutic administration of 131I for differentiated thyroid cancer, radiation dose to ovaries and outcome of pregnancies

    International Nuclear Information System (INIS)

    Garsi, Jerome-Philippe; Rubino, Carole; Labbe, Martine; Vathaire, Florent de; Schlumberger, Martin; Ricard, Marcel; Ceccarelli, Claudia; Schvartz, Claire; Henri- Amar, Michel; Bardet, Stephane

    2008-01-01

    Full text: Background: Radiation is known to be mutagenic. In thyroid cancer treatment, 131 I is usually administered, for the first treatment, at a 3.7 GMBq activity, corresponding to an estimated mean radiation dose of 140 mGy to the ovaries. However data on the effects of 131 I therapy on pregnancy outcomes, especially untoward, are scarce. Methods: Data on 2673 pregnancies were obtained by interviewing female patients treated for thyroid carcinoma who had not received external radiation to the ovaries, in three French hospitals and one Italian hospital. Results: The incidence of miscarriages was 10 % before any treatment for thyroid cancer; this percentage increased after surgery for thyroid cancer, both before (20 %) and after (19 %) 131 I treatment, with no variation according to the cumulative dose. Miscarriages were not significantly more frequent in women treated with 131 I during the year before conception, even in subjects who had received more than 370 MBq during that year, as compared to women never treated with 131 I. The incidence of stillbirths, preterm births, a low birth weight, congenital malformation and death during the first year of life was not significantly different before or after 131 I therapy. The incidence of thyroid and non thyroidal cancers was similar in children born either before or after the mother's exposure to 131 I. Conclusion: In our data, we found no evidence that exposure to 131 I affects the outcome of subsequent pregnancies and offspring. Whether the number of malformations, or thyroid and non thyroidal cancers are related to gonadal irradiation remains to be established. Our findings allowed us to fuel the debate on the doubling dose: the concept is still heatedly debated and the value of 1 Gy as the doubling dose in humans should be rediscussed. (author)

  19. Evaluation of a pharmacogenetic-based warfarin dosing algorithm in patients with low time in therapeutic range - study protocol for a randomized controlled trial.

    Science.gov (United States)

    Marcatto, Leiliane Rodrigues; Sacilotto, Luciana; Bueno, Carolina Tosin; Facin, Mirella; Strunz, Celia Maria Cassaro; Darrieux, Francisco Carlos Costa; Scanavacca, Maurício Ibrahim; Krieger, Jose Eduardo; Pereira, Alexandre Costa; Santos, Paulo Caleb Junior Lima

    2016-11-17

    Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy and lower TTR values (algorithm specifically calibrated for a Brazilian patient sample. The aims of this study are: to evaluate the impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of genotype-guided warfarin dosing in a specific cohort of patients with low TTR (algorithm will be used. At the second, third, fourth and fifth consultations (with an interval of 7 days each) INR will be measured and, if necessary, the dose will be adjusted based on guidelines. Afterwards, patients who are INR stable will begin measuring their INR in 30 day intervals; if the patient's INR is not stable, the patient will return in 7 days for a new measurement of the INR. Outcomes measures will include the time to achieve the therapeutic target and the percentage of TTR at 4 and 12 weeks. In addition, as a secondary end-point, pharmacoeconomic analysis will be carried out. Ethical approval was granted by the Ethics Committee for Medical Research on Human Beings of the Clinical Hospital of the University of São Paulo Medical School. This randomized study will include patients with low TTR and it will evaluate whether a population-specific genetic algorithm might be more effective than traditional anticoagulation for a selected group of poorly anticoagulated patients. ClinicalTrials.gov, NCT02592980 . Registered on 29 October 2015.

  20. Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer's Disease: Results from a Double-Blind, Placebo-Controlled Trial.

    Science.gov (United States)

    Decourt, Boris; Drumm-Gurnee, Denise; Wilson, Jeffrey; Jacobson, Sandra; Belden, Christine; Sirrel, Sherye; Ahmadi, Michael; Shill, Holly; Powell, Jessica; Walker, Aaron; Gonzales, Amanda; Macias, Mimi; Sabbagh, Marwan N

    2017-01-01

    To date there is no cure for Alzheimer's disease (AD). After amyloid beta immunotherapies have failed to meet primary endpoints of slowing cognitive decline in AD subjects, the inhibition of the beta-secretase BACE1 appears as a promising therapeutic approach. Pre-clinical data obtained in APP23 mice suggested that the anti-cancer drug thalidomide decreases brainBACE1 and Aβ levels. This prompted us to develop an NIH-supported Phase IIa clinical trial to test the potential of thalidomide for AD. We hypothesized that thalidomide can decrease or stabilize brain amyloid deposits, which would result in slower cognitive decline in drug- versus placebo-treated subjects. This was a 24-week, randomized, double-blind, placebo-controlled, parallel group study with escalating dose regimen of thalidomide with a target dose of 400mg daily in patients with mild to moderate AD. The primary outcome measures were tolerability and cognitive performance assessed by a battery of tests. A total of 185 subjects have been pre-screened, out of which25 were randomized. Mean age of the sample at baseline was 73.64 (±7.20) years; mean education was 14.24 (±2.3) years; mean MMSE score was 21.00 (±5.32); and mean GDS score was 2.76 (±2.28).Among the 25 participants, 14 (56%) terminated early due to adverse events, dramatically decreasing the power of the study. In addition, those who completed the study (44%) never reached the estimated therapeutic dose of 400 mg/day thalidomide because of reported adverse events. The cognitive data showed no difference between the treated and placebo groups at the end of the trial. This study demonstrates AD patients have poor tolerability for thalidomide, and are unable to reach a therapeutic dose felt to be sufficient to have effects on BACE1. Because of poor tolerability, this study failed to demonstrate a beneficial effect on cognition. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Therapeutic riding followed by rhythmic auditory stimulation to improve balance and gait in a subject with orthopedic pathologies.

    Science.gov (United States)

    Ungermann, Cathryn M; Gras, Laura Z

    2011-12-01

    The study objectives were to investigate the effect of therapeutic riding with a subject who had an orthopedic diagnosis. This is a single-subject case report. The study was conducted at an equestrian facility with an indoor riding arena. The subject was a 59-year-old woman with grade I spondylolisthesis at L4/L5 and multilevel lumbar spinal stenosis in central and foraminal canals. The subject had an anterior cervical fusion of C3-C7. The subject has been ambulating with a straight cane due to her history of frequent falls. Gait, agility, strength, range of motion, and balance testing were performed. The subject had impairments of bilateral lower extremities with an ataxic gait pattern and was at risk for continued falls according to the balance measures. The intervention comprised therapeutic riding sessions 3 times a week for 20 minutes for 4 weeks. Each riding session was immediately followed by a 10-minute independent walking program with a metronome for rhythmic auditory stimulation. The outcome measures were as follows: Manual muscle testing and range of motion of the lower extremities, Gait Speed Test, Dynamic Gait Index, Four-Square Step Test, Chair Stand Test, Single Leg Stance. Improvements were seen in lower extremity strength and range of motion and balance. The subject improved on balance scores, placing her out of the risk for falls category. Therapeutic riding followed by rhythmic auditory stimulation improved lower extremity range of motion, strength, and balance with this subject.

  2. Improvement of dose distributions in abutment regions of intensity modulated radiation therapy and electron fields

    International Nuclear Information System (INIS)

    Dogan, Nesrin; Leybovich, Leonid B.; Sethi, Anil; Emami, Bahman

    2002-01-01

    In recent years, intensity modulated radiation therapy (IMRT) is used to radiate tumors that are in close proximity to vital organs. Targets consisting of a deep-seated region followed by a superficial one may be treated with abutting photon and electron fields. However, no systematic study regarding matching of IMRT and electron beams was reported. In this work, a study of dose distributions in the abutment region between tomographic and step-and-shoot IMRT and electron fields was carried out. A method that significantly improves dose homogeneity between abutting tomographic IMRT and electron fields was developed and tested. In this method, a target region that is covered by IMRT was extended into the superficial target area by ∼2.0 cm. The length and shape of IMRT target extension was chosen such that high isodose lines bent away from the region treated by the electrons. This reduced the magnitude of hot spots caused by the 'bulging effect' of electron field penumbra. To account for the uncertainties in positioning of the IMRT and electron fields, electron field penumbra was modified using conventional (photon) multileaf collimator (MLC). The electron beam was delivered in two steps: half of the dose delivered with MLCs in retracted position and another half with MLCs extended to the edge of electron field that abuts tomographic IMRT field. The experimental testing of this method using film dosimetry has demonstrated that the magnitude of the hot spots was reduced from ∼45% to ∼5% of the prescription dose. When an error of ±1.5 mm in field positioning was introduced, the dose inhomogeneity in the abutment region did not exceed ±15% of the prescription dose. With step-and-shoot IMRT, the most homogeneous dose distribution was achieved when there was a 3 mm gap between the IMRT and electron fields

  3. 3D representation of radioisotopic dose rates within nuclear plants for improved radioprotection and plant safety

    International Nuclear Information System (INIS)

    Vabo, Rune; Rindahl, Grete; Piotrowski, Leon

    2010-01-01

    A better awareness of the origin and nature of gamma doses in nuclear environments is demonstrated by visualizing the dose maps created by individual radionucleides that are present in radioactive contaminations. This isotopic representation of doses is much more informative than showing a map of the measured total doses. Two practical examples are given : (a) the placing of protections, and (b) using radiation decay to help plan dismantling operations. The necessary radionucleide information can be easily obtained by the new EDF CZT gamma spectrometer that is now used by all its NPPs. Defining radioactive sources based on such information enables the reconstruction of the radiation situation in a virtual 3-D environment. In such a virtual environment, dose rates can be calculated in any position in space and information about how much each radionucleide contributes can be extracted. Such 3D visualisations increase the awareness and knowledge of the distribution of radiation in a nuclear facility and can be considered as an educational tool for training and improved ALARA procedures. (author)

  4. Low and moderate doses of caffeine late in exercise improve performance in trained cyclists.

    Science.gov (United States)

    Talanian, Jason L; Spriet, Lawrence L

    2016-08-01

    The aim of the present study was to assess if low and moderate doses of caffeine delivered in a carbohydrate-electrolyte solution (CES) late in exercise improved time-trial (TT) performance. Fifteen (11 male, 4 female) cyclists (age, 22.5 ± 0.9 years; body mass, 69.3 ± 2.6 kg; peak oxygen consumption, 64.6 ± 1.9 mL·min(-1)·kg(-1)) completed 4 double-blinded randomized trials. Subjects completed 120 min of cycling at ∼60% peak oxygen consumption with 5 interspersed 120-s intervals at ∼82% peak oxygen consumption, immediately followed by 40-s intervals at 50 W. Following 80 min of cycling, subjects either ingested a 6% CES (PL), a CES with 100 mg (low dose, 1.5 ± 0.1 mg·kg body mass(-1)) of caffeine (CAF1), or a CES with 200 mg (moderate dose, 2.9 ± 0.1 mg·kg body mass(-1)) of caffeine (CAF2). Following the 120-min cycling challenge, cyclists completed a 6-kJ·kg body mass(-1) TT. There was no difference between respiratory, heart rate, glucose, free fatty acid, body mass, hematocrit, or urine specific gravity measurements between treatments. The CAF2 (26:36 ± 0:22 min:s) TT was completed faster than CAF1 (27:36 ± 0:32 min:s, p caffeine delivered late in exercise improved TT performance over the PL trial and the moderate dose (CAF2) improved performance to a greater extent than the low dose (CAF1).

  5. Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tome, Wolfgang A. [Department of Human Oncology, University of Wisconsin-Madison, WI, 53792 (United States); Department of Physical Sciences, Peter MacCallum Cancer Centre, Melbourne, VIC 3002 (Australia) and Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia); Department of Human Oncology, University of Wisconsin-Madison, WI 53792 (United States); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia) and Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia); Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53792 (United States); Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin 53792 (United States); Einstein Institute of Oncophysics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461 (United States) and Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia)

    2012-08-15

    Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed 'Super Sampling' involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.

  6. Improvements in dose calculation accuracy for small off-axis targets in high dose per fraction tomotherapy

    International Nuclear Information System (INIS)

    Hardcastle, Nicholas; Bayliss, Adam; Wong, Jeannie Hsiu Ding; Rosenfeld, Anatoly B.; Tomé, Wolfgang A.

    2012-01-01

    Purpose: A recent field safety notice from TomoTherapy detailed the underdosing of small, off-axis targets when receiving high doses per fraction. This is due to angular undersampling in the dose calculation gantry angles. This study evaluates a correction method to reduce the underdosing, to be implemented in the current version (v4.1) of the TomoTherapy treatment planning software. Methods: The correction method, termed “Super Sampling” involved the tripling of the number of gantry angles from which the dose is calculated during optimization and dose calculation. Radiochromic film was used to measure the dose to small targets at various off-axis distances receiving a minimum of 21 Gy in one fraction. Measurements were also performed for single small targets at the center of the Lucy phantom, using radiochromic film and the dose magnifying glass (DMG). Results: Without super sampling, the peak dose deficit increased from 0% to 18% for a 10 mm target and 0% to 30% for a 5 mm target as off-axis target distances increased from 0 to 16.5 cm. When super sampling was turned on, the dose deficit trend was removed and all peak doses were within 5% of the planned dose. For measurements in the Lucy phantom at 9.7 cm off-axis, the positional and dose magnitude accuracy using super sampling was verified using radiochromic film and the DMG. Conclusions: A correction method implemented in the TomoTherapy treatment planning system which triples the angular sampling of the gantry angles used during optimization and dose calculation removes the underdosing for targets as small as 5 mm diameter, up to 16.5 cm off-axis receiving up to 21 Gy.

  7. Dose-dependent response of Trichoderma harzianum in improving drought tolerance in rice genotypes.

    Science.gov (United States)

    Pandey, Veena; Ansari, Mohammad W; Tula, Suresh; Yadav, Sandep; Sahoo, Ranjan K; Shukla, Nandini; Bains, Gurdeep; Badal, Shail; Chandra, Subhash; Gaur, A K; Kumar, Atul; Shukla, Alok; Kumar, J; Tuteja, Narendra

    2016-05-01

    This study demonstrates a dose-dependent response of Trichoderma harzianum Th-56 in improving drought tolerance in rice by modulating proline, SOD, lipid peroxidation product and DHN / AQU transcript level, and the growth attributes. In the present study, the effect of colonization of different doses of T. harzianum Th-56 strain in rice genotypes were evaluated under drought stress. The rice genotypes treated with increasing dose of T. harzianum strain Th-56 showed better drought tolerance as compared with untreated control plant. There was significant change in malondialdehyde, proline, higher superoxide dismutase level, plant height, total dry matter, relative chlorophyll content, leaf rolling, leaf tip burn, and the number of scorched/senesced leaves in T. harzianum Th-56 treated rice genotypes under drought stress. This was corroborated with altered expression of aquaporin and dehydrin genes in T. harzianum Th-56 treated rice genotypes. The present findings suggest that a dose of 30 g/L was the most effective in improving drought tolerance in rice, and its potential exploitation will contribute to the advancement of rice genotypes to sustain crop productivity under drought stress. Interaction studies of T. harzianum with three aromatic rice genotypes suggested that PSD-17 was highly benefitted from T. harzianum colonization under drought stress.

  8. Renal excretion of iodine-131 labelled meta-iodobenzylguanidine and metabolites after therapeutic doses in patients suffering from different neural crest-derived tumours

    International Nuclear Information System (INIS)

    Wafelman, A.R.; Hoefnagel, C.A.; Maessen, H.J.M.; Maes, R.A.A.; Beijnen, J.H.

    1997-01-01

    Iodine-131 labelled meta-iodobenzylguanidine ([ 131 I[MIBG) is used for diagnostic scintigraphy and radionuclide therapy of neural crest-derived tumours. After administration of therapeutic doses of [ 131 I[MIBG (3.1-7.5 GBq) to 17 patients (n=32 courses), aged 2-73 years, 56%±10%, 73%±11%, 80%±10% and 83%±10% of the dose was cumulatively excreted as total radioactivity in urine at t=24 h, 48 h, 72 h and 96 h, respectively. Except for two adult patients, who showed excretion of 14%-18% of [ 131 I[meta-iodohippuric acid ([ 131 I[MIHA), the cumulatively excreted radioactivity consisted of >85% [ 131 I[MIBG, with 6% of the dose excreted as free [ 131 I[iodide, 4% as [ 131 I[MIHA and 2.5% as an unknown iodine-131 labelled metabolite. Cumulative renal excretion rates of total radioactivity and of [ 131 I[MIBG appeared to be higher in neuroblastoma and phaeochromocytoma patients than in carcinoid patients. Based on the excretion of small amounts of [ 131 I[meta-iodobenzoic acid in two patients, a possible metabolic pathway for [ 131 I[MIBG is suggested. The degree of metabolism was not related to the extent of liver uptake of radioactivity. (orig.). With 2 figs., 5 tabs

  9. Measurement of charged particle yields from therapeutic beams in view of the design of an innovative hadrontherapy dose monitor

    CERN Document Server

    Battistoni, G; Bini, F; Collamati, F; Collini, F; De Lucia, E; Durante, M; Faccini, R; Ferroni, F; Frallicciardi, P M; La Tessa, C; Marafini, M; Mattei, I; Miraglia, F; Morganti, S; Ortega, P G; Patera, V; Piersanti, L; Pinci, D; Russomando, A; Sarti, A; Schuy, C; Sciubba, A; Senzacqua, M; Solfaroli Camillocci, E; Vanstalle, M; Voena, C

    2015-01-01

    Particle Therapy (PT) is an emerging technique, which makes use of charged particles to efficiently cure different kinds of solid tumors. The high precision in the hadrons dose deposition requires an accurate monitoring to prevent the risk of under-dosage of the cancer region or of over-dosage of healthy tissues. Monitoring techniques are currently being developed and are based on the detection of particles produced by the beam interaction into the target, in particular: charged particles, result of target and/or projectile fragmentation, prompt photons coming from nucleus de-excitation and back-to-back γ s, produced in the positron annihilation from β + emitters created in the beam interaction with the target. It has been showed that the hadron beam dose release peak can be spatially correlated with the emission pattern of these secondary particles. Here we report about secondary particles production (charged fragments and prompt γ s) performed at different beam and energies that have a particular relevan...

  10. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses

    Directory of Open Access Journals (Sweden)

    Mahmoud Ameri

    2014-05-01

    Full Text Available This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC. Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  11. Human Growth Hormone Delivery with a Microneedle Transdermal System: Preclinical Formulation, Stability, Delivery and PK of Therapeutically Relevant Doses.

    Science.gov (United States)

    Ameri, Mahmoud; Kadkhodayan, Miryam; Nguyen, Joe; Bravo, Joseph A; Su, Rebeca; Chan, Kenneth; Samiee, Ahmad; Daddona, Peter E

    2014-05-15

    This study evaluated the feasibility of coating formulated recombinant human growth hormone (rhGH) on a titanium microneedle transdermal delivery system, Zosano Pharma (ZP)-hGH, and assessed preclinical patch delivery performance. Formulation rheology and surface activity were assessed by viscometry and contact angle measurement. rhGH liquid formulation was coated onto titanium microneedles by dip-coating and drying. The stability of coated rhGH was determined by size exclusion chromatography-high performance liquid chromatography (SEC-HPLC). Preclinical delivery and pharmacokinetic studies were conducted in female hairless guinea pigs (HGP) using rhGH coated microneedle patches at 0.5 and 1 mg doses and compared to Norditropin® a commercially approved rhGH subcutaneous injection. Studies demonstrated successful rhGH formulation development and coating on microneedle arrays. The ZP-hGH patches remained stable at 40 °C for six months with no significant change in % aggregates. Pharmacokinetic studies showed that the rhGH-coated microneedle patches, delivered with high efficiency and the doses delivered indicated linearity with average Tmax of 30 min. The absolute bioavailability of the microneedle rhGH patches was similar to subcutaneous Norditropin® injections. These results suggest that ZP-transdermal microneedle patch delivery of rhGH is feasible and may offer an effective and patient-friendly alternative to currently marketed rhGH injectables.

  12. Low-dose budesonide treatment improves lung function in patients with infrequent asthma symptoms at baseline

    DEFF Research Database (Denmark)

    Reddel, H. K.; Busse, W. W.; Pedersen, Søren

    2015-01-01

    symptom frequency groups (Figure). CONCLUSIONS: Long-term, once-daily, low-dose budesonide treatment plus usual asthma medication improves lung function in patients with mild, recent-onset asthma. These beneficial effects were seen even in patients with the lowest baseline asthma symptom frequency (0......RATIONALE: Inhaled corticosteroids (ICS) are highly effective in low doses for improving asthma outcomes, including lung function. In the past, ICS treatment was recommended for patients with 'persistent' asthma, defined by symptoms >2 days/week.1 However, evidence is lacking for the benefit of ICS...... in patients with less frequent symptoms at presentation. This was investigated in a post-hoc analysis of the multinational inhaled Steroid Treatment As Regular Therapy in early asthma (START) study.2 METHODS: Patients aged 4-66 years (median 21 years) with a history of recent-onset mild asthma (11 years...

  13. Improvement in erection hardness and intercourse success with first dose of sildenafil citrate 100 mg

    Directory of Open Access Journals (Sweden)

    Mulhall JP

    2013-11-01

    Full Text Available John P Mulhall,1 Dana L Creanga,2 Vera J Stecher31Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; 2Consultant to Pfizer Inc., New York, NY, USA; 3Medical Affairs, Primary Care Business Unit, Pfizer Inc., New York, NY, USAPurpose: To determine, in men with erectile dysfunction (ED, the extent of improvement in erection hardness and in the rate of successful sexual intercourse (SSI during the final intercourse attempt using sildenafil 50 mg compared with the subsequent initial attempt after a dose increase to 100 mg.Patients and methods: This post hoc analysis used data from two randomized, double-blind, placebo-controlled studies of flexible-dose sildenafil for the treatment of men with ED, who were given sildenafil 50 mg or matching placebo, to be taken as needed before sexual intercourse. After 2 weeks, those with no tolerability concerns were titrated up to 100 mg, forming the subgroup of this analysis. The main outcome measures were event log data, including an Erection Hardness Score (EHS and a question on SSI (“Did your erection last long enough for you to have successful sexual intercourse?”, for each attempt at sexual intercourse, analyzed by study and treatment group (sildenafil or placebo. Statistical comparisons were conducted by using the Fisher's exact test.Results: In both studies, the sildenafil group had a larger proportion of EHS4 (completely hard and fully rigid erections (P < 0.001 and SSI (P < 0.005 compared with the placebo group, both before and after the dose increase. Between the final 50 mg sildenafil dose and the initial 100 mg sildenafil dose, the outcomes improved and significantly so in the larger study.Conclusion: The improved efficacy with sildenafil 100 mg versus 50 mg, which occurs rapidly, suggests that patients should be encouraged to use 100 mg if they are unable to achieve completely hard and fully rigid erections or SSI with the 50 mg dose

  14. Development of a methodology to determine optimized therapeutic doses of {sup 131}I for the treatment of hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Araujo, F.; Moura, M.B.; Pereira, A.C., E-mail: faraujo@ird.gov.br [Instituto de Medicna Nuclear (IMEN), Goiania, GO (Brazil); Dantas, B.M.; Dantas, A.L.A.; Lucena, E.A. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Melo, R.C.; Rebelo, A.M.O. [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil). Faculdade de Medicina

    2008-07-01

    Several methods can be used to determine the activity of {sup 131}I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology for individualized treatment with {sup 131}I in patients with hyperthyroidism of the Grave's Disease. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of {sup 131}I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro and Instituto de Medicina Nuclear - IMEN, of Goiania. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were (39.3 ± 0.78), (58.1 ± 2.38) to uptake probe SCT-13004 e 13002, respectively and 4.3 ± 0.17 to scintillation camera. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use of diagnose equipment available at the hospital (scintillation camera and uptake probe) has shown to be a suitable procedure in terms of effectiveness, simplicity and cost

  15. Development of a methodology to determine optimized therapeutic doses of 131I for the treatment of hyperthyroidism

    International Nuclear Information System (INIS)

    Araujo, F.; Moura, M.B.; Pereira, A.C.; Dantas, B.M.; Dantas, A.L.A.; Lucena, E.A.; Melo, R.C.; Rebelo, A.M.O.

    2008-01-01

    Several methods can be used to determine the activity of 131 I to be administered for the treatment of hyperthyroidism. However, some of them do not take into consideration the dose absorbed by the thyroid, while others do not consider all the parameters necessary for dose calculation. The relationship between the dose absorbed by the thyroid and the activity administered depends basically on three parameters: mass of the organ, iodine uptake and effective half-life of iodine in the thyroid. Such parameters should be individually determined for each patient in order to optimize the administered activity. The objective of this work is to develop a methodology for individualized treatment with 131 I in patients with hyperthyroidism of the Grave's Disease. A neck-thyroid phantom developed at the In Vivo Monitoring Laboratory of IRD, containing a known amount of 131 I, was used to calibrate a scintillation camera and a uptake probe available at the Nuclear Medicine Center of the University Hospital of Rio de Janeiro and Instituto de Medicina Nuclear - IMEN, of Goiania. The optimization of the counting geometry was carried out by the determination of the characteristic curves of the view angle of the collimator-detector assembly. The view angle of the collimator-detector assembly presented values compatible with the size of the organ for distances of 25 cm (uptake probe) and 45.8 cm (scintillation camera). The calibration factors (in cpm/kBq) and the associated uncertainty related to these distances were (39.3 ± 0.78), (58.1 ± 2.38) to uptake probe SCT-13004 e 13002, respectively and 4.3 ± 0.17 to scintillation camera. The time period between 14 and 30 hours of the retention curve allows the calculation of the activity between those two points. It is concluded that the use of diagnose equipment available at the hospital (scintillation camera and uptake probe) has shown to be a suitable procedure in terms of effectiveness, simplicity and cost. (author)

  16. Experimental investigation on electrical characteristics and dose measurement of dielectric barrier discharge plasma device used for therapeutic application.

    Science.gov (United States)

    Shahbazi Rad, Zahra; Abbasi Davani, Fereydoun

    2017-04-01

    In this research, a Dielectric Barrier Discharge (DBD) plasma device operating in air has been made. The electrical characteristics of this device like instantaneous power, dissipated power, and discharge capacitance have been measured. Also, the effects of applied voltage on the dissipated power and discharge capacitance of the device have been investigated. The determination of electrical parameters is important in DBD plasma device used in living tissue treatment for choosing the proper treatment doses and preventing the destructive effects. The non-thermal atmospheric pressure DBD plasma source was applied for studying the acceleration of blood coagulation time, in vitro and wound healing time, in vivo. The citrated blood drops coagulated within 5 s treatment time by DBD plasma. The effects of plasma temperature and electric field on blood coagulation have been studied as an affirmation of the applicability of the constructed device. Also, the effect of constructed DBD plasma on wound healing acceleration has been investigated.

  17. Clinical relevance of consolidation radiotherapy and other main therapeutic issues in primary central nervous system lymphomas treated with upfront high-dose methotrexate

    International Nuclear Information System (INIS)

    Reni, Michele; Ferreri, Andres J.M.; Guha-Thakurta, Nandita; Blay, Jean-Yves; Dell'Oro, Stefania; Biron, Pierre; Hochberg, Fred H.

    2001-01-01

    Purpose: To evaluate the optimal dose of methotrexate (MTX) and the efficacy of other drugs, intrathecal chemotherapy (CHT), and radiotherapy (RT) in primary brain lymphomas. Methods and Materials: Two hundred eighty-eight immunocompetent patients with histologically documented, previously untreated primary brain lymphomas, receiving CHT containing high-dose MTX (≥1 g/m 2 ) with or without RT were selected from 19 prospective series. The impact on survival of the MTX dose ( 2 vs.≥3 g/m 2 ), the main drugs, intrathecal CHT, and combination CHT (mono-CHT vs. poly-CHT) was assessed, according to the intention-to-treat principle. The role of post-CHT irradiation (immediate vs. delayed RT) was evaluated in 119 patients with a complete response to CHT. The whole brain and tumor bed dose ( 2 (p=0.04), thiotepa (p=0.03), and intrathecal CHT (p=0.03) improved the OS, and nitrosoureas (p 0.01) correlated with a worse survival. In multivariate analysis, limited to patients receiving MTX ≥3 g/m 2 , only the addition of cytarabine improved the OS; nitrosoureas reduced MTX efficacy. Of the 119 complete responders, 70 received immediate RT. A RT dose of ≥40 Gy to the whole brain or tumor bed did not improve OS. The 3-year OS was similar between the immediate and delayed RT groups. In multivariate analysis, RT delay had no negative impact on survival. Conclusions: MTX ≥3 g/m 2 seems to improve survival in primary brain lymphoma patients. The efficacy of additional drugs, except for cytarabine, remains unproved. Randomized trials are needed to confirm that RT withdrawal yields no detrimental effect in complete responders

  18. Improving the Accuracy of a Heliocentric Potential (HCP Prediction Model for the Aviation Radiation Dose

    Directory of Open Access Journals (Sweden)

    Junga Hwang

    2016-12-01

    Full Text Available The space radiation dose over air routes including polar routes should be carefully considered, especially when space weather shows sudden disturbances such as coronal mass ejections (CMEs, flares, and accompanying solar energetic particle events. We recently established a heliocentric potential (HCP prediction model for real-time operation of the CARI-6 and CARI-6M programs. Specifically, the HCP value is used as a critical input value in the CARI-6/6M programs, which estimate the aviation route dose based on the effective dose rate. The CARI-6/6M approach is the most widely used technique, and the programs can be obtained from the U.S. Federal Aviation Administration (FAA. However, HCP values are given at a one month delay on the FAA official webpage, which makes it difficult to obtain real-time information on the aviation route dose. In order to overcome this critical limitation regarding the time delay for space weather customers, we developed a HCP prediction model based on sunspot number variations (Hwang et al. 2015. In this paper, we focus on improvements to our HCP prediction model and update it with neutron monitoring data. We found that the most accurate method to derive the HCP value involves (1 real-time daily sunspot assessments, (2 predictions of the daily HCP by our prediction algorithm, and (3 calculations of the resultant daily effective dose rate. Additionally, we also derived the HCP prediction algorithm in this paper by using ground neutron counts. With the compensation stemming from the use of ground neutron count data, the newly developed HCP prediction model was improved.

  19. Functionalized bioengineered spider silk spheres improve nuclease resistance and activity of oligonucleotide therapeutics providing a strategy for cancer treatment.

    Science.gov (United States)

    Kozlowska, Anna Karolina; Florczak, Anna; Smialek, Maciej; Dondajewska, Ewelina; Mackiewicz, Andrzej; Kortylewski, Marcin; Dams-Kozlowska, Hanna

    2017-09-01

    Cell-selective delivery and sensitivity to serum nucleases remain major hurdles to the clinical application of RNA-based oligonucleotide therapeutics, such as siRNA. Spider silk shows great potential as a biomaterial due to its biocompatibility and biodegradability. Self-assembling properties of silk proteins allow for processing into several different morphologies such as fibers, scaffolds, films, hydrogels, capsules and spheres. Moreover, bioengineering of spider silk protein sequences can functionalize silk by adding peptide moieties with specific features including binding or cell recognition domains. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel oligonucleotide delivery system that can be utilized to improve pharmacokinetics of RNA-based therapeutics, such as CpG-siRNA. The MS2 bioengineered silk was functionalized with poly-lysine domain (KN) to generate hybrid silk MS2KN. CpG-siRNA efficiently bound to MS2KN in contrary to control MS2. Both MS2KN complexes and spheres protected CpG-siRNA from degradation by serum nucleases. CpG-siRNA molecules encapsulated into MS2KN spheres were efficiently internalized and processed by TLR9-positive macrophages. Importantly, CpG-STAT3siRNA loaded in silk spheres showed delayed and extended target gene silencing compared to naked oligonucleotides. The prolonged Stat3 silencing resulted in the more pronounced downregulation of interleukin 6 (IL-6), a proinflammatory cytokine and upstream activator of STAT3, which limits the efficacy of TLR9 immunostimulation. Our results demonstrate the feasibility of using spider silk spheres as a carrier of therapeutic nucleic acids. Moreover, the modified kinetic and activity of the CpG-STAT3siRNA embedded into silk spheres is likely to improve immunotherapeutic effects in vivo. We demonstrated that modification of silk protein by adding the nucleic acid binding domain enabled the development of a novel

  20. 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.

  1. Improving Therapeutic Ratio in Head and Neck Cancer with Adjuvant and Cisplatin-Based Treatments

    Directory of Open Access Journals (Sweden)

    Loredana G. Marcu

    2013-01-01

    Full Text Available Advanced head and neck cancers are difficult to manage despite the large treatment arsenal currently available. The multidisciplinary effort to increase disease-free survival and diminish normal tissue toxicity was rewarded with better locoregional control and sometimes fewer side effects. Nevertheless, locoregional recurrence is still one of the main reasons for treatment failure. Today, the standard of care in head and neck cancer management is represented by altered fractionation radiotherapy combined with platinum-based chemotherapy. Targeted therapies as well as chronotherapy were trialled with more or less success. The aim of the current work is to review the available techniques, which could contribute towards a higher therapeutic ratio in the treatment of advanced head and neck cancer patients.

  2. Challenges to improved therapeutics for metastatic castrate resistant prostate cancer: from recent successes and failures

    Directory of Open Access Journals (Sweden)

    Huang Xuan

    2012-07-01

    Full Text Available Abstract Men with metastatic castration-resistant prostate cancer (mCRPC carry poor prognosis despite the use of docetaxel-based regimens which has modest survival benefit shown by randomized clinical trials. Significant progress in the discovery of novel therapeutic agents has been made in the past few years. While sipuleucel-T, cabazitaxel, and abiraterone gained regulatory approval in 2010 and 2011, several highly promising candidates/regimens have failed in large scale clinical trials. Challenges remain to optimize the design and interpretation of clinical trial results and develop more effective strategies for mCRPC. In this review, we examined the positive and negative clinical trials in mCRPC in the past and discussed the various aspects of clinical trial design including selection of targets and appropriate outcome measures, biomarker development and implementation, and strategies for combination therapy.

  3. Therapeutic mild hypothermia improves early outcomes in rats subjected to severe sepsis.

    Science.gov (United States)

    Ding, Wu; Shen, Yuehong; Li, Qiang; Jiang, Shouyin; Shen, Huahao

    2018-04-15

    Therapeutic hypothermia has shown beneficial effects in sepsis. This study focused on its mechanism. Sixteen male Sprague-Dawley rats underwent cecal ligation and perforation and subsequently were treated with either hypothermia (HT; body temperature cooled and maintained at 34 °C by ice pad for 10 h; n = 8) or normothermia (NT; n = 8). Three additional rats underwent sham surgery. The body temperatures of the sham-operated and NT groups were maintained at 38 °C with a thermal pad. After the hypothermia treatment, the HT rats were rewarmed for 2 h. The groups were compared for circulating cytokines (IL-6, IL-10), lactate, high mobility group box-1 protein (HMGB1), and lung and intestinal lesions. Animals were observed for 24 h. Compared with the sham-operated group, the 2 sepsis group rats had significantly higher circulating IL-6, HMGB1, and lactate levels, and tissue injury. In the HT rats, the levels of IL-6, HMGB1, and lactate, the lung wet-to-dry ratio, and lung and intestinal damage were significantly lower than that of the NT group. Circulating IL-10 levels increased significantly after 12 h in the sepsis groups compared with sham animals, while that of the NT and HT groups were comparable. The survival rates of the NT and HT rats were also comparable. Therapeutic hypothermia in a rat model of sepsis was associated with lower levels of circulating IL-6 and HMGB1, and less capillary leakage and tissue edema. These results suggest that mild hypothermia has potential as a therapy in sepsis. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Improvement of radiation dose estimation due to nuclear accidents using deep neural network and GPU

    Energy Technology Data Exchange (ETDEWEB)

    Desterro, Filipe S.M.; Almeida, Adino A.H.; Pereira, Claudio M.N.A., E-mail: filipesantana18@gmail.com, E-mail: adino@ien.gov.br, E-mail: cmcoelho@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2017-07-01

    Recently, the use of mobile devices has been proposed for dose assessment during nuclear accidents. The idea is to support field teams, providing an approximated estimation of the dose distribution map in the vicinity of the nuclear power plant (NPP), without needing to be connected to the NPP systems. In order to provide such stand-alone execution, the use of artificial neural networks (ANN) has been proposed in substitution of the complex and time consuming physical models executed by the atmospheric dispersion radionuclide (ADR) system. One limitation observed on such approach is the very time-consuming training of the ANNs. Moreover, if the number of input parameters increases the performance of standard ANNs, like Multilayer-Perceptron (MLP) with backpropagation training, is affected leading to unreasonable training time. To improve learning, allowing better dose estimations, more complex ANN architectures are required. ANNs with many layers (much more than a typical number of layers), referred to as Deep Neural Networks (DNN), for example, have demonstrating to achieve better results. On the other hand, the training of such ANNs is very much slow. In order to allow the use of such DNNs in a reasonable training time, a parallel programming solution, using Graphic Processing Units (GPU) and Computing Unified Device Architecture (CUDA) is proposed. This work focuses on the study of computational technologies for improvement of the ANNs to be used in the mobile application, as well as their training algorithms. (author)

  5. Improvement of radiation dose estimation due to nuclear accidents using deep neural network and GPU

    International Nuclear Information System (INIS)

    Desterro, Filipe S.M.; Almeida, Adino A.H.; Pereira, Claudio M.N.A.

    2017-01-01

    Recently, the use of mobile devices has been proposed for dose assessment during nuclear accidents. The idea is to support field teams, providing an approximated estimation of the dose distribution map in the vicinity of the nuclear power plant (NPP), without needing to be connected to the NPP systems. In order to provide such stand-alone execution, the use of artificial neural networks (ANN) has been proposed in substitution of the complex and time consuming physical models executed by the atmospheric dispersion radionuclide (ADR) system. One limitation observed on such approach is the very time-consuming training of the ANNs. Moreover, if the number of input parameters increases the performance of standard ANNs, like Multilayer-Perceptron (MLP) with backpropagation training, is affected leading to unreasonable training time. To improve learning, allowing better dose estimations, more complex ANN architectures are required. ANNs with many layers (much more than a typical number of layers), referred to as Deep Neural Networks (DNN), for example, have demonstrating to achieve better results. On the other hand, the training of such ANNs is very much slow. In order to allow the use of such DNNs in a reasonable training time, a parallel programming solution, using Graphic Processing Units (GPU) and Computing Unified Device Architecture (CUDA) is proposed. This work focuses on the study of computational technologies for improvement of the ANNs to be used in the mobile application, as well as their training algorithms. (author)

  6. Radioactivity of flour, wheat, bread improvers and dose estimates in Sudan

    International Nuclear Information System (INIS)

    Hamdan, Adam Mahana

    2015-10-01

    The steady rise in the use of isotopes and nuclear technology in various purposes in human life, both agro-industrial military, medical, may increase the chances of radioactive contamination that increases the exposure of ionizing radiation which raise awareness in increasing the need to know how to assess that exposure. Control of imported foodstuffs to ensure that not contaminated with radioactive materials is very important at this stage. The present study aims to investigating radioactivity in foodstuff consumed in Sudan to measure radionuclide in wheat flour, bread improvers specific objectives to measure radioactive contaminants and to estimate radiation dose from this consumption. The health impact of radionuclide ingestion from foodstuffs was evaluated by the committed effective doses determined in 30 samples of foodstuff. collected in the Port Sudan on the red sea, the radioactivity tracer of K-40, U-238 and Th-232 were measured by gamma ray spectrometry employing an using Nal (Ti) calibration process carried out for gamma spectrometry using MW652 as a reference source which recommended by International Atomic Energy Agency (IAEA) including source Cs-137 and Co-60 with two energy levels. The K-40 activity concentration in the flour samples, rang (303.07-40.48) (Bq/kg), 238U (4.81-1.95) (Bq/kg), Th-232 (7.60-1.61) Bq/kg) wheat samples range k-40 (250.62-27.22) (Bq/kg), U-238 (4.92-190) (Bq/kg), Th-232 (5.74-1.61) (Bq/kg) and bread improvers samples k-40 (68.60-13.61 (Bq/kg) U-238 (5.73-194) (Bq/kg). The total average effective dose for age (>17 years) was found in to flour be 2.35±7.12 mSv/y, 1.15±0.95 mSv/y, 1.65±2.02 mSv/y, the maximum dose values obtained were 6.01 mSv/y, 1.95 mSv/y, 1.57 mSv/y. The total average effective dose for age (>17 years) was found in to wheat 1.58±6.85 mSv/y 1.16±1.33 mSv/y, 0.48±1.14 mSv/y, the maximum dose values obtained were 4.14 mSv/y, 1.66 mSv/y, 0.99 mSv/y. The total average effective dose for age (>17 years) was

  7. Improving the in vivo therapeutic index of siRNA polymer conjugates through increasing pH responsiveness.

    Science.gov (United States)

    Guidry, Erin N; Farand, Julie; Soheili, Arash; Parish, Craig A; Kevin, Nancy J; Pipik, Brenda; Calati, Kathleen B; Ikemoto, Nori; Waldman, Jacob H; Latham, Andrew H; Howell, Bonnie J; Leone, Anthony; Garbaccio, Robert M; Barrett, Stephanie E; Parmar, Rubina Giare; Truong, Quang T; Mao, Bing; Davies, Ian W; Colletti, Steven L; Sepp-Lorenzino, Laura

    2014-02-19

    Polymer based carriers that aid in endosomal escape have proven to be efficacious siRNA delivery agents in vitro and in vivo; however, most suffer from cytotoxicity due in part to a lack of selectivity for endosomal versus cell membrane lysis. For polymer based carriers to move beyond the laboratory and into the clinic, it is critical to find carriers that are not only efficacious, but also have margins that are clinically relevant. In this paper we report three distinct categories of polymer conjugates that improve the selectivity of endosomal membrane lysis by relying on the change in pH associated with endosomal trafficking, including incorporation of low pKa heterocycles, acid cleavable amino side chains, or carboxylic acid pH sensitive charge switches. Additionally, we determine the therapeutic index of our polymer conjugates in vivo and demonstrate that the incorporation of pH responsive elements dramatically expands the therapeutic index to 10-15, beyond that of the therapeutic index (less than 3), for polymer conjugates previously reported.

  8. High-dose therapy improved the bone remodelling compartment canopy and bone formation in multiple myeloma

    DEFF Research Database (Denmark)

    Hinge, Maja; Delaissé, Jean-Marie; Plesner, Torben

    2015-01-01

    transplantation, and from 20 control patients with monoclonal gammopathy of undetermined significance were histomorphometrically investigated. This investigation confirmed that MM patients exhibited uncoupled bone formation to resorption and reduced canopy coverage. More importantly, this study revealed......Bone loss in multiple myeloma (MM) is caused by an uncoupling of bone formation to resorption trigged by malignant plasma cells. Increasing evidence indicates that the bone remodelling compartment (BRC) canopy, which normally covers the remodelling sites, is important for coupled bone remodelling....... Loss of this canopy has been associated with bone loss. This study addresses whether the bone remodelling in MM is improved by high-dose therapy. Bone marrow biopsies obtained from 20 MM patients, before and after first-line treatment with high-dose melphalan followed by autologous stem cell...

  9. Improving the quality control program for patient dose calibrator according to IEC 60580

    International Nuclear Information System (INIS)

    Costa, Nathalia Almeida; Potiens, Maria da Penha Albuquerque

    2013-01-01

    The objective of this work was to improve the program quality control of this equipment based on the International Standard IEC 60580 - Medical electrical equipment - Dose area product meters . The initial program was established following the recommendations of IEC 61674 quoting dosimeters with ionization chambers and / or semiconductor detectors used in diagnostic X-ray image, however, the IEC 60580 is referred specifically to gauges and KAP (kerma-area product) presents additional tests. Tests included: intrinsic relative error, repeatability, scanning resolution, settling time, restarting, float values, response time and spatial uniformity of response. As a rule, all measurements are within the range characteristic of equipment performance. Thus, the PDC (Patient Dose Calibrator) again shows a device with excellent functionality and reliability in characterization tests carried out to quality control as( for the test in clinical PKA meters

  10. Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    D. W. Nigg

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  11. Tumor blood vessel 'normalization' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    International Nuclear Information System (INIS)

    Nigg, D.W.

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  12. IMRT: Improvement in treatment planning efficiency using NTCP calculation independent of the dose-volume-histogram

    International Nuclear Information System (INIS)

    Grigorov, Grigor N.; Chow, James C.L.; Grigorov, Lenko; Jiang, Runqing; Barnett, Rob B.

    2006-01-01

    The normal tissue complication probability (NTCP) is a predictor of radiobiological effect for organs at risk (OAR). The calculation of the NTCP is based on the dose-volume-histogram (DVH) which is generated by the treatment planning system after calculation of the 3D dose distribution. Including the NTCP in the objective function for intensity modulated radiation therapy (IMRT) plan optimization would make the planning more effective in reducing the postradiation effects. However, doing so would lengthen the total planning time. The purpose of this work is to establish a method for NTCP determination, independent of a DVH calculation, as a quality assurance check and also as a mean of improving the treatment planning efficiency. In the study, the CTs of ten randomly selected prostate patients were used. IMRT optimization was performed with a PINNACLE3 V 6.2b planning system, using planning target volume (PTV) with margins in the range of 2 to 10 mm. The DVH control points of the PTV and OAR were adapted from the prescriptions of Radiation Therapy Oncology Group protocol P-0126 for an escalated prescribed dose of 82 Gy. This paper presents a new model for the determination of the rectal NTCP ( R NTCP). The method uses a special function, named GVN (from Gy, Volume, NTCP), which describes the R NTCP if 1 cm 3 of the volume of intersection of the PTV and rectum (R int ) is irradiated uniformly by a dose of 1 Gy. The function was 'geometrically' normalized using a prostate-prostate ratio (PPR) of the patients' prostates. A correction of the R NTCP for different prescribed doses, ranging from 70 to 82 Gy, was employed in our model. The argument of the normalized function is the R int , and parameters are the prescribed dose, prostate volume, PTV margin, and PPR. The R NTCPs of another group of patients were calculated by the new method and the resulting difference was <±5% in comparison to the NTCP calculated by the PINNACLE3 software where Kutcher's dose

  13. Improved Therapeutic Regimens for Treatment of Post-Traumatic Ocular Infections

    National Research Council Canada - National Science Library

    Callegan, Michelle C

    2008-01-01

    .... This proposal was designed to analyze the effectiveness of antibiotics, anti-inflammatory drugs, and non-conventional agents targeting bacterial and host virulence factors, with the goal of improving...

  14. Improving the Therapeutic Potential of Human Granzyme B for Targeted Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Georg Melmer

    2013-01-01

    Full Text Available Conventional cancer treatments lack specificity and often cause severe side effects. Targeted therapeutic approaches are therefore preferred, including the use of immunotoxins (ITs that comprise cell-binding and cell death-inducing components to allow the direct and specific delivery of pro-apoptotic agents into malignant cells. The first generation of ITs consisted of toxins derived from bacteria or plants, making them immunogenic in humans. The recent development of human cytolytic fusion proteins (hCFP consisting of human effector enzymes offers the prospect of highly-effective targeted therapies with minimal side effects. One of the most promising candidates is granzyme B (GrB and this enzyme has already demonstrated its potential for targeted cancer therapy. However, the clinical application of GrB may be limited because it is inactivated by the overexpression in tumors of its specific inhibitor serpin B9 (PI-9. It is also highly charged, which means it can bind non-specifically to the surface of non-target cells. Furthermore, human enzymes generally lack an endogenous translocation domain, thus the endosomal release of GrB following receptor-mediated endocytosis can be inefficient. In this review we provide a detailed overview of these challenges and introduce promising solutions to increase the cytotoxic potency of GrB for clinical applications.

  15. Therapeutic ion-releasing bioactive glass ionomer cements with improved mechanical strength and radiopacity

    Directory of Open Access Journals (Sweden)

    Maximilian eFuchs

    2015-10-01

    Full Text Available Bioactive glasses (BG are used to regenerate bone, as they degrade and release therapeutic ions. Glass ionomer cements (GIC are used in dentistry, can be delivered by injection and set in situ by a reaction between an acid-degradable glass and a polymeric acid. Our aim was to combine the advantages of BG and GIC, and we investigated the use of alkali-free BG (SiO2-CaO-CaF2-MgO with 0 to 50% of calcium replaced by strontium, as the beneficial effects of strontium on bone formation are well documented. When mixing BG and poly(vinyl phosphonic-co-acrylic acid, ions were released fast (up to 90% within 15 minutes at pH 1, which resulted in GIC setting, as followed by infrared spectroscopy. GIC mixed well and set to hard cements (compressive strength up to 35 MPa, staying hard when in contact with aqueous solution. This is in contrast to GIC prepared with poly(acrylic acid, which were shown previously to become soft in contact with water. Strontium release from GIC increased linearly with strontium for calcium substitution, allowing for tailoring of strontium release depending on clinical requirements. Furthermore, strontium substitution increased GIC radiopacity. GIC passed ISO10993 cytotoxicity test, making them promising candidates for use as injectable bone cements.

  16. Mechanistic Systems Modeling to Improve Understanding and Prediction of Cardiotoxicity Caused by Targeted Cancer Therapeutics

    Directory of Open Access Journals (Sweden)

    Jaehee V. Shim

    2017-09-01

    Full Text Available Tyrosine kinase inhibitors (TKIs are highly potent cancer therapeutics that have been linked with serious cardiotoxicity, including left ventricular dysfunction, heart failure, and QT prolongation. TKI-induced cardiotoxicity is thought to result from interference with tyrosine kinase activity in cardiomyocytes, where these signaling pathways help to control critical processes such as survival signaling, energy homeostasis, and excitation–contraction coupling. However, mechanistic understanding is limited at present due to the complexities of tyrosine kinase signaling, and the wide range of targets inhibited by TKIs. Here, we review the use of TKIs in cancer and the cardiotoxicities that have been reported, discuss potential mechanisms underlying cardiotoxicity, and describe recent progress in achieving a more systematic understanding of cardiotoxicity via the use of mechanistic models. In particular, we argue that future advances are likely to be enabled by studies that combine large-scale experimental measurements with Quantitative Systems Pharmacology (QSP models describing biological mechanisms and dynamics. As such approaches have proven extremely valuable for understanding and predicting other drug toxicities, it is likely that QSP modeling can be successfully applied to cardiotoxicity induced by TKIs. We conclude by discussing a potential strategy for integrating genome-wide expression measurements with models, illustrate initial advances in applying this approach to cardiotoxicity, and describe challenges that must be overcome to truly develop a mechanistic and systematic understanding of cardiotoxicity caused by TKIs.

  17. Cellulose degradation: a therapeutic strategy in the improved treatment of Acanthamoeba infections.

    Science.gov (United States)

    Lakhundi, Sahreena; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2015-01-14

    Acanthamoeba is an opportunistic free-living amoeba that can cause blinding keratitis and fatal brain infection. Early diagnosis, followed by aggressive treatment is a pre-requisite in the successful treatment but even then the prognosis remains poor. A major drawback during the course of treatment is the ability of the amoeba to enclose itself within a shell (a process known as encystment), making it resistant to chemotherapeutic agents. As the cyst wall is partly made of cellulose, thus cellulose degradation offers a potential therapeutic strategy in the effective targeting of trophozoite encased within the cyst walls. Here, we present a comprehensive report on the structure of cellulose and cellulases, as well as known cellulose degradation mechanisms with an eye to target the Acanthamoeba cyst wall. The disruption of the cyst wall will make amoeba (concealed within) susceptible to chemotherapeutic agents, and at the very least inhibition of the excystment process will impede infection recurrence, as we bring these promising drug targets into focus so that they can be explored to their fullest.

  18. Optical microscopy of targeted drug delivery and local distribution in skin of a topical minocycline: implications in translational research and guidance for therapeutic dose selection (Conference Presentation)

    Science.gov (United States)

    Hermsmeier, Maiko; Sawant, Tanvee; Lac, Diana; Yamamoto, Akira; Chen, Xin; Huang, Susan Y.; Nagavarapu, Usha; Evans, Conor L.; Chan, Kin Foong; Daniels, AnnaMarie

    2017-02-01

    Acne vulgaris is a chronic inflammatory skin condition commonly resulting in negative aesthetic and social impacts on those affected. Minocycline, currently available as an oral antibiotic for moderate to severe acne, has a known minimum inhibitory concentration (MIC) for the acne-causing bacterium Propionibacterium acnes (P. acnes) in vitro, with its anti-inflammatory properties also eliciting inhibitory effects on pro-inflammatory molecules. A novel topical gel composition containing solubilized minocycline (BPX-01) has been developed to directly deliver the drug to the skin. Because minocycline is a known fluorophore, fluorescence microscopy and concurrent quantitative measurements were performed on excised human facial skin dosed with different concentrations, in order to determine the spatial distribution of the drug and quantification of its local concentration in the epidermis and the pilosebaceous unit where P. acnes generally reside. Local minocycline delivery confirmed achievement of an adequate therapeutic dose to support clinical studies. Subsequently, a 4-week double-blind, randomized, vehicle controlled clinical study was performed to assess the safety and efficacy of 1% minocycline BPX-01 applied daily. No instances of cutaneous toxicity were reported, and a greater than 1 log reduction of P. acnes count was observed at week 4 with statistical significance from baseline and vehicle control. In addition, no detectable amounts of minocycline in the plasma were reported, suggesting the potential of this new formulation to diminish the known systemic adverse effects associated with oral minocycline. Follow-on clinical plans are underway to further establish the safety of BPX-01 and to evaluate its efficacy against inflammatory acne lesions in a 225 patient multi-center dose-finding study.

  19. Intensity modulated radiation therapy (IMRT: differences in target volumes and improvement in clinically relevant doses to small bowel in rectal carcinoma

    Directory of Open Access Journals (Sweden)

    Delclos Marc E

    2011-06-01

    covered by classic bony landmark-derived fields, without incurring penalty with respect to adjacent organs-at-risk. Conclusions For rectal carcinoma, IMRT, compared to 3DCRT, yielded plans superior with respect to target coverage, homogeneity, and conformality, while lowering dose to adjacent organs-at-risk. This is achieved despite treating larger volumes, raising the possibility of a clinically-relevant improvement in the therapeutic ratio through the use of IMRT with a belly-board apparatus.

  20. Emergency preparedness in Finland: improvement of the measurement equipment used in the assessment of internal doses

    Energy Technology Data Exchange (ETDEWEB)

    Muikku, M.; Rahola, T. [STUK - Radiation and nuclear safety authority, Helsinki (Finland)

    2006-07-01

    The need for assessing internal radiation doses in emergency situations is evident. Internal exposure can be assessed using direct measurement results or by using information on activity concentrations in inhaled air and in foodstuffs combined with inhalation and consumption data. As a part of the continuous improving of emergency preparedness in Finland, S.T.U.K. - Radiation and Nuclear Safety Authority has obtained 35 monitors for thyroid measurements in field conditions and initiated a project to revise the radiation measurement equipment in local food and environmental laboratories. (authors)

  1. Cellular Chaperones As Therapeutic Targets in ALS to Restore Protein Homeostasis and Improve Cellular Function

    Directory of Open Access Journals (Sweden)

    Bernadett Kalmar

    2017-09-01

    Full Text Available Heat shock proteins (Hsps are ubiquitously expressed chaperone proteins that enable cells to cope with environmental stresses that cause misfolding and denaturation of proteins. With aging this protein quality control machinery becomes less effective, reducing the ability of cells to cope with damaging environmental stresses and disease-causing mutations. In neurodegenerative disorders such as Amyotrophic Lateral Sclerosis (ALS, such mutations are known to result in protein misfolding, which in turn results in the formation of intracellular aggregates cellular dysfunction and eventual neuronal death. The exact cellular pathology of ALS and other neurodegenerative diseases has been elusive and thus, hindering the development of effective therapies. However, a common scheme has emerged across these “protein misfolding” disorders, in that the mechanism of disease involves one or more aspects of proteostasis; from DNA transcription, RNA translation, to protein folding, transport and degradation via proteosomal and autophagic pathways. Interestingly, members of the Hsp family are involved in each of these steps facilitating normal protein folding, regulating the rate of protein synthesis and degradation. In this short review we summarize the evidence that suggests that ALS is a disease of protein dyshomeostasis in which Hsps may play a key role. Overwhelming evidence now indicates that enabling protein homeostasis to cope with disease-causing mutations might be a successful therapeutic strategy in ALS, as well as other neurodegenerative diseases. Novel small molecule co-inducers of Hsps appear to be able to achieve this aim. Arimoclomol, a hydroxylamine derivative, has shown promising results in cellular and animal models of ALS, as well as other protein misfolding diseases such as Inclusion Body Myositis (IBM. Initial clinical investigations of Arimoclomol have shown promising results. Therefore, it is possible that the long series of

  2. Therapeutic doll play in the treatment of a severely impaired psychiatric inpatient: dramatic clinical improvements with a nontraditional nursing intervention.

    Science.gov (United States)

    Birnbaum, Shira; Hanchuk, Hilary; Nelson, Marjorie

    2015-05-01

    Interest has grown in the use of doll therapy, particularly in geropsychiatric and dementia care settings. In a long-term state psychiatric hospital, a dollhouse-play activity was implemented in an effort to engage an acutely disturbed, middle-aged woman undergoing medication trials and whose symptoms had been refractory to conventional treatments. A schedule of nondirective dollhouse-play activities was implemented over an 8-week period. Measures of behavioral change were tracked. Dramatic clinical improvements were seen, including significant reductions in verbal and physical aggression, use of as-needed medications, and need for close one-to-one monitoring. Improvements were seen prior to achievement of therapeutic drug levels. The patient was successfully discharged from the hospital. Doll play has recently been associated with clinical benefits in the care of patients with dementia and has long been deployed in childhood mental health treatment. The current findings suggest doll play may have applications as a time-limited intervention in the treatment of major psychiatric disorders in adults and warrants consideration when achieving therapeutic alliance has proven particularly challenging. Copyright 2015, SLACK Incorporated.

  3. Evaluation of the radioprotective effect of turmeric extract and vitamin E in mice exposed to therapeutic dose of radioiodine

    International Nuclear Information System (INIS)

    Bhartiya, Uma S.; Raut, Yogita S.; Joseph, Lebana J.; Hawaldar, Rohini W.; Rao, Badanidiyoor S.

    2008-01-01

    The aim of this study was to evaluate the radioprotective effect of turmeric extract (40 mg/kg body weight) and vitamin E (α - tocopherol acetate, 400 IU/kg body weight) supplementation on lipid peroxidation, reduced glutathione and antioxidant defense enzymes in various organs like liver, kidney and salivary glands at 24 h in adult Swiss mice. 131 Iodine exposure significantly increased lipid peroxidation in kidney and salivary glands in comparison to control animals. Pre supplementation with turmeric extract for 15 days showed significant lowering of lipid peroxidation in kidney. On the other hand vitamin E pre supplementation showed marked reduction in lipid peroxidation in salivary glands. Reduced glutathione levels decreased significantly in liver after radiation exposure. However, pre supplementation with turmeric extract and vitamin E did not improve glutathione levels in liver. In conclusion we have observed differential radioprotective effect of turmeric extract and vitamin E in kidney and salivary glands. However, Vitamin E seems to offer better radioprotection for salivary glands which is known to be the major site of cellular destruction after radioiodine therapy in patients. (author)

  4. Global NDE Best Practice for Technology Improvement, Outage Management, Foreign Material Exclusion and Dose Control

    International Nuclear Information System (INIS)

    Glass, S. W.; Mohr, F.

    2010-01-01

    Non Destructive Examination (NDE) is a critical element of both Boiling Water and Pressurized Water Reactor outages. Frequently this includes critical path activity so both the utility and the inspection vendor are under intense pressure to perform the work quickly. Concurrent with AREVA's new global organization of NDE resources, AREVA NDE SOLUTIONS, efforts have intensified for global application of lessons learned and best practices. These best practices include new developments as well as continuous improvements to well established tools and NDE techniques. Advancements range from steam generator robots, advanced steam generator deposit characterization sensors and method, new phased array approaches for PWR and BWR reactor vessel examination, new sensors and approaches for RPV head examinations, plus advanced internals examination robots and methods. In addition to specialized tools and techniques, best practice includes numerous management innovations. AREVA's multi-disciplined integrated nuclear worker strategy helps to minimize the total number of personnel deployed to multi-task outages. Specific design and on-site practice has been implemented to minimize or eliminate foreign material from the reactor system and vigorous pursuit of dose management practices keeps our nuclear worker dose as low as reasonably achievable. The industry is moving to much more conservative nuclear worker dose limits. While this is proving to be an issue with many vendors, AREVA has had an internal policy of <2R since 2006. Globalizing the organization also helps AREVA manage peaks and unplanned emergency inspections from an enlarged pool of globally qualified inspection personnel and tools. (Author)

  5. Improved consistency in dosing anti-tuberculosis drugs in Taipei, Taiwan.

    Science.gov (United States)

    Chiang, Chen-Yuan; Yu, Ming-Chih; Shih, Hsiu-Chen; Yen, Muh-Yong; Hsu, Yu-Ling; Yang, Shiang-Lin; Lin, Tao-Ping; Bai, Kuan-Jen

    2012-01-01

    It was reported that 35.5% of tuberculosis (TB) cases reported in 2003 in Taipei City had no recorded pre-treatment body weight and that among those who had, inconsistent dosing of anti-TB drugs was frequent. Taiwan Centers for Disease Control (CDC) have taken actions to strengthen dosing of anti-TB drugs among general practitioners. Prescribing practices of anti-TB drugs in Taipei City in 2007-2010 were investigated to assess whether interventions on dosing were effective. Lists of all notified culture positive TB cases in 2007-2010 were obtained from National TB Registry at Taiwan CDC. A medical audit of TB case management files was performed to collect pretreatment body weight and regimens prescribed at commencement of treatment. Dosages prescribed were compared with dosages recommended. The proportion of patients with recorded pre-treatment body weight was 64.5% in 2003, which increased to 96.5% in 2007-2010 (pTaipei City has remarkably improved after health authorities implemented a series of interventions.

  6. Therapeutic analysis of high-dose-rate {sup 192}Ir vaginal cuff brachytherapy for endometrial cancer using a cylindrical target volume model and varied cancer cell distributions

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hualin, E-mail: hualin.zhang@northwestern.edu; Donnelly, Eric D.; Strauss, Jonathan B. [Department of Radiation Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Chicago, Illinois 60611 (United States); Qi, Yujin [Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW 2522 (Australia)

    2016-01-15

    Purpose: To evaluate high-dose-rate (HDR) vaginal cuff brachytherapy (VCBT) in the treatment of endometrial cancer in a cylindrical target volume with either a varied or a constant cancer cell distributions using the linear quadratic (LQ) model. Methods: A Monte Carlo (MC) technique was used to calculate the 3D dose distribution of HDR VCBT over a variety of cylinder diameters and treatment lengths. A treatment planning system (TPS) was used to make plans for the various cylinder diameters, treatment lengths, and prescriptions using the clinical protocol. The dwell times obtained from the TPS were fed into MC. The LQ model was used to evaluate the therapeutic outcome of two brachytherapy regimens prescribed either at 0.5 cm depth (5.5 Gy × 4 fractions) or at the vaginal mucosal surface (8.8 Gy × 4 fractions) for the treatment of endometrial cancer. An experimentally determined endometrial cancer cell distribution, which showed a varied and resembled a half-Gaussian distribution, was used in radiobiology modeling. The equivalent uniform dose (EUD) to cancer cells was calculated for each treatment scenario. The therapeutic ratio (TR) was defined by comparing VCBT with a uniform dose radiotherapy plan in term of normal cell survival at the same level of cancer cell killing. Calculations of clinical impact were run twice assuming two different types of cancer cell density distributions in the cylindrical target volume: (1) a half-Gaussian or (2) a uniform distribution. Results: EUDs were weakly dependent on cylinder size, treatment length, and the prescription depth, but strongly dependent on the cancer cell distribution. TRs were strongly dependent on the cylinder size, treatment length, types of the cancer cell distributions, and the sensitivity of normal tissue. With a half-Gaussian distribution of cancer cells which populated at the vaginal mucosa the most, the EUDs were between 6.9 Gy × 4 and 7.8 Gy × 4, the TRs were in the range from (5.0){sup 4} to (13

  7. Improved dose localization with dual energy photon irradiation in treatment of lateralized intracranial malignancies

    International Nuclear Information System (INIS)

    Cooley, G.; Gillin, M.T.; Murray, K.J.; Wilson, J.F.; Janjan, N.A.

    1991-01-01

    Dual energy photon irradiation (6 MV and 20 MV) was compared to conventional treatment planning with 6 MV photons in a lateralized intracranial malignancy. Dose volume analysis was performed of both the tumor plus a 2 cm margin (target volume, TV) and normal tissues (NT). Parallel opposed treatment using weightings of 1:1, 1.5:1, and 2:1 were compared for 6 MV photons alone or in combination with 20 MV photons. Uniform treatment of the TV was accomplished within the 60 Gy isodose. Significant differences were observed, however, in NT volumes receiving greater than or equal to 60 Gy and 45-59 Gy. Dual photon energy reduced treatment of NT volumes to greater than or equal to 60 Gy by 13% (177 cm3 vs 204 cm3 in 2:1 weighting) to 70% (147 cm3 vs 498 cm3 in 1:1 weighting) for comparable plans. Dose optimization was also performed for both 6 MV alone or in combination with 20 MV photons. Usual approaches to achieve dose lateralization with conventional isocentric techniques were applied including parallel opposed 6 MV photons ipsilaterally weighted 3.4:1 (POP), and a 110 degrees arc rotational field used to limit treatment to the eye (ARC). Dual energy photon optimized plans included a three beam parallel opposed plan (TOP) and a mixed photon ipsilateral (IPSI) approach. The technique using parallel opposed 20 MV photons and ipsilateral 6 MV photons (TOP) used beam weightings of 1.1 (contralateral 20 MVX): 1.6 (ipsilateral 6 MVX): 1 (ipsilateral 20 MVX) to achieve dose optimization. The ipsilateral approach with 6 MVX and 20 MVX (IPSI) used beam weightings of 1:1.4, respectively. All optimized plans demonstrated a 41% (120 cm3; POP) to 53% (95 cm3; TOP) improvement over parallel opposed 6 MV photons weighted 2:1 (204 cm3) in NT volume receiving greater than or equal to 60 Gy

  8. Determination of Therapeutic Dose of I-131 for First High Dose Radioiodine Therapy in Patients with Differentiated Thyroid Cancer: Comparison of Usefulness between Pathological Staging, Serum Thyroglobulin Level and Finding of I-123 Whole Body Scan

    International Nuclear Information System (INIS)

    Jeong, Hwan Jeong; Lim, Seok Tae; Youn, Hyun Jo; Sohn, Myung-Hee

    2008-01-01

    Recently, a number of patients needed total thyroidectomy and high dose radioiodine therapy (HD-RAI) get increased more. The aim of this study is to evaluate whether pathological staging (PS) and serum thyroglobulin (sTG) level could replace the diagnostic I-123 scan for the determination of therapeutic dose of HD-RAI in patients with differentiated thyroid cancer. Fifty eight patients (M:F=13;45, age 44.5±11.5 yrs) who underwent total thyroidectomy and central or regional lymph node dissection due to differentiated thyroid cancer were enrolled. Diagnostic scan of I-123 and sTG assay were also performed on off state of thyroid hormone. The therapeutic doses of I-131 (TD) were determined by the extent of uptakes on diagnostic I-123 scan as a gold standard. PS was graded by the criteria recommended in 6th edition of AJCC cancer staging manual except consideration of age. For comparison of the determination of therapeutic doses, PS and sTG were compared with the results of I-123 scan. All patients were underwent HD-RAI. Among them, five patients (8.6%) were treated with 100 mCi of I-131, forty three (74.1%) with 150 mCi, six (10.3%) with 180 mCi, three (5.2%) with 200 mCi, and one (1.7%) with 250 mCi, respectively. On the assessment of PS, average TDs were 154±25 mCi in stage I (n=9), 175±50 mCi in stage II (n=4), 149±21 mCi in stage III (n=38), and 161±20 mCi in stage IV (n=7). The statistical significance was not shown between PS and TD (p=0.169). Among fifty two patients who had available sTG, 25 patients (48.1%) having below 2 ng/mL of sTG were treated with 149±26 mCi of I-131, 9 patients (17.3%) having 2≤ sTG <5 ng/mL with 156±17 mCi, 5 patients (9.6%) having 5≤ sTG <10 ng/mL with 156±13 mCi, 7 patients (13.5%) having 10≤ sTG <50 ng/mL with 147±24 mCi, and 6 patients (11.5%) having above 50 ng/mL with 175±42 mCi. The statistical significance between sTG level and TD (p=0.252) was not shown. In conclusion, PS and sTG could not replace the

  9. The Therapeutic Potential of Exercise to Improve Mood, Cognition, and Sleep in Parkinson’s Disease

    Science.gov (United States)

    Reynolds, Gretchen O.; Otto, Michael W.; Ellis, Terry D.; Cronin-Golomb, Alice

    2015-01-01

    In addition to the classic motor symptoms, Parkinson’s disease (PD) is associated with a variety of non-motor symptoms that significantly reduce quality of life, even in the early stages of the disease. There is an urgent need to develop evidence-based treatments for these symptoms, which include mood disturbances, cognitive dysfunction, and sleep disruption. We focus here on exercise interventions, which have been used to improve mood, cognition, and sleep in healthy older adults and clinical populations, but to date have primarily targeted motor symptoms in PD. We synthesize the existing literature on the benefits of aerobic exercise and strength training on mood, sleep, and cognition as demonstrated in healthy older adults and adults with PD, and suggest that these types of exercise offer a feasible and promising adjunct treatment for mood, cognition, and sleep difficulties in PD. Across stages of the disease, exercise interventions represent a treatment strategy with the unique ability to improve a range of non-motor symptoms while also alleviating the classic motor symptoms of the disease. Future research in PD should include non-motor outcomes in exercise trials with the goal of developing evidence-based exercise interventions as a safe, broad-spectrum treatment approach to improve mood, cognition, and sleep for individuals with PD. PMID:26715466

  10. Lifetime attributable risk as an alternative to effective dose to describe the risk of cancer for patients in diagnostic and therapeutic nuclear medicine

    Science.gov (United States)

    Andersson, Martin; Eckerman, Keith; Mattsson, Sören

    2017-12-01

    The aim of this study is to implement lifetime attributable risk (LAR) predictions of cancer for patients of various age and gender, undergoing diagnostic investigations or treatments in nuclear medicine and to compare the outcome with a population risk estimate using effective dose and the International Commission on Radiological Protection risk coefficients. The radiation induced risk of cancer occurrence (incidence) or death from four nuclear medicine procedures are estimated for both male and female between 0 and 120 years. Estimations of cancer risk are performed using recommended administered activities for two diagnostic (18F-FDG and 99mTc-phosphonate complex) and two therapeutic (131I-iodide and 223Ra-dichloride) radiopharmaceuticals to illustrate the use of cancer risk estimations in nuclear medicine. For 18F-FDG, the cancer incidence for a male of 5, 25, 50 and 75 years at exposure is 0.0021, 0.0010, 0.0008 and 0.0003, respectively. For 99mTc phosphonates complex the corresponding values are 0.000 59, 0.000 34, 0.000 27 and 0.000 13, respectively. For an 131I-iodide treatment with 3.7 GBq and 1% uptake 24 h after administration, the cancer incidence for a male of 25, 50 and 75 years at exposure is 0.041, 0.029 and 0.012, respectively. For 223Ra-dichloride with an administration of 21.9 MBq the cancer incidence for a male of 25, 50 and 75 years is 0.31, 0.21 and 0.09, respectively. The LAR estimations are more suitable in health care situations involving individual patients or specific groups of patients than the health detriment based on effective dose, which represents a population average. The detriment consideration in effective dose adjusts the cancer incidence for suffering of non-lethal cancers while LAR predicts morbidity (incidence) or mortality (cancer). The advantages of these LARs are that they are gender and age specific, allowing risk estimations for specific patients or subgroups thus better representing individuals in health care

  11. Optimizing hyaluronidase dose and plasmid DNA delivery greatly improves gene electrotransfer efficiency in rat skeletal muscle

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Vedel, Kenneth; Needham Andersen, Josefine

    2015-01-01

    Transfection of rat skeletal muscle in vivo is a widely used research model. However, gene electrotransfer protocols have been developed for mice and yield variable results in rats. We investigated whether changes in hyaluronidase pre-treatment and plasmid DNA delivery can improve transfection...... with a homogenous distribution. We also show that transfection was stable over five weeks of regular exercise or inactivity. Our findings show that species-specific plasmid DNA delivery and hyaluronidase pre-treatment greatly improves transfection efficiency in rat skeletal muscle....... efficiency in rat skeletal muscle. We found that pre-treating the muscle with a hyaluronidase dose suitable for rats (0.56. U/g b.w.) prior to plasmid DNA injection increased transfection efficiency by >200% whereas timing of the pre-treatment did not affect efficiency. Uniformly distributing plasmid DNA...

  12. The role of intercomparisons and intercalibrations in the improvement of internal dose assessment

    International Nuclear Information System (INIS)

    Griffith, R.V.

    2000-01-01

    In vivo monitoring and dose assessment is a highly technical field. Moreover, it is carried out by a relatively small number of specialists. A number of technical steps can be taken to improve internal dosimetry programmes. However, one of the most valuable activities for overall improvement of measurement programmes is active participation in national and international intercomparisons and intercalibrations. These bring a number of benefits to the internal dosimetry programme, including validation of measurement practices, harmonisation of techniques, information exchange, and training. The number of intercalibration and intercomparison activities conducted on the national and international level has grown in recent years. These activities may involve actual measurement programmes or calculation exercises to compare approaches used for assessment of internal dose from measurement results. When conducted effectively such programmes are a highly cost effective use of limited resources. They also contribute to the credibility of the overall dosimetry process. Intercomparisons should be an important component of the in vivo measurement programme. Cooperation between the organisers of various intercomparison activities is essential to avoid unnecessary duplication and ensure the most effective use of the participants' time and energy. Future activities should address the use of simplified phantoms and source arrays to expedite shipping, reduce cost, and contribute to more timely conduct of intercomparisons. It is also important that managers and regulatory authorities be prepared to support intercomparison and intercalibration programmes. (author)

  13. Combined MRI and MRS improves pre-therapeutic diagnoses of pediatric brain tumors over MRI alone

    Energy Technology Data Exchange (ETDEWEB)

    Shiroishi, Mark S.; Nelson, Marvin D. [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Panigrahy, Ashok [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Department of Pediatric Radiology, Pittsburgh, PA (United States); Moore, Kevin R. [Primary Children' s Medical Center, Department of Radiology, Salt Lake City, UT (United States); Gilles, Floyd H. [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Pathology, Los Angeles, CA (United States); Gonzalez-Gomez, Ignacio [All Children' s Hospital, Department of Pathology, St. Petersburg, FL (United States); Blueml, Stefan [Children' s Hospital Los Angeles/Keck School of Medicine of USC, Department of Radiology, Los Angeles, CA (United States); Rudi Schulte Research Institute, Santa Barbara, CA (United States)

    2015-09-15

    The specific goal of this study was to determine whether the inclusion of MRS had a measureable and positive impact on the accuracy of pre-surgical MR examinations of untreated pediatric brain tumors over that of MRI alone in clinical practice. Final imaging reports of 120 pediatric patients with newly detected brain tumors who underwent combined MRI/MRS examinations were retrospectively reviewed. Final pathology was available in all cases. Group A comprised 60 subjects studied between June 2001 and January 2005, when MRS was considered exploratory and radiologists utilized only conventional MRI to arrive at a diagnosis. For group B, comprising 60 subjects studied between January 2005 and March 2008, the radiologists utilized information from both MRI and MRS. Furthermore, radiologists revisited group A (blind review, time lapse >4 years) to determine whether the additional information from MRS would have altered their interpretation. Sixty-three percent of patients in group A were diagnosed correctly, whereas in 10 % the report was partially correct with the final tumor type mentioned (but not mentioned as most likely tumor), while in 27 % of cases the reports were wrong. For group B, the diagnoses were correct in 87 %, partially correct in 5 %, and incorrect in 8 % of the cases, which is a significant improvement (p < 0.005). Re-review of combined MRI and MRS of group A resulted 87 % correct, 7 % partially correct, and 7 % incorrect diagnoses, which is a significant improvement over the original diagnoses (p < 0.05). Adding MRS to conventional MRI significantly improved diagnostic accuracy in preoperative pediatric patients with untreated brain tumors. (orig.)

  14. Combined MRI and MRS improves pre-therapeutic diagnoses of pediatric brain tumors over MRI alone

    International Nuclear Information System (INIS)

    Shiroishi, Mark S.; Nelson, Marvin D.; Panigrahy, Ashok; Moore, Kevin R.; Gilles, Floyd H.; Gonzalez-Gomez, Ignacio; Blueml, Stefan

    2015-01-01

    The specific goal of this study was to determine whether the inclusion of MRS had a measureable and positive impact on the accuracy of pre-surgical MR examinations of untreated pediatric brain tumors over that of MRI alone in clinical practice. Final imaging reports of 120 pediatric patients with newly detected brain tumors who underwent combined MRI/MRS examinations were retrospectively reviewed. Final pathology was available in all cases. Group A comprised 60 subjects studied between June 2001 and January 2005, when MRS was considered exploratory and radiologists utilized only conventional MRI to arrive at a diagnosis. For group B, comprising 60 subjects studied between January 2005 and March 2008, the radiologists utilized information from both MRI and MRS. Furthermore, radiologists revisited group A (blind review, time lapse >4 years) to determine whether the additional information from MRS would have altered their interpretation. Sixty-three percent of patients in group A were diagnosed correctly, whereas in 10 % the report was partially correct with the final tumor type mentioned (but not mentioned as most likely tumor), while in 27 % of cases the reports were wrong. For group B, the diagnoses were correct in 87 %, partially correct in 5 %, and incorrect in 8 % of the cases, which is a significant improvement (p < 0.005). Re-review of combined MRI and MRS of group A resulted 87 % correct, 7 % partially correct, and 7 % incorrect diagnoses, which is a significant improvement over the original diagnoses (p < 0.05). Adding MRS to conventional MRI significantly improved diagnostic accuracy in preoperative pediatric patients with untreated brain tumors. (orig.)

  15. Red palm oil: nutritional, physiological and therapeutic roles in improving human wellbeing and quality of life.

    Science.gov (United States)

    Oguntibeju, O O; Esterhuyse, A J; Truter, E J

    2009-01-01

    The link between dietary fats and cardiovascular disease has created a growing interest in dietary red palm oil research. Also, the link between nutrition and health, oxidative stress and the severity or progression of disease has stimulated further interest in the potential role of red palm oil (a natural antioxidant product) to improve oxidative status by reducing oxidative stress in patients with cardiovascular disease, cancer and other chronic diseases. In spite of its level of saturated fatty acid content (50%), red palm oil has not been found to promote atherosclerosis and/or arterial thrombosis. This is probably due to the ratio of its saturated fatty acid to unsaturated fatty acid content and its high concentration of antioxidants such as beta-carotene, tocotrienols, tocopherols and vitamin E. It has also been reported that the consumption of red palm oil reduces the level of endogenous cholesterol, and this seems to be due to the presence of the tocotrienols and the peculiar isomeric position of its fatty acids. The benefits of red palm oil to health include a reduction in the risk of arterial thrombosis and/or atherosclerosis, inhibition of endogenous cholesterol biosynthesis, platelet aggregation, a reduction in oxidative stress and a reduction in blood pressure. It has also been shown that dietary red palm oil, taken in moderation in animals and humans, promotes the efficient utilisation of nutrients, activates hepatic drug metabolising enzymes, facilitates the haemoglobinisation of red blood cells and improves immune function. This review provides a comprehensive overview of the nutritional, physiological and biochemical roles of red palm oil in improving wellbeing and quality of life.

  16. Improving the physical health of patients with schizophrenia: therapeutic nihilism or realism?

    Science.gov (United States)

    Le Fevre, P D

    2001-02-01

    Schizophrenia is associated with a raised mortality due to both an increase in suicide and factors related to poor physical health. The increased rates of gastrointestinal, respiratory and cardiovascular disease in this population are likely to be due to high rates of smoking and obesity accompanied by a poor diet, lack of exercise and the side effects of medication. The evidence suggests that such risk factors in the schizophrenic population are largely ignored by the medical profession. Research to date has failed to address the health needs of this vulnerable population. Systematic research, with the aim of assessing the potential benefits of health improvement measures, should be a matter of priority.

  17. Therapeutic improvements expected in the near future for schizophrenia and schizoaffective disorder

    DEFF Research Database (Denmark)

    Garay, Ricardo P; Citrome, Leslie; Samalin, Ludovic

    2016-01-01

    INTRODUCTION: In this review, the authors describe medications in phase III of clinical development for schizophrenia and schizoaffective disorder, and provide an opinion on how current treatment can be improved in the near future. Areas covered: Recent (post 2013) phase III clinical trials...... and schizoaffective disorder. In addition to better-tolerated antipsychotics that treat positive symptoms, we could see the arrival of the first effective drug for negative symptoms and CIAS, which would strongly facilitate the ultimate goal of recovery in persons with schizophrenia....

  18. Effect on therapeutic ratio of planning a boosted radiotherapy dose to the dominant intraprostatic tumour lesion within the prostate based on multifunctional MR parameters

    Science.gov (United States)

    Payne, G S; deSouza, N M; Dearnaley, D; Morgan, V A; Morgan, S C; Partridge, M

    2014-01-01

    Objective: To demonstrate the feasibility of an 8-Gy focal radiation boost to a dominant intraprostatic lesion (DIL), identified using multiparametric MRI (mpMRI), and to assess the potential outcome compared with a uniform 74-Gy prostate dose. Methods: The DIL location was predicted in 23 patients using a histopathologically verified model combining diffusion-weighted imaging, dynamic contrast-enhanced imaging, T2 maps and three-dimensional MR spectroscopic imaging. The DIL defined prior to neoadjuvant hormone downregulation was firstly registered to MRI-acquired post-hormone therapy and subsequently to CT radiotherapy scans. Intensity-modulated radiotherapy (IMRT) treatment was planned for an 8-Gy focal boost with 74-Gy dose to the remaining prostate. Areas under the dose–volume histograms (DVHs) for prostate, bladder and rectum, the tumour control probability (TCP) and normal tissue complication probabilities (NTCPs) were compared with those of the uniform 74-Gy IMRT plan. Results: Deliverable IMRT plans were feasible for all patients with identifiable DILs (20/23). Areas under the DVHs were increased for the prostate (75.1 ± 0.6 vs 72.7 ± 0.3 Gy; p < 0.001) and decreased for the rectum (38.2 ± 2.5 vs 43.5 ± 2.5 Gy; p < 0.001) and the bladder (29.1 ± 9.0 vs 36.9 ± 9.3 Gy; p < 0.001) for the boosted plan. The prostate TCP was increased (80.1 ± 1.3 vs 75.3 ± 0.9 Gy; p < 0.001) and rectal NTCP lowered (3.84 ± 3.65 vs 9.70 ± 5.68 Gy; p = 0.04) in the boosted plan. The bladder NTCP was negligible for both plans. Conclusion: Delivery of a focal boost to an mpMRI-defined DIL is feasible, and significant increases in TCP and therapeutic ratio were found. Advances in knowledge: The delivery of a focal boost to an mpMRI-defined DIL demonstrates statistically significant increases in TCP and therapeutic ratio. PMID:24601648

  19. Isocentric integration of intensity-modulated radiotherapy with electron fields improves field junction dose uniformity in postmastectomy radiotherapy.

    Science.gov (United States)

    Wright, Pauliina; Suilamo, Sami; Lindholm, Paula; Kulmala, Jarmo

    2014-08-01

    In postmastectomy radiotherapy (PMRT), the dose coverage of the planning target volume (PTV) with additional margins, including the chest wall, supraclavicular, interpectoral, internal mammary and axillar level I-III lymph nodes, is often compromised. Electron fields may improve the medial dose coverage while maintaining organ at risk (OAR) doses at an acceptable level, but at the cost of hot and cold spots at the electron and photon field junction. To improve PMRT dose coverage and uniformity, an isocentric technique combining tangential intensity-modulated (IM)RT fields with one medial electron field was implemented. For 10 postmastectomy patients isocentric IMRT with electron plans were created and compared with a standard electron/photon mix and a standard tangent technique. PTV dose uniformity was evaluated based on the tolerance range (TR), i.e. the ratio of the standard deviation to the mean dose, a dice similarity coefficient (DSC) and the 90% isodose coverage and the hot spot volumes. OAR and contralateral breast doses were also recorded. IMRT with electrons significantly improved the PTV dose homogeneity and conformity based on the TR and DSC values when compared with the standard electron/photon and tangent technique (p < 0.02). The 90% isodose coverage improved to 86% compared with 82% and 80% for the standard techniques (p < 0.02). Compared with the standard electron/photon mix, IMRT smoothed the dose gradient in the electron and photon field junction and the volumes receiving a dose of 110% or more were reduced by a third. For all three strategies, the OAR and contralateral breast doses were within clinically tolerable limits. Based on these results two-field IMRT combined with an electron field is a suitable strategy for PMRT.

  20. Use of LEGO as a therapeutic medium for improving social competence.

    Science.gov (United States)

    LeGoff, Daniel B

    2004-10-01

    A repeated-measures, waiting list control design was used to assess efficacy of a social skills intervention for autistic spectrum children focused on individual and group LEGO play. The intervention combined aspects of behavior therapy, peer modeling and naturalistic communication strategies. Close interaction and joint attention to task play an important role in both group and individual therapy activities. The goal of treatment was to improve social competence (SC) which was construed as reflecting three components: (1) motivation to initiate social contact with peers; (2) ability to sustain interaction with peers for a period of time: and (3) overcoming autistic symptoms of aloofness and rigidity. Measures for the first two variables were based on observation of subjects in unstructured situations with peers; and the third variable was assessed using a structured rating scale, the SI subscale of the GARS. Results revealed significant improvement on all three measures at both 12 and 24 weeks with no evidence of gains during the waiting list period. No gender differences were found on outcome, and age of clients was not correlated with outcome. LEGO play appears to be a particularly effective medium for social skills intervention, and other researchers and clinicians are encouraged to attempt replication of this work, as well as to explore use of LEGO in other methodologies, or with different clinical populations.

  1. Postimplantation Analysis Enables Improvement of Dose-Volume Histograms and Reduction of Toxicity for Permanent Seed Implantation

    International Nuclear Information System (INIS)

    Wust, Peter; Postrach, Johanna; Kahmann, Frank; Henkel, Thomas; Graf, Reinhold; Cho, Chie Hee; Budach, Volker; Boehmer, Dirk

    2008-01-01

    Purpose: To demonstrate how postimplantation analysis is useful for improving permanent seed implantation and reducing toxicity. Patients and Methods: We evaluated 197 questionnaires completed by patients after permanent seed implantation (monotherapy between 1999 and 2003). For 70% of these patients, a computed tomography was available to perform postimplantation analysis. The index doses and volumes of the dose-volume histograms (DVHs) were determined and categorized with respect to the date of implantation. Differences in symptom scores relative to pretherapeutic status were analyzed with regard to follow-up times and DVH descriptors. Acute and subacute toxicities in a control group of 117 patients from an earlier study (June 1999 to September 2001) by Wust et al. (2004) were compared with a matched subgroup from this study equaling 110 patients treated between October 2001 and August 2003. Results: Improved performance, identifying a characteristic time dependency of DVH parameters (after implantation) and toxicity scores, was demonstrated. Although coverage (volume covered by 100% of the prescription dose of the prostate) increased slightly, high-dose regions decreased with the growing experience of the users. Improvement in the DVH and a reduction of toxicities were found in the patient group implanted in the later period. A decline in symptoms with follow-up time counteracts this gain of experience and must be considered. Urinary and sexual discomfort was enhanced by dose heterogeneities (e.g., dose covering 10% of the prostate volume, volume covered by 200% of prescription dose). In contrast, rectal toxicities correlated with exposed rectal volumes, especially the rectal volume covered by 100% of the prescription dose. Conclusion: The typical side effects occurring after permanent seed implantation can be reduced by improving the dose distributions. An improvement in dose distributions and a reduction of toxicities were identified with elapsed time between

  2. 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.

  3. Therapeutic Nanodevices

    Science.gov (United States)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  4. An Automated Inpatient Split-dose Bowel Preparation System Improves Colonoscopy Quality and Reduces Repeat Procedures.

    Science.gov (United States)

    Yadlapati, Rena; Johnston, Elyse R; Gluskin, Adam B; Gregory, Dyanna L; Cyrus, Rachel; Werth, Lindsay; Ciolino, Jody D; Grande, David P; Keswani, Rajesh N

    2017-07-19

    Inpatient colonoscopy preparations are often inadequate, compromising patient safety and procedure quality, while resulting in greater hospital costs. The aims of this study were to: (1) design and implement an electronic inpatient split-dose bowel preparation order set; (2) assess the intervention's impact upon preparation adequacy, repeated colonoscopies, hospital days, and costs. We conducted a single center prospective pragmatic quasiexperimental study of hospitalized adults undergoing colonoscopy. The experimental intervention was designed using DMAIC (define, measure, analyze, improve, and control) methodology. Prospective data collected over 12 months were compared with data from a historical preintervention cohort. The primary outcome was bowel preparation quality and secondary outcomes included number of repeated procedures, hospital days, and costs. On the basis of a Delphi method and DMAIC process, we created an electronic inpatient bowel preparation order set inclusive of a split-dose bowel preparation algorithm, automated orders for rescue medications, and nursing bowel preparation checks. The analysis data set included 969 patients, 445 (46%) in the postintervention group. The adequacy of bowel preparation significantly increased following intervention (86% vs. 43%; P<0.01) and proportion of repeated procedures decreased (2.0% vs. 4.6%; P=0.03). Mean hospital days from bowel preparation initiation to discharge decreased from 8.0 to 6.9 days (P=0.02). The intervention resulted in an estimated 1-year cost-savings of $46,076 based on a reduction in excess hospital days associated with repeated and delayed procedures. Our interdisciplinary initiative targeting inpatient colonoscopy preparations significantly improved quality and reduced repeat procedures, and hospital days. Other institutions should consider utilizing this framework to improve inpatient colonoscopy value.

  5. TU-H-CAMPUS-TeP2-02: FLASH Irradiation Improves the Therapeutic Index Following GI Tract Irradiation

    International Nuclear Information System (INIS)

    Schueler, E; Trovati, S; King, G; Lartey, F; Rafat, M; Loo, B; Maxim, P

    2016-01-01

    Purpose: To investigate and characterize the radiobiological effectiveness of very high dose rate radiotherapy (FLASH) compared to conventional irradiation in an in vivo model. Methods: The gastrointestinal (GI) tract of C57BL/6 mice were irradiated with doses ranging between 10 and 18 Gy using a custom stereotactic jig. A Varian Clinac 21EX was modified to allow dose rates ranging from 0.05 to 240 Gy/s at the position of the mirror. With the gantry at 180 degrees, the jig holding the individual animals was placed above the mirror to take advantage of the reduced source to target distance. Mice were irradiated with 20MeV electrons. Following irradiation, the mice were monitored twice daily for morbidity and daily for weight changes. Results: Mice irradiated with FLASH irradiation had lower weight loss compared to the mice receiving conventional irradiation. Following FLASH irradiation, a maximum weight loss of ∼20% was observed at day 6 with subsequent recovery, while following conventional irradiation, higher weight losses was observed with fewer instances of recovery. Concerning survival, all mice in the conventionally irradiated groups had a 100% mortality in the range of 15.5–18 Gy, while the mice irradiated with FLASH irradiation had a 100% survival in the same range. Conclusion: These results have demonstrated proof of principle that FLASH irradiations have a dramatic impact on the overall survival of mice following GI tract irradiations. If the increase in the therapeutic window can be validated and understood, this would revolutionize the field of radiation oncology and lead to increased cure rates with reduced side effects following treatment, resulting in increased quality of life for cancer survivors. Funding: DoD, Award#:W81XWH-14-1-0014, Weston Havens Foundation, Bio-X (Stanford University), the Office of the Dean of the Medical School, the Office of the Provost (Stanford University), and the Swedish Childhood Cancer Foundation; BL and PM are

  6. TU-H-CAMPUS-TeP2-02: FLASH Irradiation Improves the Therapeutic Index Following GI Tract Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Schueler, E; Trovati, S; King, G; Lartey, F; Rafat, M; Loo, B; Maxim, P [Stanford University School of Medicine, Palo Alto, California (United States)

    2016-06-15

    Purpose: To investigate and characterize the radiobiological effectiveness of very high dose rate radiotherapy (FLASH) compared to conventional irradiation in an in vivo model. Methods: The gastrointestinal (GI) tract of C57BL/6 mice were irradiated with doses ranging between 10 and 18 Gy using a custom stereotactic jig. A Varian Clinac 21EX was modified to allow dose rates ranging from 0.05 to 240 Gy/s at the position of the mirror. With the gantry at 180 degrees, the jig holding the individual animals was placed above the mirror to take advantage of the reduced source to target distance. Mice were irradiated with 20MeV electrons. Following irradiation, the mice were monitored twice daily for morbidity and daily for weight changes. Results: Mice irradiated with FLASH irradiation had lower weight loss compared to the mice receiving conventional irradiation. Following FLASH irradiation, a maximum weight loss of ∼20% was observed at day 6 with subsequent recovery, while following conventional irradiation, higher weight losses was observed with fewer instances of recovery. Concerning survival, all mice in the conventionally irradiated groups had a 100% mortality in the range of 15.5–18 Gy, while the mice irradiated with FLASH irradiation had a 100% survival in the same range. Conclusion: These results have demonstrated proof of principle that FLASH irradiations have a dramatic impact on the overall survival of mice following GI tract irradiations. If the increase in the therapeutic window can be validated and understood, this would revolutionize the field of radiation oncology and lead to increased cure rates with reduced side effects following treatment, resulting in increased quality of life for cancer survivors. Funding: DoD, Award#:W81XWH-14-1-0014, Weston Havens Foundation, Bio-X (Stanford University), the Office of the Dean of the Medical School, the Office of the Provost (Stanford University), and the Swedish Childhood Cancer Foundation; BL and PM are

  7. Conformal technique dose escalation in prostate cancer: improved cancer control with higher doses in patients with pretreatment PSA {>=} 10 ngm/ml

    Energy Technology Data Exchange (ETDEWEB)

    Hanks, G E; Lee, W R; Hanlon, A L; Kaplan, E; Epstein, B; Schultheiss, T

    1995-07-01

    Purpose: Single institutions and an NCI supported group of institutions have been investigating the value of dose escalation in patients with prostate cancer treated by conformal treatment techniques. Improvement in morbidity has been previously established, while this report identifies the pretreatment PSA level subgroups of patients who benefitted in cancer control from higher dose. Materials and Methods: We report actuarial bNED survival rates for 375 consecutive patients with known pretreatment PSA levels treated with conformal technique between 5/89 and 12/93. The whole pelvis was treated to 45 Gy in 25 fractions in all T2C,3, all Gleason 8, 9, 10 and all patients with pretreatment PSA {>=}20. The prostate {+-} seminal vesicles was boosted at 2.1 Gy/day to the center of the prostate to 65-79 Gy (65-69 N=50), 70-72.49 N=94, 72.5-74.9 N=82, 75-77.49 N=129 and {>=}77.5 N=20). The median followup is 21 mos with a range of 3 to 67 mos. The highest dose patients have the least followup, reducing the impact of the highest dose levels at this time. Patients are analyzed for the entire group divided at 71 Gy and at 73 Gy calculated at the center of the prostate. Each dose group is then subdivided by pretreatment PSA levels <10, 10-19.9, and {>=}20 ngm/ml and dose levels are compared within pretreatment PSA level group. bNED failure is defined as PSA {>=}1.5 ngm/ml and rising on two consecutive values. Results: Table 1 shows the bNED survival rates at 24 and 36 mos for all patients and the three pretreatment PSA level groups. For all patients pooled, there is an overall advantage to using doses {>=}71 Gy (64% vs 85% at 36 mo, p=.006) and {>=}73 Gy (71% vs 86% at 36 mo, p=.07). The subgroup of PSA <10 ngm/ml, however, shows no benefit in bNED survival when using doses over 71 Gy (90% vs 93% at 36 mo) or 73 Gy (91 vs 94% at 36 mo). The subgroup PSA 10 ngm/ml to 19.9 ngm/ml shows improved cancer control when using doses over 71 Gy (61% vs 88% at 36 mo, p=.03) and over 73

  8. Creating an effort tracking tool to improve therapeutic cancer clinical trials workload management and budgeting.

    Science.gov (United States)

    James, Pam; Bebee, Patty; Beekman, Linda; Browning, David; Innes, Mathew; Kain, Jeannie; Royce-Westcott, Theresa; Waldinger, Marcy

    2011-11-01

    Quantifying data management and regulatory workload for clinical research is a difficult task that would benefit from a robust tool to assess and allocate effort. As in most clinical research environments, The University of Michigan Comprehensive Cancer Center (UMCCC) Clinical Trials Office (CTO) struggled to effectively allocate data management and regulatory time with frequently inaccurate estimates of how much time was required to complete the specific tasks performed by each role. In a dynamic clinical research environment in which volume and intensity of work ebbs and flows, determining requisite effort to meet study objectives was challenging. In addition, a data-driven understanding of how much staff time was required to complete a clinical trial was desired to ensure accurate trial budget development and effective cost recovery. Accordingly, the UMCCC CTO developed and implemented a Web-based effort-tracking application with the goal of determining the true costs of data management and regulatory staff effort in clinical trials. This tool was developed, implemented, and refined over a 3-year period. This article describes the process improvement and subsequent leveling of workload within data management and regulatory that enhanced the efficiency of UMCCC's clinical trials operation.

  9. Designed Amino Acid Feed in Improvement of Production and Quality Targets of a Therapeutic Monoclonal Antibody.

    Directory of Open Access Journals (Sweden)

    Fatemeh Torkashvand

    Full Text Available Cell culture feeds optimization is a critical step in process development of pharmaceutical recombinant protein production. Amino acids are the basic supplements of mammalian cell culture feeds with known effect on their growth promotion and productivity. In this study, we reported the implementation of the Plackett-Burman (PB multifactorial design to screen the effects of amino acids on the growth promotion and productivity of a Chinese hamster ovary DG-44 (CHO-DG44 cell line producing bevacizumab. After this screening, the amino acid combinations were optimized by the response surface methodology (RSM to determine the most effective concentration in feeds. Through this strategy, the final monoclonal antibody (mAb titre was enhanced by 70%, compared to the control group. For this particular cell line, aspartic acid, glutamic acid, arginine and glycine had the highest positive effects on the final mAb titre. Simultaneously, the impact of the designed amino acid feed on some critical quality attributes of bevacizumab was examined in the group with highest productivity. The product was analysed for N-glycan profiles, charge variant distribution, and low molecular weight forms. The results showed that the target product quality has been improved using this feeding strategy. It was shown how this strategy could significantly diminish the time and number of experiments in identifying the most effective amino acids and related concentrations in target product enhancement. This model could be successfully applied to other components of culture media and feeds.

  10. Influence of Exercise Intensity for Improving Depressed Mood in Depression: A Dose-Response Study.

    Science.gov (United States)

    Meyer, Jacob D; Koltyn, Kelli F; Stegner, Aaron J; Kim, Jee-Seon; Cook, Dane B

    2016-07-01

    Exercise effectively improves mood in major depressive disorder (MDD), but the optimal exercise stimulus to improve depressed mood is unknown. To determine the dose-response relationship of acute exercise intensity with depressed mood responses to exercise in MDD. We hypothesized that the acute response to exercise would differ between light, moderate, and hard intensity exercise with higher intensities yielding more beneficial responses. Once weekly, 24 women (age: 38.6±14.0) diagnosed with MDD underwent a 30-minute session at one of three steady-state exercise intensities (light, moderate, hard; rating of perceived exertion 11, 13 or 15) or quiet rest on a stationary bicycle. Depressed mood was evaluated with the Profile of Mood States before, 10 and 30 minutes post-exercise. Exercise reduced depressed mood 10 and 30 minutes following exercise, but this effect was not influenced by exercise intensity. Participants not currently taking antidepressants (n=10) had higher baseline depression scores, but did not demonstrate a different antidepressant response to exercise compared to those taking antidepressants. To acutely improve depressed mood, exercise of any intensity significantly improved feelings of depression with no differential effect following light, moderate, or hard exercise. Pharmacological antidepressant usage did not limit the mood-enhancing effect of acute exercise. Acute exercise should be used as a symptom management tool to improve mood in depression, with even light exercise an effective recommendation. These results need to be replicated and extended to other components of exercise prescription (e.g., duration, frequency, mode) to optimize exercise guidelines for improving depression. Copyright © 2016. Published by Elsevier Ltd.

  11. Polynitroxylated Pegylated Hemoglobin-A Novel, Small Volume Therapeutic for Traumatic Brain Injury Resuscitation: Comparison to Whole Blood and Dose Response Evaluation.

    Science.gov (United States)

    Brockman, Erik C; Jackson, Travis C; Dixon, C Edward; Bayɪr, Hülya; Clark, Robert S B; Vagni, Vincent; Feldman, Keri; Byrd, Catherine; Ma, Li; Hsia, Carleton; Kochanek, Patrick M

    2017-04-01

    Resuscitation with polynitroxylated pegylated hemoglobin (PNPH), a pegylated bovine hemoglobin decorated with nitroxides, eliminated the need for fluid administration, reduced intracranial pressure (ICP) and brain edema, and produced neuroprotection in vitro and in vivo versus Lactated Ringer's solution (LR) in experimental traumatic brain injury (TBI) plus hemorrhagic shock (HS). We hypothesized that resuscitation with PNPH would improve acute physiology versus whole blood after TBI+HS and would be safe and effective across a wide dosage range. Anesthetized mice underwent controlled cortical impact and severe HS to mean arterial pressure (MAP) of 25-27 mm Hg for 35 min, then were resuscitated with PNPH, autologous whole blood, or LR. Markers of acute physiology, including mean arterial blood pressure (MAP), heart rate (HR), blood gases/chemistries, and brain oxygenation (PbtO 2 ), were monitored for 90 min on room air followed by 15 min on 100% oxygen. In a second experiment, the protocol was repeated, except mice were resuscitated with PNPH with doses between 2 and 100 mL/kg. ICP and 24 h %-brain water were evaluated. PNPH-resuscitated mice had higher MAP and lower HR post-resuscitation versus blood or LR (p < 0.01). PNPH-resuscitated mice, versus those resuscitated with blood or LR, also had higher pH and lower serum potassium (p < 0.05). Blood-resuscitated mice, however, had higher PbtO 2 versus those resuscitated with LR and PNPH, although PNPH had higher PbtO 2 versus LR (p < 0.05). PNPH was well tolerated across the dosing range and dramatically reduced fluid requirements in all doses-even 2 or 5 mL/kg (p < 0.001). ICP was significantly lower in PNPH-treated mice for most doses tested versus in LR-treated mice, although %-brain water did not differ between groups. Resuscitation with PNPH, versus resuscitation with LR or blood, improved MAP, HR, and ICP, reduced acidosis and hyperkalemia, and was well tolerated and effective

  12. SU-E-T-622: Identification and Improvement of Patients Eligible for Dose Escalation with Matched Plans

    International Nuclear Information System (INIS)

    Bush, K; Holcombe, C; Kapp, D; Buyyounouski, M; Hancock, S; Xing, L; Atwood, T; King, M

    2014-01-01

    Purpose: Radiation-therapy dose-escalation beyond 80Gy may improve tumor control rates for patients with localized prostate cancer. Since toxicity remains a concern, treatment planners must achieve dose-escalation while still adhering to dose-constraints for surrounding structures. Patientmatching is a machine-learning technique that identifies prior patients that dosimetrically match DVH parameters of target volumes and critical structures prior to actual treatment planning. We evaluated the feasibility of patient-matching in (1)identifying candidates for safe dose-escalation; and (2)improving DVH parameters for critical structures in actual dose-escalated plans. Methods: We analyzed DVH parameters from 319 historical treatment plans to determine which plans could achieve dose-escalation (8640cGy) without exceeding Zelefsky dose-constraints (rectal and bladder V47Gy<53%, and V75.6Gy<30%, max-point dose to rectum of 8550cGy, max dose to PTV< 9504cGy). We then estimated the percentage of cases that could achieve safe dose-escalation using software that enables patient matching (QuickMatch, Siris Medical, Mountain View, CA). We then replanned a case that had violated DVH constraints with DVH parameters from patient matching, in order to determine whether this previously unacceptable plan could be made eligible with this automated technique. Results: Patient-matching improved the percentage of patients eligible for dose-escalation from 40% to 63% (p=4.7e-4, t-test). Using a commercial optimizer augmented with patient-matching, we demonstrated a case where patient-matching improved the toxicity-profile such that dose-escalation would have been possible; this plan was rapidly achieved using patientmatching software. In this patient, all lower-dose constraints were met with both the denovo and patient-matching plan. In the patient-matching plan, maximum dose to the rectum was 8385cGy, while the denovo plan failed to meet the maximum rectal constraint at 8571c

  13. Effects of a MATE protein inhibitor, pyrimethamine, on the renal elimination of metformin at oral microdose and at therapeutic dose in healthy subjects.

    Science.gov (United States)

    Kusuhara, H; Ito, S; Kumagai, Y; Jiang, M; Shiroshita, T; Moriyama, Y; Inoue, K; Yuasa, H; Sugiyama, Y

    2011-06-01

    A microdose study of metformin was conducted to investigate the predictability of drug-drug interactions at the therapeutic dose (ThD). Healthy subjects received a microdose (100 µg) or ThD (250 mg) of metformin orally, with or without a potent and competitive multidrug and toxin extrusion (MATE) inhibitor, pyrimethamine (50 mg, p.o.), in a crossover fashion. Pyrimethamine significantly reduced the renal clearance of metformin by 23 and 35% at the microdose and ThD, respectively. At ThD, but not at microdose, it caused significant increases in the maximum concentration (C(max)) and area under the plasma concentration-time curve (AUC) of metformin (142 and 139% of control values, respectively). Human canalicular membrane vesicles showed pyrimethamine-inhibitable metformin uptake. Pyrimethamine did not affect plasma lactate/pyruvate after ThD of metformin but significantly reduced the renal clearance of creatinine, thereby causing elevation of plasma creatinine level. This microdose study quantitatively predicted a drug-drug interaction involving the renal clearance of metformin at ThD by pyrimethamine. Pyrimethamine is a useful in vivo inhibitor of MATE proteins.

  14. Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects.

    Science.gov (United States)

    Mathur, Anupam; Prashant, Vrinda; Sakhare, Navin; Chakraborty, Sudipta; Vimalnath, K V; Mohan, Repaka Krishna; Arjun, Chanda; Karkhanis, Barkha; Seshan, Ravi; Basu, Sandip; Korde, Aruna; Banerjee, Sharmila; Dash, Ashutosh; Sachdev, Satbir Singh

    2017-09-01

    177 Lu-DOTA-TATE is a clinically useful and promising therapeutic radiopharmaceutical for peptide receptor radionuclide therapy of neuroendocrine tumors (NETs) overexpressing somatostatin receptors. Currently, the radiopharmaceutical is prepared in-house at nuclear medicine centers, thereby restricting its use to limited centers only. In this article, the authors describe systematic studies toward bulk scale formulation of "ready-to-use" 177 Lu-DOTA-TATE using medium specific activity 177 Lu (740-1110 GBq/mg) at a centralized radiopharmacy facility. In an optimized protocol, 177 Lu-DOTA-TATE synthesis was carried out by direct heating of 177 LuCl 3 (Sp. act. 740-1110 GBq/mg) with DOTA-TATE peptide (1.5-3.0 equivalents) in ammonium acetate buffer (0.2 M) containing 2,5-dihydroxy benzoic acid (gentisic acid). Thereafter, the crude labeled product was purified using a Sep-Pak ® C18 column and diluted with acetate buffer-gentisic acid (1.5% w/v) solution to final radioactive concentration of 740 MBq/mL. This was further sterilized and dispensed as 7.4 GBq patient dose/vial with 2 days postformulation calibration. A peptide/metal ratio of 1.5-3.0 is essential for complexation wherein radiolabeling yields >90% are obtained minimizing free 177 Lu waste. For formulation of 7.4 GBq patient dose (2 days postproduction), even specific activity of about 555 GBq/mg was found to be adequate for the radiometal. The ready-to-use 740 MBq/mL 177 Lu-DOTA-TATE formulation with gentisic acid (1.5% w/v) is observed to be safe for human use for more than 1 week (radiochemical purity >98%) from the day of production when stored at -70°C. However, the target specificity may get affected beyond 2 days as the total peptide content for 7.4 GBq dose may exceed the critical peptide limit of 300 μg. Patient treatment carried with several batches of present formulation in diseased NET patients exhibited desired distribution at the tumor and its metastatic site. A ready

  15. [Therapeutic follow-up using automatic perimetry in chronic cerebroretinal ischemia in elderly patients. Prospective double-blind study with graduated dose ginkgo biloba treatment (EGb 761)].

    Science.gov (United States)

    Raabe, A; Raabe, M; Ihm, P

    1991-12-01

    The chronic cerebral retinal insufficiency syndrome in elderly patients is an organ specific expression of a generalized vascular cerebral deficiency. The progress of the disease is characterized by complex symptoms, variation in course, spontaneous remissions and, until recently inadequate diagnostic measurement methods. The new method of automated perimetry with the octopus 2000 P offers a patient-friendly procedure for indirect non-invasive diagnosis of circulatory state in limited cerebral retinal perfusion. In the present study measurements were made with this method on 24 patients (4 men and 20 women with an age of 74.9 +/- 6.9 years). The effect of the extract of Ginkgo biloba (EGb 761) on the reversibility of visual field disturbances was tested using a randomized and double blind study-design in two phases and with two dose levels. The main parameter investigated in this study was the change in the luminous density difference threshold after therapy with EGb 761. In group B (EGb 761 dose 160 mg/day) a significant increase in retinal sensitivity was seen within 4 weeks (p less than 0.05). In the lower dose (80 mg EGb 761/day) group (A), this change in retinal sensitivity was first seen after increasing the dose to 160 mg/day (p less than 0.01). The relative sensitivity of damaged retinal areas was more strongly influenced than "healthy" areas. The assessment by both doctors and patients of the general condition of the patients showed a significant improvement after the course of therapy. The results presented here show that damage to the visual field by chronic lack of bloodflow are significantly reversible.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. WE-AB-303-06: Combining DAO with MV + KV Optimization to Improve Skin Dose Sparing with Real-Time Fluoroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Grelewicz, Z; Wiersma, R [The University of Chicago, Chicago, IL (United States)

    2015-06-15

    Purpose: Real-time fluoroscopy may allow for improved patient positioning and tumor tracking, particularly in the treatment of lung tumors. In order to mitigate the effects of the imaging dose, previous studies have demonstrated the effect of including both imaging dose and imaging constraints into the inverse treatment planning object function. That method of combined MV+kV optimization may Result in plans with treatment beams chosen to allow for more gentle imaging beam-on times. Direct-aperture optimization (DAO) is also known to produce treatment plans with fluence maps more conducive to lower beam-on times. Therefore, in this work we demonstrate the feasibility of a combination of DAO and MV+kV optimization for further optimized real-time kV imaging. Methods: Therapeutic and imaging beams were modeled in the EGSnrc Monte Carlo environment, and applied to a patient model for a previously treated lung patient to provide dose influence matrices from DOSXYZnrc. An MV + kV IMRT DAO treatment planning system was developed to compare DAO treatment plans with and without MV+kV optimization. The objective function was optimized using simulated annealing. In order to allow for comparisons between different cases of the stochastically optimized plans, the optimization was repeated twenty times. Results: Across twenty optimizations, combined MV+kV IMRT resulted in an average of 12.8% reduction in peak skin dose. Both non-optimized and MV+kV optimized imaging beams delivered, on average, mean dose of approximately 1 cGy per fraction to the target, with peak doses to target of approximately 6 cGy per fraction. Conclusion: When using DAO, MV+kV optimization is shown to Result in improvements to plan quality in terms of skin dose, when compared to the case of MV optimization with non-optimized kV imaging. The combination of DAO and MV+kV optimization may allow for real-time imaging without excessive imaging dose. Financial support for the work has been provided in part by NIH

  17. Allium Sativum Methanolic Extract (garlic) Improve Therapeutic Efficacy of Albendazole Against Hydatid Cyst: In Vivo Study.

    Science.gov (United States)

    Haji Mohammadi, K H; Heidarpour, M; Borji, H

    2018-04-25

    After gas chromatography and mass spectrometry of prepared methanolic extract of Allium sativum, 40 laboratory BALB/c mice were infected intraperitoneally by injection of 1,500 viable protoscoleces. Five months after infection, the infected mice were allocated into four treatment groups, including 1- Albendazole (100 mg/kg); 2- Allium sativum methanolic extract (10 mL/L); 3- A. sativum methanolic extract (10 mL/L) + Albendazole (50 mg /kg); and 4- untreated control group. After 30 days of daily treatment, total number and weight of cysts and size of the largest cyst as well as blood serum bilirubin and liver enzymes were compared between the mice of different groups. The total number and weight of cysts and size of the largest cyst were significantly lower in treated groups A. sativum 10 mL/L + Albendazole 50 and Albendazole 100 in comparison to those of the control group (p sativum 10 mL/L and A. sativum 10 mL/L + Albendazole 50, when compared to the control group. In addition, bilirubin concentration revealed significant decrease in A. sativum 10 mL/L and A. sativum 10 mL/L + Albendazole 50 groups, when compared to the Albendazole group. In conclusion, administration of A. sativum 10 mL/L improved the anti-hydatidosis activity of Albendazole 50 mg /kg, due to parasitological effects similar to Albendazole 100 mg /kg but less hepatotoxic effects.

  18. 75 FR 25279 - Device Improvements to Reduce the Number of Under-Doses, Over-Doses, and Misaligned Exposures...

    Science.gov (United States)

    2010-05-07

    ... with new equipment? C. Quality Assurance Measures 1. Is there a model QA program that exists which is... software (afternoon session). Day 2 will focus on steps manufacturers should take to improve training of individuals who use these devices (morning session) and steps to improve quality assurance (QA) at medical...

  19. A systematic review protocol on the effectiveness of therapeutic exercises utilised by physiotherapists to improve function in patients with burns.

    Science.gov (United States)

    Mudawarima, Tapfuma; Chiwaridzo, Matthew; Jelsma, Jennifer; Grimmer, Karen; Muchemwa, Faith Chengetayi

    2017-10-23

    Therapeutic exercises play a crucial role in the management of burn injuries. The broad objective of this review is to systematically evaluate the effectiveness, safety and applicability to low-income countries of therapeutic exercises utilised by physiotherapists to improve function in patients with burns. Population = adults and children/adolescents with burns of any aspect of their bodies. Interventions = any aerobic and/or strength exercises delivered as part of a rehabilitation programme by anyone (e.g. physiotherapists, occupational therapists, nurses, doctors, community workers and patients themselves). Comparators = any comparator. Outcomes = any measure of outcome (e.g. quality of life, pain, muscle strength, range of movement, fear or quality of movement). Settings = any setting in any country. A systematic review will be conducted by two blinded independent reviewers who will search articles on PubMed, CiNAHL, Cochrane library, Medline, Pedro, OTseeker, EMBASE, PsychINFO and EBSCOhost using predefined criteria. Studies of human participants of any age suffering from burns will be eligible, and there will be no restrictions on total body surface area. Only randomised controlled trials will be considered for this review, and the methodological quality of studies meeting the selection criteria will be evaluated using the Cochrane Collaboration tool for assessing risk of bias. The PRISMA reporting standards will be used to write the review. A narrative analysis of the findings will be done, but if pooling is possible, meta-analysis will be considered. Burns may have a long-lasting impact on both psychological and physical functioning and thus it is important to identify and evaluate the effects of current and past aerobic and strength exercises on patients with burns. By identifying the characteristics of effective exercise programmes, guidelines can be suggested for developing intervention programmes aimed at improving the function of patients with burns

  20. Simple and Robust N-Glycan Analysis Based on Improved 2-Aminobenzoic Acid Labeling for Recombinant Therapeutic Glycoproteins.

    Science.gov (United States)

    Jeong, Yeong Ran; Kim, Sun Young; Park, Young Sam; Lee, Gyun Min

    2018-03-21

    N-glycans of therapeutic glycoproteins are critical quality attributes that should be monitored throughout all stages of biopharmaceutical development. To reduce both the time for sample preparation and the variations in analytical results, we have developed an N-glycan analysis method that includes improved 2-aminobenzoic acid (2-AA) labeling to easily remove deglycosylated proteins. Using this analytical method, 15 major 2-AA-labeled N-glycans of Enbrel ® were separated into single peaks in hydrophilic interaction chromatography mode and therefore could be quantitated. 2-AA-labeled N-glycans were also highly compatible with in-line quadrupole time-of-flight mass spectrometry (MS) for structural identification. The structures of 15 major and 18 minor N-glycans were identified from their mass values determined by quadrupole time-of-flight MS. Furthermore, the structures of 14 major N-glycans were confirmed by interpreting the MS/MS data of each N-glycan. This analytical method was also successfully applied to neutral N-glycans of Humira ® and highly sialylated N-glycans of NESP ® . Furthermore, the analysis data of Enbrel ® that were accumulated for 2.5 years demonstrated the high-level consistency of this analytical method. Taken together, the results show that a wide repertoire of N-glycans of therapeutic glycoproteins can be analyzed with high efficiency and consistency using the improved 2-AA labeling-based N-glycan analysis method. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  1. Patient-Specific Tailored Intervention Improves INR Time in Therapeutic Range and INR Variability in Heart Failure Patients.

    Science.gov (United States)

    Gotsman, Israel; Ezra, Orly; Hirsh Raccah, Bruria; Admon, Dan; Lotan, Chaim; Dekeyser Ganz, Freda

    2017-08-01

    Many patients with heart failure need anticoagulants, including warfarin. Good control is particularly challenging in heart failure patients, with range, thereby increasing the risk of complications. This study aimed to evaluate the effect of a patient-specific tailored intervention on anticoagulation control in patients with heart failure. Patients with heart failure taking warfarin therapy (n = 145) were randomized to either standard care or a 1-time intervention assessing potential risk factors for lability of INR, in which they received patient-specific instructions. Time in therapeutic range (TTR) using Rosendaal's linear model was assessed 3 months before and after the intervention. The patient-tailored intervention significantly increased anticoagulation control. The median TTR levels before intervention were suboptimal in the interventional and control groups (53% vs 45%, P = .14). After intervention the median TTR increased significantly in the interventional group compared with the control group (80% [interquartile range, 62%-93%] vs 44% [29%-61%], P <.0001). The intervention resulted in a significant improvement in the interventional group before versus after intervention (53% vs 80%, P <.0001) but not in the control group (45% vs 44%, P = .95). The percentage of patients with a TTR ≥60%, considered therapeutic, was substantially higher in the interventional group: 79% versus 25% (P <.0001). The INR variability (standard deviation of each patient's INR measurements) decreased significantly in the interventional group, from 0.53 to 0.32 (P <.0001) after intervention but not in the control group. Patient-specific tailored intervention significantly improves anticoagulation therapy in patients with heart failure. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Does the addition of Serenoa repens to tamsulosin improve its therapeutical efficacy in benign prostatic hyperplasia?

    Directory of Open Access Journals (Sweden)

    Argirović Aleksandar

    2013-01-01

    Full Text Available Background/Aim. It has been observed that a large number of patients with low urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH has been treated with a combination of tamsulosin (TAM + Serenoa repens (SR (TAM + SR. The aim of this study was to compare a combination TAM + SR with TAM and SR alone, to see if there was any difference in efficacy and tolerance of each in patients with LUTS/BPH. Methods. In this prospective study patients had to have prostate volume (PV 3, a maximal flow rate (Qmax of 5-15 mL/s, with post voiding residual volume (PVR < 150 mL and serum prostatic antigen (PSA < 4 ng/mL. TAM (0.4 mg was administered once a day, SR (320 mg daily or SR (320 mg + TAM (0.4 mg daily for a median period of 6 months. Results. A total of 297 patients were recruited, whereas 265 patients were fully available: 87 into the group TAM, 97 into the group SR and 81 into the group TAM + SR. There was no statistically significant difference between the treatment groups in the sense of demographic and other baseline parameters. No difference was found among the 3 treatment groups, neither in the major endpoint of the study in the sense of a change between baseline and final evaluation in total IPSS, obstructive and irritative subscores, improvement of QoLs, increase in Qmax, nor for the second endpoint including diminution of PV, PSA and PVR. During the treatment period 20 (23% of the patients managed with TAM and 17 (21% with TAM + SR had drug-treated with related adverse reactions. No adverse effect was detected in the group SR. Conclusion. Treatment of BPH by both SR and TAM seems to be efficacious alone. None of them had superiority over another and, additionally, a combined therapy (TAM + SR does not provide extra benefits. Furthermore, SR is a well-tolerated agent that can be used alternatively in the treatment of LUTS/BPH.

  3. Improving DNA double-strand repair inhibitor KU55933 therapeutic index in cancer radiotherapy using nanoparticle drug delivery

    Science.gov (United States)

    Tian, Xi; Lara, Haydee; Wagner, Kyle T.; Saripalli, Srinivas; Hyder, Syed Nabeel; Foote, Michael; Sethi, Manish; Wang, Edina; Caster, Joseph M.; Zhang, Longzhen; Wang, Andrew Z.

    2015-11-01

    Radiotherapy is a key component of cancer treatment. Because of its importance, there has been high interest in developing agents and strategies to further improve the therapeutic index of radiotherapy. DNA double-strand repair inhibitors (DSBRIs) are among the most promising agents to improve radiotherapy. However, their clinical translation has been limited by their potential toxicity to normal tissue. Recent advances in nanomedicine offer an opportunity to overcome this limitation. In this study, we aim to demonstrate the proof of principle by developing and evaluating nanoparticle (NP) formulations of KU55933, a DSBRI. We engineered a NP formulation of KU55933 using nanoprecipitation method with different lipid polymer nanoparticle formulation. NP KU55933 using PLGA formulation has the best loading efficacy as well as prolonged drug release profile. We demonstrated that NP KU55933 is a potent radiosensitizer in vitro using clonogenic assay and is more effective as a radiosensitizer than free KU55933 in vivo using mouse xenograft models of non-small cell lung cancer (NSCLC). Western blots and immunofluorescence showed NP KU55933 exhibited more prolonged inhibition of DNA repair pathway. In addition, NP KU55933 leads to lower skin toxicity than KU55933. Our study supports further investigations using NP to deliver DSBRIs to improve cancer radiotherapy treatment.

  4. Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide.

    Science.gov (United States)

    Jacobson, Lisa A; Rane, Shruti; McReynolds, Lisa J; Steppan, Diana A; Chen, Allen R; Paz-Priel, Ido

    2016-07-01

    Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare, generally progressive, and potentially fatal syndrome of unclear etiology. The syndrome is characterized by normal development followed by a sudden, rapid hyperphagic weight gain beginning during the preschool period, hypothalamic dysfunction, and central hypoventilation, and is often accompanied by personality changes and developmental regression, leading to substantial morbidity and mortality. We describe 2 children who had symptomatic and neuropsychological improvement after high-dose cyclophosphamide treatment. Our experience supports an autoimmune pathogenesis and provides the first neuropsychological profile of patients with rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation. Copyright © 2016 by the American Academy of Pediatrics.

  5. Homeopathic Doses of Gelsemium sempervirens Improve the Behavior of Mice in Response to Novel Environments

    Directory of Open Access Journals (Sweden)

    Paolo Bellavite

    2011-01-01

    Full Text Available Gelsemium sempervirens is used in homeopathy for treating patients with anxiety related symptoms, however there have been few experimental studies evaluating its pharmacological activity. We have investigated the effects of homeopathic doses of G. sempervirens on mice, using validated behavioral models. Centesimal (CH dilutions/dynamizations of G. sempervirens, the reference drug diazepam (1 mg/kg body weight or a placebo (solvent vehicle were intraperitoneally delivered to groups of mice of CD1 strain during 8 days, then the effects were assessed by the Light-Dark (LD choice test and by the Open-Field (OF exploration test, in a fully blind manner. In the LD test, the mean time spent in the illuminated area by control and placebo-treated animals was 15.98%, for mice treated with diazepam it increased to 19.91% (P = .047, while with G. sempervirens 5 CH it was 18.11% (P = .341, non-significant. The number of transitions between the two compartments increased with diazepam from 6.19 to 9.64 (P < .001 but not with G. Sempervirens. In the OF test, G. sempervirens 5 CH significantly increased the time spent and the distance traveled in the central zone (P = .009 and P = .003, resp., while diazepam had no effect on these OF test parameters. In a subsequent series of experiments, G. sempervirens 7 and 30 CH also significantly improved the behavioral responses of mice in the OF test (P < .01 for all tested variables. Neither dilutions of G. sempervirens affected the total distance traveled, indicating that the behavioral effect was not due to unspecific changes in locomotor activity. In conclusion, homeopathic doses of G. sempervirens influence the emotional responses of mice to novel environments, suggesting an improvement in exploratory behavior and a diminution of thigmotaxis or neophobia.

  6. Combination With Low-dose Dextromethorphan Improves the Effect of Amlodipine Monotherapy in Clinical Hypertension

    Science.gov (United States)

    Yin, Wei-Hsian; Chen, Pei; Yeh, Hung-I; Wang, Kuo-Yang; Hung, Yi-Jen; Tseng, Wei-Kung; Wen, Ming-Shien; Wu, Tao-Cheng; Wu, Chau-Chung; Cheng, Shu-Meng; Chen, Jaw-Wen

    2016-01-01

    Abstract The combination of low rather than high dose of dextromethorphan (DXM) with amlodipine (AM) could improve blood pressure (BP) reduction in hypertensive animals. The study aimed to evaluate the feasibility of different doses of DXM combined with standard AM treatment in clinical hypertension. This was a prospective, 14-week, dose-escalation, multicenter study. After 2-week run-in period with AM 5 mg/day, hypertensive patients who got the BP goal of 140/90 mmHg kept receiving AM monotherapy for another 12 weeks. The nonresponders, while kept on AM 5 mg/day, received additional DXM treatment for 3 sequential dose-titrated periods with initially 2.5 mg/day, followed by 7.5 mg/day, and finally 30 mg/day. Each period was for 4 weeks. The patients at BP goal after each treatment period were defined as the responders and kept on the same combination till the end of the study. The responder rate of each treatment period was recorded. The changes of BP and serum antioxidant/endothelial markers between week 14 and week 2 were evaluated. Of the 103 patients initially enrolled, 89 entered the treatment period. In the 78 patients completing the study, 31 (40%) at BP goal after 2-week AM run-in kept on AM monotherapy (DXM0). The addition of 2.5 (DXM2.5) and 7.5 mg/day (DXM7.5) of DXM enabled BP goal achievement in 22 (47%) nonresponders to AM monotherapy including 16 (29%) with DXM2.5 and 6 (18%) with DXM7.5. Only 4 patients (16%) reached BP goal with the combination of DXM 30 mg/day (DXM30). Overall, 73% of the 78 patients reached BP goal at the end of the 14-week study. Mean systolic BP was reduced by 7.9% ± 7.0% with DXM2.5 (P < 0.001) and by 5.4% ± 2.4% with DXM7.5 (P = 0.003) respectively at week 14 from that at week 2, which was unchanged in either DXM0 or DXM30 group. Besides, the effects of combination treatment were particularly significant in the patients with impaired endothelial function suggested by reduced serum NOx level

  7. Iterative metal artifact reduction improves dose calculation accuracy. Phantom study with dental implants

    Energy Technology Data Exchange (ETDEWEB)

    Maerz, Manuel; Mittermair, Pia; Koelbl, Oliver; Dobler, Barbara [Regensburg University Medical Center, Department of Radiotherapy, Regensburg (Germany); Krauss, Andreas [Siemens Healthcare GmbH, Forchheim (Germany)

    2016-06-15

    Metallic dental implants cause severe streaking artifacts in computed tomography (CT) data, which affect the accuracy of dose calculations in radiation therapy. The aim of this study was to investigate the benefit of the metal artifact reduction algorithm iterative metal artifact reduction (iMAR) in terms of correct representation of Hounsfield units (HU) and dose calculation accuracy. Heterogeneous phantoms consisting of different types of tissue equivalent material surrounding metallic dental implants were designed. Artifact-containing CT data of the phantoms were corrected using iMAR. Corrected and uncorrected CT data were compared to synthetic CT data to evaluate accuracy of HU reproduction. Intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were calculated in Oncentra v4.3 on corrected and uncorrected CT data and compared to Gafchromic trademark EBT3 films to assess accuracy of dose calculation. The use of iMAR increased the accuracy of HU reproduction. The average deviation of HU decreased from 1006 HU to 408 HU in areas including metal and from 283 HU to 33 HU in tissue areas excluding metal. Dose calculation accuracy could be significantly improved for all phantoms and plans: The mean passing rate for gamma evaluation with 3 % dose tolerance and 3 mm distance to agreement increased from 90.6 % to 96.2 % if artifacts were corrected by iMAR. The application of iMAR allows metal artifacts to be removed to a great extent which leads to a significant increase in dose calculation accuracy. (orig.) [German] Metallische Implantate verursachen streifenfoermige Artefakte in CT-Bildern, welche die Dosisberechnung beeinflussen. In dieser Studie soll der Nutzen des iterativen Metall-Artefakt-Reduktions-Algorithmus iMAR hinsichtlich der Wiedergabetreue von Hounsfield-Werten (HU) und der Genauigkeit von Dosisberechnungen untersucht werden. Es wurden heterogene Phantome aus verschiedenen Arten gewebeaequivalenten Materials mit

  8. EcoDoses improving radiological assessment of doses to man from terrestrial ecosystems. A status report for the NKS-B project 2003

    Energy Technology Data Exchange (ETDEWEB)

    Bergan, T. [Lavrans Skuterud, Haevard Thoerring (Norway); Liland, A. [Norwegian Radiation Protection Authority (NRPA) (Denmark)] (eds.)

    2004-05-01

    The NKS B-programme EcoDoses project started in 2003 as a collaboration between all the Nordic countries. The aim of the project is to improve the radiological assessments of doses to man from terrestrial ecosystems. The first part, conducted in 2003, has focussed on an extensive collation and review of both published and unpublished data from all the Nordic countries for the nuclear weapons fallout period and the post-Chemobyl period. This included data on radionuclides in air filters, precipitation, soil samples, milk and reindeer. Based on this, an improved model for estimating radioactive fallout based on precipitation data during the nuclear weapons fallout period has been developed. Effective ecological half- lives for 137Cs and 90Sr in milk have been calculated for the nuclear weapons fallout period. For reindeer the ecological half- lives for 137Cs have been calculated for both the nuclear weapons fallout period and the post-Chemobyl period. The data were also used to compare modelling results with observed concentrations. This was done at a workshop where the radioecological food-and-dose module in the ARGOS decision support system was used to predict transfer of deposited radionuclides to foodstuffs and subsequent radiation doses to man. The work conducted the first year is presented in this report and gives interesting, new results relevant for terrestrial radioecology. (au)

  9. Effect of different single-session educational modalities on improving medical students' ability to demonstrate proper pressurized metered dose inhaler technique.

    Science.gov (United States)

    Dominelli, Giulio S; Dominelli, Paolo B; Rathgeber, Steven L; Webster, Sheila B

    2012-05-01

    Pressurized metered dose inhalers (pMDIs) remain important therapeutic options for obstructive lung diseases. The ability to instruct and evaluate inhaler technique is a crucial skill that all medical professionals should possess; unfortunately, many professionals lack proficiency with pMDIs. We aimed to determine if brief education interventions of differing modalities can positively affect medical students' skills over the long term. The baseline ability of medical students and first year residents to use pMDIs was scored via a 10-point scoring system. Students were randomized to receive no education, one-on-one instruction, or video instruction. Students were then retested immediately after the education and at the 3-month mark for retention of acquired skills. Video, one-on-one and the placebo groups modalities statistically improved the average medical student's score in the immediate retesting (7.5 and 7.4 vs. 4.7, p grades at the immediate recall significantly improved for both modalities. During retention testing, only video education had a statistically significant improvement in pass rate over the control group, as defined by an average score of 7 or better (8 vs. 1, p improve medical students' ability to use pMDIs in short-term testing. However, only video education retained significant improvement compared with control after 3 months. This suggests that compared with traditional one-on-one teaching, video education is an effective means of teaching medical students how to improve their pMDI technique.

  10. Polynitroxylated Pegylated Hemoglobin—A Novel, Small Volume Therapeutic for Traumatic Brain Injury Resuscitation: Comparison to Whole Blood and Dose Response Evaluation

    Science.gov (United States)

    Brockman, Erik C.; Jackson, Travis C.; Dixon, C. Edward; Bayɪr, Hülya; Clark, Robert S. B.; Vagni, Vincent; Feldman, Keri; Byrd, Catherine; Ma, Li; Hsia, Carleton

    2017-01-01

    Abstract Resuscitation with polynitroxylated pegylated hemoglobin (PNPH), a pegylated bovine hemoglobin decorated with nitroxides, eliminated the need for fluid administration, reduced intracranial pressure (ICP) and brain edema, and produced neuroprotection in vitro and in vivo versus Lactated Ringer's solution (LR) in experimental traumatic brain injury (TBI) plus hemorrhagic shock (HS). We hypothesized that resuscitation with PNPH would improve acute physiology versus whole blood after TBI+HS and would be safe and effective across a wide dosage range. Anesthetized mice underwent controlled cortical impact and severe HS to mean arterial pressure (MAP) of 25–27 mm Hg for 35 min, then were resuscitated with PNPH, autologous whole blood, or LR. Markers of acute physiology, including mean arterial blood pressure (MAP), heart rate (HR), blood gases/chemistries, and brain oxygenation (PbtO2), were monitored for 90 min on room air followed by 15 min on 100% oxygen. In a second experiment, the protocol was repeated, except mice were resuscitated with PNPH with doses between 2 and 100 mL/kg. ICP and 24 h %-brain water were evaluated. PNPH-resuscitated mice had higher MAP and lower HR post-resuscitation versus blood or LR (p < 0.01). PNPH-resuscitated mice, versus those resuscitated with blood or LR, also had higher pH and lower serum potassium (p < 0.05). Blood-resuscitated mice, however, had higher PbtO2 versus those resuscitated with LR and PNPH, although PNPH had higher PbtO2 versus LR (p < 0.05). PNPH was well tolerated across the dosing range and dramatically reduced fluid requirements in all doses—even 2 or 5 mL/kg (p < 0.001). ICP was significantly lower in PNPH-treated mice for most doses tested versus in LR-treated mice, although %-brain water did not differ between groups. Resuscitation with PNPH, versus resuscitation with LR or blood, improved MAP, HR, and ICP, reduced acidosis and hyperkalemia, and was well tolerated and

  11. An improved distance-to-dose correlation for predicting bladder and rectum dose-volumes in knowledge-based VMAT planning for prostate cancer

    Science.gov (United States)

    Wall, Phillip D. H.; Carver, Robert L.; Fontenot, Jonas D.

    2018-01-01

    The overlap volume histogram (OVH) is an anatomical metric commonly used to quantify the geometric relationship between an organ at risk (OAR) and target volume when predicting expected dose-volumes in knowledge-based planning (KBP). This work investigated the influence of additional variables contributing to variations in the assumed linear DVH-OVH correlation for the bladder and rectum in VMAT plans of prostate patients, with the goal of increasing prediction accuracy and achievability of knowledge-based planning methods. VMAT plans were retrospectively generated for 124 prostate patients using multi-criteria optimization. DVHs quantified patient dosimetric data while OVHs quantified patient anatomical information. The DVH-OVH correlations were calculated for fractional bladder and rectum volumes of 30, 50, 65, and 80%. Correlations between potential influencing factors and dose were quantified using the Pearson product-moment correlation coefficient (R). Factors analyzed included the derivative of the OVH, prescribed dose, PTV volume, bladder volume, rectum volume, and in-field OAR volume. Out of the selected factors, only the in-field bladder volume (mean R  =  0.86) showed a strong correlation with bladder doses. Similarly, only the in-field rectal volume (mean R  =  0.76) showed a strong correlation with rectal doses. Therefore, an OVH formalism accounting for in-field OAR volumes was developed to determine the extent to which it improved the DVH-OVH correlation. Including the in-field factor improved the DVH-OVH correlation, with the mean R values over the fractional volumes studied improving from  -0.79 to  -0.85 and  -0.82 to  -0.86 for the bladder and rectum, respectively. A re-planning study was performed on 31 randomly selected database patients to verify the increased accuracy of KBP dose predictions by accounting for bladder and rectum volume within treatment fields. The in-field OVH led to significantly more precise

  12. Promising Therapeutics with Natural Bioactive Compounds for Improving Learning and Memory — A Review of Randomized Trials

    Directory of Open Access Journals (Sweden)

    Jin-Yong Choi

    2012-09-01

    Full Text Available Cognitive disorders can be associated with brain trauma, neurodegenerative disease or as a part of physiological aging. Aging in humans is generally associated with deterioration of cognitive performance and, in particular, learning and memory. Different therapeutic approaches are available to treat cognitive impairment during physiological aging and neurodegenerative or psychiatric disorders. Traditional herbal medicine and numerous plants, either directly as supplements or indirectly in the form of food, improve brain functions including memory and attention. More than a hundred herbal medicinal plants have been traditionally used for learning and memory improvement, but only a few have been tested in randomized clinical trials. Here, we will enumerate those medicinal plants that show positive effects on various cognitive functions in learning and memory clinical trials. Moreover, besides natural products that show promising effects in clinical trials, we briefly discuss medicinal plants that have promising experimental data or initial clinical data and might have potential to reach a clinical trial in the near future.

  13. Improved oral bioavailability and therapeutic efficacy of dabigatran etexilate via Soluplus-TPGS binary mixed micelles system.

    Science.gov (United States)

    Hu, Mei; Zhang, Jinjie; Ding, Rui; Fu, Yao; Gong, Tao; Zhang, Zhirong

    2017-04-01

    The clinical use of dabigatran etexilate (DABE) is limited by its poor absorption and relatively low bioavailability. Our study aimed to explore the potential of a mixed micelle system composed of Soluplus ® and D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) to improve the oral absorption and bioavailability of DBAE. DBAE was first encapsulated into Soluplus/TPGS mixed micelles by a simple thin film hydration method. The DBAE loaded micelles displayed an average size distribution of around 83.13 nm. The cellular uptake of DBAE loaded micelles in Caco-2 cell monolayer was significantly enhanced by 2-2.6 fold over time as compared with DBAE suspension. Both lipid raft/caveolae and macropinocytosis-mediated the cell uptake of DBAE loaded micelles through P-glycoprotein (P-gp)-independent pathway. Compared with the DBAE suspension, the intestinal absorption of DBAE from DBAE mixed micelles in rats was significantly improved by 8 and 5-fold in ileum at 2 h and 4 h, respectively. Moreover, DBAE mixed micelles were absorbed into systemic circulation via both portal vein and lymphatic pathway. The oral bioavailability of DBAE mixed micelles in rats was 3.37 fold higher than that of DBAE suspension. DBAE mixed micelles exhibited a comparable anti-thrombolytic activity with a thrombosis inhibition rate of 63.18% compared with DBAE suspension in vivo. Thus, our study provides a promising drug delivery system to enhance the oral bioavailability and therapeutic efficacy of DBAE.

  14. Dose metric considerations in in vitro assays to improve quantitative in vitro–in vivo dose extrapolations

    NARCIS (Netherlands)

    Groothuis, Floris|info:eu-repo/dai/nl/37343586X; Heringa, M.B.; Nicol, B; Hermens, Joop|info:eu-repo/dai/nl/069681384; Blaauboer, B|info:eu-repo/dai/nl/068359802; Kramer, Nynke|info:eu-repo/dai/nl/304836125

    2015-01-01

    Challenges to improve toxicological risk assessment to meet the demands of the EU chemical’s legisla- tion, REACH, and the EU 7th Amendment of the Cosmetics Directive have accelerated the development of non-animal based methods. Unfortunately, uncertainties remain surrounding the power of alterna-

  15. EcoDoses. Improving radiological assessment of doses to man from terrestrial ecosystems: A status report for the NKS-B activity 2006

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, S.; Andersson, K.G. (Technical Univ. of Denmark, Risoe National Lab. for Sustainable Energy, Roskilde (Denmark)); Thoerring, H.; Liland, A. (Norwegian Radiation Protection Authority (Norway)); Joensen, H.P. (Frooskaparsetur Foeroya, Faroe Islands, Torshavn (Denmark)); Isaksson, M. (Goeteborg Univ. (Sweden)); Saxen, R.; Kostiainen, E. (Radiation and Nuclear Safety Authority (STUK) (Finland)); Suolanen, V. (VTT Technical Research Centre of Finland, Espoo (Finland)); Palsson, S.E. (Geislavarnir rikisins (Iceland))

    2009-03-15

    The overall aim of the NKS-B EcoDoses activity is to improve the prediction of doses to humans from consumption of radioactively contaminated food. For this purpose, various published and unpublished datasets have been compiled and applied in developing refined parameterisation for existing food dose models. The ECOSYS model developed in Germany after the Chernobyl accident has been applied as the basis for the investigations. This model can be operated both with discrete releases adequately representing a nuclear power plant accident, and with continuous or multiple releases, as observed in the nuclear weapons testing period. The modelling has revealed that it is essential to ensure that case-specific values are applied for a range of parameters, adequately reflecting the actual conditions with respect to geology, season, climate and demography. In connection with this year's work on the activity, sensitivity studies have been conducted with the ECOSYS model, in which the influence on ingestion dose estimates of a number of parameters has been evaluated in relation to Faroese conditions. The importance of applying location specific data to estimate dose is pinpointed, and it is also concluded that dose predictions for a small and distinct area like the Faroese, where not all of the many parameters required to run ECOSYS optimally have been adequately assessed in recent years, can be associated with considerable uncertainty. A Finnish study has been made in relation to modelling of radiocaesium behaviour in lakes. This study was carried out using a compartmental model that is included as a module in the DETRA dose assessment tool. A total of nine different input parameters (distribution coefficients, run-off from the catchment, erosion from the catchment, sedimentation rate in the lakes, lake water exchange rate, and biological half-lives in four fish species) were varied, and particularly distribution coefficients and lake water exchange rates were

  16. EcoDoses. Improving radiological assessment of doses to man from terrestrial ecosystems: A status report for the NKS-B activity 2006

    International Nuclear Information System (INIS)

    Nielsen, S.; Andersson, K.G.; Thoerring, H.; Liland, A.; Joensen, H.P.; Isaksson, M.; Saxen, R.; Kostiainen, E.; Suolanen, V.; Palsson, S.E.

    2009-03-01

    The overall aim of the NKS-B EcoDoses activity is to improve the prediction of doses to humans from consumption of radioactively contaminated food. For this purpose, various published and unpublished datasets have been compiled and applied in developing refined parameterisation for existing food dose models. The ECOSYS model developed in Germany after the Chernobyl accident has been applied as the basis for the investigations. This model can be operated both with discrete releases adequately representing a nuclear power plant accident, and with continuous or multiple releases, as observed in the nuclear weapons testing period. The modelling has revealed that it is essential to ensure that case-specific values are applied for a range of parameters, adequately reflecting the actual conditions with respect to geology, season, climate and demography. In connection with this year's work on the activity, sensitivity studies have been conducted with the ECOSYS model, in which the influence on ingestion dose estimates of a number of parameters has been evaluated in relation to Faroese conditions. The importance of applying location specific data to estimate dose is pinpointed, and it is also concluded that dose predictions for a small and distinct area like the Faroese, where not all of the many parameters required to run ECOSYS optimally have been adequately assessed in recent years, can be associated with considerable uncertainty. A Finnish study has been made in relation to modelling of radiocaesium behaviour in lakes. This study was carried out using a compartmental model that is included as a module in the DETRA dose assessment tool. A total of nine different input parameters (distribution coefficients, run-off from the catchment, erosion from the catchment, sedimentation rate in the lakes, lake water exchange rate, and biological half-lives in four fish species) were varied, and particularly distribution coefficients and lake water exchange rates were demonstrated to

  17. Does inverse planning applied to Iridium192 high dose rate prostate brachytherapy improve the optimization of the dose afforded by the Paris system?

    International Nuclear Information System (INIS)

    Nickers, Philippe; Lenaerts, Eric; Thissen, Benedicte; Deneufbourg, Jean-Marie

    2005-01-01

    Background and purpose: The purpose of the work is to analyse for 192 Ir prostate brachytherapy (BT) some of the different steps in optimizing the dose delivered to the CTV, urethra and rectum. Materials and methods: Between 07/1998 and 12/2001, 166 patients were treated with 192 Ir wires providing a low dose rate, according to the Paris system philosophy and with the 2D version of the treatment planning Isis R . 40-45 Gy were delivered after an external beam radiotherapy of 40 Gy. The maximum tolerable doses for BT were 25 Gy to the anterior third of the rectum on the whole length of the implant (R dose) and 52 Gy to the urethra on a 1 cm length (U max ). A U max /CTV dose ratio >1.3 represented a pejorative value as the planned dose of 40-45 Gy could not be achieved. On the other side a ratio ≤1.25 was considered optimal and the intermediate values satisfactory. A R/CTV dose ratio 192 Ir sources. Results: At the end of a learning curve reaching a plateau after the first 71 patients, 90% of the implants with 192 Ir wires were stated at least satisfactory for a total rate of 82% for the whole population. When the 3D dosimetry for SST was used, the initial values >1.25 decreased significantly with optimization required on CTV contours and additional constraints on urethra while the R/CTV ratio was maintained under 0.55. For initial U max /CTV >1.3 or >1.25 but ≤1.3 indeed, the mean respective values of 1.41±0.16 and 1.28±0.01 decreased to 1.28±0.24 and 1.17±0.09 (P<0.001), allowing to increase the total dose to the CTV by 4 Gy. Conclusions: The Paris system which assumes a homogeneous distribution of a minimum number of catheters inside the CTV allowed to anticipate a satisfactory dosimetry in 82% of cases. However, this precision rate could be improved until 95% with an optimization approach based on an inverse planning philosophy. These new 3D optimization methods, ideally based on good quality implants at first allow to deliver the highest doses with

  18. Mathematical modeling improves EC50 estimations from classical dose-response curves.

    Science.gov (United States)

    Nyman, Elin; Lindgren, Isa; Lövfors, William; Lundengård, Karin; Cervin, Ida; Sjöström, Theresia Arbring; Altimiras, Jordi; Cedersund, Gunnar

    2015-03-01

    The β-adrenergic response is impaired in failing hearts. When studying β-adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observed a decreasing response at high concentrations. The classical interpretation of such data is to assume a maximal response before the decrease, and to fit a sigmoid curve to the remaining data to determine EC50 . Instead, we have applied a mathematical modeling approach to interpret the full dose-response curve in a new way. The developed model predicts a non-steady-state caused by a short resting time between increased concentrations of agonist, which affect the dose-response characterization. Therefore, an improved estimate of EC50 may be calculated using steady-state simulations of the model. The model-based estimation of EC50 is further refined using additional time-resolved data to decrease the uncertainty of the prediction. The resulting model-based EC50 (180-525 nm) is higher than the classically interpreted EC50 (46-191 nm). Mathematical modeling thus makes it possible to re-interpret previously obtained datasets, and to make accurate estimates of EC50 even when steady-state measurements are not experimentally feasible. The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database, and may be accessed at http://jjj.bio.vu.nl/database/nyman. © 2015 FEBS.

  19. Accuracy of intermediate dose of furosemide injection to improve multidetector row CT urography

    International Nuclear Information System (INIS)

    Roy, Catherine; Jeantroux, Jeremy; Irani, Farah G.; Sauer, Benoit; Lang, Herve; Saussine, Christian

    2008-01-01

    Objective: Evaluate the usefulness of intermediate dose furosemide to improve visualization of the intrarenal collecting system and ureter using MDCTU. Materials and methods: Two groups of 100 patients without urinary tract disease or major abdominal pathology underwent MDCTU. Group I (various abdominal indications) was performed without any additional preparation and Group II (suspicion of urinary tract disease) 10 min after injection of furosemide (20 mg). MIP images of the excretory phase were post-processed. Maximal short-axis diameter of the pelvis and ureter were measured on axial images for all phases. Visualization of the collecting system wall and the identification of the whole ureter were assessed. Results: Mean pelvic diameter before contrast was (7.4 mm, S.D. ± 2.7; 13.4 mm, S.D. ± 4.1), on cortico-medullary phase (8.4 mm, S.D. ± 4.2; 14.3 mm, S.D. ± 4), on nephrographic phase (8.1 mm, S.D. ± 2.5; 14.8 mm, S.D. ± 4) and on excretory phase (9.7 mm, S.D. ± 3.4; 14.9 mm, S.D. ± 4.5), respectively, for Groups I and II. Intrarenal collecting system wall was clearly identified on both corticomedullary and nephrographic phases in 91% of Group II against 20% of Group I. Opacification of the entire ureter was excellent on excretory phase in 96% of Group II against 13% of Group I. The difference between the mean values for the two groups was statistically significant for all phases (p -9 ). Conclusion: Intermediate-dose furosemide (20 mg) before MDCTU is a very simple add-on for accurate depiction of pelvicalyceal details and collecting system wall without artefacts. The procedure is associated with a constant and complete visualisation of the entire urete

  20. Accuracy of intermediate dose of furosemide injection to improve multidetector row CT urography

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Catherine [Department of Radiology B, Universitary Hospital of Strasbourg-Civil Hospital, 1, Place de l' hopital BP 426, 67091 Strasbourg Cedex (France)], E-mail: catherine.roy@chru-strasbourg.fr; Jeantroux, Jeremy; Irani, Farah G.; Sauer, Benoit [Department of Radiology B, Universitary Hospital of Strasbourg-Civil Hospital, 1, Place de l' hopital BP 426, 67091 Strasbourg Cedex (France); Lang, Herve; Saussine, Christian [Department of Urology, Universitary Hospital of Strasbourg-Civil Hospital, 1, Place de l' hopital BP 426, 67091 Strasbourg Cedex (France)

    2008-05-15

    Objective: Evaluate the usefulness of intermediate dose furosemide to improve visualization of the intrarenal collecting system and ureter using MDCTU. Materials and methods: Two groups of 100 patients without urinary tract disease or major abdominal pathology underwent MDCTU. Group I (various abdominal indications) was performed without any additional preparation and Group II (suspicion of urinary tract disease) 10 min after injection of furosemide (20 mg). MIP images of the excretory phase were post-processed. Maximal short-axis diameter of the pelvis and ureter were measured on axial images for all phases. Visualization of the collecting system wall and the identification of the whole ureter were assessed. Results: Mean pelvic diameter before contrast was (7.4 mm, S.D. {+-} 2.7; 13.4 mm, S.D. {+-} 4.1), on cortico-medullary phase (8.4 mm, S.D. {+-} 4.2; 14.3 mm, S.D. {+-} 4), on nephrographic phase (8.1 mm, S.D. {+-} 2.5; 14.8 mm, S.D. {+-} 4) and on excretory phase (9.7 mm, S.D. {+-} 3.4; 14.9 mm, S.D. {+-} 4.5), respectively, for Groups I and II. Intrarenal collecting system wall was clearly identified on both corticomedullary and nephrographic phases in 91% of Group II against 20% of Group I. Opacification of the entire ureter was excellent on excretory phase in 96% of Group II against 13% of Group I. The difference between the mean values for the two groups was statistically significant for all phases (p < 10{sup -9}). Conclusion: Intermediate-dose furosemide (20 mg) before MDCTU is a very simple add-on for accurate depiction of pelvicalyceal details and collecting system wall without artefacts. The procedure is associated with a constant and complete visualisation of the entire urete.

  1. Prescription dose and fractionation predict improved survival after stereotactic radiotherapy for brainstem metastases

    Directory of Open Access Journals (Sweden)

    Leeman Jonathan E

    2012-07-01

    nausea (n = 1 and headaches (n = 2 that resolved with a short-course of dexamethasone. Conclusion SRT/SRS for brainstem metastases is safe and achieves a high rate of local control. We found higher GPA as well as greater number of treatment fractions and higher prescription dose to be correlated with improved overall survival. Despite this approach, prognosis remains poor and distant intracranial control remains an issue, even in patients previously treated with WBRT.

  2. A second dose of kisspeptin-54 improves oocyte maturation in women at high risk of ovarian hyperstimulation syndrome: a Phase 2 randomized controlled trial.

    Science.gov (United States)

    Abbara, Ali; Clarke, Sophie; Islam, Rumana; Prague, Julia K; Comninos, Alexander N; Narayanaswamy, Shakunthala; Papadopoulou, Deborah; Roberts, Rachel; Izzi-Engbeaya, Chioma; Ratnasabapathy, Risheka; Nesbitt, Alexander; Vimalesvaran, Sunitha; Salim, Rehan; Lavery, Stuart A; Bloom, Stephen R; Huson, Les; Trew, Geoffrey H; Dhillo, Waljit S

    2017-09-01

    Can increasing the duration of LH-exposure with a second dose of kisspeptin-54 improve oocyte maturation in women at high risk of ovarian hyperstimulation syndrome (OHSS)? A second dose of kisspeptin-54 at 10 h following the first improves oocyte yield in women at high risk of OHSS. Kisspeptin acts at the hypothalamus to stimulate the release of an endogenous pool of GnRH from the hypothalamus. We have previously reported that a single dose of kisspeptin-54 results in an LH-surge of ~12-14 h duration, which safely triggers oocyte maturation in women at high risk of OHSS. Phase-2 randomized placebo-controlled trial of 62 women at high risk of OHSS recruited between August 2015 and May 2016. Following controlled ovarian stimulation, all patients (n = 62) received a subcutaneous injection of kisspeptin-54 (9.6 nmol/kg) 36 h prior to oocyte retrieval. Patients were randomized 1:1 to receive either a second dose of kisspeptin-54 (D; Double, n = 31), or saline (S; Single, n = 31) 10 h thereafter. Patients, embryologists, and IVF clinicians remained blinded to the dosing allocation. Study participants: Sixty-two women aged 18-34 years at high risk of OHSS (antral follicle count ≥23 or anti-Mullerian hormone level ≥40 pmol/L). Setting: Single centre study carried out at Hammersmith Hospital IVF unit, London, UK. Primary outcome: Proportion of patients achieving an oocyte yield (percentage of mature oocytes retrieved from follicles ≥14 mm on morning of first kisspeptin-54 trigger administration) of at least 60%. Secondary outcomes: Reproductive hormone levels, implantation rate and OHSS occurrence. A second dose of kisspeptin-54 at 10 h following the first induced further LH-secretion at 4 h after administration. A higher proportion of patients achieved an oocyte yield ≥60% following a second dose of kisspeptin-54 (Single: 14/31, 45%, Double: 21/31, 71%; absolute difference +26%, CI 2-50%, P = 0.042). Patients receiving two doses of kisspeptin-54 had a variable LH

  3. Improvement in therapeutic ability of wharton's jelly derived mesenchymal stem cells with vitamin e in breast cancer

    International Nuclear Information System (INIS)

    Wajid, N.; Azam, M.; Khalid, S.; Qazi, M.H.

    2017-01-01

    To assess the role of Vitamin E to improve the survival of Wharton's jelly derived mesenchymal stem cells (WJMSCs) in breast cancer conditions. Study Design:An experimental study. Place and Duration of Study:Centre for Research in Molecular Medicine, University of Lahore, from November 2016 to March 2017. Methodology:WJMSCs were obtained from umbilical cord tissue with enzyme digestion method. Isolated cells were characterized for CD90 and CD45 by immunocytochemistry. Pretreatment and conjugation therapies of vitamin E in 50mM and 100mM concentration were used on WJMSCs and breast cancer plasma was provided to mimic the cancer conditions, while WJMSCs provided with normal plasma were considered control. Cells' viability, proliferation and death were evaluated by crystal violet staining, MTT assay and LDH assay, respectively. Oxidative stress was observed by activity of anti-oxidant enzymes (GSH, catalase, SOD) and reactive oxygen species (MDA). Results:The isolated cells expressed mesenchymal stem cells marker CD90 and lacked hematopoietic marker CD45. Vitamin E improved the viability and proliferation of WJMSCs in normal plasma, in conjugation with breast cancer plasma and in pretreatment groups but conjugation group showed even better results with concentration of 100mM as compared to the pretreatment group and opposite was observed for LDH assay for cells death analysis. Vitamin E also reduced the oxidative stress in 100mM more pronounced in conjugation group as compared to pretreatment group while left no harmful effects on WJMSCs in normal plasma. Conclusion:Vitamin E conjugation with breast cancer conditions significantly improved growth of WJMSCs. Thus vitamin E treated WJMSCs are better therapeutic options for breast cancer. (author)

  4. Low-dose hydrocortisone (HC) replacement therapy is associated with improved bone remodeling balance in hypopituitary subjects

    LENUS (Irish Health Repository)

    Behan, L A

    2011-06-01

    The effect of commonly used glucocorticoid replacement regimens on bone health in hypopituitary subjects is not well known. We aimed to assess the effect of 3 hydrocortisone (HC) replacement dose regimens on bone turnover in this group.10 hypopituitary men with severe ACTH deficiency were randomised in a crossover design to 3 HC dose regimens, Dose A (20mg mane, 10mg tarde), Dose B (10mg twice daily) and Dose C (10mg mane, 5mg tarde). Following 6 weeks of each regimen participants underwent fasting sampling of bone turnover markers.Data from matched controls were used to produce a Z score for subject bone formation and resorption markers and to calculate the bone remodeling balance (formation Z score-resorption Z score) and turnover index ((formation Z + resorption Z)\\/2). A positive bone remodeling balance with increased turnover is consistent with a favourable bone cycle. Data are expressed as median (range).The Pro Collagen Type 1 Peptide (PINP) bone formation Z-score was significantly increased in Dose C, (1.805 (-0.6-10.24)) compared to Dose A (0.035 (-1.0-8.1)) p<0.05 while there was no difference in the C-terminal crosslinking telopeptide (CTx) resorption Z score. The bone remodeling balance was significantly lower for dose A -0.02 (-1.05-4.12) compared to dose C 1.13 (0.13-6.4) (p<0.05). Although there was a trend to an increased bone turnover index with the lower dose regimen, this was not statistically significant.Low dose HC replacement (10mg mane\\/5 mg tarde) was associated with increased bone formation and improved bone remodeling balance which is associated with a more favourable bone cycle. This may have a long term beneficial effect on bone health.

  5. A systematic review protocol on the effectiveness of therapeutic exercises utilised by physiotherapists to improve function in patients with burns

    Directory of Open Access Journals (Sweden)

    Tapfuma Mudawarima

    2017-10-01

    Full Text Available Abstract Background Therapeutic exercises play a crucial role in the management of burn injuries. The broad objective of this review is to systematically evaluate the effectiveness, safety and applicability to low-income countries of therapeutic exercises utilised by physiotherapists to improve function in patients with burns. Population = adults and children/adolescents with burns of any aspect of their bodies. Interventions = any aerobic and/or strength exercises delivered as part of a rehabilitation programme by anyone (e.g. physiotherapists, occupational therapists, nurses, doctors, community workers and patients themselves. Comparators = any comparator. Outcomes = any measure of outcome (e.g. quality of life, pain, muscle strength, range of movement, fear or quality of movement. Settings = any setting in any country. Methods/design A systematic review will be conducted by two blinded independent reviewers who will search articles on PubMed, CiNAHL, Cochrane library, Medline, Pedro, OTseeker, EMBASE, PsychINFO and EBSCOhost using predefined criteria. Studies of human participants of any age suffering from burns will be eligible, and there will be no restrictions on total body surface area. Only randomised controlled trials will be considered for this review, and the methodological quality of studies meeting the selection criteria will be evaluated using the Cochrane Collaboration tool for assessing risk of bias. The PRISMA reporting standards will be used to write the review. A narrative analysis of the findings will be done, but if pooling is possible, meta-analysis will be considered. Discussion Burns may have a long-lasting impact on both psychological and physical functioning and thus it is important to identify and evaluate the effects of current and past aerobic and strength exercises on patients with burns. By identifying the characteristics of effective exercise programmes, guidelines can be suggested for developing intervention

  6. EcoDoses. Improving radiological assessment of doses to man from terrestrial ecosystems. A status report for the NKS-B project 2004

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Sven P.; Isaksson, M.; Nilsson, Elisabeth (and others)

    2005-07-01

    The NKS B-programme EcoDoses project started in 2003 as a collaboration between all the Nordic countries. The aim of the project is to improve the radiological assessments of doses to man from terrestrial ecosystems. The present report sums up the work performed in the second phase of the project. The main topics in 2004 have been: (i) A continuation of previous work with a better approach for estimating global fallout on a regional or national scale, based on a correlation between precipitation and deposition rates. (ii) Fur-ther extension of the EcoDoses milk database. Estimation of effective ecological half lives of {sup 137}Cs in cows milk focussing on suitable post-Chernobyl time-series. Modelling integrated transfer of {sup 13}7{sup C}s to cow's milk from Nordic countries. (iii) Determination of effective ecological half lives for fresh water fish from Nordic lakes. (iv) Investigate ra-dioecological sensitivity for Nordic populations. (v) Food-chain modelling using the Eco-sys-model, which is the underlying food- and dose-module in several computerised deci-sion-making systems. (au)

  7. EcoDoses. Improving radiological assessment of doses to man from terrestrial ecosystems. A status report for the NKS-B project 2004

    International Nuclear Information System (INIS)

    Nielsen, Sven P.; Isaksson, M.; Nilsson, Elisabeth

    2005-07-01

    The NKS B-programme EcoDoses project started in 2003 as a collaboration between all the Nordic countries. The aim of the project is to improve the radiological assessments of doses to man from terrestrial ecosystems. The present report sums up the work performed in the second phase of the project. The main topics in 2004 have been: (i) A continuation of previous work with a better approach for estimating global fallout on a regional or national scale, based on a correlation between precipitation and deposition rates. (ii) Fur-ther extension of the EcoDoses milk database. Estimation of effective ecological half lives of 137 Cs in cows milk focussing on suitable post-Chernobyl time-series. Modelling integrated transfer of 13 7 C s to cow's milk from Nordic countries. (iii) Determination of effective ecological half lives for fresh water fish from Nordic lakes. (iv) Investigate ra-dioecological sensitivity for Nordic populations. (v) Food-chain modelling using the Eco-sys-model, which is the underlying food- and dose-module in several computerised deci-sion-making systems. (au)

  8. Pre-therapeutic blood dosimetry in patients with differentiated thyroid carcinoma using 124-iodine. Predicted blood doses correlate with changes in blood cell counts after radioiodine therapy and depend on modes of TSH stimulation and number of preceding radioiodine therapies

    International Nuclear Information System (INIS)

    Hartung-Knemeyer, V.; Nagarajah, J.; Jentzen, W.; Ruhlmann, M.; Freudenberg, L.S.; Stahl, A.R.; Bockisch, A.; Rosenbaum-Krumme, S.J.

    2012-01-01

    Pre-therapeutic blood dosimetry prior to a high-dose radioiodine therapy (RAIT) is recommended and a blood dose of 2 Gy is considered to be safe. In this study, changes in the blood cell count after radioiodine therapy of high risk differentiated thyroid carcinoma (DTC) were analyzed and compared with the results of the pre-therapeutic blood dosimetry using 124 I. Moreover, the influence of different modes of TSH stimulation and the number of preceding radioiodine therapies on the blood dose were assessed. 198 patients with locally advanced or metastasized DTC received a pre-therapeutic blood dosimetry using 124 I. To analyze the influence of the modes of TSH stimulation and the number of preceding RAITs on blood dose subgroups were built as follows: patients with endogenous TSH stimulation versus patients with exogenous TSH stimulation and patients with no preceding RAIT versus patients with at least one preceding RAIT. In 124/198 patients subsequent RAIT was performed. In 73/124 patients, hemograms were performed from day 2 to 12 month after RAIT. There was no high-grade bone marrow toxicity (id est (i.e.) ≥grade 3) in patients receiving less than 2 Gy blood dose-independent of the therapeutic history. Within the first month after radioiodine therapy, there was an overall decrease in the white blood cell and platelet counts. The erythrocyte count was essentially stable. There was a correlation between cell count decrease and predicted blood doses (Spearman's correlation coefficient >-0.6 each) for the white cell line and the platelets. With regard to the subgroups, the blood dose per administered 131 I activity (BDpA) was significantly higher in patients with endogenous TSH stimulation (median 0.08 Gy/GBq) than in patients with exogenous TSH stimulation (0.06 Gy/GBq) and in patients with no previous RAIT (0.08 Gy/GBq) compared to patients who had previously undergone at least one RAIT (0.07 Gy/GBq). The range of BDpA among DTC patients is rather wide. Our

  9. Cranial CT with adaptive statistical iterative reconstruction: improved image quality with concomitant radiation dose reduction.

    Science.gov (United States)

    Rapalino, O; Kamalian, Shervin; Kamalian, Shahmir; Payabvash, S; Souza, L C S; Zhang, D; Mukta, J; Sahani, D V; Lev, M H; Pomerantz, S R

    2012-04-01

    To safeguard patient health, there is great interest in CT radiation-dose reduction. The purpose of this study was to evaluate the impact of an iterative-reconstruction algorithm, ASIR, on image-quality measures in reduced-dose head CT scans for adult patients. Using a 64-section scanner, we analyzed 100 reduced-dose adult head CT scans at 6 predefined levels of ASIR blended with FBP reconstruction. These scans were compared with 50 CT scans previously obtained at a higher routine dose without ASIR reconstruction. SNR and CNR were computed from Hounsfield unit measurements of normal GM and WM of brain parenchyma. A blinded qualitative analysis was performed in 10 lower-dose CT datasets compared with higher-dose ones without ASIR. Phantom data analysis was also performed. Lower-dose scans without ASIR had significantly lower mean GM and WM SNR (P = .003) and similar GM-WM CNR values compared with higher routine-dose scans. However, at ASIR levels of 20%-40%, there was no statistically significant difference in SNR, and at ASIR levels of ≥60%, the SNR values of the reduced-dose scans were significantly higher (P ASIR levels of ≥40% (P ASIR levels ≥60% (P ASIR in adult head CT scans reduces image noise and increases low-contrast resolution, while allowing lower radiation doses without affecting spatial resolution.

  10. Use of an electron reflector to improve dose uniformity at the vertex during total skin electron therapy

    International Nuclear Information System (INIS)

    Peters, V.G.

    2000-01-01

    Purpose: The vertex of the scalp is always tangentially irradiated during total skin electron therapy (TSET). This study was conducted to determine the dose distribution at the vertex for a commonly used irradiation technique and to evaluate the use of an electron reflector, positioned above the head, as a means of improving the dose uniformity. Methods and Materials: Phantoms, simulating the head of a patient, were irradiated using our standard procedure for TSET. The technique is a six-field irradiation using dual angled electron beams at a treatment distance of 3.6 meters. Vertex dosimetry was performed using ionization methods and film. Measurements were made for an unmodified 6 MeV electron beam and for a 4 MeV beam obtained by placing an acrylic scattering plate in the beam line. Studies were performed to examine the effect of electron scattering on vertex dose when a lead reflector, 50 x 50 cm in area, was positioned above the phantom. Results: The surface dose at the vertex, in the absence of the reflector, was found to be less than 40% of the prescribed skin dose. Use of the lead reflector increased this value to 73% for the 6 MeV beam and 99% for the degraded 4 MeV beam. Significant improvements in depth dose were also observed. The dose enhancement is not strongly dependent on reflector distance or angulation since the reflector acts as a large source of broadly scattered electrons. Conclusion: The vertex may be significantly underdosed using standard techniques for total skin electron therapy. Use of an electron reflector improves the dose uniformity at the vertex and may reduce or eliminate the need for supplemental irradiation

  11. Focal Radiation Therapy Dose Escalation Improves Overall Survival in Locally Advanced Pancreatic Cancer Patients Receiving Induction Chemotherapy and Consolidative Chemoradiation

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, Sunil, E-mail: skrishnan@mdanderson.org [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Chadha, Awalpreet S. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Suh, Yelin [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Chen, Hsiang-Chun [Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas (United States); Rao, Arvind [Department of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, Texas (United States); Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States); Sawakuchi, Gabriel O. [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Graduate School of Biomedical Sciences, The University of Texas, Houston, Texas (United States); Beddar, Sam [Department of Radiation Physics, The University of Texas, Houston, Texas (United States); Katz, Matthew H.; Fleming, Jason B. [Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Javle, Milind M.; Varadhachary, Gauri R.; Wolff, Robert A. [Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Crane, Christopher H. [Department of Radiation Oncology, The University of Texas, Houston, Texas (United States)

    2016-03-15

    Purpose: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent. Methods and Materials: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2- to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to local-regional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest. Results: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED >70 Gy had a superior OS (17.8 vs 15.0 months, P=.03), which was preserved throughout the follow-up period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=.05) as compared with those receiving BED ≤70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis. Conclusion: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS.

  12. H-Ferritin Enriches the Curcumin Uptake and Improves the Therapeutic Efficacy in Triple Negative Breast Cancer Cells.

    Science.gov (United States)

    Pandolfi, Laura; Bellini, Michela; Vanna, Renzo; Morasso, Carlo; Zago, Andrea; Carcano, Sofia; Avvakumova, Svetlana; Bertolini, Jessica Armida; Rizzuto, Maria Antonietta; Colombo, Miriam; Prosperi, Davide

    2017-10-09

    Triple negative breast cancer (TNBC) is a highly aggressive, invasive, and metastatic tumor. Although it is reported to be sensitive to cytotoxic chemotherapeutics, frequent relapse and chemoresistance often result in treatment failure. In this study, we developed a biomimetic nanodrug consisting of a self-assembling variant (HFn) of human apoferritin loaded with curcumin. HFn nanocage improved the solubility, chemical stability, and bioavailability of curcumin, allowing us to reliably carry out several experiments in the attempt to establish the potential of this molecule as a therapeutic agent and elucidate the mechanism of action in TNBC. HFn biopolymer was designed to bind selectively to the TfR1 receptor overexpressed in TNBC cells. HFn-curcumin (CFn) proved to be more effective in viability assays compared to the drug alone using MDA-MB-468 and MDA-MB-231 cell lines, representative of basal and claudin-low TNBC subtypes, respectively. Cellular uptake of CFn was demonstrated by flow cytometry and label-free confocal Raman imaging. CFn could act as a chemosensitizer enhancing the cytotoxic effect of doxorubicin by interfering with the activity of multidrug resistance transporters. In addition, CFn exhibited different cell cycle effects on these two TNBC cell lines, blocking MDA-MB-231 in G0/G1 phase, whereas MDA-MB-468 accumulated in G2/M phase. CFn was able to inhibit the Akt phosphorylation, suggesting that the effect on the proliferation and cell cycle involved the alteration of PI3K/Akt pathway.

  13. 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

  14. Improvement of single detector proton radiography by incorporating intensity of time-resolved dose rate functions

    Science.gov (United States)

    Zhang, Rongxiao; Jee, Kyung-Wook; Cascio, Ethan; Sharp, Gregory C.; Flanz, Jacob B.; Lu, Hsiao-Ming

    2018-01-01

    Proton radiography, which images patients with the same type of particles as those with which they are to be treated, is a promising approach to image guidance and water equivalent path length (WEPL) verification in proton radiation therapy. We have shown recently that proton radiographs could be obtained by measuring time-resolved dose rate functions (DRFs) using an x-ray amorphous silicon flat panel. The WEPL values were derived solely from the root-mean-square (RMS) of DRFs, while the intensity information in the DRFs was filtered out. In this work, we explored the use of such intensity information for potential improvement in WEPL accuracy and imaging quality. Three WEPL derivation methods based on, respectively, the RMS only, the intensity only, and the intensity-weighted RMS were tested and compared in terms of the quality of obtained radiograph images and the accuracy of WEPL values. A Gammex CT calibration phantom containing inserts made of various tissue substitute materials with independently measured relative stopping powers (RSP) was used to assess the imaging performances. Improved image quality with enhanced interfaces was achieved while preserving the accuracy by using intensity information in the calibration. Other objects, including an anthropomorphic head phantom, a proton therapy range compensator, a frozen lamb’s head and an ‘image quality phantom’ were also imaged. Both the RMS only and the intensity-weighted RMS methods derived RSPs within  ±  1% for most of the Gammex phantom inserts, with a mean absolute percentage error of 0.66% for all inserts. In the case of the insert with a titanium rod, the method based on RMS completely failed, whereas that based on the intensity-weighted RMS was qualitatively valid. The use of intensity greatly enhanced the interfaces between different materials in the obtained WEPL images, suggesting the potential for image guidance in areas such as patient positioning and tumor tracking by proton

  15. Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

    Science.gov (United States)

    Ahmed, Lamiaa A; Rizk, Sherine M; El-Maraghy, Shohda A

    2017-08-15

    Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being i.v. injected into rats 2weeks after monocrotaline administration. Four weeks after monocrotaline administration, blood pressure, electrocardiography and right ventricular systolic pressure were recorded. Rats were sacrificed and serum was separated for determination of endothelin-1 and asymmetric dimethylarginine levels. Right ventricles and lungs were isolated for estimation of tumor necrosis factor-alpha and transforming growth factor-beta contents as well as caspase-3 activity. Moreover, protein expression of matrix metalloproteinase-9 and endothelial nitric oxide synthase in addition to myocardial connexin-43 was assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte cross-sectional area and right ventricular hypertrophy was performed and cryosections were done for estimation of cell homing. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells' effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a significant amelioration of endothelial markers and cell homing and prevented monocrotaline-induced changes in right ventricular function and histological analysis compared with native cells alone. In conclusion, pinocembrin significantly improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats

  16. High dose vitamin D may improve lower urinary tract symptoms in postmenopausal women.

    Science.gov (United States)

    Oberg, Johanna; Verelst, Margareta; Jorde, Rolf; Cashman, Kevin; Grimnes, Guri

    2017-10-01

    Lower urinary tract symptoms (LUTS) are common in postmenopausal women, and have been reported inversely associated with vitamin D intake and serum 25-hydroxyvitamin D (25(OH)D) levels. The aim of this study was to investigate if high dose vitamin D supplementation would affect LUTS in comparison to standard dose. In a randomized controlled study including 297 postmenopausal women with low bone mineral density, the participants were allocated to receive capsules of 20 000IU of vitamin D 3 twice a week (high dose group) or similar looking placebo (standard dose group). In addition, all the participants received 1g of calcium and 800IU of vitamin D daily. A validated questionnaire regarding LUTS was filled in at baseline and after 12 months. At baseline, 76 women in the high dose group and 82 in the standard dose group reported any LUTS. Levels of serum 25(OH)D increased significantly more in the high dose group (from 64.7 to 164.1nmol/l compared to from 64.1 to 81.8nmol/l, p<0.01). No differences between the groups were seen regarding change in LUTS except for a statistically significant reduction in the reported severity of urine incontinence in the high dose group as compared to the standard dose group after one year (p<0.05). The results need confirmation in a study specifically designed for this purpose. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Org 214007-0: a novel non-steroidal selective glucocorticoid receptor modulator with full anti-inflammatory properties and improved therapeutic index.

    Science.gov (United States)

    van Lierop, Marie-José C; Alkema, Wynand; Laskewitz, Anke J; Dijkema, Rein; van der Maaden, Hans M; Smit, Martin J; Plate, Ralf; Conti, Paolo G M; Jans, Christan G J M; Timmers, C Marco; van Boeckel, Constant A A; Lusher, Scott J; McGuire, Ross; van Schaik, Rene C; de Vlieg, Jacob; Smeets, Ruben L; Hofstra, Claudia L; Boots, Annemieke M H; van Duin, Marcel; Ingelse, Benno A; Schoonen, Willem G E J; Grefhorst, Aldo; van Dijk, Theo H; Kuipers, Folkert; Dokter, Wim H A

    2012-01-01

    Glucocorticoids (GCs) such as prednisolone are potent immunosuppressive drugs but suffer from severe adverse effects, including the induction of insulin resistance. Therefore, development of so-called Selective Glucocorticoid Receptor Modulators (SGRM) is highly desirable. Here we describe a non-steroidal Glucocorticoid Receptor (GR)-selective compound (Org 214007-0) with a binding affinity to GR similar to that of prednisolone. Structural modelling of the GR-Org 214007-0 binding site shows disturbance of the loop between helix 11 and helix 12 of GR, confirmed by partial recruitment of the TIF2-3 peptide. Using various cell lines and primary human cells, we show here that Org 214007-0 acts as a partial GC agonist, since it repressed inflammatory genes and was less effective in induction of metabolic genes. More importantly, in vivo studies in mice indicated that Org 214007-0 retained full efficacy in acute inflammation models as well as in a chronic collagen-induced arthritis (CIA) model. Gene expression profiling of muscle tissue derived from arthritic mice showed a partial activity of Org 214007-0 at an equi-efficacious dosage of prednisolone, with an increased ratio in repression versus induction of genes. Finally, in mice Org 214007-0 did not induce elevated fasting glucose nor the shift in glucose/glycogen balance in the liver seen with an equi-efficacious dose of prednisolone. All together, our data demonstrate that Org 214007-0 is a novel SGRMs with an improved therapeutic index compared to prednisolone. This class of SGRMs can contribute to effective anti-inflammatory therapy with a lower risk for metabolic side effects.

  18. Xylitol improves pancreatic islets morphology to ameliorate type 2 diabetes in rats: a dose response study.

    Science.gov (United States)

    Rahman, Md Atiar; Islam, Md Shahdiul

    2014-07-01

    Xylitol has been reported as a potential antidiabetic sweetener in a number of recent studies; however, the most effective dietary dose and organ-specific effects are still unclear. Six-week-old male Sprague-Dawley rats were randomly divided into 5 groups: normal control (NC), diabetic control (DBC), diabetic xylitol 2.5% (DXL2.5), diabetic xylitol 5.0% (DXL5), and diabetic xylitol 10.0% (DXL10). Diabetes was induced only in the animals in DBC and DXL groups and considered diabetic when their nonfasting blood glucose level was >300 mg/dL. The DXL groups were fed with 2.5%, 5.0%, and 10% xylitol solution, whereas the NC and DBC groups were supplied with normal drinking water. After 4-wk intervention, body weight, food and fluid intake, blood glucose, serum fructosamine, liver glycogen, serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, creatine kinase, uric acid, creatinine, and most serum lipids were significantly decreased, and serum insulin concentration, glucose tolerance ability, and pancreatic islets morphology were significantly improved in the DXL10 group compared to the DBC group. The data of this study suggest that 10% xylitol has the better antidiabetic effects compared to 2.5% and 5.0% and it can be used as an excellent antidiabetic sweetener and food supplement in antidiabetic foods. Xylitol is widely used as a potential anticariogenic and sweetening agent in a number of oral care and food products when many of its health benefits are still unknown. Due to its similar sweetening power but lower calorific value (2.5 compared with 4 kcal) and lower glycemic index (13 compared with 65) compared to sucrose, recently it has been widely used as a sugar substitute particularly by overweight, obese, and diabetic patients in order to reduce their calorie intake from sucrose. However, the potential antidiabetic effects of xylitol have been discovered recently. The results of this study confirmed the effective dietary dose of xylitol for

  19. Chloroquine Improves Survival and Hematopoietic Recovery After Lethal Low-Dose-Rate Radiation

    International Nuclear Information System (INIS)

    Lim Yiting; Hedayati, Mohammad; Merchant, Akil A.; Zhang Yonggang; Yu, Hsiang-Hsuan M.; Kastan, Michael B.; Matsui, William; DeWeese, Theodore L.

    2012-01-01

    Purpose: We have previously shown that the antimalarial agent chloroquine can abrogate the lethal cellular effects of low-dose-rate (LDR) radiation in vitro, most likely by activating the ataxia-telangiectasia mutated (ATM) protein. Here, we demonstrate that chloroquine treatment also protects against lethal doses of LDR radiation in vivo. Methods and Materials: C57BL/6 mice were irradiated with a total of 12.8 Gy delivered at 9.4 cGy/hour. ATM null mice from the same background were used to determine the influence of ATM. Chloroquine was administered by two intraperitoneal injections of 59.4 μg per 17 g of body weight, 24 hours and 4 hours before irradiation. Bone marrow cells isolated from tibia, fibula, and vertebral bones were transplanted into lethally irradiated CD45 congenic recipient mice by retroorbital injection. Chimerism was assessed by flow cytometry. In vitro methylcellulose colony-forming assay of whole bone marrow cells and fluorescence activated cell sorting analysis of lineage depleted cells were used to assess the effect of chloroquine on progenitor cells. Results: Mice pretreated with chloroquine before radiation exhibited a significantly higher survival rate than did mice treated with radiation alone (80% vs. 31%, p = 0.0026). Chloroquine administration before radiation did not affect the survival of ATM null mice (p = 0.86). Chloroquine also had a significant effect on the early engraftment of bone marrow cells from the irradiated donor mice 6 weeks after transplantation (4.2% vs. 0.4%, p = 0.015). Conclusion: Chloroquine administration before radiation had a significant effect on the survival of normal but not ATM null mice, strongly suggesting that the in vivo effect, like the in vitro effect, is also ATM dependent. Chloroquine improved the early engraftment of bone marrow cells from LDR-irradiated mice, presumably by protecting the progenitor cells from radiation injury. Chloroquine thus could serve as a very useful drug for protection

  20. Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with high-dose Interleukin-2: evaluation of biomarkers of immunologic and therapeutic response.

    Science.gov (United States)

    Ridolfi, Laura; de Rosa, Francesco; Ridolfi, Ruggero; Gentili, Giorgia; Valmorri, Linda; Scarpi, Emanuela; Parisi, Elisabetta; Romeo, Antonino; Guidoboni, Massimo

    2014-09-23

    Tumor cells killed by radiation therapy (RT) are a potentially good source of antigens for dendritic cell (DC) uptake and presentation to T-cells. RT upregulates cell death receptors such as Fas/CD95 and MHC-I, induces the expression of co-stimulatory molecules on tumor cells, and promotes production of pro-inflammatory cytokines. High-dose interleukin-2 (HD-IL-2) bolus has been shown to obtain objective response rates ranging from 15% to 17% in patients with metastatic melanoma or renal cell carcinoma (RCC), with 6% to 8% of cases experiencing a durable complete response. However, HD-IL-2 is also associated with severe side-effects; if it is to remain a component of the curative treatment strategy in patients with metastatic melanoma or RCC, its therapeutic efficacy must be improved and patients who are most likely to benefit from treatment must be identified a priori. We designed a clinical study combining immunomodulating RT and HD-IL-2 to evaluate their clinical and immunological efficacy and to explore the predictive and prognostic value of 1) tumor-specific immune response and 2) serum levels of proangiogenic cytokines. The primary endpoint of this proof-of-principle phase II study is immune response. Secondary endpoints are the identification of biomarkers potentially predictive of response, toxicity, response rate and overall survival. Three daily doses of booster radiotherapy (XRT) at 6-12 Gy will be administered to at least one metastatic field on days -3 to -1 before the first and third cycle. Treatment with IL-2 (dose 18 MIU/m2/day by continuous IV infusion for 72 hours) will start on day +1 and will be repeated every 3 weeks for up to 4 cycles and then every 4 weeks for a further 2 cycles. Immune response against tumor antigens expressed by melanoma and/or RCC will be evaluated during treatment. Circulating immune effectors and regulators, e.g. cytotoxic T lymphocytes and regulatory T cells, as well as serum levels of proangiogenic

  1. A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.

    Directory of Open Access Journals (Sweden)

    Simon D Angus

    Full Text Available Multi-dose radiotherapy protocols (fraction dose and timing currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5% and 7.1% (13.3% improvement (reduction on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h, leading to the discovery that the performance of the GA search candidates could be replicated by 17-18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost

  2. A matter of timing: identifying significant multi-dose radiotherapy improvements by numerical simulation and genetic algorithm search.

    Science.gov (United States)

    Angus, Simon D; Piotrowska, Monika Joanna

    2014-01-01

    Multi-dose radiotherapy protocols (fraction dose and timing) currently used in the clinic are the product of human selection based on habit, received wisdom, physician experience and intra-day patient timetabling. However, due to combinatorial considerations, the potential treatment protocol space for a given total dose or treatment length is enormous, even for relatively coarse search; well beyond the capacity of traditional in-vitro methods. In constrast, high fidelity numerical simulation of tumor development is well suited to the challenge. Building on our previous single-dose numerical simulation model of EMT6/Ro spheroids, a multi-dose irradiation response module is added and calibrated to the effective dose arising from 18 independent multi-dose treatment programs available in the experimental literature. With the developed model a constrained, non-linear, search for better performing cadidate protocols is conducted within the vicinity of two benchmarks by genetic algorithm (GA) techniques. After evaluating less than 0.01% of the potential benchmark protocol space, candidate protocols were identified by the GA which conferred an average of 9.4% (max benefit 16.5%) and 7.1% (13.3%) improvement (reduction) on tumour cell count compared to the two benchmarks, respectively. Noticing that a convergent phenomenon of the top performing protocols was their temporal synchronicity, a further series of numerical experiments was conducted with periodic time-gap protocols (10 h to 23 h), leading to the discovery that the performance of the GA search candidates could be replicated by 17-18 h periodic candidates. Further dynamic irradiation-response cell-phase analysis revealed that such periodicity cohered with latent EMT6/Ro cell-phase temporal patterning. Taken together, this study provides powerful evidence towards the hypothesis that even simple inter-fraction timing variations for a given fractional dose program may present a facile, and highly cost-effecitive means

  3. Improvements on a patient-specific dose estimation system in nuclear medicine examination

    International Nuclear Information System (INIS)

    Chuang, K. S.; Lu, J. C.; Lin, H. H.; Dong, S. L.; Yang, H. J.; Shih, C. T.; Lin, C. H.; Yao, W. J.; Ni, Y. C.; Jan, M. L.; Chang, S. J.

    2014-01-01

    The purpose of this paper is to develop a patient-specific dose estimation system in nuclear medicine examination. A dose deposition routine to store the deposited energy of the photons during their flights was embedded in the widely used SimSET Monte Carlo code and a user-friendly interface for reading PET and CT images was developed. Dose calculated on ORNL phantom was used to validate the accuracy of this system. The ratios of S value for 99m Tc, 18 F and 131 I computed by this system to those obtained with OLINDA for various organs were ranged from 0.93 to 1.18, which were comparable to that obtained from MCNPX2.6 code (0.88-1.22). Our system developed provides opportunity for tumor dose estimation which cannot be known from the MIRD. The radiation dose can provide useful information in the amount of radioisotopes to be administered in radioimmunotherapy. (authors)

  4. Citation trend and suggestions for improvement of impact factor of Journal of Korean Therapeutic Radiology and Oncology

    International Nuclear Information System (INIS)

    Kim, Seong Hwan; Hwang, Seong Su; Ahn, Myeong Im; Jeong, So Na

    2006-01-01

    To analyze the recent citation trend and to find a way to improve impact factor (IF) of the Journal of Korean Therapeutic Radiology and Oncology (JKSTRO) by analysis of Korean Medical Citation index (KoMCI) citation data of JKSTRO and comparison with that of mean citation data of all journals enlisted on KoMCI (KoMCI journals) during 2000-2005. All citation data of entire journals enlisted on KoMCI and JKSTRO from 2000 to 2005 were obtained from KoMCI. The trend of total and annual number of published articles and reference citations, total citations and self-citations per paper, IF and impact factor excluding self-citations (ZIF) were described and compared on both KoMCI journals an JKSTRO. Annual number of published articles was decreased for 6 years on both KoMCI journals and JKSTRO (32% and 38% reduction rate). The number of Korean journal references per article is 1.6 papers of JKSTRO comparing to 2.0 papers on KoMCI journals. The percentage of Korean references/total references increased from 5.0% in 2000 to 7.7% in 2005 on JKSTRO and from 8.5% in 2000 to 10.1% on KoMCI journals. The number of total citations received/paper on JKSTRO (average 1.333) is smaller than that of KoMCI journals (average 1.694), there was an increased rate of 67% in 2005 comparing to 2000. The percentage of self-citations/total citations (average 72%) on JKSTRO is slightly higher than that of KoMCI journals (average 61%)/ IF of JKSTRO was gradually improved and 0.144, 0.125, 0.088, 0.107, 0.187 and 0.203 in 2000-2005 respectively. However, ZIF of JKSTRO is steadily decreased from 0.038 in 2000 to 0.013 in 2005 except 0.044 in 2004. IF of JKSTRO was slightly improved but had some innate problem of smaller number of citations received . To make JKSTRO as a highly cited journal, the awareness of academic status of JKSTRO and active participation of every member of JKSTRO including encouraging self-citations of papers published recent 2 years and submission of English written papers, and

  5. [Therapeutic approaches to improve blood glucose control in a patient with type 2 diabetes on a metformin-sulfonylurea combination].

    Science.gov (United States)

    Scheen, A J; Paquot, N

    2011-04-01

    Beyond lifestyle changes, the management of type 2 diabetes comprises the administration of oral glucose-lowering agents, especially the classical metformin-sulfonylurea combination. If such a dual oral therapy could not (any more) obtain an adequate glucose control, intensified management becomes mandatory. Several therapeutic approaches may be proposed at this stage, with some advantages and disadvantages of each of them. The present clinical case aims at illustrating such difficult therapeutic choice. We will provide the pro-contra arguments concerning each therapeutic alternative and describe the practical modalities of an appropriate management according to the patient's characteristics.

  6. Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography.

    Directory of Open Access Journals (Sweden)

    M G Gerritsen

    Full Text Available We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4% had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197. Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.

  7. Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography.

    Science.gov (United States)

    Gerritsen, M G; Willemink, M J; Pompe, E; van der Bruggen, T; van Rhenen, A; Lammers, J W J; Wessels, F; Sprengers, R W; de Jong, P A; Minnema, M C

    2017-01-01

    We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.

  8. An LC-MS Assay with Isocratic Separation and On-Line Solid Phase Extraction to Improve the Routine Therapeutic Drug Monitoring of Busulfan in Plasma

    Directory of Open Access Journals (Sweden)

    Ialongo Cristiano

    2017-04-01

    Full Text Available Background: Busulfan (Bu requires therapeutic drug monitoring (TDM in subjects undergoing a conditioning regimen for hematopoietic stem cell transplantation (HSCT. To speed up the procedure and increase reproducibility, we improved our routine LC-MS/MS assay using the on-line solid-phase extraction (SPE of samples.

  9. Head CT: Image quality improvement with ASIR-V using a reduced radiation dose protocol for children.

    Science.gov (United States)

    Kim, Hyun Gi; Lee, Ho-Joon; Lee, Seung-Koo; Kim, Hyun Ji; Kim, Myung-Joon

    2017-09-01

    To investigate the quality of images reconstructed with adaptive statistical iterative reconstruction V (ASIR-V), using pediatric head CT protocols. A phantom was scanned at decreasing 20% mA intervals using our standard pediatric head CT protocols. Each study was then reconstructed at 10% ASIR-V intervals. After the phantom study, we reduced mA by 10% in the protocol for ASIR-V and by 30% in the protocol for 3- to 15-year-old patients and applied 40% ASIR-V. Increasing the percentage of ASIR-V resulted in lower noise and higher contrast-to-noise ratio (CNR) and preserved spatial resolution in the phantom study. Compared to a conventional-protocol, reduced-dose protocol with ASIR-V achieved 12.8% to 34.0% of dose reduction and showed images of lower noise (9.22 vs. 10.73, P = 0.043) and higher CNR in different levels (centrum semiovale, 2.14 vs. 1.52, P = 0.003; basal ganglia, 1.46 vs. 1.07, P = 0.001; and cerebellum, 2.18 vs. 1.33, P ASIR-V. Use of ASIR-V allowed a 12.8% to 34.0% dose reduction in each age group with potential to improve image quality. • It is possible to reduce radiation dose and improve image quality with ASIR-V. • We improved noise and CNR and decreased radiation dose. • Sharpness improved with ASIR-V. • Total radiation dose was decreased by 12.8% to 34.0%.

  10. High dose sapropterin dihydrochloride therapy improves monoamine neurotransmitter turnover in murine phenylketonuria (PKU).

    Science.gov (United States)

    Winn, Shelley R; Scherer, Tanja; Thöny, Beat; Harding, Cary O

    2016-01-01

    Central nervous system (CNS) deficiencies of the monoamine neurotransmitters, dopamine and serotonin, have been implicated in the pathophysiology of neuropsychiatric dysfunction in phenylketonuria (PKU). Increased brain phenylalanine concentration likely competitively inhibits the activities of tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH), the rate limiting steps in dopamine and serotonin synthesis respectively. Tetrahydrobiopterin (BH4) is a required cofactor for TH and TPH activity. Our hypothesis was that treatment of hyperphenylalaninemic Pah(enu2/enu2) mice, a model of human PKU, with sapropterin dihydrochloride, a synthetic form of BH4, would stimulate TH and TPH activities leading to improved dopamine and serotonin synthesis despite persistently elevated brain phenylalanine. Sapropterin (20, 40, or 100mg/kg body weight in 1% ascorbic acid) was administered daily for 4 days by oral gavage to Pah(enu2/enu2) mice followed by measurement of brain biopterin, phenylalanine, tyrosine, tryptophan and monoamine neurotransmitter content. A significant increase in brain biopterin content was detected only in mice that had received the highest sapropterin dose, 100mg/kg. Blood and brain phenylalanine concentrations were unchanged by sapropterin therapy. Sapropterin therapy also did not alter the absolute amounts of dopamine and serotonin in brain but was associated with increased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), dopamine and serotonin metabolites respectively, in both wild type and Pah(enu2/enu2) mice. Oral sapropterin therapy likely does not directly affect central nervous system monoamine synthesis in either wild type or hyperphenylalaninemic mice but may stimulate synaptic neurotransmitter release and subsequent metabolism. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Acute personalized habitual caffeine doses improve attention and have selective effects when considering the fractionation of executive functions.

    Science.gov (United States)

    Lanini, Juliana; Galduróz, José Carlos Fernandes; Pompéia, Sabine

    2016-01-01

    Caffeine is widely used, often consumed with food, and improves simple and complex/executive attention under fasting conditions. We investigated whether these cognitive effects are observed when personalized habitual doses of caffeine are ingested by caffeine consumers, whether they are influenced by nutriments and if various executive domains are susceptible to improvement. This was a double-blind, placebo-controlled study including 60 young, healthy, rested males randomly assigned to one of four treatments: placebo fasting, caffeine fasting, placebo meal and caffeine meal. Caffeine doses were individualized for each participant based on their self-reported caffeine consumption at the time of testing (morning). The test battery included measures of simple and sustained attention, executive domains (inhibiting, updating, shifting, dual tasking, planning and accessing long-term memory), control measures of subjective alterations, glucose and insulin levels, skin conductance, heart rate and pupil dilation. Regardless of meal intake, acute habitual doses of caffeine decreased fatigue, and improved simple and sustained attention and executive updating. This executive effect was not secondary to the habitual weekly dose consumed, changes in simple and sustained attention, mood, meal ingestion and increases in cognitive effort. We conclude that the morning caffeine "fix" has positive attentional effects and selectively improved executive updating whether or not caffeine is consumed with food. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Improved Patient Size Estimates for Accurate Dose Calculations in Abdomen Computed Tomography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chang-Lae [Yonsei University, Wonju (Korea, Republic of)

    2017-07-15

    The radiation dose of CT (computed tomography) is generally represented by the CTDI (CT dose index). CTDI, however, does not accurately predict the actual patient doses for different human body sizes because it relies on a cylinder-shaped head (diameter : 16 cm) and body (diameter : 32 cm) phantom. The purpose of this study was to eliminate the drawbacks of the conventional CTDI and to provide more accurate radiation dose information. Projection radiographs were obtained from water cylinder phantoms of various sizes, and the sizes of the water cylinder phantoms were calculated and verified using attenuation profiles. The effective diameter was also calculated using the attenuation of the abdominal projection radiographs of 10 patients. When the results of the attenuation-based method and the geometry-based method shown were compared with the results of the reconstructed-axial-CT-image-based method, the effective diameter of the attenuation-based method was found to be similar to the effective diameter of the reconstructed-axial-CT-image-based method, with a difference of less than 3.8%, but the geometry-based method showed a difference of less than 11.4%. This paper proposes a new method of accurately computing the radiation dose of CT based on the patient sizes. This method computes and provides the exact patient dose before the CT scan, and can therefore be effectively used for imaging and dose control.

  13. Improved tissue assignment using dual-energy computed tomography in low-dose rate prostate brachytherapy for Monte Carlo dose calculation

    Energy Technology Data Exchange (ETDEWEB)

    Côté, Nicolas [Département de Physique, Université de Montréal, Pavillon Roger-Gaudry (D-428), 2900 Boulevard Édouard-Montpetit, Montréal, Québec H3T 1J4 (Canada); Bedwani, Stéphane [Département de Radio-Oncologie, Centre Hospitalier de l’Université de Montréal (CHUM), 1560 Rue Sherbrooke Est, Montréal, Québec H2L 4M1 (Canada); Carrier, Jean-François, E-mail: jean-francois.carrier.chum@ssss.gouv.qc.ca [Département de Physique, Université de Montréal, Pavillon Roger-Gaudry (D-428), 2900 Boulevard Édouard-Montpetit, Montréal, Québec H3T 1J4, Canada and Département de Radio-Oncologie, Centre Hospitalier de l’Université de Montréal (CHUM), 1560 Rue Sherbrooke Est, Montréal, Québec H2L 4M1 (Canada)

    2016-05-15

    Purpose: An improvement in tissue assignment for low-dose rate brachytherapy (LDRB) patients using more accurate Monte Carlo (MC) dose calculation was accomplished with a metallic artifact reduction (MAR) method specific to dual-energy computed tomography (DECT). Methods: The proposed MAR algorithm followed a four-step procedure. The first step involved applying a weighted blend of both DECT scans (I {sub H/L}) to generate a new image (I {sub Mix}). This action minimized Hounsfield unit (HU) variations surrounding the brachytherapy seeds. In the second step, the mean HU of the prostate in I {sub Mix} was calculated and shifted toward the mean HU of the two original DECT images (I {sub H/L}). The third step involved smoothing the newly shifted I {sub Mix} and the two original I {sub H/L}, followed by a subtraction of both, generating an image that represented the metallic artifact (I {sub A,(H/L)}) of reduced noise levels. The final step consisted of subtracting the original I {sub H/L} from the newly generated I {sub A,(H/L)} and obtaining a final image corrected for metallic artifacts. Following the completion of the algorithm, a DECT stoichiometric method was used to extract the relative electronic density (ρ{sub e}) and effective atomic number (Z {sub eff}) at each voxel of the corrected scans. Tissue assignment could then be determined with these two newly acquired physical parameters. Each voxel was assigned the tissue bearing the closest resemblance in terms of ρ{sub e} and Z {sub eff}, comparing with values from the ICRU 42 database. A MC study was then performed to compare the dosimetric impacts of alternative MAR algorithms. Results: An improvement in tissue assignment was observed with the DECT MAR algorithm, compared to the single-energy computed tomography (SECT) approach. In a phantom study, tissue misassignment was found to reach 0.05% of voxels using the DECT approach, compared with 0.40% using the SECT method. Comparison of the DECT and SECT D

  14. Multi-targeted therapy for leprosy: insilico strategy to overcome multi drug resistance and to improve therapeutic efficacy.

    Science.gov (United States)

    Anusuya, Shanmugam; Natarajan, Jeyakumar

    2012-12-01

    Leprosy remains a major public health problem, since single and multi-drug resistance has been reported worldwide over the last two decades. In the present study, we report the novel multi-targeted therapy for leprosy to overcome multi drug resistance and to improve therapeutic efficacy. If multiple enzymes of an essential metabolic pathway of a bacterium were targeted, then the therapy would become more effective and can prevent the occurrence of drug resistance. The MurC, MurD, MurE and MurF enzymes of peptidoglycan biosynthetic pathway were selected for multi targeted therapy. The conserved or class specific active site residues important for function or stability were predicted using evolutionary trace analysis and site directed mutagenesis studies. Ten such residues which were present in at least any three of the four Mur enzymes (MurC, MurD, MurE and MurF) were identified. Among the ten residues G125, K126, T127 and G293 (numbered based on their position in MurC) were found to be conserved in all the four Mur enzymes of the entire bacterial kingdom. In addition K143, T144, T166, G168, H234 and Y329 (numbered based on their position in MurE) were significant in binding substrates and/co-factors needed for the functional events in any three of the Mur enzymes. These are the probable residues for designing newer anti-leprosy drugs in an attempt to reduce drug resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Poster - 53: Improving inter-linac DMLC IMRT dose precision by fine tuning of MLC leaf calibration

    International Nuclear Information System (INIS)

    Nakonechny, Keith; Tran, Muoi; Sasaki, David; Beck, James; Poirier, Yannick; Malkoske, Kyle

    2016-01-01

    Purpose: To develop a method to improve the inter-linac precision of DMLC IMRT dosimetry. Methods: The distance between opposing MLC leaf banks (“gap size”) can be finely tuned on Varian linacs. The dosimetric effect due to small deviations from the nominal gap size (“gap error”) was studied by introducing known errors for several DMLC sliding gap sizes, and for clinical plans based on the TG119 test cases. The plans were delivered on a single Varian linac and the relationship between gap error and the corresponding change in dose was measured. The plans were also delivered on eight Varian 2100 series linacs (at two institutions) in order to quantify the inter-linac variation in dose before and after fine tuning the MLC calibration. Results: The measured dose differences for each field agreed well with the predictions of LoSasso et al. Using the default MLC calibration, the variation in the physical MLC gap size was determined to be less than 0.4 mm between all linacs studied. The dose difference between the linacs with the largest and smallest physical gap was up to 5.4% (spinal cord region of the head and neck TG119 test case). This difference was reduced to 2.5% after fine tuning the MLC gap calibration. Conclusions: The inter-linac dose precision for DMLC IMRT on Varian linacs can be improved using a simple modification of the MLC calibration procedure that involves fine adjustment of the nominal gap size.

  16. Improvement of the equivalent sphere model for better estimates of skin or eye dose in space radiation environments

    International Nuclear Information System (INIS)

    Lin, Z.W.

    2011-01-01

    It is often useful to get a quick estimate of the dose or dose equivalent of an organ, such as blood-forming organs, the eye or the skin, in a radiation field. Sometimes an equivalent sphere is used to represent the organ for this purpose. For space radiation environments, recently it has been shown that the equivalent sphere model does not work for the eye or the skin in solar particle event environments. In this study, we improve the representation of the eye and the skin using a two-component equivalent sphere model. Motivated by the two-peak structure of the body organ shielding distribution for the eye and the skin, we use an equivalent sphere with two radius parameters, for example a partial spherical shell of a smaller thickness over a proper fraction of the full solid angle combined with a concentric partial spherical shell of a larger thickness over the rest of the full solid angle, to represent the eye or the skin. We find that using an equivalent sphere with two radius parameters instead of one drastically improves the accuracy of the estimates of dose and dose equivalent in space radiation environments. For example, in solar particle event environments the average error in the estimate of the skin dose equivalent using an equivalent sphere with two radius parameters is about 8%, while the average error of the conventional equivalent sphere model using one radius parameter is around 100%.

  17. Poster - 53: Improving inter-linac DMLC IMRT dose precision by fine tuning of MLC leaf calibration

    Energy Technology Data Exchange (ETDEWEB)

    Nakonechny, Keith; Tran, Muoi; Sasaki, David; Beck, James; Poirier, Yannick; Malkoske, Kyle [Simcoe-Muskoka Regional Cancer Centre (Canada)

    2016-08-15

    Purpose: To develop a method to improve the inter-linac precision of DMLC IMRT dosimetry. Methods: The distance between opposing MLC leaf banks (“gap size”) can be finely tuned on Varian linacs. The dosimetric effect due to small deviations from the nominal gap size (“gap error”) was studied by introducing known errors for several DMLC sliding gap sizes, and for clinical plans based on the TG119 test cases. The plans were delivered on a single Varian linac and the relationship between gap error and the corresponding change in dose was measured. The plans were also delivered on eight Varian 2100 series linacs (at two institutions) in order to quantify the inter-linac variation in dose before and after fine tuning the MLC calibration. Results: The measured dose differences for each field agreed well with the predictions of LoSasso et al. Using the default MLC calibration, the variation in the physical MLC gap size was determined to be less than 0.4 mm between all linacs studied. The dose difference between the linacs with the largest and smallest physical gap was up to 5.4% (spinal cord region of the head and neck TG119 test case). This difference was reduced to 2.5% after fine tuning the MLC gap calibration. Conclusions: The inter-linac dose precision for DMLC IMRT on Varian linacs can be improved using a simple modification of the MLC calibration procedure that involves fine adjustment of the nominal gap size.

  18. Design and dosimetry of an eye plaque containing I-125 seeds: An improved dose distribution

    International Nuclear Information System (INIS)

    Detorie, N.A.; Tkacik, M.F.; Neglia, W.J.; Jenkins, D.; Shadday, J.

    1986-01-01

    To treat intraocular tumors, a temporarily implanted eye plaque, containing 24 I-125 seeds (3M model 6711), was fabricated from 0.6-mm-thick lead disk with a 1.5-cm diameter. The I-125 seeds were distributed in a particular geometric pattern to average the dose anisotropy of each individual seed. Water phantom measurements made with TLD chips (LiF) and film over the approximate depth range of 1-25 mm were compared with treatment planning computer calculations (Capintec RT-108). Data indicate that the specified geometry produces a dose distribution delivering a tumor dose of 10,000 rad to the tumor apex (7 mm) without exceeding a sclera dose (1 mm) of 40,000 rad. Information regarding fabrication, dosimetry, and radiation safety is presented

  19. Cone beam CT with zonal filters for simultaneous dose reduction, improved target contrast and automated set-up in radiotherapy

    International Nuclear Information System (INIS)

    Moore, C J; Marchant, T E; Amer, A M

    2006-01-01

    Cone beam CT (CBCT) using a zonal filter is introduced. The aims are reduced concomitant imaging dose to the patient, simultaneous control of body scatter for improved image quality in the tumour target zone and preserved set-up detail for radiotherapy. Aluminium transmission diaphragms added to the CBCT x-ray tube of the Elekta Synergy TM linear accelerator produced an unattenuated beam for a central 'target zone' and a partially attenuated beam for an outer 'set-up zone'. Imaging doses and contrast noise ratios (CNR) were measured in a test phantom for transmission diaphragms 12 and 24 mm thick, for 5 and 10 cm long target zones. The effect on automatic registration of zonal CBCT to conventional CT was assessed relative to full-field and lead-collimated images of an anthropomorphic phantom. Doses along the axis of rotation were reduced by up to 50% in both target and set-up zones, and weighted dose (two thirds surface dose plus one third central dose) was reduced by 10-20% for a 10 cm long target zone. CNR increased by up to 15% in zonally filtered CBCT images compared to full-field images. Automatic image registration remained as robust as that with full-field images and was superior to CBCT coned down using lead-collimation. Zonal CBCT significantly reduces imaging dose and is expected to benefit radiotherapy through improved target contrast, required to assess target coverage, and wide-field edge detail, needed for robust automatic measurement of patient set-up error

  20. SU-D-BRB-02: Combining a Commercial Autoplanning Engine with Database Dose Predictions to Further Improve Plan Quality

    Energy Technology Data Exchange (ETDEWEB)

    Robertson, SP; Moore, JA; Hui, X; Cheng, Z; McNutt, TR [Johns Hopkins University, Baltimore, MD (United States); DeWeese, TL; Tran, P; Quon, H [John Hopkins Hospital, Baltimore, MD (United States); Bzdusek, K [Philips, Fitchburg, WI (United States); Kumar, P [Philips India Limited, Bangalore, Karnataka (India)

    2016-06-15

    Purpose: Database dose predictions and a commercial autoplanning engine both improve treatment plan quality in different but complimentary ways. The combination of these planning techniques is hypothesized to further improve plan quality. Methods: Four treatment plans were generated for each of 10 head and neck (HN) and 10 prostate cancer patients, including Plan-A: traditional IMRT optimization using clinically relevant default objectives; Plan-B: traditional IMRT optimization using database dose predictions; Plan-C: autoplanning using default objectives; and Plan-D: autoplanning using database dose predictions. One optimization was used for each planning method. Dose distributions were normalized to 95% of the planning target volume (prostate: 8000 cGy; HN: 7000 cGy). Objectives used in plan optimization and analysis were the larynx (25%, 50%, 90%), left and right parotid glands (50%, 85%), spinal cord (0%, 50%), rectum and bladder (0%, 20%, 50%, 80%), and left and right femoral heads (0%, 70%). Results: All objectives except larynx 25% and 50% resulted in statistically significant differences between plans (Friedman’s χ{sup 2} ≥ 11.2; p ≤ 0.011). Maximum dose to the rectum (Plans A-D: 8328, 8395, 8489, 8537 cGy) and bladder (Plans A-D: 8403, 8448, 8527, 8569 cGy) were significantly increased. All other significant differences reflected a decrease in dose. Plans B-D were significantly different from Plan-A for 3, 17, and 19 objectives, respectively. Plans C-D were also significantly different from Plan-B for 8 and 13 objectives, respectively. In one case (cord 50%), Plan-D provided significantly lower dose than plan C (p = 0.003). Conclusion: Combining database dose predictions with a commercial autoplanning engine resulted in significant plan quality differences for the greatest number of objectives. This translated to plan quality improvements in most cases, although special care may be needed for maximum dose constraints. Further evaluation is warranted

  1. Determination of the dose equivalents due to neutrons produced during therapeutic irradiations with a Varian CLINAC 2500; Determinacion de la dosis equivalente debida a neutrones producidos durante irradiaciones terapeuticas con un Varian CLINAC 2500

    Energy Technology Data Exchange (ETDEWEB)

    Carrillo, Ricardo E [Centro de Investigacion y de Estudios Avanzados del IPN, Unidad Merida, Yucatan (Mexico)

    1991-07-01

    This experiment it was designed to quantify that so important it is the dose equivalent deposited by the neutron flow that is generated by photonuclear reactions during therapeutic irradiations with X rays of produced high-energy for an accelerator Varian CLINAC 2500. This accelerator type is routinely used in the Department of Radiotherapy of the Hospital of the University of Wisconsin, E.U. The equivalent dose was measured in diverse towns of the room of irradiations using the activation of thin sheets of gold put in the center of plastic recipients full with water. In general, the recipients were 1 m or more than the floor and at distances still bigger than the walls. The irradiations were made using photons with the highest energy that you can select with this team - 24 MeV. The due equivalent dose to neutrons taken place here by the energy photons used they were measured and reported. (author)

  2. Comparable Senescence Induction in Three-dimensional Human Cartilage Model by Exposure to Therapeutic Doses of X-rays or C-ions.

    Science.gov (United States)

    Hamdi, Dounia Houria; Chevalier, François; Groetz, Jean-Emmanuel; Durantel, Florent; Thuret, Jean-Yves; Mann, Carl; Saintigny, Yannick

    2016-05-01

    Particle therapy using carbon ions (C-ions) has been successfully used in the treatment of tumors resistant to conventional radiation therapy. However, the potential side effects to healthy cartilage exposed to lower linear energy transfer (LET) ions in the beam track before the tumor have not been evaluated. The aim of the present study was to assess the extent of damage after C-ion irradiation in a 3-dimensional (3D) cartilage model close to human homeostasis. Primary human articular chondrocytes from a healthy donor were cultured in a collagen scaffold to construct a physioxic 3D cartilage model. A 2-dimensional (2D) culture was used as a reference. The cells were irradiated with a single dose of a monoenergetic C-ion beam with a LET of approximatively 30 keV/μm. This LET corresponds to the entrance channel of C-ions in the shallow healthy tissues before the spread-out Bragg peak (∼100 keV/μm) during hadron therapy protocols. The same dose of X-rays was used as a reference. Survival, cell death, and senescence assays were performed. As expected, in the 2D culture, C-ions were more efficient than X-rays in reducing cell survival with a relative biological effectiveness of 2.6. This correlated with stronger radiation-induced senescence (two-fold) but not with higher cell death induction. This differential effect was not reflected in the 3D culture. Both ionizing radiation types induced a comparable rate of senescence induction in the 3D model. The greater biological effectiveness of C-ions compared with low LET radiation when evaluated in treatment planning systems might be misevaluated using 2D culture experiments. Radiation-induced senescence is an important factor of potential cartilage attrition. The present data should encourage the scientific community to use relevant models and beams to improve the use of charged particles with better safety for patients. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Comparable Senescence Induction in Three-dimensional Human Cartilage Model by Exposure to Therapeutic Doses of X-rays or C-ions

    Energy Technology Data Exchange (ETDEWEB)

    Hamdi, Dounia Houria; Chevalier, François [Laboratoire d' Accueil et de Recherche avec les Ions Accélérés (LARIA), Institut de Radiobiologie Cellulaire et Moléculaire (IRCM), Direction de la Recherche Fondamentale - DRF, Commissariat à l' Energie Atomique et aux Energies Alternatives, Caen (France); Groetz, Jean-Emmanuel [UMR6249, Université de Franche-Comté, Besançon (France); Durantel, Florent [UMR6252, Centre de Recherche sur les Ions, les Matériaux et la Photonique (CIMAP), Direction de la Recherche Fondamentale (DRF), Commissariat à l' Energie Atomique et aux Energies Alternatives, Caen (France); Thuret, Jean-Yves; Mann, Carl [FRE3377, Service de Biologie Intégrative et Génétique Moléculaire SBIGeM, Institut de Biologie et de Technologies de Saclay (iBiTec-S), Direction de la Recherche Fondamentale (DRF), Commissariat à l' Energie Atomique et aux Energies Alternatives, Gif-sur-Yvette (France); Institut de Biologie Intégrative de la Cellule I2BC / Université Paris Saclay, Gif-sur-Yvette (France); and others

    2016-05-01

    Purpose: Particle therapy using carbon ions (C-ions) has been successfully used in the treatment of tumors resistant to conventional radiation therapy. However, the potential side effects to healthy cartilage exposed to lower linear energy transfer (LET) ions in the beam track before the tumor have not been evaluated. The aim of the present study was to assess the extent of damage after C-ion irradiation in a 3-dimensional (3D) cartilage model close to human homeostasis. Methods and Materials: Primary human articular chondrocytes from a healthy donor were cultured in a collagen scaffold to construct a physioxic 3D cartilage model. A 2-dimensional (2D) culture was used as a reference. The cells were irradiated with a single dose of a monoenergetic C-ion beam with a LET of approximatively 30 keV/μm. This LET corresponds to the entrance channel of C-ions in the shallow healthy tissues before the spread-out Bragg peak (∼100 keV/μm) during hadron therapy protocols. The same dose of X-rays was used as a reference. Survival, cell death, and senescence assays were performed. Results: As expected, in the 2D culture, C-ions were more efficient than X-rays in reducing cell survival with a relative biological effectiveness of 2.6. This correlated with stronger radiation-induced senescence (two-fold) but not with higher cell death induction. This differential effect was not reflected in the 3D culture. Both ionizing radiation types induced a comparable rate of senescence induction in the 3D model. Conclusions: The greater biological effectiveness of C-ions compared with low LET radiation when evaluated in treatment planning systems might be misevaluated using 2D culture experiments. Radiation-induced senescence is an important factor of potential cartilage attrition. The present data should encourage the scientific community to use relevant models and beams to improve the use of charged particles with better safety for patients.

  4. What is the best dose of nature and green exercise for improving mental health? A multi-study analysis.

    Science.gov (United States)

    Barton, Jo; Pretty, Jules

    2010-05-15

    Green exercise is activity in the presence of nature. Evidence shows it leads to positive short and long-term health outcomes. This multistudy analysis assessed the best regime of dose(s) of acute exposure to green exercise required to improve self-esteem and mood (indicators of mental health). The research used meta-analysis methodology to analyze 10 UK studies involving 1252 participants. Outcomes were identified through a priori subgroup analyses, and dose-responses were assessed for exercise intensity and exposure duration. Other subgroup analyses included gender, age group, starting health status, and type of habitat. The overall effect size for improved self-esteem was d = 0.46 (CI 0.34-0.59, p exercise, and then diminishing but still positive returns. Every green environment improved both self-esteem and mood; the presence of water generated greater effects. Both men and women had similar improvements in self-esteem after green exercise, though men showed a difference for mood. Age groups: for self-esteem, the greatest change was in the youngest, with diminishing effects with age; for mood, the least change was in the young and old. The mentally ill had one of the greatest self-esteem improvements. This study confirms that the environment provides an important health service.

  5. Improvement of heart function in postinfarct heart failure swine models after hepatocyte growth factor gene transfer: comparison of low-, medium- and high-dose groups.

    Science.gov (United States)

    Yang, Zhi-jian; Chen, Bo; Sheng, Zhang; Zhang, Ding-guo; Jia, En-zhi; Wang, Wei; Ma, Dong-chao; Zhu, Tie-bing; Wang, Lian-sheng; Li, Chun-jian; Wang, Hui; Cao, Ke-jiang; Ma, Wen-zhu

    2010-04-01

    Despite advances in surgical and reperfusion therapy, there is no effective therapy currently exists to prevent the progressive decline in cardiac function following myocardial infarction. Hepatocyte growth factor has potent angiogenic and anti-apoptotic activities. The aim of this study was to investigate the therapeutic effect and dose-effect relationship on postinfarction heart failure with different doses of adenovirus-mediated human hepatocyte growth factor (Ad(5)-HGF) transference in swine models. Totally twenty swine were randomly divided into four groups: (a) control group (null- Ad(5), 1 ml); (b) low-dose group (1 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (c) medium-dose group (5 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (d) high-dose group (1 x 10(10) Pfu/ml Ad(5)-HGF, 1 ml). Four weeks after left anterior descending coronary artery (LAD) ligation, different doses of Ad(5)-HGF were transferred in three therapeutic groups via right coronary artery. Four and seven weeks after LAD ligation, gate cardiac perfusion imaging was performed to evaluate cardiac perfusion and left ventricular ejection fraction (LVEF). Seven weeks after surgery, the apoptotic index of cardiocyte was observed by TUNEL, the expression of Bcl-2, Bax, alpha-SMA and Factor VIII in the border zones were evaluated by immunohistochemistry, respectively. Four weeks after myocardial infarction, no significant difference was observed among four groups. Three weeks after Ad(5)-HGF transfer, the improvement of cardiac perfusion and LVEF was obviously observed, especially after 1 x 10(10) Pfu Ad(5)-HGF transfer. TUNEL assay showed that 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF treatment had a obvious reduction in the apoptotic index compared with the null-Ad(5) group, especially after 1 x 10(10) Pfu Ad(5)-HGF treatment. The expression of Bcl-2 protein was increased and the expression of Bax protein was inhibited in the 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF groups compared with the null-Ad(5) group. The vessel

  6. Comparison of therapeutic efficacy and clinical parameters between recombinant human thyroid stimulating hormone and thyroid hormone withdrawal in high-dose radioiodine treatment with differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Se Hun; Na, Chang Ju; Kim, Jeong Hun; Han, Yeon Hee; KIm, Hee Kwon; Jeong, Hwan Jeong; Sohn, Myung Hee; Lim, Seok Tae [Dept. of Nuclear Medicine, Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2015-06-15

    High-dose radioiodine treatment (HD-RIT) after injection of recombinant human thyroid stimulating hormone (rh-TSH) has become widely used. This study compared the therapeutic efficacy of HD-RIT and clinical parameters between rh-TSH supplement and thyroid hormone withdrawal (THW) after total thyroidectomy in patients with differentiated thyroid cancer. We retrospectively reviewed 266 patients (47 male and 219 female; age, 49.0 ± 10.9 years) with differentiated thyroid cancer detected from September 2011 to September 2012. Patients comprised THW (217, 81.6 %) and rh-TSH (49, 18.4 %). Inclusion criteria were: first HD-RIT; any TN stage; absence of distant metastasis. To evaluate the complete ablation of the remnant thyroid tissue or metastasis, we reviewed stimulated serum thyroglobulin (sTg), I-123 whole-body scan (RxWBS) on T4 off-state, and thyroid ultrasonography (US) or [F-18]-fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) 6–8 months after HD-RIT. We defined a complete ablation state when all three of the follow-up conditions were satisfied; <2.0 ng/ml of the sTg, I-123 RxWBS (−), and thyroid US or F-18 FDG PET/CT (−). If one of the three was positive, ablation was considered incomplete. We also compared various clinical biomarkers (body weight, body mass index, liver and kidney function) between THW and rh-TSH groups. The rates of complete ablation were 73.7 % (160/217) for the THW group and 73.5 % (36/49) for the rh-TSH group. There was no significant difference between the two groups (p = 0.970). The follow-up aspartate transaminase (p = 0.001) and alanine transaminase (p = 0.001) were significantly higher in the THW group. The renal function parameters of blood urea nitrogen (p = 0.001) and creatinine (p = 0.005) tended to increase in the THW group. The change of body weight was + Δ0.96 (±1.9) kg for the THW group and was decreased by -Δ1.39 (±1.5) kg for the rh-TSH group. The change

  7. Cost reduction from resolution/improvement of carcinoid syndrome symptoms following treatment with above-standard dose of octreotide LAR.

    Science.gov (United States)

    Huynh, Lynn; Totev, Todor; Vekeman, Francis; Neary, Maureen P; Duh, Mei S; Benson, Al B

    2017-09-01

    To calculate the cost reduction associated with diarrhea/flushing symptom resolution/improvement following treatment with above-standard dose octreotide-LAR from the commercial payor's perspective. Diarrhea and flushing are two major carcinoid syndrome symptoms of neuroendocrine tumor (NET). Previously, a study of NET patients from three US tertiary oncology centers (NET 3-Center Study) demonstrated that dose escalation of octreotide LAR to above-standard dose resolved/improved diarrhea/flushing in 79% of the patients within 1 year. Time course of diarrhea/flushing symptom data were collected from the NET 3-Center Study. Daily healthcare costs were calculated from a commercial claims database analysis. For the patient cohort experiencing any diarrhea/flushing symptom resolution/improvement, their observation period was divided into days of symptom resolution/improvement or no improvement, which were then multiplied by the respective daily healthcare cost and summed over 1 year to yield the blended mean annual cost per patient. For patients who experienced no diarrhea/flushing symptom improvement, mean annual daily healthcare cost of diarrhea/flushing over a 1-year period was calculated. The economic model found that 108 NET patients who experienced diarrhea/flushing symptom resolution/improvement within 1 year had statistically significantly lower mean annual healthcare cost/patient than patients with no symptom improvement, by $14,766 (p = .03). For the sub-set of 85 patients experiencing resolution/improvement of diarrhea, their cost reduction was more pronounced, at $18,740 (p = .01), statistically significantly lower than those with no improvement; outpatient costs accounted for 56% of the cost reduction (p = .02); inpatient costs, emergency department costs, and pharmacy costs accounted for the remaining 44%. The economic model relied on two different sources of data, with some heterogeneity in the prior treatment and disease status of patients

  8. Improved method for calculation of population doses from nuclear complexes over large geographical areas

    International Nuclear Information System (INIS)

    Corley, J.P.; Baker, D.A.; Hill, E.R.; Wendell, L.L.

    1977-09-01

    To simplify the calculation of potential long-distance environmental impacts, an overall average population exposure coefficient (P.E.C.) for the entire contiguous United States was calculated for releases to the atmosphere from Hanford facilities. The method, requiring machine computation, combines Bureau of Census population data by census enumeration district and an annual average atmospheric dilution factor (anti chi/Q') derived from 12-hourly gridded wind analyses provided by the NOAA's National Meteorological Center. A variable-trajectory puff-advection model was used to calculate an hourly anti chi/Q' for each grid square, assuming uniform hourly releases; seasonal and annual averages were then calculated. For Hanford, using 1970 census data, a P.E.C. of 2 x 10 -3 man-seconds per cubic meter was calculated. The P.E.C. is useful for both radioactive and nonradioactive releases. To calculate population doses for the entire contiguous United States, the P.E.C. is multiplied by the annual average release rate and then by the dose factor (rem/yr per Ci/m 3 ) for each radionuclide, and the dose contribution in man-rem is summed for all radionuclides. For multiple pathways, the P.E.C. is still useful, provided that doses from a unit release can be obtained from a set of atmospheric dose factors. The methodology is applicable to any point source, any set of population data by map grid coordinates, and any geographical area covered by equivalent meteorological data

  9. Improvement of image quality and dose management in CT fluoroscopy by iterative 3D image reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Grosser, Oliver S.; Kupitz, Dennis; Powerski, Maciej; Mohnike, Konrad; Ricke, Jens [University Hospital Magdeburg, Department of Radiology and Nuclear Medicine, Magdeburg (Germany); Wybranski, Christian [University Hospital Magdeburg, Department of Radiology and Nuclear Medicine, Magdeburg (Germany); University Hospital Cologne, Institute for Diagnostic and Interventional Radiology, Cologne (Germany); Pech, Maciej [University Hospital Magdeburg, Department of Radiology and Nuclear Medicine, Magdeburg (Germany); Medical University of Gdansk, Second Department of Radiology, Gdansk (Poland); Amthauer, Holger [University Hospital Magdeburg, Department of Radiology and Nuclear Medicine, Magdeburg (Germany); Charite, Department of Nuclear Medicine, Berlin (Germany)

    2017-09-15

    The objective of this study was to assess the influence of an iterative CT reconstruction algorithm (IA), newly available for CT-fluoroscopy (CTF), on image noise, readers' confidence and effective dose compared to filtered back projection (FBP). Data from 165 patients (FBP/IA = 82/74) with CTF in the thorax, abdomen and pelvis were included. Noise was analysed in a large-diameter vessel. The impact of reconstruction and variables (e.g. X-ray tube current I) influencing noise and effective dose were analysed by ANOVA and a pairwise t-test with Bonferroni-Holm correction. Noise and readers' confidence were evaluated by three readers. Noise was significantly influenced by reconstruction, I, body region and circumference (all p ≤ 0.0002). IA reduced the noise significantly compared to FBP (p = 0.02). The effect varied for body regions and circumferences (p ≤ 0.001). The effective dose was influenced by the reconstruction, body region, interventional procedure and I (all p ≤ 0.02). The inter-rater reliability for noise and readers' confidence was good (W ≥ 0.75, p < 0.0001). Noise and readers' confidence were significantly better in AIDR-3D compared to FBP (p ≤ 0.03). Generally, IA yielded a significant reduction of the median effective dose. The CTF reconstruction by IA showed a significant reduction in noise and effective dose while readers' confidence increased. (orig.)

  10. Improving the performance of membrane bioreactors by powdered activated carbon dosing with cost considerations.

    Science.gov (United States)

    Yang, W; Paetkau, M; Cicek, N

    2010-01-01

    Effects of powdered activated carbon (PAC) dosing on the overall performance of membrane bioreactors (MBR) were investigated in two bench-scale submerged MBRs. Positive impacts of PAC dosing on membrane fouling and the removal of 17beta-estradiol (E2) and 17alpha-ethyinylestradiol (EE2) were demonstrated over a six-month stable operational period. PAC dosing in the MBR increased the removal rates of E2 and EE2 by 3.4% and 15.8%, respectively. The average soluble extracellular polymeric substances (EPS) and colloidal total organic carbon (TOC) concentrations in the PAC-MBR sludge was 60.1% and 61.8% lower than the control MBR sludge, respectively. Lower soluble EPS and colloidal TOC concentrations in the PAC-MBR sludge resulted in a slower rate of trans-membrane pressure (TMP) increase during MBRs operation, which could prolong the lifespan of membranes. Cost assessment showed that PAC dosing could reduce the operating cost for membrane cleaning and/or membrane replacement by about 25%. The operating cost for PAC dosing could be offset by the benefit from its reducing the cost for membrane maintenance.

  11. Improvement of dose evaluation system for employees at severe accident in a nuclear power plant. Introduction of the dose rate conversion coefficient and addition of the access route edit function

    International Nuclear Information System (INIS)

    Sasaki, Yasuhiro; Minami, Noritoshi; Yoshida, Yoshitaka

    2006-01-01

    Institute of Nuclear Safety System, Inc. had developed the dose evaluation system to evaluate the radiation dose of employees at severe accident in a nuclear power plant. This system has features, which are (1) the dose rate of any evaluation point can be evaluated, (2) the dose rate at any time can be evaluated in consideration of the change in the radioactive source, (3) the dose rate map in the plant can be displayed (4) the dose along the access route when moving can be evaluated, and it is possible to use it for examination of the accident management guideline on the dose side etc.. To upgrade the dose evaluation function of this system, the improvements had been done which were introduction of the dose rate conversion coefficient and addition of the access route edit function. By introducing the dose rate conversion coefficient, the calculation time of the dose rate map in the plant was shortened at about 20 seconds, and a new function to evaluate time-dependent dose rate of any evaluation point was added. By adding the access route edit function, it became possible to re-calculate the dose easily at the route change. (author)

  12. CORK Study in Cystic Fibrosis: Sustained Improvements in Ultra-Low-Dose Chest CT Scores After CFTR Modulation With Ivacaftor.

    Science.gov (United States)

    Ronan, Nicola J; Einarsson, Gisli G; Twomey, Maria; Mooney, Denver; Mullane, David; NiChroinin, Muireann; O'Callaghan, Grace; Shanahan, Fergus; Murphy, Desmond M; O'Connor, Owen J; Shortt, Cathy A; Tunney, Michael M; Eustace, Joseph A; Maher, Michael M; Elborn, J Stuart; Plant, Barry J

    2018-02-01

    Ivacaftor produces significant clinical benefit in patients with cystic fibrosis (CF) with the G551D mutation. Prevalence of this mutation at the Cork CF Centre is 23%. This study assessed the impact of cystic fibrosis transmembrane conductance regulator modulation on multiple modalities of patient assessment. Thirty-three patients with the G551D mutation were assessed at baseline and prospectively every 3 months for 1 year after initiation of ivacaftor. Change in ultra-low-dose chest CT scans, blood inflammatory mediators, and the sputum microbiome were assessed. Significant improvements in FEV 1 , BMI, and sweat chloride levels were observed post-ivacaftor treatment. Improvement in ultra-low-dose CT imaging scores were observed after treatment, with significant mean reductions in total Bhalla score (P < .01), peribronchial thickening (P = .035), and extent of mucous plugging (P < .001). Reductions in circulating inflammatory markers, including interleukin (IL)-1β, IL-6, and IL-8 were demonstrated. There was a 30% reduction in the relative abundance of Pseudomonas species and an increase in the relative abundance of bacteria associated with more stable community structures. Posttreatment community richness increased significantly (P = .03). Early and sustained improvements on ultra-low-dose CT scores suggest it may be a useful method of evaluating treatment response. It paralleled improvement in symptoms, circulating inflammatory markers, and changes in the lung microbiota. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  13. 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

  14. 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.

  15. Absorbed dose to ovaries or uterus during a 131I-therapeutic of cancer or hyperthyroidism: comparison between in vivo measurements by TLD and calculations

    International Nuclear Information System (INIS)

    Briere, J.; Philippon, B.

    1979-01-01

    An LiF dosimeter placed inside the uterus will only give an approximate value of the dose delivered to gonads during therapy by iodine-131. But it was easily demonstrated that the dose measured by LTD dosimeter does not significantly differ for uterus and for ovaries, because of the similar position of the source organs. Consequently a LiF dosimeter was placed in volunteer patients inside the uterus. Experimental results were compared to the dose calculated by Robertson and Gorman (J. Nucl. Med. 17, 826, (1976)) method for ovaries and for uterus. (author)

  16. Improving therapeutic outcomes in autism spectrum disorders: Enhancing social communication and sensory processing through the use of interactive robots.

    Science.gov (United States)

    Sartorato, Felippe; Przybylowski, Leon; Sarko, Diana K

    2017-07-01

    For children with autism spectrum disorders (ASDs), social robots are increasingly utilized as therapeutic tools in order to enhance social skills and communication. Robots have been shown to generate a number of social and behavioral benefits in children with ASD including heightened engagement, increased attention, and decreased social anxiety. Although social robots appear to be effective social reinforcement tools in assistive therapies, the perceptual mechanism underlying these benefits remains unknown. To date, social robot studies have primarily relied on expertise in fields such as engineering and clinical psychology, with measures of social robot efficacy principally limited to qualitative observational assessments of children's interactions with robots. In this review, we examine a range of socially interactive robots that currently have the most widespread use as well as the utility of these robots and their therapeutic effects. In addition, given that social interactions rely on audiovisual communication, we discuss how enhanced sensory processing and integration of robotic social cues may underlie the perceptual and behavioral benefits that social robots confer. Although overall multisensory processing (including audiovisual integration) is impaired in individuals with ASD, social robot interactions may provide therapeutic benefits by allowing audiovisual social cues to be experienced through a simplified version of a human interaction. By applying systems neuroscience tools to identify, analyze, and extend the multisensory perceptual substrates that may underlie the therapeutic benefits of social robots, future studies have the potential to strengthen the clinical utility of social robots for individuals with ASD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Development of a multi-layer ion chamber for measurement of depth dose distributions of heavy-ion therapeutic beam for individual patients

    International Nuclear Information System (INIS)

    Shimbo, Munefumi; Futami, Yasuyuki; Yusa, Ken; Matsufuji, Naruhiro; Kanai, Tatsuaki; Urakabe, Eriko; Yamashita, Haruo; Akagi, Takashi; Higashi, Akio

    2000-01-01

    In heavy-ion radiotherapy, an accelerated beam is modified to realize a desired dose distribution in patients. The set-up of the beam-modifying devices in the irradiation system is changed according to the patient, and it is important to check the depth dose distributions in the patient. In order to measure dose distributions realized by an irradiation system for heavy-ion radiotherapy, a multi-layer ionization chamber (MLIC) was developed. The MLIC consists of 64 ionization chambers, which are stacked mutually. The interval between each ionization chamber is about 4.1 mm water. There are signal and high voltage plates in the MLIC, which are used as electrodes of the ionization chambers and phantom. Depth dose distribution from 5.09 mm to 261.92 mm water can be measured in about 30 seconds using this MLIC. Thus, it is possible to check beam quality in a short amount of time. (author)

  18. Improving ingestion dose modelling for the ARGOS and RODOS decision support systems: A Nordic Initiative

    DEFF Research Database (Denmark)

    Andersson, Kasper Grann; Nielsen, Sven Poul; Thørring, Håvard

    2011-01-01

    A Nordic work group under the NKS-B activity PARDNOR has revised the input parameters in the ECOSYS model that is incorporated for ingestion dose modelling in the ARGOS and RODOS decision support systems. The new parameterisation takes into account recent measurement data, and targets the model f...

  19. Efficiency improvement in proton dose calculations with an equivalent restricted stopping power formalism

    Science.gov (United States)

    Maneval, Daniel; Bouchard, Hugo; Ozell, Benoît; Després, Philippe

    2018-01-01

    The equivalent restricted stopping power formalism is introduced for proton mean energy loss calculations under the continuous slowing down approximation. The objective is the acceleration of Monte Carlo dose calculations by allowing larger steps while preserving accuracy. The fractional energy loss per step length ɛ was obtained with a secant method and a Gauss-Kronrod quadrature estimation of the integral equation relating the mean energy loss to the step length. The midpoint rule of the Newton-Cotes formulae was then used to solve this equation, allowing the creation of a lookup table linking ɛ to the equivalent restricted stopping power L eq, used here as a key physical quantity. The mean energy loss for any step length was simply defined as the product of the step length with L eq. Proton inelastic collisions with electrons were added to GPUMCD, a GPU-based Monte Carlo dose calculation code. The proton continuous slowing-down was modelled with the L eq formalism. GPUMCD was compared to Geant4 in a validation study where ionization processes alone were activated and a voxelized geometry was used. The energy straggling was first switched off to validate the L eq formalism alone. Dose differences between Geant4 and GPUMCD were smaller than 0.31% for the L eq formalism. The mean error and the standard deviation were below 0.035% and 0.038% respectively. 99.4 to 100% of GPUMCD dose points were consistent with a 0.3% dose tolerance. GPUMCD 80% falloff positions (R80 ) matched Geant’s R80 within 1 μm. With the energy straggling, dose differences were below 2.7% in the Bragg peak falloff and smaller than 0.83% elsewhere. The R80 positions matched within 100 μm. The overall computation times to transport one million protons with GPUMCD were 31-173 ms. Under similar conditions, Geant4 computation times were 1.4-20 h. The L eq formalism led to an intrinsic efficiency gain factor ranging between 30-630, increasing with the prescribed accuracy of simulations. The

  20. Improved image quality and radiation dose reduction in liver dynamic CT scan with the protocol change

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Yu Jin; Cho, Pyong Kon [Radiological Science, Catholic University of Daegu, Daegu (Korea, Republic of)

    2015-06-15

    The purpose is reducing radiation dose while maintaining of image quality in liver dynamic CT(LDCT) scan, by protocols generally used and the tube voltage set at a low level protocol compared to the radiation dose and image quality. The target is body mass index, 18.5-24 patients out of 40 patients who underwent the ACT(abdominal CT). Group A(tube voltage : 120 kVp, SAFIRE strength 1) of 20 people among 40 people, to apply the general abdominal CT scan protocol, group B(tube voltage : 100 kVp, apply SAFIRE strength 0-5) was 20 people, set a lower tube voltage. Image quality evaluation was setting a region of interest(ROI) in the liver parenchyma, aorta, superior mesenteric artery (SMA), celiac trunk, visceral fat of arterial phase. In the ROI were compared by measuring the noise, signal to noise ratio(SNR), contrast to noise ratio(CNR), CT number. In addition, qualitative assessments to evaluate two people in the rich professional experience in Radiology by 0-3 points. We compared the total radiation dose, dose length product(DLP) and effective dose, volume computed tomography dose index(CTDIvol). The higher SAFIRE in the tube voltage 100 kVp, noise is reduced, CT number was increased. Thus, SNR and CNR was increased higher the SAFIRE step. Compared with the tube voltage 120 kVp, noise, SNR, CNR was most similar in SAFIRE strength 2 and 3. Qualitative assessment SAFIRE strength 2 is the most common SAFIRE strength 2 the most common qualitative assessment, if the tube voltage of 100 kVp when the quality of the images better evaluated was SAFIRE strength 1. Dose was reduced from 21.69%, in 100 kVp than 120 kVp. In the case of a relatively high BMI is not LDCT scan, When it is shipped from the factory tube voltage is set higher, unnecessary radiation exposure when considering the reality that is concerned, when according to the results of this study, set a lower tube voltage and adjust the SAFIRE strength to 1 or 2, the radiation without compromising image quality

  1. Preparation of therapeutic dose of 177Lu-DOTA-TATE using a novel single vial freeze-dried kit: a comparison with 'in-situ' preparation at hospital radiopharmacy.

    Science.gov (United States)

    Das, Tapas; Banerjee, Sharmila; Shinto, Ajit; Kamaleshwaran, K K; Sarma, H D

    2014-01-01

    Patient dose of (177)Lu-DOTA-TATE, used for providing radiotherapeutic treatment to the patients suffering from cancers of neuroendocrine origin, could be prepared at the hospital radiopharmacy either 'in-situ' or by using freezedried kits. The objective of the present work is to formulate and evaluate a single vial freeze-dried DOTA-TATE kit, which is capable of producing up to 7.4 GBq (200 mCi) dose of (177)Lu-DOTA-TATE and to compare the two methodologies presently used for the preparation of the agent. Freeze-dried DOTA-TATE kits, comprising a lyophilized mixture of DOTA-TATE, gentisic acid and ammonium acetate, were prepared and used for the formulation of patient doses of (177)Lu-DOTA-TATE. The kits were subjected to detailed radiochemical evaluation and the shelf-life of the kits was determined. The pharmacokinetic behavior of the agent was studied in normal Wistar rats. These kits were utilized for treating the patients suffering from various types of neuroendocrine cancers. The freeze-dried kits were used for the preparation of up to 7.4 GBq (200 mCi) therapeutic doses of (177)Lu- DOTA-TATE with a radiochemical purity of >99% and were found to have sufficiently long shelf-life. Biological studies carried out in normal Wistar rats exhibited no significant accumulation of activity in any of the vital organs/tissue except in kidneys and non-accumulated activity showed major renal clearance. Clinical studies carried out in cancer patients exhibited accumulation of activity in the cancerous lesions and metastatic sites. The kit was useful for the convenient preparation of therapeutic dose of (177)Lu-DOTA-TATE, suitable for human administration. The use of kit is expected to reduce the batch failure and radiation exposure to the working personnel.

  2. Therapeutic efficiency of synthokine SC-55494, a human IL-3 receptor agonist, in a nonhuman primate model of HIGH dose, sublethal, radiation-induced marrow aplasia

    International Nuclear Information System (INIS)

    Herodin, F.; Farese, A.; Grab, L.; McKearn, J.P.; Mestries, J.C.; McVittie, T.J.

    1994-01-01

    The synthetic cytokine (Synthokine) SC-55494 is a high affinity IL-3 receptor ligand. The therapeutic administration of Synthokine to total body irradiated (TBI) monkeys (7 Gy gamma) from day 1 post TBI for 23 days, significantly enhanced platelet recovery and modulated aneutrophil nadir. (author)

  3. Cocoa consumption dose-dependently improves flow-mediated dilation and arterial stiffness decreasing blood pressure in healthy individuals.

    Science.gov (United States)

    Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; di Giosia, Paolo; Barnabei, Remo; Allegaert, Leen; Bernaert, Herwig; Ferri, Claudio

    2015-02-01

    Cocoa flavonoids exert beneficial vascular effects and reduce the risk of cardiovascular morbidity and mortality. Nevertheless, the involved mechanisms have not been clarified and no study has yet focused on the dose-response effects. We aimed to investigate the effects of different doses of cocoa flavonoids on flow-mediated dilation (FMD), endothelin-1 (ET-1), pulse wave velocity (PWV), and SBP and DBP. According to a randomized, double-blind, controlled, cross-over design, 20 healthy volunteers (1.5% improvement in FMD in 20 individuals: 0.99 at alpha = 0.05) were assigned to receive either five treatments with daily intake of 10 g cocoa (0, 80, 200, 500 and 800 mg cocoa flavonoids/day) in five periods lasting 1 week each. Cocoa dose-dependently increased FMD from 6.2% (control) to 7.3, 7.6, 8.1 and 8.2% after the different flavonoid doses, respectively (P cocoa flavonoids per day increased FMD (P Cocoa dose-dependently decreased PWV (P Cocoa intake decreased office blood pressure (BP) (SBP: -4.8 ± 1.03  mmHg, P cocoa ingestion decreased 24-h (P = 0.05) and daytime (P = 0.038) SBP, and 24-h (P = 0.0064), daytime (P = 0.0088) and night-time (P = 0.0352) pulse pressure. Compared with the control, cocoa dose-dependently decreased ET-1 levels [from 17.1 (control) to 15.2, 14.5, 14.2 and 14.1 pg/ml, after the different flavonoid doses, respectively (P for treatment cocoa dose-dependently improved FMD and decreased PWV and ET-1 also by ameliorating office and monitored BP. Our findings are clinically relevant, suggesting cocoa, with very low calorie intake, might be reasonably incorporated into a dietary approach, representing a consistent tool in cardiovascular prevention.

  4. Improvement of the clinical use of computed radiography for mobile chest imaging: Image quality and patient dose

    Science.gov (United States)

    Rill, Lynn Neitzey

    Chest radiography is technically difficult because of the wide variation of tissue attenuations in the chest and limitations of screen-film systems. Mobile chest radiography, performed bedside on hospital inpatients, presents additional difficulties due to geometrical and equipment limitations inherent to mobile x-ray procedures and the severity of illness in patients. Computed radiography (CR) offers a new approach for mobile chest radiography by utilizing a photostimulable phosphor. Photostimulable phosphors are more efficient in absorbing lower-energy x-rays than standard intensifying screens and overcome some image quality limitations of mobile chest imaging, particularly because of the inherent latitude. This study evaluated changes in imaging parameters for CR to take advantage of differences between CR and screen-film radiography. Two chest phantoms, made of acrylic and aluminum, simulated x-ray attenuation for average-sized and large- sized adult chests. The phantoms contained regions representing the lungs, heart and subdiaphragm. Acrylic and aluminum disks (1.9 cm diameter) were positioned in the chest regions to make signal-to-noise ratio (SNR) measurements for different combinations of imaging parameters. Disk thicknesses (contrast) were determined from disk visibility. Effective dose to the phantom was also measured for technique combinations. The results indicated that using an anti-scatter grid and lowering x- ray tube potential improved the SNR significantly; however, the dose to the phantom also increased. An evaluation was performed to examine the clinical applicability of the observed improvements in SNR. Parameter adjustments that improved phantom SNRs by more than 50% resulted in perceived image quality improvements in the lung region of clinical mobile chest radiographs. Parameters that produced smaller improvements in SNR had no apparent effect on clinical image quality. Based on this study, it is recommended that a 3:1 grid be used for

  5. Intestinal morphological effect of brachytherapy of low rate of dose, administrated in therapeutic form and its clinical manifestations in uterine cervix tumors

    International Nuclear Information System (INIS)

    Mendoza, Carmen; Contreras, Manuel

    2005-01-01

    Brachytherapy is effective to eradicate cancer in the cervix, in order to obtain the control of disease we use high dose with vesical and rectum toxicity. The objective is to investigate if brachytherapy by itself is the cause of intestinal damage, to know in addition if the intensity of the clinic manifestations is in direct relation to the given radiation dose and this gets worse when it is received in several applications. Hypothesis: The intensity of the radiation with brachytherapy of low rate of dose is proportional to the degree of clinical manifestations and morphologic damage of the intestine. A prospective analysis was made inpatients with cancer of cervix from september 2000 to june 2004. Each patient who enters to the department of brachytherapy of the hospital must be done laboratory examination that includes plaque and coagulation test before being accepted. We use the clinical card and a table in order to register data concerning teletherapy, implants of brachytherapy of low rate of dose, symptoms of intestinal toxicity and details of colonoscopia. Subsequent to the hospitable discharge the patient is sent to gastroenterology for clinical evaluation and to realize colonoscopia. From september 2000 to june 2004, 540 patients entered, 80 patients (15%) displayed intestinal manifestations, all received teletherapy and brachytherapy, nobody else received brachytherapy in exclusive form and only one patient (0.1%) received the total of the dose in 2 applications. The equipment of teletherapy Primus with energy of 6 and 18 Mv and implants of brachytherapy Manchester were used (70/55 patients). 79 (98%) patients received dose between 85-75 Gy in one single application, 58 (72%) received the total of the dose to the tumor, 21 (26%) in vaginal mucosa. Discussion: Brachytherapy is the cause of the damages in the intestinal mucosa. (The author)

  6. Caprylic Triglyceride as a Novel Therapeutic Approach to Effectively Improve the Performance and Attenuate the Symptoms Due to the Motor Neuron Loss in ALS Disease

    OpenAIRE

    Zhao, Wei; Varghese, Merina; Vempati, Prashant; Dzhun, Anastasiya; Cheng, Alice; Wang, Jun; Lange, Dale; Bilski, Amanda; Faravelli, Irene; Pasinetti, Giulio Maria

    2012-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approac...

  7. Ultra-low-dose continuous combined estradiol and norethisterone acetate: improved bleeding profile in postmenopausal women

    DEFF Research Database (Denmark)

    Sturdee, D.W.; Archer, D.F.; Rakov, V.

    2008-01-01

    OBJECTIVE: To evaluate the effect of two ultra-low-dose hormone treatments containing estradiol (E2) 0.5 mg and norethisterone acetate (NETA) 0.1 or 0.25 mg on the endometrium and bleeding. METHODS: A prospective, randomized, placebo-controlled trial of 6 months. Local Ethics Committee approval...... and informed consent were obtained prior to initiation and enrollment. Out of 577 postmenopausal women randomized, 575 took E2/NETA 0.1 (n = 194), or E2/NETA 0.25 (n = 181) or placebo (n = 200). Endometrial bleeding was monitored by daily diary cards and endometrial thickness by transvaginal ultrasound......: The ultra-low-dose combination of E2/NETA 0.1 or E2/NETA 0.25 resulted in a high incidence of amenorrhea and no bleeding in postmenopausal women, and a corresponding high level of compliance. Overall, there was no significant change in mean endometrial thickness during 6 months of active treatment...

  8. Parenteral nutrition support for patients with pancreatic cancer--improvement of the nutritional status and the therapeutic outcome.

    Science.gov (United States)

    Richter, Eva; Denecke, Almut; Klapdor, Silke; Klapdor, Rainer

    2012-05-01

    Malnutrition is a frequent and serious problem of patients with pancreatic cancer (i.e. due to exocrine pancreatic insufficiency, postoperative syndromes, anorexia, chemotherapy, and/or tumor progression). In many cases it has negative effects on the quality of life or on the tumor therapy. We investigated if malnutrition can be resolved or corrected by adequate home parenteral nutrition (PN) of pancreatic cancer (PaCa) patients, in cases where dietary advice and oral nutrition supplementation failed to correct the deficiencies. The energy supply via PN was analyzed in patients with PaCa, with focus on the single components in compounded PN. We examined a group of six women and eleven men with assured PaCa disease at different tumor stages (mean age: 64 years). Indications for PN were a reduction of body weight of >5 % in three months and/or a long-term reduced nutritional status, reduced results of the bio-electrical impedance analysis (BIA), malassimilation and/or clinical symptoms like severe diarrhoea/vomitus, preventing adequate oral nutrition for weeks. The PN, administered via port-catheter, was initiated while the patients were undergoing chemotherapy. The course of treatment was assessed based on body weight, BIA (Data-Input Nutriguard-M), on laboratory parameters and on personal evaluation of the patients' quality of life. Retrospectively, the patients were subdivided into two groups (Gr): Gr1 (n=10) had a survival period of more than 5, up to more than 37 months, after the start of PN and Gr2 (n=7) had a survival between 1-4 months after start of PN. The calculations of the energy supply were based on the patients' body weight (per kg). Fluid volume, relation of macronutrients and addition of fish oil to PN are described in detail. Gr1: Eight of ten patients already showed an increase of body weight with the initial PN, two patients after dose adaption. This positive impact was also observable on the cellular level by means of BIA results (phase angle

  9. Comparison of depth-dose distributions of proton therapeutic beams calculated by means of logical detectors and ionization chamber modeled in Monte Carlo codes

    Energy Technology Data Exchange (ETDEWEB)

    Pietrzak, Robert [Department of Nuclear Physics and Its Applications, Institute of Physics, University of Silesia, Katowice (Poland); Konefał, Adam, E-mail: adam.konefal@us.edu.pl [Department of Nuclear Physics and Its Applications, Institute of Physics, University of Silesia, Katowice (Poland); Sokół, Maria; Orlef, Andrzej [Department of Medical Physics, Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology, Gliwice (Poland)

    2016-08-01

    The success of proton therapy depends strongly on the precision of treatment planning. Dose distribution in biological tissue may be obtained from Monte Carlo simulations using various scientific codes making it possible to perform very accurate calculations. However, there are many factors affecting the accuracy of modeling. One of them is a structure of objects called bins registering a dose. In this work the influence of bin structure on the dose distributions was examined. The MCNPX code calculations of Bragg curve for the 60 MeV proton beam were done in two ways: using simple logical detectors being the volumes determined in water, and using a precise model of ionization chamber used in clinical dosimetry. The results of the simulations were verified experimentally in the water phantom with Marcus ionization chamber. The average local dose difference between the measured relative doses in the water phantom and those calculated by means of the logical detectors was 1.4% at first 25 mm, whereas in the full depth range this difference was 1.6% for the maximum uncertainty in the calculations less than 2.4% and for the maximum measuring error of 1%. In case of the relative doses calculated with the use of the ionization chamber model this average difference was somewhat greater, being 2.3% at depths up to 25 mm and 2.4% in the full range of depths for the maximum uncertainty in the calculations of 3%. In the dose calculations the ionization chamber model does not offer any additional advantages over the logical detectors. The results provided by both models are similar and in good agreement with the measurements, however, the logical detector approach is a more time-effective method. - Highlights: • Influence of the bin structure on the proton dose distributions was examined for the MC simulations. • The considered relative proton dose distributions in water correspond to the clinical application. • MC simulations performed with the logical detectors and the

  10. “Specificity Determinants” Improve Therapeutic Indices of Two Antimicrobial Peptides Piscidin 1 and Dermaseptin S4 Against the Gram-negative Pathogens Acinetobacter baumannii and Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Ziqing Jiang

    2014-03-01

    Full Text Available A new class of antimicrobial agents with lower rates of resistance and different targets is urgently needed because of the rapidly increasing resistance to classical antibiotics. Amphipathic cationic α-helical antimicrobial peptides (AMPs represent such a class of compounds. In our previous studies, using a 26-residue de novo designed antimicrobial peptide, we proposed the concept of “specificity determinant(s”: positively charged residue(s in the center of the non-polar face of AMPs that could decrease hemolytic activity/toxicity but increase or maintain the same level of antimicrobial activity to increase dramatically the therapeutic index. In the current study, we used d-enantiomers of two AMPs, Piscidin 1 isolated from fish and dermaseptin S4 isolated from frog. We substituted different positions in the center of the hydrophobic face with one or two lysine residue(s (one or two “specificity determinant(s”. This simple modification not only maintained or improved antimicrobial activity against Gram-negative pathogens Acinetobacter baumannii (11 strains and Pseudomonas aeruginosa (6 strains, but also dramatically decreased hemolytic activity of human red blood cells, as predicted. Therapeutic indices improved by 55-fold and 730-fold for piscidin 1 (I9K and dermaseptin S4 (L7K, A14K, respectively, against A. baumannii. Similarly, the therapeutic indices improved 32-fold and 980-fold for piscidin 1 (I9K and dermaseptin S4 (L7K, A14K, respectively, against P. aeruginosa.

  11. Targeting the Immune System’s Natural Response to Cell Death to Improve Therapeutic Response in Breast Cancers

    Science.gov (United States)

    2016-09-01

    pharmacological MerTK inhibition, measuring intra-tumoral leukocytes and tumor epithelial cell signaling in the post-therapeutic setting using flow...7Department of Pediatrics, National Jewish Health, Denver, Colorado, USA. 8Departments of Pharmacology and Medicine and UNC Lineberger Comprehensive...tail vein injection into lethally irradiated 6-week-old female MMTV-PyVmT recipients. (B) Average tumor volume ± SEM measured in live mice by MRI at

  12. A METHOD TO IMPROVE DOSE ASSESSMENT BY RECONSTRUCTION OF THE COMPLETE ISOTOPES INVENTORY.

    Science.gov (United States)

    Bonin, Alice; Tsilanizara, Aimé

    2017-06-01

    Radiation shielding assessments may underestimate the expected dose if some isotopes at trace level are not considered in the isotopes inventory of the shielded radioactive materials. Indeed, information about traces is not often available. Nevertheless, the activation of some minor isotopic traces may significantly contribute to the dose build-up. This paper presents a new method (Isotopes Inventory Reconstruction-IIR) estimating the concentration of the minor isotopes in the irradiated material at the beginning of the cooling period. The method requires the solution of the inverse problem describing the irradiated material's decay. In a mixture of an irradiated uranium-plutonium oxide shielded by a set-up made of stainless-steel, porous polyethylene plaster and lead methyl methacrylate, the comparison between different methods proves that the IIR-method allows better assessment of the dose than other approximate methods. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Improvements in the methods for optimising dose rate CTOR NPPs in the Russian Federation

    International Nuclear Information System (INIS)

    Noskov, A.A.

    1995-01-01

    The paper describes the results of a model investigation and an occupational radiation exposure analysis for reducing the collective doses on LWGMR nuclear power plants. The first RBMK NPP had been commissioned more than twenty years ago. It was the new generation unit of the Light Water Graphite Moderated Reactor (LWGMR). The RBMK-1000 occupational exposures were the same as or smaller than BWR doses. For example in 1980-1983 US BWR collective doses were 12.30-10.17 man-Sv per unit-year and the equivalent RBMK-1000 were 5.00-9.05 man-Sv per unit-year. A new generation of LWGMR, the MKER-800, is currently at the design stage and the design target for the plant is 1.0 man-Sv per GW(e)-year. There were three principal trends in the investigation of the occupational radiation exposure mechanism on LWMGR units. They were: (1) ionizing radiation sources; (2) radiation field distribution in the NPP compartments; (3) occupational radiation exposure profile. (author)

  14. Addition of low-dose ketamine to midazolam and low-dose bupivacaine improves hemodynamics and postoperative analgesia during spinal anesthesia for cesarean section

    Directory of Open Access Journals (Sweden)

    Ahmed Sobhy Basuni

    2016-01-01

    Conclusion: Intrathecal low-dose ketamine combined with midazolam and low-dose bupivacaine stabilizes hemodynamics and prolongs postoperative analgesia without significant side-effects in parturients undergoing CS.

  15. Improved dose-volume histogram estimates for radiopharmaceutical therapy by optimizing quantitative SPECT reconstruction parameters

    Science.gov (United States)

    Cheng, Lishui; Hobbs, Robert F.; Segars, Paul W.; Sgouros, George; Frey, Eric C.

    2013-06-01

    In radiopharmaceutical therapy, an understanding of the dose distribution in normal and target tissues is important for optimizing treatment. Three-dimensional (3D) dosimetry takes into account patient anatomy and the nonuniform uptake of radiopharmaceuticals in tissues. Dose-volume histograms (DVHs) provide a useful summary representation of the 3D dose distribution and have been widely used for external beam treatment planning. Reliable 3D dosimetry requires an accurate 3D radioactivity distribution as the input. However, activity distribution estimates from SPECT are corrupted by noise and partial volume effects (PVEs). In this work, we systematically investigated OS-EM based quantitative SPECT (QSPECT) image reconstruction in terms of its effect on DVHs estimates. A modified 3D NURBS-based Cardiac-Torso (NCAT) phantom that incorporated a non-uniform kidney model and clinically realistic organ activities and biokinetics was used. Projections were generated using a Monte Carlo (MC) simulation; noise effects were studied using 50 noise realizations with clinical count levels. Activity images were reconstructed using QSPECT with compensation for attenuation, scatter and collimator-detector response (CDR). Dose rate distributions were estimated by convolution of the activity image with a voxel S kernel. Cumulative DVHs were calculated from the phantom and QSPECT images and compared both qualitatively and quantitatively. We found that noise, PVEs, and ringing artifacts due to CDR compensation all degraded histogram estimates. Low-pass filtering and early termination of the iterative process were needed to reduce the effects of noise and ringing artifacts on DVHs, but resulted in increased degradations due to PVEs. Large objects with few features, such as the liver, had more accurate histogram estimates and required fewer iterations and more smoothing for optimal results. Smaller objects with fine details, such as the kidneys, required more iterations and less

  16. Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

    Science.gov (United States)

    Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas

    2016-05-01

    The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. ©2016 American Association for Cancer Research.

  17. Therapeutic doses of doxorubicin induce premature senescence of human mesenchymal stem cells derived from menstrual blood, bone marrow and adipose tissue.

    Science.gov (United States)

    Kozhukharova, Irina; Zemelko, Victoria; Kovaleva, Zoya; Alekseenko, Larisa; Lyublinskaya, Olga; Nikolsky, Nikolay

    2018-03-01

    Doxorubicin (Dox) is an effective anticancer drug with known activity against a wide spectrum of malignancies, hematologic malignancies in particular. Despite extensive clinical use, the mechanisms of its side effects and negative action on normal cells remain under study. The aim of this study was to investigate the effect of Dox on cultured human mesenchymal stem cells (MSCs) derived from menstrual blood (eMSCs), bone marrow (BMSCs) and adipose tissue (AMSCs). Dox treatment in high doses decreased the survival of MSCs in a dose-dependent manner. Clinically relevant low doses of Dox induced premature senescence of eMSCs, BMSCs and AMSCs, but did not kill the cells. Dox caused cell cycle arrest and formation of γ-H2AX foci, and increased the number of SA-β-gal-positive cells. BMSCs entered premature senescence earlier than other MSCs. It has been reported that neural-like cells differentiated from MSCs of various origins are more sensitive to Dox than their parent cells. Dox-treated differentiated MSCs exhibited lower viability and earlier generation of γ-H2AX foci. Dox administration inhibited secretory activity in neural-like cells. These findings suggest that a clinically relevant Dox dose damages cultured MSCs, inducing their premature senescence. MSCs are more resistant to this damage than differentiated cells.

  18. Improvement of quality of radiation indicators used for food irradiation in dose range of 3-10 kGy

    International Nuclear Information System (INIS)

    Hoang Hoa Mai; Pham Duy Duong; Nguyen Dinh Duong

    2007-01-01

    A sensitive indicators based on the polyvinyl butyral dyed with leuco-malachite green and methyl orange were made for use as devices for discriminating and monitoring radiation treatment in food irradiation. The sensitivity and stability of the indicator have been improved by using several additives such as CCl 4 in combination with di(nonylphenyl) isophthalate [dinonyl phthalate -C 6 H 4 (COOC 9 H 19 ) 2 ]. The dosimeters change their color from orange to greenish when irradiated with gamma rays or electrons to dose just about 2 kGy. The greenish continue to develop to deep-green upon the increase of dose to 7 kGy. This makes the indicators useful for the dose range of food irradiation application, especially in treatment of frozen meat and sea products for elimination of micro-organism. The quality of indicators are also improved by adjusting of factors and procedures during preparation of film and dosimeters. The indicators were produced in a stick-on label type showing attractive characteristics in use. The orange color before irradiation keep well stable for as long as 20 months under normal conditions in laboratory. The green after irradiation was maintained up to 12 months in piratical conditions of products. The indicator can be produced in big amount to supply to the irradiation facilities in Vietnam instead of imported devices. (author)

  19. CT image quality improvement using adaptive iterative dose reduction with wide-volume acquisition on 320-detector CT

    International Nuclear Information System (INIS)

    Gervaise, Alban; Osemont, Benoit; Lecocq, Sophie; Blum, Alain; Noel, Alain; Micard, Emilien; Felblinger, Jacques

    2012-01-01

    To evaluate the impact of Adaptive Iterative Dose Reduction (AIDR) on image quality and radiation dose in phantom and patient studies. A phantom was examined in volumetric mode on a 320-detector CT at different tube currents from 25 to 550 mAs. CT images were reconstructed with AIDR and with Filtered Back Projection (FBP) reconstruction algorithm. Image noise, Contrast-to-Noise Ratio (CNR), Signal-to-Noise Ratio (SNR) and spatial resolution were compared between FBP and AIDR images. AIDR was then tested on 15 CT examinations of the lumbar spine in a prospective study. Again, FBP and AIDR images were compared. Image noise and SNR were analysed using a Wilcoxon signed-rank test. In the phantom, spatial resolution assessment showed no significant difference between FBP and AIDR reconstructions. Image noise was lower with AIDR than with FBP images with a mean reduction of 40%. CNR and SNR were also improved with AIDR. In patients, quantitative and subjective evaluation showed that image noise was significantly lower with AIDR than with FBP. SNR was also greater with AIDR than with FBP. Compared to traditional FBP reconstruction techniques, AIDR significantly improves image quality and has the potential to decrease radiation dose. (orig.)

  20. Calculations on the dose decreasing and image quality improving effects of an abdomen dodger

    International Nuclear Information System (INIS)

    Koblinger, L.

    1974-07-01

    A Monte Carlo computer program is performed to study the effects of an abdomen dodger. For this study the inhomogeneous Snyder phantom is assumed to be irradiated by an X-ray tube operated at 80 kV. By the use of a dodger which compensates the varying thickness of the body the exposure distribution on the photoreceptor can be made more uniform and the absorbed dose decreases. As different patients have different dimensions, the results presented here cannot be applied for any given abdomen examination, but can be used as average values, characteristic for an average examination, thus applicable in the estimations for the total population. (K.A.)