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Sample records for isoniazid doses vary

  1. Bioequivalence assessment of rifampicin, isoniazid and pyrazinamide in a fixed dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol vs. separate formulations.

    Science.gov (United States)

    Agrawal, S; Singh, I; Kaur, K J; Bhade, S R; Kaul, C L; Panchagnula, R

    2002-10-01

    Depending on the patient category, tuberculosis requires treatment with 3 to 5 drugs which means that patient's compliance to therapy may not be optimal. To increase patient's adherence to treatment schedules, these drugs can be given as single drug preparations or fixed dose combinations (FDCs) of 2 or more drugs in a single formulation. However, an important issue associated with a rifampicin-containing FDC is its quality. Hence, to avoid spurious formulations entering the market, the World Health Organization and the International Union Against Tuberculosis and Lung Disease have recommended FDCs only of proven bioavailability. In this study, the relative bioavailability of rifampicin, isoniazid and pyrazinamide was assessed in a group of 14 healthy male subjects using the FDC tablet containing 4 drugs versus separate formulations at the same dose levels. The study was designed as an open, crossover trial. A total of 9 blood samples were collected over a period of 24 h. The concentration of rifampicin, its main metabolite desacetyl rifampicin, isoniazid and pyrazinamide in plasma were assessed using HPLC analysis. The pharmacokinetic parameters AUC(0-24) and Cmax were subjected to parametric and non-parametric statistical tests at 90% confidence interval. In addition, time to reach peak concentration (tmax), elimination rate constant (Kel) and terminal elimination half-life (t1/2) for each drug were also calculated. It was concluded that the FDC tablet containing 4 drugs is bioequivalent to separate rifampicin, isoniazid and pyrazinamide formulations at the same dose levels.

  2. Population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children with tuberculosis: in silico evaluation of currently recommended doses.

    Science.gov (United States)

    Zvada, Simbarashe P; Denti, Paolo; Donald, Peter R; Schaaf, H Simon; Thee, Stephanie; Seddon, James A; Seifart, Heiner I; Smith, Peter J; McIlleron, Helen M; Simonsson, Ulrika S H

    2014-05-01

    To describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid in children and evaluate the adequacy of steady-state exposures. We used previously published data for 76 South African children with tuberculosis to describe the population pharmacokinetics of rifampicin, pyrazinamide and isoniazid. Monte Carlo simulations were used to predict steady-state exposures in children following doses in fixed-dose combination tablets in accordance with the revised guidelines. Reference exposures were derived from an ethnically similar adult population with tuberculosis taking currently recommended doses. The final models included allometric scaling of clearance and volume of distribution using body weight. Maturation was included for clearance of isoniazid and clearance and absorption transit time of rifampicin. For a 2-year-old child weighing 12.5 kg, the estimated typical oral clearances of rifampicin and pyrazinamide were 8.15 and 1.08 L/h, respectively. Isoniazid typical oral clearance (adjusted for bioavailability) was predicted to be 4.44, 11.6 and 14.6 L/h for slow, intermediate and fast acetylators, respectively. Higher oral clearance values in intermediate and fast acetylators also resulted from 23% lower bioavailability compared with slow acetylators. Simulations based on our models suggest that with the new WHO dosing guidelines and utilizing available paediatric fixed-dose combinations, children will receive adequate rifampicin exposures when compared with adults, but with a larger degree of variability. However, pyrazinamide and isoniazid exposures in many children will be lower than in adults. Further studies are needed to confirm these findings in children administered the revised dosages and to optimize pragmatic approaches to dosing.

  3. Isoniazid, pyrazinamide and rifampicin content variation in split fixed-dose combination tablets.

    Science.gov (United States)

    Pouplin, Thomas; Phuong, Pham Nguyen; Toi, Pham Van; Nguyen Pouplin, Julie; Farrar, Jeremy

    2014-01-01

    In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets. To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis. Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets. All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings. In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis.

  4. Comparative bioavailability of rifampicin, isoniazid and pyrazinamide from a four drug fixed dose combination with separate formulations at the same dose levels.

    Science.gov (United States)

    Agrawal, Shrutidevi; Singh, Inderjit; Kaur, Kanwal Jit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

    2004-05-19

    Fixed dose combination (FDC) formulations became popular in the treatment of tuberculosis (TB) because of the better patient compliance, reduced risk of monotherapy and emergence of drug resistance in contrast to treatment with separate formulations of two to four first-line drugs. However, its successful implementation in national programs is limited by probable bioinequivalency of rifampicin if present in FDC form. In this regard, World Health Organization (WHO) and International Union Against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. Hence, bioequivalence study of four drug FDC tablet was conducted using 22 healthy male volunteers according to WHO recommended protocol to determine bioavailability of rifampicin, isoniazid and pyrazinamide compared to standard separate combination at the same dose level. The study was designed as two period, two treatment crossover experiment with a washout period of 1 week. Bioequivalence of rifampicin was estimated by plasma and urinary method for both rifampicin and its active metabolite, des-acetyl rifampicin whereas isoniazid and pyrazinamide were estimated from plasma. Mean concentration time profiles and all the pharmacokinetic parameters of rifampicin, isoniazid and pyrazinamide from FDC tablet were comparable to individual formulations and passed the bioequivalence test with power of the test above 95%. Further, bioequivalence of both rifampicin and isoniazid shows that in vitro interaction of rifampicin and isoniazid is clinically insignificant. Thus, it was concluded that FDC formulation is bioequivalent for rifampicin, isoniazid and pyrazinamide and ensures the successful treatment of TB without compromising therapeutic efficacy of any of these components of anti-TB therapy.

  5. Bioequivalence of isoniazid in a two drug fixed dose combination and in a single drug dosage form.

    Science.gov (United States)

    Agrawal, S; Kaul, C L; Panchagnula, R

    2001-08-01

    To increase the patient compliance and reduce the risk of drug resistant strains, WHO and IUATLD recommend the use of Fixed Dose Combination (FDC) tablets as a routine therapeutic regimen in Directly Observed Treatment Shortcourse (DOTS). But the main issue in the use of FDC is the quality of the formulation. At present WHO and IUATLD suggest the bioequivalence assessment of only rifampicin from FDC compared to separate formulations. For the therapeutic effectiveness all the components of the FDCs should be bioavailable at tissue site. Also, the primary and acquired resistance rate of isoniazid is much higher compared to other anti-tubercular drugs. Hence, a comparative bioavailability study of isoniazid from a two drugs FDC compared to a separate formulation was carried out on a group of 12 healthy volunteers. When evaluated by normal or log transformed confidence interval, Two Way ANOVA and Hauschke analysis, the bioequivalence limits for AUC0-8 and AUC0-24 were within 0.8-1.25. For Cmax and Tmax, these limits were within 0.7-1.43. Hence, isoniazid from a FDC formulation was found to be bioequivalent to a separate formulation at same dose levels.

  6. Oral pyridoxine can substitute for intravenous pyridoxine in managing patients with severe poisoning with isoniazid and rifampicin fixed dose combination tablets: a case report.

    Science.gov (United States)

    Dilrukshi, M D S A; Ratnayake, C A P; Gnanathasan, C A

    2017-08-08

    Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka. A 22 year old, Sri Lankan female presented to a local hospital 1 h after self-ingestion of 28 tablets of fixed drug combination of isoniazid and rifampicin which contained 4.2 g of standard isoniazid and 7.2 g of rifampicin. One and half hours after ingestion she developed generalized tonic-clonic seizure with loss of consciousness. She was given intravenous diazepam 5 mg immediately and transferred to national hospital of Sri Lanka, for further care. Upon arrival to tertiary care hospital in 3.5 h of poisoning she had persistent vomiting, dizziness and headache. On examination, she was drowsy but arousable, orange-red discoloration of the body was noted even with the dark skin complexion. She also had orange-red colour urine and vomitus. Pulse rate was 104 beats/min, blood pressure 130/80 mmHg, respiratory rate was 20 breaths/min. The arterial blood gas analysis revealed compensated metabolic acidosis and mildly elevated lactic acid level. Considering the clinical presentation with neurological toxicity and the large amount of isoniazid dose ingested, crushed oral tablets of pyridoxine 4.2 g (equal to standard isoniazid dose ingested) administered immediately via a nasogastric tube since intravenous preparation was not available in the hospital. Simultaneously forced diuresis using intravenous 0.9% saline was commenced in order to enhance excretion of toxic metabolites via kidneys. She had no recurrence of seizures but had

  7. Improved Stability of Tuberculosis Drug Fixed-Dose Combination Using Isoniazid-Caffeic Acid and Vanillic Acid Cocrystal.

    Science.gov (United States)

    Battini, Swapna; Mannava, M K Chaitanya; Nangia, Ashwini

    2018-06-01

    The classic fixed-dose combination (FDC) of 4 tuberculosis drugs, namely rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol dihydrochloride (EDH) has the twin issues of physical stability and RIF cross-reaction in the 4-FDC. The major reason for these quality issues is the interaction between RIF and INH to yield isonicotinyl hydrazone in drug tablets. Pharmaceutical cocrystals of INH with caffeic acid (CFA) (PZA + EDH + RIF + INH-CFA cocrystal) and vanillic acid (VLA) (PZA + EDH + RIF + INH-VLA cocrystal) are able to stabilize the FDC formulation compared with the reference batch (PZA + EDH + RIF + INH). Stability studies under accelerated humidity and temperature stress conditions of 40°C and 75% relative humidity showed that the physical stability of the cocrystal formulation was superior by powder X-ray diffraction and scanning electron microscopy analysis, and chemical purity was analyzed by high-performance liquid chromatography. Changes in the composition and structure were monitored on samples drawn at 7, 15, 22, and 30 days of storage. FDC-INH-CFA cocrystal batch exhibited greater stability compared with FDC-INH-VLA cocrystal and FDC reference drug batches. The superior stability of INH-CFA cocrystal is attributed to the presence of stronger hydrogen bonds and cyclic O-H⋯O synthon in the crystal structure. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  8. Assessment of bioequivalence of rifampicin, isoniazid and pyrazinamide in a four drug fixed dose combination with separate formulations at the same dose levels.

    Science.gov (United States)

    Agrawal, Shrutidevi; Kaur, Kanwal Jit; Singh, Inderjit; Bhade, Shantaram R; Kaul, Chaman Lal; Panchagnula, Ramesh

    2002-02-21

    Tuberculosis (TB) needs treatment with three to five different drugs simultaneously, depending on the patient category. These drugs can be given as single drug preparations or fixed dose combinations (FDCs) of two more drugs in a single formulation. World Health Organization and International Union against Tuberculosis and Lung Disease (IUATLD) recommend FDCs only of proven bioavailability. The relative bioavailability of rifampicin (RIF), isoniazid (INH) and pyrazinamide (PYZ) was assessed on a group of 13 healthy male subjects from a four drug FDC versus separate formulations at the same dose levels. The study was designed to be an open, crossover experiment. A total of nine blood samples each of 3 ml volume were collected over a period of 24-h. The concentrations of RIF, its main metabolite desacetyl RIF (DRIF), INH and PYZ in plasma were assessed by HPLC analysis. Pharmacokinetic parameters namely AUC(0-24), AUC(0-inf), C(max), T(max), were calculated and subjected to different statistical tests (Hauschke analysis, two way ANOVA, normal and log transformed confidence interval) at 90% confidence interval. In addition, elimination rate constant (K(el)) and absorption efficiencies for each drug were also calculated. It was concluded that four drugs FDC tablet is bioequivalent for RIF, INH and PYZ to separate formulation at the same dose levels.

  9. Benefits of combined preventive therapy with co-trimoxazole and isoniazid in adults living with HIV: time to consider a fixed-dose, single tablet coformulation.

    Science.gov (United States)

    Harries, Anthony D; Lawn, Stephen D; Suthar, Amitabh B; Granich, Reuben

    2015-12-01

    Antiretroviral therapy (ART) is the main intervention needed to reduce morbidity and mortality and to prevent tuberculosis in adults living with HIV. However, in most resource-limited countries, especially in sub-Saharan Africa, ART is started too late to have an effect with substantial early morbidity and mortality, and in high tuberculosis burden settings ART does not reduce the tuberculosis risk to that reported in individuals not infected with HIV. Co-trimoxazole preventive therapy started before or with ART, irrespective of CD4 cell count, reduces morbidity and mortality with benefits that continue indefinitely. Isoniazid preventive therapy as an adjunct to ART prevents tuberculosis in high-exposure settings, with long-term treatment likely to be needed to sustain this benefit. Unfortunately, both preventive therapies are underused in low-income and high-burden settings. ART development has benefited from patient-centred simplification with several effective regimens now available as a one per day pill. We argue that co-trimoxazole and isoniazid should also be combined into a single fixed-dose pill, along with pyridoxine (vitamin B6), that would be taken once per day to help with individual uptake and national scale-up of therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Isoniazid toxicosis in dogs: 137 cases (2004-2014).

    Science.gov (United States)

    Schmid, Dustin R; Lee, Justine A; Wismer, Tina A; Diniz, Pedro Paulo V P; Murtaugh, Robert J

    2017-09-15

    OBJECTIVE To establish the minimum toxic dose of isoniazid in dogs, characterize the clinical signs and outcomes for dogs following isoniazid ingestion, and determine whether IV administration of pyridoxine to dogs with isoniazid toxicosis is protective against death. DESIGN Retrospective case series. ANIMALS 137 dogs with isoniazid toxicosis. PROCEDURES The electronic database of the American Society for the Prevention of Cruelty to Animals Animal Poison Control Center was reviewed from January 2004 through December 2014 to identify dogs with isoniazid toxicosis. For each dog identified, information extracted from the medical record included signalment, estimated dose of isoniazid ingested, clinical signs, treatment, and outcome. Follow-up communication with pet owners or primary care veterinarians was performed when necessary to obtain missing information. RESULTS Clinical signs of isoniazid toxicosis were observed in 134 of 137 (98%) dogs and included seizures (n = 104), CNS signs without seizures (94), and gastrointestinal (41), cardiovascular (19), urogenital (4), and respiratory (1) abnormalities. Of the 87 dogs for which the outcome was available, 61 survived, 18 died, and 8 were euthanized. Probability of survival was positively associated with body weight and IV administration of pyridoxine and negatively associated with dose of isoniazid ingested and presence of seizures. Dogs that received pyridoxine IV were 29 times as likely to survive as dogs that did not receive pyridoxine IV. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated rapid diagnosis of isoniazid toxicosis and prompt treatment of affected dogs with pyridoxine and other supportive care were imperative for achieving a successful outcome.

  11. Effect of antacids in didanosine tablet on bioavailability of isoniazid.

    OpenAIRE

    Gallicano, K; Sahai, J; Zaror-Behrens, G; Pakuts, A

    1994-01-01

    The antacids in two didanosine placebo tablets had no significant effect on the plasma pharmacokinetics of a single oral dose of 300 mg of isoniazid administered to 12 healthy volunteers. These results suggest that isoniazid bioavailability will be unaffected by the antacids in didanosine tablets when the two medications are administered simultaneously to human immunodeficiency virus-seropositive patients.

  12. Effect of antacids in didanosine tablet on bioavailability of isoniazid.

    Science.gov (United States)

    Gallicano, K; Sahai, J; Zaror-Behrens, G; Pakuts, A

    1994-04-01

    The antacids in two didanosine placebo tablets had no significant effect on the plasma pharmacokinetics of a single oral dose of 300 mg of isoniazid administered to 12 healthy volunteers. These results suggest that isoniazid bioavailability will be unaffected by the antacids in didanosine tablets when the two medications are administered simultaneously to human immunodeficiency virus-seropositive patients.

  13. An explanation for the physical instability of a marketed fixed dose combination (FDC) formulation containing isoniazid and ethambutol and proposed solutions.

    Science.gov (United States)

    Bhutani, Hemant; Mariappan, T T; Singh, Saranjit

    2004-07-01

    An investigation was carried out to explore the possible reason for the physical instability of a marketed strip packaged anti-TB fixed dose combination (FDC) tablet containing 300 mg of isoniazid (H) and 800 mg of ethambutol hydrochloride (E). The instability was in the form of distribution of white powder inside the strip pockets. High-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS-MS) studies confirmed that both H and E were present in the powder. The same was also confirmed through Fourier-transform infrared (FTIR) spectroscopy, which also indicated absence of interaction between the two drugs. No sublimation of the drugs was observed up to 110 degrees C, indicating that the observed instability was not due to this reason. Subsequently, attention was paid to the possibility of moisture gain by the tablets through defective packaging (which was established) due to hygroscopicity of E. To understand the phenomenon further, pure drugs and their mixtures were stored under accelerated conditions of temperature and humidity [40 degrees C/75% relative humidity (RH)] and both increase in weight and physical changes were recorded periodically. The mixtures gained moisture at a higher rate than pure E and those with higher content of E became liquid, which on withdrawal from the chambers, became crystallized. The drug mixture containing H:E at a ratio of 30:70 w/w, which was similar to the ratio of the drugs in the tablets (27:73 w/w), crystallized fastest, indicating formation of a rapid crystallizing saturated system at this ratio of the drugs. It is postulated that the problem of instability arises because of the formation of a saturated layer of drugs upon moisture gain through the defective packaging material and drying of this layer with time. The study suggests that barrier packaging free from defects and alternatively (or in combination) film coating of the tablets with water-resistant polymers are essential for this

  14. HPLC identification of isoniazid residues in bovine milk

    Directory of Open Access Journals (Sweden)

    Leite R.M.H.

    2000-01-01

    Full Text Available The high pressure liquid chromatography (HPLC was used for the identification of isoniazid (isonicotinic acid hydrazide in the milk of cattle treated with a dose of 25 mg/kg/day in alternated days. The effect of milk pasteurization on the isoniazid residue concentration was also studied. The drug excretion presented a cyclic variation, with higher levels in the first day after administration (aa, a mean of 1104.48µg/l, and a decrease two days aa, with a mean of 104.12µg/l. Four days after the last administration of the drug it was not possible to identify residues of isoniazid in the milk of treated animals. Body weight and milk yield influenced the amount of the excreted drug, and pasteurization decreased (mean 47.07% the concentration of isoniazid residue in milk.

  15. Optimization of a reversed-phase-high-performance thin-layer chromatography method for the separation of isoniazid, ethambutol, rifampicin and pyrazinamide in fixed-dose combination antituberculosis tablets.

    Science.gov (United States)

    Shewiyo, D H; Kaale, E; Risha, P G; Dejaegher, B; Smeyers-Verbeke, J; Vander Heyden, Y

    2012-10-19

    This paper presents the development of a new RP-HPTLC method for the separation of pyrazinamide, isoniazid, rifampicin and ethambutol in a four fixed-dose combination (4 FDC) tablet formulation. It is a single method with two steps in which after plate development pyrazinamide, isoniazid and rifampicin are detected at an UV wavelength of 280 nm. Then ethambutol is derivatized and detected at a VIS wavelength of 450 nm. Methanol, ethanol and propan-1-ol were evaluated modifiers to form alcohol-water mobile phases. Systematic optimization of the composition of each alcohol in the mobile phase was carried out using the window diagramming concept to obtain the best separation. Examination of the Rf distribution of the separated compounds showed that separation of the compounds with the mobile phase containing ethanol at the optimal fraction was almost situated within the optimal Rf-values region of 0.20-0.80. Therefore, ethanol was selected as organic modifier and the optimal mobile phase composition was found to be ethanol, water, glacial acetic acid (>99% acetic acid) and 37% ammonia solution (70/30/5/1, v/v/v/v). The method is new, quick and cheap compared to the actual method in the International Pharmacopoeia for the assay of the 4 FDC tablets, which involves the use of two separate HPLC methods. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Relative bioavailability of rifampicin, isoniazid and ethambutol from a combination tablet vs. concomitant administration of a capsule containing rifampicin and a tablet containing isoniazid and ethambutol.

    Science.gov (United States)

    Schall, R; Müller, F O; Duursema, L; Groenewoud, G; Hundt, H K; Middle, M V; Mogilnicka, E M; Swart, K J

    1995-11-01

    Twenty male volunteers who were slow metabolisers of isoniazid, completed this single-blind, single-dose, randomised, cross-over study to compare the bioavailability of rifampicin (CAS 13292-46-1), isoniazid (CAS 54-85-3) and ethambutol (CAS 1070-11-7) from Myrin tablets (test preparation) with the bioavailability of these drugs from a combination of capsules containing rifampicin and tablets containing isoniazid and ethambutol (reference). There were 2 treatment periods and on clinic days volunteers were given either the reference (300 mig rifampicin plus 200 mg isoniazid and 600 mg ethambutol HCl), or the test preparation (300 mg rifampicin, 150 mg isoniazid and 600 mg ethambutol HCl). Serial blood samples were drawn from the volunteers and rifampicin, isoniazid and ethambutol assays were performed. The results of this study indicate that the test preparation is equivalent to the reference with respect to both the rate and the extent of absorption of rifampicin, isoniazid (after adjustment for the different doses of isoniazid and ethambutol).

  17. Influence of isoniazid on naturally acquired tuberculin allergy and on induction of allergy by BCG vaccination*

    Science.gov (United States)

    Narain, Raj; Bagga, A. S.; Naganna, K.; Mayurnath, S.

    1970-01-01

    Previous studies on the influence of isoniazid on the size of the tuberculin reaction have given conflicting results. A controlled study in an area with high prevalence of low-grade allergy has been carried out by the administration of isoniazid or placebo tablets. For those not vaccinated with BCG, isoniazid in a single daily dose of 5 mg/kg body-weight tended to reduce somewhat the size of the tuberculin reaction among those with reactions of 12 mm or more at the initial tuberculin test. In people who were vaccinated with BCG, isoniazid given simultaneously resulted in significantly less increase in the size of post-vaccination tuberculin reactions as compared with controls; the difference was still significant, in tests conducted 4½ months after the discontinuation of isoniazid. However, in spite of isoniazid, the post-vaccination allergy induced by BCG was quite considerable. This considerable increase in post-vaccination allergy suggests that the vaccination was successful in spite of the administration of isoniazid and makes it clear that primary chemoprophylaxis could be combined with BCG vaccination. Administration of isoniazid for 2 months is estimated to have killed about 90% of the bacilli in the BCG vaccine injected intracutaneously. PMID:5312322

  18. Compound list: isoniazid [Open TG-GATEs

    Lifescience Database Archive (English)

    Full Text Available isoniazid INAH 00002 ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Human/i...n_vitro/isoniazid.Human.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vit...ro/isoniazid.Rat.in_vitro.Liver.zip ftp://ftp.biosciencedbc.jp/archive/open-tggates/LATEST/Rat/in_vivo/Liver.../Single/isoniazid.Rat.in_vivo.Liver.Single.zip ftp://ftp.biosciencedbc.jp/archive

  19. Dose variations with varying calculation grid size in head and neck IMRT

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Heeteak [Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, Fl 32611-8300 (United States); Jin, Hosang [Department of Nuclear and Radiological Engineering, University of Florida, Gainesville, Fl 32611-8300 (United States); Palta, Jatinder [Department of Radiation Oncology, University of Florida, Gainesville, Fl 32610-0385 (United States); Suh, Tae-Suk [Department of Biomedical Engineering, Catholic University of Korea (Korea, Republic of); Kim, Siyong [Department of Radiation Oncology, University of Florida, Gainesville, Fl 32610-0385 (United States)

    2006-10-07

    Ever since the advent and development of treatment planning systems, the uncertainty associated with calculation grid size has been an issue. Even to this day, with highly sophisticated 3D conformal and intensity-modulated radiation therapy (IMRT) treatment planning systems (TPS), dose uncertainty due to grid size is still a concern. A phantom simulating head and neck treatment was prepared from two semi-cylindrical solid water slabs and a radiochromic film was inserted between the two slabs for measurement. Plans were generated for a 5400 cGy prescribed dose using Philips Pinnacle{sup 3} TPS for two targets, one shallow ({approx}0.5 cm depth) and one deep ({approx}6 cm depth). Calculation grid sizes of 1.5, 2, 3 and 4 mm were considered. Three clinical cases were also evaluated. The dose differences for the varying grid sizes (2 mm, 3 mm and 4 mm from 1.5 mm) in the phantom study were 126 cGy (2.3% of the 5400 cGy dose prescription), 248.2 cGy (4.6% of the 5400 cGy dose prescription) and 301.8 cGy (5.6% of the 5400 cGy dose prescription), respectively for the shallow target case. It was found that the dose could be varied to about 100 cGy (1.9% of the 5400 cGy dose prescription), 148.9 cGy (2.8% of the 5400 cGy dose prescription) and 202.9 cGy (3.8% of the 5400 cGy dose prescription) for 2 mm, 3 mm and 4 mm grid sizes, respectively, simply by shifting the calculation grid origin. Dose difference with a different range of the relative dose gradient was evaluated and we found that the relative dose difference increased with an increase in the range of the relative dose gradient. When comparing varying calculation grid sizes and measurements, the variation of the dose difference histogram was insignificant, but a local effect was observed in the dose difference map. Similar results were observed in the case of the deep target and the three clinical cases also showed results comparable to those from the phantom study.

  20. Dose variations with varying calculation grid size in head and neck IMRT

    International Nuclear Information System (INIS)

    Chung, Heeteak; Jin, Hosang; Palta, Jatinder; Suh, Tae-Suk; Kim, Siyong

    2006-01-01

    Ever since the advent and development of treatment planning systems, the uncertainty associated with calculation grid size has been an issue. Even to this day, with highly sophisticated 3D conformal and intensity-modulated radiation therapy (IMRT) treatment planning systems (TPS), dose uncertainty due to grid size is still a concern. A phantom simulating head and neck treatment was prepared from two semi-cylindrical solid water slabs and a radiochromic film was inserted between the two slabs for measurement. Plans were generated for a 5400 cGy prescribed dose using Philips Pinnacle 3 TPS for two targets, one shallow (∼0.5 cm depth) and one deep (∼6 cm depth). Calculation grid sizes of 1.5, 2, 3 and 4 mm were considered. Three clinical cases were also evaluated. The dose differences for the varying grid sizes (2 mm, 3 mm and 4 mm from 1.5 mm) in the phantom study were 126 cGy (2.3% of the 5400 cGy dose prescription), 248.2 cGy (4.6% of the 5400 cGy dose prescription) and 301.8 cGy (5.6% of the 5400 cGy dose prescription), respectively for the shallow target case. It was found that the dose could be varied to about 100 cGy (1.9% of the 5400 cGy dose prescription), 148.9 cGy (2.8% of the 5400 cGy dose prescription) and 202.9 cGy (3.8% of the 5400 cGy dose prescription) for 2 mm, 3 mm and 4 mm grid sizes, respectively, simply by shifting the calculation grid origin. Dose difference with a different range of the relative dose gradient was evaluated and we found that the relative dose difference increased with an increase in the range of the relative dose gradient. When comparing varying calculation grid sizes and measurements, the variation of the dose difference histogram was insignificant, but a local effect was observed in the dose difference map. Similar results were observed in the case of the deep target and the three clinical cases also showed results comparable to those from the phantom study

  1. Calculation of rectal dose surface histograms in the presence of time varying deformations

    International Nuclear Information System (INIS)

    Roeske, John C.; Spelbring, Danny R.; Vijayakumar, S.; Forman, Jeffrey D.; Chen, George T.Y.

    1996-01-01

    Purpose: Dose volume (DVH) and dose surface histograms (DSH) of the bladder and rectum are usually calculated from a single treatment planning scan. These DVHs and DSHs will eventually be correlated with complications to determine parameters for normal tissue complication probabilities (NTCP). However, from day to day, the size and shape of the rectum and bladder may vary. The purpose of this study is to compare a more accurate estimate of the time integrated DVHs and DSHs of the rectum (in the presence of daily variations in rectal shape) to initial DVHs/DSHs. Methods: 10 patients were scanned once per week during the course of fractionated radiotherapy, typically accumulating a total of six scans. The rectum and bladder were contoured on each of the studies. The model used to assess effects of rectal contour deformation is as follows: the contour on a given axial slice (see figure) is boxed within a rectangle. A line drawn parallel to the AP axis through the rectangle equally partitions the box. Starting at the intersection of the vertical line and the rectal contour, points on the contour are marked off representing the same rectal dose point, even in the presence of distortion. Corresponding numbered points are used to sample the dose matrix and create a composite DSH. The model assumes uniform stretching of the rectal contour for any given axial cut, and no twist of the structure or vertical displacement. A similar model is developed for the bladder with spherical symmetry. Results: Normalized DSHs (nDSH) for each CT scan were calculated as well as the time averaged nDSH over all scans. These were compared with the nDSH from the initial planning scan. Individual nDSHs differed by 8% surface area irradiated at the 80% dose level, to as much as 20% surface area in the 70-100% dose range. DSH variations are due to position and shape changes in the rectum during different CT scans. The spatial distribution of dose is highly variable, and depends on the field

  2. Analysis of the importance for the doses of varying parameters in the BIOPATH-program

    International Nuclear Information System (INIS)

    Bergstroem, U.

    1981-01-01

    The doses to individuals and populations from water-borne nuclides leaked from a repository have been calculated earlier using the computer program BIOPATH. The turnover of nuclides in the biosphere is thereby simulated by the application of compartment theory. For the dominant nuclides in the disposal an analysis of the importance of varying parameters has been done, to decide how strongly uncertainties in data will affect resulting doses. The essential part has been the transfer coefficients but also the uptake in the food-chains has been studied. The purpose of the study has also been to make proposals for forthcoming efforts to improve the basis for such calculations. The study shows the great importance of the surface water-soil-groundwater-drinking water system for the dose. Thereby the most important question is the solubility of the nuclides in the different water reservoirs. (Auth.)

  3. Histomorphological effects of isoniazid induced hepatotoxicity in male albino mice

    International Nuclear Information System (INIS)

    Humayun, F.; Zareen, N.

    2017-01-01

    To observe the histomorphological changes of isoniazid induced hepatotoxicity in male albino mice. Methodology: This experimental study was carried out at University of Health Sciences, Lahore, Pakistan from January to December 2013. Forty male albino mice selected by simple random technique, were divided into two groups; A-Control, and B-experimental. Group A comprised of 15, while Group B comprised 25 mice. Both the groups were kept under identical conditions and diet. However, experimental group was treated with an additional oral hepatotoxic dose of isoniazid i.e. 100mg/kg bodyweight daily for 30 days. After 30 days, the animals were sacrificed and livers were dissected out. Gross comparison of the organ and stained sections were histologically compared for morphological differences between the groups. Fischer Exact test was used to analyze the qualitative data and a p<0.05 was considered significant. Results: Group A animals showed the normal liver architecture. Whereas, those of Group B showed deranged hepatic histomorphology. Conclusion: Hepatotoxic dose of Isoniazid caused histomorphological alterations in the liver of male albino mice. (author)

  4. Acute Psychosis after Recent Isoniazid Initiation

    Science.gov (United States)

    Sukhija, Gagandeep; Singh, Harpreet

    2015-01-01

    Isoniazid as part of Directly Observed Treatment-Short course (DOTS) regimen is universally used. Although, associated psychosis in certain cases is documented earlier, type of symptoms and onset of symptoms remains highly variable. We describe a case of 54-year-old female on anti-tubercular therapy with onset of psychosis within three days of Isoniazid initiation characterised by agitation, loosening of association, echolalia with spontaneous remission after drug stoppage. This case highlights the importance of remaining vigilant and considering isoniazid as possible causative agent for psychosis even within days of its intiation and avoiding delay in management. PMID:26266198

  5. Isoniazid

    Science.gov (United States)

    ... beverages include certain cheeses, red wine, and certain fish (e.g., tuna, other tropical fish). Talk to your doctor or dietitian about which ... victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency ...

  6. Transdermal delivery of isoniazid and rifampin in guinea pigs by electro-phonophoresis.

    Science.gov (United States)

    Chen, Suting; Han, Yi; Yu, Daping; Huo, Fengmin; Wang, Fen; Li, Yunxu; Dong, Lingling; Liu, Zhidong; Huang, Hairong

    2017-11-01

    Electro-phonophoresis (EP) has been used as a drug delivery approach in clinical fields. The objective of the present study is to evaluate the skin permeability of isoniazid and rifampin in guinea pigs by EP to provide reference basis for clinical applications of such transdermal delivery system in the treatment of patients with superficial tuberculosis. Isoniazid and rifampin solutions were delivered transdermally with or without EP in health guinea pigs for 0.5 h. Local skin and blood samples were collected serially at 0, 1/2, 1, 2, 4, 6 and 24 h after dosing. Drug concentrations in local skin and blood were evaluated by high-performance liquid chromatography. Isoniazid concentrations in local skin of guinea pigs receiving isoniazid through EP transdermal delivery were significantly higher than in animals receiving only isoniazid with transdermal patch. However, for rifampin, patches alone group presented almost uniform concentration versus time curve with that of EP group, and both groups had concentrations much higher than the therapeutic concentration of the drug over sustainable time. After EP transdermal delivery, the mean peak concentrations of isoniazid and rifampin in skin were 771.0 ± 163.4 μg/mL and 81.2 ± 17.3 μg/mL respectively. Neither isoniazid nor rifampin concentration in blood could be detected (below the lower detection limit of 1 μg/mL) at any time point. The present study showed that application of EP significantly enhanced INH penetration through skin in guinea pigs, while RIF patch alone obtained therapeutic concentration in local skin. Our work suggests several possible medication approaches for efficient treatment of superficial tuberculosis.

  7. [The use of fenazid in patients with pulmonary tuberculosis with poor isoniazid tolerance].

    Science.gov (United States)

    Borisova, M I; Stakhanov, V A; Sharkova, T I; Ivashchenko, N A

    2003-01-01

    The paper shows the experience gained in the use of the new Russian antituberculous drug fenazid in patients with different forms of active pulmonary tuberculosis and with neuro- and angiotoxic reactions to isoniazid. The study group comprised 25 patients aged 23 to 70 years who received fenazid as tablets in a daily dose of 0.5 g for 2 months at the first stage of the basic course of chemotherapy. The control group including 24 patients of the same age was given the routine antituberculous chemotherapy regimen, including isoniazid. The use of fenazid permits adequate therapy in patients with poor isoniazid tolerance, which may recommend fenazid to individuals at high risk for adverse reactions as their prevention.

  8. On different types of hereditable changes in the viability of Amoeba protens cells x-irradiated with varying doses

    International Nuclear Information System (INIS)

    Bychkovskaya, I.B.; Ochinskaya, G.K.; Erokhina, G.M.

    1976-01-01

    Qualitatively different types of cells lethality have been observed in the posterity of amoebae irradiated with doses ranging from 0.5 to 40 kR and from 60 to 120 kR. At doses of 0.5 to 40 kR, a certain part of cells in a population dies, and the effect is characterized by stability and independency of a radiation dose, hereditable radiation damage of all the cells in the population, and by the fact that it might be caused not only by a derect action of radiation but also by a preirradiated culture medium. Higher doses (60 to 120 kR) cause a more drastic but sell stable effect. Depending on a dose value, a varying percentage of cells has shown the effect not being caused by the action of the preirradiated medium. The data obtained indicate that there are different mechanisms of hereditable radiation damages to cells caused by varying radiation doses

  9. SU-E-T-196: Comparative Analysis of Surface Dose Measurements Using MOSFET Detector and Dose Predicted by Eclipse - AAA with Varying Dose Calculation Grid Size

    Energy Technology Data Exchange (ETDEWEB)

    Badkul, R; Nejaiman, S; Pokhrel, D; Jiang, H; Kumar, P [University of Kansas Medical Center, Kansas City, KS (United States)

    2015-06-15

    Purpose: Skin dose can be the limiting factor and fairly common reason to interrupt the treatment, especially for treating head-and-neck with Intensity-modulated-radiation-therapy(IMRT) or Volumetrically-modulated - arc-therapy (VMAT) and breast with tangentially-directed-beams. Aim of this study was to investigate accuracy of near-surface dose predicted by Eclipse treatment-planning-system (TPS) using Anisotropic-Analytic Algorithm (AAA)with varying calculation grid-size and comparing with metal-oxide-semiconductor-field-effect-transistors(MOSFETs)measurements for a range of clinical-conditions (open-field,dynamic-wedge, physical-wedge, IMRT,VMAT). Methods: QUASAR™-Body-Phantom was used in this study with oval curved-surfaces to mimic breast, chest wall and head-and-neck sites.A CT-scan was obtained with five radio-opaque markers(ROM) placed on the surface of phantom to mimic the range of incident angles for measurements and dose prediction using 2mm slice thickness.At each ROM, small structure(1mmx2mm) were contoured to obtain mean-doses from TPS.Calculations were performed for open-field,dynamic-wedge,physical-wedge,IMRT and VMAT using Varian-21EX,6&15MV photons using twogrid-sizes:2.5mm and 1mm.Calibration checks were performed to ensure that MOSFETs response were within ±5%.Surface-doses were measured at five locations and compared with TPS calculations. Results: For 6MV: 2.5mm grid-size,mean calculated doses(MCD)were higher by 10%(±7.6),10%(±7.6),20%(±8.5),40%(±7.5),30%(±6.9) and for 1mm grid-size MCD were higher by 0%(±5.7),0%(±4.2),0%(±5.5),1.2%(±5.0),1.1% (±7.8) for open-field,dynamic-wedge,physical-wedge,IMRT,VMAT respectively.For 15MV: 2.5mm grid-size,MCD were higher by 30%(±14.6),30%(±14.6),30%(±14.0),40%(±11.0),30%(±3.5)and for 1mm grid-size MCD were higher by 10% (±10.6), 10%(±9.8),10%(±8.0),30%(±7.8),10%(±3.8) for open-field, dynamic-wedge, physical-wedge, IMRT, VMAT respectively.For 6MV, 86% and 56% of all measured values

  10. Simultaneous determination of isoniazid and pyrazinamide in ...

    African Journals Online (AJOL)

    Finally, 20 µL was injected into the HPLC system. HPLC analysis ... The method was accurate, and relative error ... Keywords: HPLC, Isoniazid, Pyrazinamide, Plasma, Simultaneous analysis. Tropical ... work, we describe a new HPLC method with UV ... pooled human plasma. ..... License, which permits unrestricted use,.

  11. Ergogenic effect of varied doses of coffee-caffeine on maximal ...

    African Journals Online (AJOL)

    Endurance performance index (VO2 max, run time & number of exercise laps) were measured and recorded. Result: Repeated measures ANOVA was used to assess the level of significant difference between caffeine doses and placebo dose in VO2 max, run time and number of exercise laps. The result showed no ...

  12. High-performance liquid chromatographic determination of isoniazid and 1-isonicotinyl-2-lactosylhydrazine in isoniazid tablet formulations.

    Science.gov (United States)

    Butterfield, A G; Lovering, E G; Sears, R W

    1980-02-01

    A high-performance liquid chromatographic procedure is presented for the simultaneous determination of isoniazid and 1-isonicotinyl-2-lactosylhydrazine (I) in isoniazid tablet formulations. An aliquot of a diluted aqueous tablet extract is introduced onto a microparticulate cyanopropyl bonded-phase column using a valve-loop injector and chromatographed using a mobile phase of acetonitrile--0.01 M, pH 3.5 aqueous acetate buffer (5:95). Compound I can be determined at levels as low as 0.5% of the isoniazid label claim. The relative standard deviations are 0.4 and 0.7% for the simultaneous determination of isoniazid and I, respectively. Seven commercial tablet formulations contained 93.8--97.0% of the labeled isoniazid amounts and 0.3--5.8% of I, expressed as equivalent isoniazid relative to the labeled isoniazid level.

  13. Quality assurance of Vari-source high dose rate (HDR) brachytherapy- remote after loader and cost effectiveness of Vari-source HDR- brachytherapy: NORI, Islamabad experience

    International Nuclear Information System (INIS)

    Ahmad, N.; Mahmood, H.; Jafri, S.R.A.

    2004-01-01

    A quality control of Vari-Source high dose rate (HDR) remote after loading brachytherapy machine was carried out and the cost effectiveness of HDR brachytherapy machine was also evaluated considering the cost of ten Iridium-192 wire sources at Nuclear Medicine, Oncology and Radiotherapy Institute (NORI), Islamabad, Pakistan. A total number of 253 intracavitary insertions were done in 98 patients from October 1996 to May 2001. The results of the quality control tests performed during 1996 to 2001 were within the acceptable limits. The cost effectiveness of Vari-Source HDR brachytherapy machine was also evaluated. The average cost per patient was calculated as US$ 491. Small number of patients was treated as the machine was used for gynecologic malignancies only. The objective was to assess the quality control status of HDR brachytherapy machine on patient treatment day, source exchange day and periodic day (monthly basis). It was found that the cost per patient can be minimized if other type of cancer patients are also treated on Vari-Source HDR machine. (author)

  14. Radiological Evaluation of the effects of varied doses of Celecoxib on fracture healing in dogs

    Directory of Open Access Journals (Sweden)

    Edwin Aihanuwa Uwagie-Ero and Rapheal Chukwujekwu Kene

    2011-04-01

    Full Text Available To determine if Cyclooxygenase -2 (COX-2 functions in fracture healing, 10 dogs were treated with COX-2-selective nonsteroidal anti-inflammatory drugs (Celecoxib to reduce and stop COX-2-dependent prostaglandin production. Radiographic testing evaluation determined that fracture healing was not affected in dogs treated with a low dose of COX-2-selective NSAIDs (celecoxib and delayed union was observed in dogs treated with a high dose of COX-2-selective NSAIDs (celecoxib. Celecoxib dose of 5 mg/kg/day did not affect fracture callus formed in the study group and did not cause a significant increase in the proportion of delayed unions, however, at a dose of 10 mg/kg/day it reduced the rate of fracture callus formation and significantly increased the proportion of delayed unions for dogs in the group. [Veterinary World 2011; 4(2.000: 75-76

  15. Bioavailability of isoniazid, rifampicin and pyrazinamide (in free combination or fixed-triple formulation) in intermittent antituberculous chemotherapy.

    Science.gov (United States)

    Acocella, G; Luisetti, M; Grassi, G G; Peona, V; Pozzi, E; Grassi, C

    1993-01-01

    A study was carried out in six human volunteers, to assess the blood kinetics of isoniazid, rifampicin and pyrazinamide, administered in a fixed-triple combination intended for use in intermittent chemotherapy of tuberculosis. The formulation employed contained 125 mg of isoniazid (H), 100 mg of rifampicin (R) and 375 mg of pyrazinamide (Z) per tablet; six tablets were administered to every subject, giving a total dosage of 750 mg of isoniazid, 600 mg of rifampicin and 2,250 mg of pyrazinamide. In each subject, the same dose of each drug was administered individually in separate sessions and the results compared. The results indicated that, at the level of dose of the intermittent tablet, no negative interactions between the drugs were observed.

  16. Isoniazid Pharmacokinetics-Pharmacodynamics in an Aerosol Infection Model of Tuberculosis

    Science.gov (United States)

    Jayaram, Ramesh; Shandil, Radha. K.; Gaonkar, Sheshagiri; Kaur, Parvinder; Suresh, B. L.; Mahesh, B. N.; Jayashree, R.; Nandi, Vrinda; Bharath, Sowmya; Kantharaj, E.; Balasubramanian, V.

    2004-01-01

    Limited data exist on the pharmacokinetic-pharmacodynamic (PK-PD) parameters of the bactericidal activities of the available antimycobacterial drugs. We report on the PK-PD relationships for isoniazid. Isoniazid exhibited concentration (C)-dependent killing of Mycobacterium tuberculosis H37Rv in vitro, with a maximum reduction of 4 log10 CFU/ml. In these studies, 50% of the maximum effect was achieved at a C/MIC ratio of 0.5, and the maximum effect did not increase with exposure times of up to 21 days. Conversely, isoniazid produced less than a 0.5-log10 CFU/ml reduction in two different intracellular infection models (J774A.1 murine macrophages and whole human blood). In a murine model of aerosol infection, isoniazid therapy for 6 days produced a reduction of 1.4 log10 CFU/lung. Dose fractionation studies demonstrated that the 24-h area under the concentration-time curve/MIC (r2 = 0.83) correlated best with the bactericidal efficacy, followed by the maximum concentration of drug in serum/MIC (r2 = 0.73). PMID:15273105

  17. Effects of varied doses of psilocybin on time interval reproduction in human subjects.

    Science.gov (United States)

    Wackermann, Jirí; Wittmann, Marc; Hasler, Felix; Vollenweider, Franz X

    2008-04-11

    Action of a hallucinogenic substance, psilocybin, on internal time representation was investigated in two double-blind, placebo-controlled studies: Experiment 1 with 12 subjects and graded doses, and Experiment 2 with 9 subjects and a very low dose. The task consisted in repeated reproductions of time intervals in the range from 1.5 to 5s. The effects were assessed by parameter kappa of the 'dual klepsydra' model of internal time representation, fitted to individual response data and intra-individually normalized with respect to initial values. The estimates kappa were in the same order of magnitude as in earlier studies. In both experiments, kappa was significantly increased by psilocybin at 90 min from the drug intake, indicating a higher loss rate of the internal duration representation. These findings are tentatively linked to qualitative alterations of subjective time in altered states of consciousness.

  18. FORMULATION AND EVALUATION OF ISONIAZID AND ETHAMBUTOL HYDROCHLORIDE COMBINATION TABLETS

    OpenAIRE

    Margret Chandira R; Jayakar B; Palanisamy P.

    2012-01-01

    Ethambutol hydrochloride and Isoniazid Drugs are used as Antituberculosis agents. It is mainly used in the initial Treatment of pulmonary tuberculosis. Here in present study compressed tablet of Ethambutol hydrochloride and Isoniazid prepared by using HPMC, HPC, and PVPK -30 as binders. Compressed tablets of Ethambutol hydrochloride and Isoniazid were prepared by wet granulation method. Among different trials of F1 to F9 with wet granulation, the trial F1 showed satisfactory in-vitro drug re...

  19. Experimental infection of cliff swallows (Petrochelidon pyrrhonota) with varying doses of West Nile virus

    Science.gov (United States)

    Oesterle, P.T.; Nemeth, N.M.; VanDalen, Kaci K.; Sullivan, H.; Bentler, K.T.; Young, G.R.; McLean, R.G.; Clark, L.; Smeraski, C.; Hall, Jeffrey S.

    2009-01-01

    Cliff swallows (Petrochelidon pyrrhonota) were inoculated with differing doses of West Nile virus (WNV) to evaluate their potential role as reservoir hosts in nature. Swallows often nest in large colonies in habitats and months associated with high mosquito abundance and early WNV transmission in North America. Additionally, cliff swallow diet consists of insects, including mosquitoes, leading to an additional potential route of WNV infection. The average peak viremia titer among infected cliff swallows was 106.3 plaque-forming units (PFU)/mL serum and the reservoir competence index was 0.34. There was no correlation between dose and probability of becoming infected or viremia peak and duration. Oral shedding was detected from 2 to 14 days post-inoculation with an average peak titer of 1044 PFU/swab. These results suggest that cliff swallows are competent reservoir hosts of WNV and therefore, they may play a role in early seasonal amplification and maintenance of WNV. Copyright ?? 2009 by The American Society of Tropical Medicine and Hygiene.

  20. Excretion of Antibiotic Resistance Genes by Dairy Calves Fed Milk Replacers with Varying Doses of Antibiotics

    Science.gov (United States)

    Thames, Callie H.; Pruden, Amy; James, Robert E.; Ray, Partha P.; Knowlton, Katharine F.

    2012-01-01

    Elevated levels of antibiotic resistance genes (ARGs) in soil and water have been linked to livestock farms and in some cases feed antibiotics may select for antibiotic resistant gut microbiota. The purpose of this study was to examine the establishment of ARGs in the feces of calves receiving milk replacer containing no antibiotics versus subtherapeutic or therapeutic doses of tetracycline and neomycin. The effect of antibiotics on calf health was also of interest. Twenty-eight male and female dairy calves were assigned to one of the three antibiotic treatment groups at birth and fecal samples were collected at weeks 6, 7 (prior to weaning), and 12 (5 weeks after weaning). ARGs corresponding to the tetracycline (tetC, tetG, tetO, tetW, and tetX), macrolide (ermB, ermF), and sulfonamide (sul1, sul2) classes of antibiotics along with the class I integron gene, intI1, were monitored by quantitative polymerase chain reaction as potential indicators of direct selection, co-selection, or horizontal gene transfer of ARGs. Surprisingly, there was no significant effect of antibiotic treatment on the absolute abundance (gene copies per gram wet manure) of any of the ARGs except ermF, which was lower in the antibiotic-treated calf manure, presumably because a significant portion of host bacterial cells carrying ermF were not resistant to tetracycline or neomycin. However, relative abundance (gene copies normalized to 16S rRNA genes) of tetO was higher in calves fed the highest dose of antibiotic than in the other treatments. All genes, except tetC and intI1, were detectable in feces from 6 weeks onward, and tetW and tetG significantly increased (P calves. Overall, the results provide new insight into the colonization of calf gut flora with ARGs in the early weeks. Although feed antibiotics exerted little effect on the ARGs monitored in this study, the fact that they also provided no health benefit suggests that the greater than conventional nutritional intake applied

  1. Comparative Study of Constant Dose Intrathecal Hypobaric Levobupivacaine with Varying Baricities in Lower Limb Surgeries.

    Science.gov (United States)

    Biji, K P; Sunil, M; Ramadas, K T

    2017-01-01

    Hypobaric spinal anesthesia is advantageous for unilateral lower extremity fractures as it obviates pain of lying on fractured limb for performing subarachnoid block. This study compares block characteristics and complications of three different baricities of constant dose intrathecal hypobaric levobupivacaine to determine an optimum baricity. One-twenty American Society of Anesthesiologists Physical Status 1 and 2 patients aged 18-65 years undergoing unilateral lower limb surgeries were divided into three equal groups for this prospective cohort study. To 2 mL intrathecal 0.5% isobaric levobupivacaine (10 mg), 0.4 mL, 0.6 mL, and 0.8 mL of distilled water were added in Groups A, B, and C, respectively. Baricities of Groups A, B, and C are 0.999294, 0.998945, and 0.998806, respectively. Development of sensory and motor block was assessed by the pinprick method and Bromage scale, respectively. The total duration of analgesia and complications were noted. Mean, standard error, one-way ANOVA, and Bonferroni were used to analyze quantitative variables; proportions and Chi-square tests for qualitative variables. Demographic parameters, motor block of operated limb, and complications were comparable. Group C had the fastest onset of sensory block (10.10 min) and maximum duration of analgesia (478.97 min; P < 0.001); but high sensory levels in 48.7%. Group B had T 10 sensory level in 92.5%; onset comparable to Group C ( P = 0.248), and reasonable duration of analgesia (332.50 min). Group A had inadequate sensory levels, slow onset, and early regression. Group B (baricity - 0.998945) has better block characteristics among three groups compared.

  2. Effects of varying doses of gamma radiation on locally adapted Tradescantia clone 02 (BNL) (Brookhaven National Laboratory)

    International Nuclear Information System (INIS)

    Dimaano, Maritess M.; Imperial V, Maria Angelica Liza

    1999-03-01

    This study determined the effects of gamma radiation on the meiotic cells of Tradescantia bracteata clone 02 (BNL). The flower buds collected were exposed through dosages ranging from 1 Gy to 5 Gy using gamma cell 220 machine (AECL) in a central axis position (c/a) and grown in Peralta's solution for three days. Out of the twenty buds designated for each dosages, ten buds were treated with 0.05% colchicine solution. The occurrence of micronuclei among the irradiated pollen mother cells suggested a linear relation with the quantity of radiation dose. The occurrence of MN among cells increased linearly from 1 Gy until it reached 3 Gy and 4 Gy. Beyond this maximum dose, cells were less responsive to the dose caused by inhibition of cell division, as demonstrated in the buds exposed to 5 Gy. This result was validated through the kruskal-Wallis test, where the computed h value was 3.44 (critical region of X 2 0 . 05 = 9.49) Experimental results also showed chromosomal breaks, sticky chromosomes, and anaphase bridges in the pollen mother cells of irradiated buds. A significant numbers of cells were also found to have micronuclei, which may vary from 1 to 6 per pollen mother cell, and this showed no relationship with radiation dose. (Author)

  3. Controlled-release tablet formulation of isoniazid.

    Science.gov (United States)

    Jain, N K; Kulkarni, K; Talwar, N

    1992-04-01

    Guar (GG) and Karaya gums (KG) alone and in combination with hydroxy-propylmethylcellulose (HPMC) were evaluated as release retarding materials to formulate a controlled-release tablet dosage form of isoniazid (1). In vitro release of 1 from tablets followed non-Fickian release profile with rapid initial release. Urinary excretion studies in normal subjects showed steady-state levels of 1 for 13 h. In vitro and in vivo data correlated (r = 0.9794). The studies suggested the potentiality of GG and KG as release retarding materials in formulating controlled-release tablet dosage forms of 1.

  4. Emergency department management of children with acute isoniazid poisoning.

    Science.gov (United States)

    Parish, R A; Brownstein, D

    1986-06-01

    We suggest that the following therapeutic regimen be followed in cases of isoniazid poisoning in children. In cases of intractable seizure activity in a child which remains unexplained, consider isoniazid poisoning. Give pyridoxine as an intravenous bolus to all children in whom isoniazid toxicity is suspected, who exhibit seizure activity and are known to have been exposed to isoniazid, or who have a history of ingesting one gram or more of isoniazid. It should be given on a gram-for-gram basis, and the clinician need not await serum isoniazid levels before administering pyridoxine. It can be safely given at a rate of five grams per three minutes in a 50 ml volume. In fact, serum isoniazid determinations are not available in many emergency departments and have not been shown to correlate closely with symptomatology. When available, serum isoniazid levels at best are subject to variability owing to sampling procedures (serum protein must be removed within two hours of sampling). The result is that serum isoniazid levels play only a minor role in the emergency department management of isoniazid poisoning. To potentiate the antidotal effects of pyridoxine, diazepam (0.1 mg/kg) may be given intravenously, preferably at a second intravenous site. Because the lactic acidosis seen after seizures resolves spontaneously, and because metabolic alkalosis may result following excess lactate loading, administration of bicarbonate is usually not necessary, and may be harmful in some cases. After pyridoxine treatment, syrup of ipecac may be given to empty the stomach.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. Metabolites Identified during Varied Doses of Aspergillus Species in Zea mays Grains, and Their Correlation with Aflatoxin Levels

    Directory of Open Access Journals (Sweden)

    Titilayo D. O. Falade

    2018-05-01

    Full Text Available Aflatoxin contamination is associated with the development of aflatoxigenic fungi such as Aspergillus flavus and A. parasiticus on food grains. This study was aimed at investigating metabolites produced during fungal development on maize and their correlation with aflatoxin levels. Maize cobs were harvested at R3 (milk, R4 (dough, and R5 (dent stages of maturity. Individual kernels were inoculated in petri dishes with four doses of fungal spores. Fungal colonisation, metabolite profile, and aflatoxin levels were examined. Grain colonisation decreased with kernel maturity: milk-, dough-, and dent-stage kernels by approximately 100%, 60%, and 30% respectively. Aflatoxin levels increased with dose at dough and dent stages. Polar metabolites including alanine, proline, serine, valine, inositol, iso-leucine, sucrose, fructose, trehalose, turanose, mannitol, glycerol, arabitol, inositol, myo-inositol, and some intermediates of the tricarboxylic acid cycle (TCA—also known as citric acid or Krebs cycle were important for dose classification. Important non-polar metabolites included arachidic, palmitic, stearic, 3,4-xylylic, and margaric acids. Aflatoxin levels correlated with levels of several polar metabolites. The strongest positive and negative correlations were with arabitol (R = 0.48 and turanose and (R = −0.53, respectively. Several metabolites were interconnected with the TCA; interconnections of the metabolites with the TCA cycle varied depending upon the grain maturity.

  6. Formulation and characterization of modified release tablets containing isoniazid using swellable polymers.

    Science.gov (United States)

    Akhtar, M F; Rabbani, M; Sharif, A; Akhtar, B; Saleem, A; Murtaza, G

    2011-01-01

    The aim of this work was to develop swellable modified release (MR) isoniazid tablets using different combinations of polyvinyl acetate (PVAc) and sodium-carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation technique and then compressed into tablets. In vitro release studies for 12 hr were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Tablets of all formulations were found to be of good physical quality with respect to appearance (width and thickness), content uniformity, hardness, weight variation and friability. In vitro release data showed that increasing total polymer content resulted in more retarding effect. Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12(th) hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that this combination can be used to formulate zero order release tablets of water soluble drugs like isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian transport is the primary mechanism of isoniazid release from PVAc and Na-CMC based tablets. The value of mean dissolution time decreased with the increase in the release rate of drug clearly showing the retarding behavior of the swellable polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may be feasible to formulate zero order release tablets of water soluble drugs like isoniazid.

  7. Pharmacokinetics and Safety of a Single Oral Dose of Mirogabalin in Japanese Subjects With Varying Degrees of Renal Impairment.

    Science.gov (United States)

    Kato, Manabu; Tajima, Naoyuki; Shimizu, Takako; Sugihara, Masahiro; Furihata, Kenichi; Harada, Kazuhiro; Ishizuka, Hitoshi

    2018-01-01

    Mirogabalin (DS-5565) is a novel preferentially selective α 2 δ-1 ligand being developed for the treatment of diabetic peripheral neuropathic pain and postherpetic neuralgia. The current multicenter open-label study determined the effect of varying degrees of renal impairment on the pharmacokinetics and safety of a single dose of mirogabalin 5 mg in Japanese subjects. A total of 30 subjects (6 subjects per renal function category [normal, mild, moderate, or severe impairment; and end-stage renal disease (ESRD)]) were enrolled and completed the study. The AUC last increased with severity of renal impairment; the geometric least-squares mean ratios of AUC last compared with subjects with normal renal function were 1.3, 1.9, 3.6, and 5.3 for patients with mild, moderate, and severe impairment and ESRD, respectively. In accordance with this AUC last increase, apparent total body clearance (CL/F), renal clearance (CLr), and the cumulative percentage of mirogabalin dose excreted into urine all decreased with severity of renal impairment. There were no deaths and no severe treatment-related adverse events (TEAEs), serious TEAEs, or TEAEs resulting in study discontinuation. Mirogabalin was well tolerated in Japanese subjects with normal renal function and those with mild to severe renal impairment. It was also tolerated in subjects with ESRD but with a higher incidence of TEAEs. The most frequently reported TEAEs were dizziness (ESRD, n = 3), somnolence (ESRD, n = 2), and vomiting (ESRD, n = 2). Based on these data, a mirogabalin dose adjustment will be considered in Japanese subjects with moderate to severe renal impairment and those with ESRD. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  8. Spirulina maxima Protects Liver From Isoniazid and Rifampicin Drug Toxicity.

    Science.gov (United States)

    Jatav, Santosh Kumar; Kulshrestha, Archana; Zacharia, Anish; Singh, Nita; Tejovathi, G; Bisen, P S; Prasad, G B K S

    2014-07-01

    Hepatotoxicity associated with isoniazid and rifampicin is one of the major impediments in antituberculosis therapy. The present study explored the prophylactic and therapeutic efficacies of Spirulina maxima in isoniazid and rifampicin induced hepatic damage in a rat model. Hepatic damage induced in Wistar rats by isoniazid and rifampicin resulted in significant alterations in biomarkers of liver function, namely, bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, and oxidative stress markers such as superoxide dismutase, catalase, glutathione, and thiobarbituric acid reactive substances. Co-administration of Spirulina maxima along with antituberculosis drugs protected liver from hepatotoxicity due to isoniazid and rifampicin. Administration of Spirulina maxima consecutively for 2 weeks to hepatodamaged animals resulted in restoration of hepatic function as evident from normalization of serum markers of liver function. Thus, the present study revealed remarkable prophylactic and therapeutic potential of Spirulina maxima. Co-administration of Spirulina maxima and antituberculosis drugs is advantageous as it provides extra nutritional benefit. © The Author(s) 2014.

  9. Implications of the 2015 World Health Organization isoniazid ...

    African Journals Online (AJOL)

    Isoniazid preventive therapy (IPT) is a key strategy recommended by the World ... In its continued effort to attain its vision of a Namibia where TB is no longer a ... In its health budget planning, the government of Namibia needs ... STATEMENT.

  10. Effects of isoniazid and niacin on experimental wound-healing

    DEFF Research Database (Denmark)

    Weinreich, Jürgen; Ågren, Sven Per Magnus; Bilali, Erol

    2010-01-01

    There is a need for effective treatments of ischemic wounds. Our aim was to test the hypothesis that systemic administration of isoniazid or niacin can enhance wound healing in ischemic as well as nonischemic tissues.......There is a need for effective treatments of ischemic wounds. Our aim was to test the hypothesis that systemic administration of isoniazid or niacin can enhance wound healing in ischemic as well as nonischemic tissues....

  11. Isoniazid release from suppositories compounded with selected bases.

    Science.gov (United States)

    Hudson, Kristofer C; Asbill, C Scott; Webster, Andrew A

    2007-01-01

    There is an increasing need for an alternative route of isoniazid adminstration for prophylaxis and treatment of tuberculosis in children. The purpose of this study is to evaluate the in vitro release of isoniazid from extemporaneously compounded isoniazid suppositories with a goal of optimizing the suppository dosage form for this indication. Suppositories were compounded using three different base formulations (cocoa butter, Witepsol H15 Base F, and a combination of polyethylene glycols 3350, 1000, and 400). The release profiles of six compounded suppositories with isoniazid (100 mg) were tested with a United States Pharmacopeial Convention-approved dissolution apparatus. Isoniazid concentrations at predetermined time points were determined using high-performance liquid chromatographic analysis. The results show that drug release from the water-solutble base (mixed polyethylene glycols) was significantly greater than that from the lipophilic bases (cocoa butter and Witepsol H15). The percentage of isoniazid release form the polyethylene glycol suppository formulation (70 +/- 1.4 mg/mL) was greater than that from the cocoa butter (55 +/- 1.1 mg/mL) and Witepsol H15 Base F (18 +/- 0.36 mg/mL) suppository formulations.

  12. [Determination of isoniazide concentration in pleural effusion and its pleural permeability in patients with tuberculous pleurisy].

    Science.gov (United States)

    Liu, Yuan; Zhang, Qing; Zhang, Junfeng; Huang, Guohua; Zhu, Shunfang; Liu, Sijia; Li, Guofeng

    2012-05-01

    To establish a high-performance liquid chromatography (HPLC)-based method for determining isoniazide concentration in pleural effusion and plasma of patients with tuberculous pleurisy, and evaluate the permeability of isoniazide from blood into pleural effusion. We collected pleural effusion from 15 patients with tuberculous pleurisy 2 h after administration 300 mg isoniazide in the morning of day 1. Pleural effusion and plasma were obtained 2 h after isoniazide administration on day 3. Isoniazide concentration was measured using HPLC, and the penetration rate of isoniazide in pleural effusion was calculated. Isoniazide concentration in the pleural effusion averaged 1.156∓1.190 µg/ml in the 15 patients at 2 h after isoniazide administration on day 1. On day 3, isoniazide concentration was 1.920∓1.294 µg/ml in the pleural effusion and 2.445∓1.463 µg/ml in the plasma, and the mean penetration rate of isoniazide from blood into the pleural effusion was 86.0%. As isoniazide has a high penetration rate into the pleural effusion in most patients, continuous oral administration of isoniazid has been sufficient to achieve an effective treatment concentration, and intrapleural injection of isoniazide may seem unnecessary for non-drug-resistant tuberculosis pleurisy.

  13. Reagent Precoated Targets for Rapid In-Tissue Derivatization of the Anti-Tuberculosis Drug Isoniazid Followed by MALDI Imaging Mass Spectrometry

    Science.gov (United States)

    Manier, M. Lisa; Reyzer, Michelle L.; Goh, Anne; Dartois, Veronique; Via, Laura E.; Barry, Clifton E.; Caprioli, Richard M.

    2011-08-01

    Isoniazid (INH) is an important component of front-line anti-tuberculosis therapy with good serum pharmacokinetics but unknown ability to penetrate tuberculous lesions. However, endogenous background interferences hinder our ability to directly analyze INH in tissues. Chemical derivatization has been successfully used to measure isoniazid directly from tissue samples using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). MALDI targets were pretreated with trans-cinnamaldehyde (CA) prior to mounting tissue slices. Isoniazid present in the tissues was efficiently derivatized and the INH-CA product measured by MS/MS. Precoating of MALDI targets allows the tissues to be directly thaw-mounted and derivatized, thus simplifying the preparation. A time-course series of tissues from tuberculosis infected/INH dosed animals were assayed and the MALDI MS/MS response correlates well with the amount of INH determined to be in the tissues by high-performance liquid chromatography (HPLC)-MS/MS.

  14. Development and Evaluation of Isoniazid Loaded Silk Fibroin Microsphere

    Directory of Open Access Journals (Sweden)

    Narinder Singh

    Full Text Available Aim: Current experimental investigation is dedicated to prepare microspheres with small size and good sphericity by Phase Separation method using Isoniazid (INH as model drug. Silk fibroin has unique intrinsic qualities like biodegradability, biocompatibility or release properties and their tunable drug loading capacity. The delivery loading proficiency of the drug molecules in silk spheres be contingent on their charge, and hydrophobicity or subsequent in altered drug release profiles. Methods: In the present work Isoniazid loaded silk fibroin microsphere was prepared by using phase separation method. Microsphere was evaluated for Ultraviolet-visible spectroscopy, Fourier Transform infrared spectroscopy, Entrapment efficiency, Scanning electron microscopy Studies. Results: Scanning electron microscopy studies revealed that Isoniazid Loaded Silk Fibroin Microspheres were spherical. Entrapment Efficiency of Isoniazid loaded Microspheres of different Formulation from F1 to F5 was in range of 53 to 68 %. F3 showed 68.47 % entrapment Efficiency and the optimized formulation drug release was 93.56 % at 24 hours. Conclusion: Experimental report disclosed a new aqueous based formulation method for silk spheres with controllable shape or size and sphere. Isoniazid loaded silk microspheres may act as ideal nano formulation with elaborated studies.

  15. Fast BIA-amperometric determination of isoniazid in tablets.

    Science.gov (United States)

    Quintino, Maria S M; Angnes, Lúcio

    2006-09-26

    This paper proposes a new, fast and precise method to analyze isoniazid based on the electrochemical oxidation of the analyte at a glassy carbon electrode in 0.1M NaOH. The quantification was performed utilizing amperometry associated with batch injection analysis (BIA) technique. Fast sequential analysis (60 determinations h(-1)) in an unusually wide linear dynamic range (from 2.5 x 10(-8) to 1.0 x 10(-3)M), with high sensitivity and low limits of detection (4.1 x 10(-9)M) and quantification (1.4 x 10(-8)M), was achieved. Such characteristics allied to a good repeatability of the current responses (relative standard deviation of 0.79% for 30 measurements), were explored for the specific determination of isoniazid in isoniazid-rifampin tablet.

  16. Synthesis and antitubercular activity of isoniazid condensed with carbohydrate derivatives

    Directory of Open Access Journals (Sweden)

    Sílvia H. Cardoso

    2009-01-01

    Full Text Available A series of 13 compounds analogous of isoniazid condensed with carbohydrate was synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv using Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC90 in μg/mL. Several compounds exhibited antitubercular activity (0.31-3.12 μg/mL when compared with first line drugs such as isoniazid (INH and rifampicin (RIP and could be a good starting point to develop new compounds against tuberculosis.

  17. Computed tomography: influence of varying tube current on patient dose and correctness of effective dose calculations; Computertomografie: Einfluss des variablen Roehrenstroms auf die Patientendosis und die Genauigkeit von Berechnungen der effektiven Dosis

    Energy Technology Data Exchange (ETDEWEB)

    Hietschold, V. [Inst. und Poliklinik fuer Radiologische Diagnostik, Universitaetsklinikum Carl-Gustav-Carus der TU Dresden (Germany); Koch, A.; Laniado, M.; Abolmaali, N.D. [OncoRay, Molecular Imaging, TU Dresden (Germany)

    2008-05-15

    Purpose: determination of the influence of tube currents varying during a CT scan on organ doses and on the effective dose as a function of patient constitution. Evaluation of the accuracy of effective dose calculations based on summarizing parameters (effective mAs, dose length product [DLP]) compared to calculations based on slice-specific tube currents. Materials and methods: investigation of the CT datasets of 806 patients acquired from the skull base to the proximal thigh with respect to the body mass index (BMI). The effective dose was calculated by means of slice-specific as well as region-specific conversion factors. Results: dose optimization by means of variable tube current resulted in a reduction of the gonad dose in patients with BMI {<=} 20.. 21 kg/m{sup 2} and of the effective dose in patients with BMI {<=} 26 kg/m{sup 2}. Effective dose values calculated with the DLP for 90% of the patients are within an interval of {+-} 20% of the values calculated using slice-specific tube currents. Conclusion: if tube current optimization during the CT scan was applied, for the scan region under investigation, at a BMI already below the German mean value, an increased effective dose was observed. Calculations of the effective dose on the basis of summarizing values such as DLP or effective mAs are of sufficient accuracy. (orig.)

  18. Penetapan Kadar Campuran Isoniazid dan Vitamin B6 dalam Sediaan Tablet Campuran Etambutol, Isoniazid dan Vitamin B6 Secara Spektrofotometri Derivatif dengan Metode Zero Crossing

    OpenAIRE

    Daulay, Elisa Fitri

    2016-01-01

    The compound of isoniazid and pyridoxine hydrochloride is one of combination in tablet. Determination of content of isoniazid and pyridoxine hydrochloride in tablet where not found in monography, either in the fourth edition Farmakope Indonesia (1995) or USP (United States Pharmacopeia) 30th edition (2007) that requires an analysis method that meets the test of validity in determining the content. The purpose of this research is to determine isoniazid and pyridoxine hydrochloride mixture us...

  19. Isoniazid prophylactic therapy for tuberculosis in HIV-seropositive ...

    African Journals Online (AJOL)

    Sensitivity analysis suggests that although a 6-month chemoprophylaxis policy appears justifiable on economic considerations, this is critically dependent on the annual risk of developing tuberculosis, patient compliance and the validity of assumptions on the efficacy and duration of protection of isoniazid prophylaxis.

  20. Mixed metal complexes of isoniazid and ascorbic acid: chelation ...

    African Journals Online (AJOL)

    Novel mixed complexes of isoniazid and ascorbic acid have been synthesized and characterized using infrared, electronic absorption data, elemental analysis, molar conductivity, melting point, thin layer chromatography and solubility. The metal ions involved in the complex formation are Cu2+, Zn2+ and Cd2+. The melting ...

  1. Uptake of isoniazid preventive therapy and its associated factors ...

    African Journals Online (AJOL)

    Background: Isoniazid Preventive Therapy (IPT) is an effective intervention for prevention of tuberculosis (TB) among HIV positive patients, and its use is recommended by the World Health Organization (WHO). Unfortunately the uptake of IPT in Kenya remains low (33%-40%) with limited knowledge on the factors that affect ...

  2. Mixed Metal Complexes of Isoniazid and Ascorbic Acid: Chelation ...

    African Journals Online (AJOL)

    HP

    these ligands and their metal complexes have revealed the bi-dentate coordination of isoniazid ligand to ... of the drugs on coordination with a metal is enhanced ..... James, O.O., Nwinyi, C.O. and. Allensela, M.A. (2008). Cobalt(II) complexes of mixed antibiotics: Synthesis,. Characterization, antimicrobial potential and their.

  3. Isoniazid prophylactic therapy for tuberculosis in HIV-seropositive ...

    African Journals Online (AJOL)

    hypothetical cohort of 100 000 HIV-seropositive people in. South Africa over a ... health sector resources can be utilised in an optimal manner. This article ... second part we estimate the costs and benefits of isoniazid preventive ... The cohort was stratified into ... population risk of dying from any cause, the number of dual.

  4. Do not overlook acute isoniazid poisoning in children with status epilepticus.

    Science.gov (United States)

    Caksen, Hüseyin; Odabas, Dursun; Erol, Mehmet; Anlar, Omer; Tuncer, Oguz; Atas, Bülent

    2003-02-01

    A previously healthy 2-year-old girl was admitted with generalized convulsive status epilepticus. She was in a stupor and could respond only to painful stimuli. She also had severe metabolic acidosis. Although initial liver function tests were normal, they were found to be moderately high on the fifth day of admission; however, they dropped to their normal ranges on the twelfth day of admission. Initially, the patient was diagnosed as having idiopathic status epilepticus, and classic anticonvulsant agents, including diazepam, phenytoin, and then phenobarbital, were given. However, her seizures did not subside, and diazepam infusion was initiated. After initiation of diazepam infusion, the seizures were completely controlled. On the fourth day of admission, her parents said that she had accidentally received 20 tablets (a total dose of 2000 mg) of isoniazid just before admission to our hospital. Later, we injected 200 mg of pyridoxine intravenously. During follow-up, her general condition improved, and anticonvulsant agents were discontinued because an electroencephalogram was found to be norma. She was discharged from the hospital on the twelfth day of admission. At the fourth month of follow-up, she was seizure free. Because of this case, we would like to re-emphasize that acute isoniazid poisoning should also be considered in a child with unexplained status epilepticus.

  5. Intestinal permeability and malabsorption of rifampin and isoniazid in active pulmonary tuberculosis

    Directory of Open Access Journals (Sweden)

    Valéria G. F. Pinheiro

    Full Text Available Low antimycobacterial drug concentrations have been observed in tuberculosis (TB patients under treatment. The lactulose/mannitol urinary excretion test (L/M, normally used to measure intestinal permeability, may be useful to assess drug absorption. The objective of this research was to study intestinal absorptive function and bioavailability of rifampin and isoniazid in TB patients. A cross sectional study was done with 41 patients and 28 healthy controls, using the L/M test. The bioavailabilities of rifampin (R and isoniazid (H were evaluated in 18 patients receiving full doses. Urinary excretion of mannitol and lactulose, measured by HPLC, was significantly lower in TB patients. The serum concentrations of the drugs were below the expected range for R (8-24 mcg/mL or H (3-6 mcg/mL in 16/18 patients. Analyzing the drugs individually, 12/18 patients had low serum concentrations of R, 13/18 for H and 8/18 for both drugs. We suggest that there is a decrease in the functional absorptive area of the intestine in TB patients, which would explain the reduced serum concentrations of antituberculosis drugs. There is a need for new approaches to improve drug bioavailability in TB patients.

  6. Development of a biocompatible nanodelivery system for tuberculosis drugs based on isoniazid-Mg/Al layered double hydroxide

    Directory of Open Access Journals (Sweden)

    Saifullah B

    2014-10-01

    Full Text Available Bullo Saifullah,1 Palanisamy Arulselvan,2 Mohamed Ezzat El Zowalaty,2,3 Sharida Fakurazi,2,4 Thomas J Webster,5,6 Benjamin M Geilich,5 Mohd Zobir Hussein1 1Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology, 2Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 3Department of Environmental Health, Faculty of Public Health and Tropical Medicine, Jazan University, Jazan, Saudi Arabia; 4Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 5Department of Chemical Engineering and Program in Bioengineering, Northeastern University, Boston, MA, USA; 6Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: The primary challenge in finding a treatment for tuberculosis (TB is patient non-compliance to treatment due to long treatment duration, high dosing frequency, and adverse effects of anti-TB drugs. This study reports on the development of a nanodelivery system that intercalates the anti-TB drug isoniazid into Mg/Al layered double hydroxides (LDHs. Isoniazid was found to be released in a sustained manner from the novel nanodelivery system in humans in simulated phosphate buffer solutions at pH 4.8 and pH 7.4. The nanodelivery formulation was highly biocompatible compared to free isoniazid against human normal lung and 3T3 mouse fibroblast cells. The formulation was active against Mycobacterium tuberculosis and gram-positive bacteria and gram-negative bacteria. Thus results show significant promise for the further study of these nanocomposites for the treatment of TB. Keywords: tuberculosis, isoniazid, Mg/Al LDH, nanodelivery system

  7. Biogenic amines in brain areas of rats and response to varying dose levels of whole body gamma irradiation

    International Nuclear Information System (INIS)

    Abdelhamid, F.M.; Elmossalamy, N.; Othman, S.A.; Roushdy, H.M.; Abdelraheem, K.

    1994-01-01

    The levels of norepinephrine (NE), dopamine (DA), 5-hydroxy-tryptamine (5-HT) and 5-hydroxy-indole acetic acid (5-HIAA) were examined in the brain areas:cortex,: cerebellum, striatum and pons in rats exposed to whole body gamma-irradiation at the dose levels 6.5 and 10 Gy. The data obtained indicated that: 6.5 Gy induced in all brain areas, a slight increase in 5-HT concomitant with significant decrease in NE, DA levels, besides a significant increase in 5-HTAA in cerebellum and pons. After the dose 10 Gy the maximum excitation of 5-HT level was in striatum whereas declines in NE, DA were recorded in all brain areas. 5-HIAA displayed significant increase in cerebellum and pons and maximum decline in the cortex. 4 tab

  8. Effects on Ferroelectric Thin-Film Stacks and Devices for Piezoelectric MEMS Applications at Varied Total Ionizing Dose (TID)

    Science.gov (United States)

    2017-03-01

    non -linearly mobile internal interfaces, e.g. domain walls and eventual phase boundaries. Radiation exposure is expected...zirconate titanate; PZT; actuator; radiation ; gamma; total ionization dose; TID; top electrode; Pt; IrO2; polarization; PE; hysteresis; permittivity...Hayashigawa, et. al., “A 2 Mbit Radiation Hardened Stackable Ferroelectric Memory” Non - Volatile Memory Technology Symposium, NVMTS 07, Nov 10-13, 2007 Albuquerque, NM, USA

  9. Penggunaan Pati Sitrat sebagai Bahan Pengembang Tablet Isoniazid

    OpenAIRE

    Darmayasari, Intan

    2016-01-01

    inder. The modified starch is a starch which its hydroxyl group has been modified or given specific treatment for example by heating. Citrate starch is a modified starch which has good flow property and ability to expand and improve the dissolution rate of poorly soluble drugs. Based on descriptions above, the researcher to do research about use of citrate starch that synthesizing from cassava starch as swelling substance of isoniazid tablet. Objective: The aim of this study is to know abo...

  10. Isoniazid-Associated Uric Acid Retention in the Lizard, Uromastix ...

    African Journals Online (AJOL)

    Reduction in uric acid excretion was observed following oral administration of 0.06 mg isoniazid per day for 5, 10 and 15 days to three groups of Uromastix hardwickii lizards. The rise of serum uric acid levels in the treated groups was 60 per cent higher on day 5, and about 4 and 5 times greater than in control groups on day ...

  11. Ultrastructural characteristics of type A epithelioid cells during BCG-granulomatosis and treatment with lysosomotropic isoniazid.

    Science.gov (United States)

    Shkurupii, V A; Kozyaev, M A; Nadeev, A P

    2006-04-01

    We studied BCG-granulomas, their cellular composition, and ultrastructure of type A epithelioid cells in the liver of male BALB/c mice with spontaneous granulomatous inflammation. The animals received free isoniazid or isoniazid conjugated with lysosomotropic intracellularly prolonged matrix (dialdehyde dextran, molecular weight 65-75 kDa). Lysosomotropic isoniazid was accumulated in the vacuolar apparatus of epithelioid cells and produced a stimulatory effect on plastic processes in these cells.

  12. Phenotypic low-level isoniazid resistance as a marker to predict ethionamide resistance in Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Salima Qamar

    2017-01-01

    Full Text Available Background: Tuberculosis is one of the most prevalent diseases in Pakistan. Pakistan has the highest burden of MDR-TB in the Eastern Mediterranean region. Ethionamide is an anti-tuberculous drug frequently used to treat MDR-TB. Its drug susceptibility testing is not easily available in resource limited settings. Since it acts on the same target protein as isoniazid (inhA protein encoded by inhA gene, we sought to find out if phenotypic isoniazid resistance can be a marker of ethionamide resistance. Materials and Methods: This was a retrospective observational study conducted at the Aga Khan University hospital section of microbiology. Data was retrieved between 2011 to 2014 for all culture positive MTB strains. All culture positive MTB isolates with susceptibilities to isoniazid and ethionamide recorded were included in the study. Isoniazid and ethionamide susceptibilities were performed using agar proportion method on Middlebrook 7H10 agar. Rate of Ethionamide resistance between low-level isoniazid resistant, high level isoniazid resistant and isoniazid sensitive MTB was compared. Results: A total of 11,274 isolates were included in the study. A statistically significant association (P < 0.001 was found between Ethionamide resistance and low-level isoniazid resistance (26.6% as compared to high-level isoniazid resistance (8.85% and isoniazid sensitivity (0.71% in MTB strains. However this association was not seen in XDR-TB strains. Conclusion: Low level isoniazid resistance may be used as marker for phenotypic ethionamide resistance and hence guide clinicians' choice of antituberculous agent for MDR-TB in Pakistan. Further studies involving detection of genotypic association of isoniazid and ethionamide susceptibilities are needed before a final conclusion can be derived.

  13. The colorimetric analysis of anti-tuberculosis fixed-dose combination tablets and capsules.

    Science.gov (United States)

    Ellard, G A

    1999-11-01

    The perceived need to demonstrate whether or not the actual amounts of rifampicin, isoniazid and pyrazinamide in fixed-dose combination tablets or capsules correspond to their stated drug contents. To adapt specific, robust and simple colorimetric methods that have been previously applied to measuring plasma and urinary rifampicin, isoniazid, pyrazinamide and ethambutol concentrations to estimate tablet and capsule drug contents. The methods were applied to the analysis of 14 commercially manufactured fixed-dose combinations: two capsule and three tablet formulations containing rifampicin and isoniazid; seven tablet formulations containing rifampicin, isoniazid and pyrazinamide; and two tablet formulations containing rifampicin, isoniazid, pyrazinamide and ethambutol. All the combined formulations contained near to their stated drug contents. Replicate analyses confirmed the excellent precision of the drug analyses. Such methods are not only rapid to perform but should be practical in many Third World situations with relatively modest laboratory facilities.

  14. Adherence with isoniazid for prevention of tuberculosis among HIV-infected adults in South Africa

    Directory of Open Access Journals (Sweden)

    Muller F James

    2006-06-01

    Full Text Available Abstract Background Tuberculosis (TB is the most common opportunistic infection in HIV-infected adults in developing countries. Isoniazid (INH is recommended for treatment of latent TB infection, however non-adherence is common. The purpose of this study was to apply in-house prepared isoniazid (INH urine test strips in a clinical setting, and identify predictors of positive test results in an adherence questionnaire in HIV-infected adults taking INH for prevention of TB. Methods Cross-sectional study of adherence using a questionnaire and urine test strips for detection of INH metabolites at two hospitals in Pietermaritzburg, South Africa. Participants were aged at least 18 years, HIV positive, and receiving INH for prevention of tuberculosis disease. Univariate and multivariate analyses are used to identify factors relevant to adherence. Results 301 consecutive patients were recruited. 28% of participants had negative urine tests. 32 (37.2%, 95% CI25.4, 45.0 of the 86 patients who received INH from peripheral pharmacies said the pharmacy had run out of INH at some time, compared with central hospital pharmacies (p = 0.0001. In univariate analysis, a negative test was associated with self-reported missed INH doses (p = 0.043. Each 12-hour increment since last reported dose increased the likelihood of a negative test by 34% (p = 0.0007. Belief in INH safety was associated with a positive test (p = 0.021. In multivariate analysis, patients who believed INH is important for prevention of TB disease were more likely to be negative (p = 0.0086. Conclusion Adequate drug availability at peripheral pharmacies remains an important intervention for TB prevention. Key questions may identify potentially non-adherent patients. In-house prepared urine tests strips are an effective and cheap method of objectively assessing INH adherence, and could be used an important tool in TB control programs.

  15. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Jie; Krausz, Kristopher W. [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States); Li, Feng; Ma, Xiaochao [Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 4089 KLSIC, MS 1018, 3901 Rainbow Boulevard, Kansas City, KS 66160 (United States); Gonzalez, Frank J., E-mail: fjgonz@helix.nih.gov [Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-01-15

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. -- Highlights: ► Isoniazid metabolites were elevated only in wild-type mice. ► Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ► Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ► Bile acid transporters were significantly decreased in isoniazid-treated mice.

  16. CYP2E1-dependent elevation of serum cholesterol, triglycerides, and hepatic bile acids by isoniazid

    International Nuclear Information System (INIS)

    Cheng, Jie; Krausz, Kristopher W.; Li, Feng; Ma, Xiaochao; Gonzalez, Frank J.

    2013-01-01

    Isoniazid is the first-line medication in the prevention and treatment of tuberculosis. Isoniazid is known to have a biphasic effect on the inhibition–induction of CYP2E1 and is also considered to be involved in isoniazid-induced hepatotoxicity. However, the full extent and mechanism of involvement of CYP2E1 in isoniazid-induced hepatotoxicity remain to be thoroughly investigated. In the current study, isoniazid was administered to wild-type and Cyp2e1-null mice to investigate the potential toxicity of isoniazid in vivo. The results revealed that isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice, but produced elevated serum cholesterol and triglycerides, and hepatic bile acids in wild-type mice, as well as decreased abundance of free fatty acids in wild-type mice and not in Cyp2e1-null mice. Metabolomic analysis demonstrated that production of isoniazid metabolites was elevated in wild-type mice along with a higher abundance of bile acids, bile acid metabolites, carnitine and carnitine derivatives; these were not observed in Cyp2e1-null mice. In addition, the enzymes responsible for bile acid synthesis were decreased and proteins involved in bile acid transport were significantly increased in wild-type mice. Lastly, treatment of targeted isoniazid metabolites to wild-type mice led to similar changes in cholesterol, triglycerides and free fatty acids. These findings suggest that while CYP2E1 is not involved in isoniazid-induced hepatotoxicity, while an isoniazid metabolite might play a role in isoniazid-induced cholestasis through enhancement of bile acid accumulation and mitochondria β-oxidation. -- Highlights: ► Isoniazid metabolites were elevated only in wild-type mice. ► Isoniazid caused no hepatotoxicity in wild-type and Cyp2e1-null mice. ► Isoniazid elevated serum cholesterol and triglycerides, and hepatic bile acids. ► Bile acid transporters were significantly decreased in isoniazid-treated mice.

  17. Isoniazid-resistant tuberculosis in Denmark: mutations, transmission and treatment outcome

    DEFF Research Database (Denmark)

    Bang, Didi; Andersen, Peter Henrik; Andersen, Ase Bengaard

    2010-01-01

    A retrospective study on isoniazid-resistant tuberculosis (TB) was conducted in the low-burden country, Denmark (DK). The aim was to describe treatment outcome and transmission and to evaluate a mutation analysis for high- and low-level isoniazid resistance detection.......A retrospective study on isoniazid-resistant tuberculosis (TB) was conducted in the low-burden country, Denmark (DK). The aim was to describe treatment outcome and transmission and to evaluate a mutation analysis for high- and low-level isoniazid resistance detection....

  18. Theoretically Guided Analytical Method Development and Validation for the Estimation of Rifampicin in a Mixture of Isoniazid and Pyrazinamide by UV Spectrophotometer.

    Science.gov (United States)

    Khan, Mohammad F; Rita, Shamima A; Kayser, Md Shahidulla; Islam, Md Shariful; Asad, Sharmeen; Bin Rashid, Ridwan; Bari, Md Abdul; Rahman, Muhammed M; Al Aman, D A Anwar; Setu, Nurul I; Banoo, Rebecca; Rashid, Mohammad A

    2017-01-01

    A simple, rapid, economic, accurate, and precise method for the estimation of rifampicin in a mixture of isoniazid and pyrazinamide by UV spectrophotometeric technique (guided by the theoretical investigation of physicochemical properties) was developed and validated. Theoretical investigations revealed that isoniazid and pyrazinamide both were freely soluble in water and slightly soluble in ethyl acetate whereas rifampicin was practically insoluble in water but freely soluble in ethyl acetate. This indicates that ethyl acetate is an effective solvent for the extraction of rifampicin from a water mixture of isoniazid and pyrazinamide. Computational study indicated that pH range of 6.0-8.0 would favor the extraction of rifampicin. Rifampicin is separated from isoniazid and pyrazinamide at pH 7.4 ± 0.1 by extracting with ethyl acetate. The ethyl acetate was then analyzed at λ max of 344.0 nm. The developed method was validated for linearity, accuracy and precision according to ICH guidelines. The proposed method exhibited good linearity over the concentration range of 2.5-35.0 μg/mL. The intraday and inter-day precision in terms of % RSD ranged from 1.09 to 1.70% and 1.63 to 2.99%, respectively. The accuracy (in terms of recovery) of the method varied from of 96.7 ± 0.9 to 101.1 ± 0.4%. The LOD and LOQ were found to be 0.83 and 2.52 μg/mL, respectively. In addition, the developed method was successfully applied to determine rifampicin combination (isoniazid and pyrazinamide) brands available in Bangladesh.

  19. Penetapan Kadar Campuran Isoniazid Dan Vitamin B6 Dalam Sediaan Tablet Secara Spektrofotometri Ultraviolet Dengan Perhitungan Multikomponen Dan Persamaan Matriks

    OpenAIRE

    Sari, Wardah Kumala

    2011-01-01

    Isoniazid is a drug that is effective in the treatment of tuberculosis. In trading Isoniazid is often combined with Vitamin B6 which aims to prevent side effects of Isoniazid in the form of peripheral neuritis. The combination of active ingredients that can cause problems in quantitative analysis for quality control preparations. In this research, determination of the combination tablet Vitamin B6 and Isoniazid by Ultraviolet spectrophotometry with multicomponent calculation and use the matri...

  20. Penetapan Kadar Campuran Rifampisin dan Isoniazid dalam Sediaan Tablet Secara Spektrofotometri Ultraviolet dengan Metode Panjang Gelombang Berganda

    OpenAIRE

    Sitorus, Riris Anugrah Rema

    2016-01-01

    The drugs used for tuberculosis were classified into two groups, there is primary drugs and secondary drugs. Rifampicin and isoniazid are the primary drugs. Combination of rifampicin and isoniazid in the tablet is one of the drugs that used in tuberculosis treatment. Combination of rifampicin and isoniazid in the tablet is one of the drugs that used in tuberculosis treatment. The purpose of this study is to determination value of rifampicin and isoniazid in tablets which circulates in the gen...

  1. Self-administered Versus Directly Observed Once-Weekly Isoniazid and Rifapentine Treatment of Latent Tuberculosis Infection

    Science.gov (United States)

    Belknap, Robert; Holland, David; Feng, Pei-Jean; Millet, Joan-Pau; Caylà, Joan A.; Martinson, Neil A.; Wright, Alicia; Chen, Michael P.; Moro, Ruth N.; Scott, Nigel A.; Arevalo, Bert; Miró, José M.; Villarino, Margarita E.; Weiner, Marc; Borisov, Andrey S.

    2017-01-01

    Background Expanding latent tuberculosis treatment is important to decrease active disease globally. Once-weekly isoniazid and rifapentine for 12 doses is effective but limited by requiring direct observation. Objective To compare treatment completion and safety of once-weekly isoniazid and rifapentine by self-administration versus direct observation. Design An open-label, phase 4 randomized clinical trial designed as a noninferiority study with a 15% margin. Seventy-five percent or more of study patients were enrolled from the United States for a prespecified subgroup analysis. (ClinicalTrials.gov: NCT01582711) Setting Outpatient tuberculosis clinics in the United States, Spain, Hong Kong, and South Africa. Participants 1002 adults (aged ≥18 years) recommended for treatment of latent tuberculosis infection. Intervention Participants received once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring. Measurements The primary outcome was treatment completion, defined as 11 or more doses within 16 weeks and measured using clinical documentation and pill counts for direct observation, and self-reports, pill counts, and medication event–monitoring devices for self-administration. The main secondary outcome was adverse events. Results Median age was 36 years, 48% of participants were women, and 77% were enrolled at the U.S. sites. Treatment completion was 87.2% (95% CI, 83.1% to 90.5%) in the direct-observation group, 74.0% (CI, 68.9% to 78.6%) in the self-administration group, and 76.4% (CI, 71.3% to 80.8%) in the self-administration–with–reminders group. In the United States, treatment completion was 85.4% (CI, 80.4% to 89.4%), 77.9% (CI, 72.7% to 82.6%), and 76.7% (CI, 70.9% to 81.7%), respectively. Self-administered therapy without reminders was noninferior to direct observation in the United States; no other comparisons met

  2. Computer-aided construction and investigation of a thermodynamically stable mouth-dissolving film containing isoniazid

    CSIR Research Space (South Africa)

    Adeleke, Oluwatoyin A

    2015-10-01

    Full Text Available The purpose of this abstract is to design and characterize a thermodynamically stable mouth-dissolving film containing isoniazid employing in silico and in vitro techniques. Isoniazid (solubility = 140 mg/mL and log P = -0.64 at 25°C) is a first...

  3. A dosing algorithm for metformin based on the relationships between exposure and renal clearance of metformin in patients with varying degrees of kidney function.

    Science.gov (United States)

    Duong, Janna K; Kroonen, M Y A M; Kumar, S S; Heerspink, H L; Kirkpatrick, C M; Graham, G G; Williams, K M; Day, R O

    2017-08-01

    The aims of this study were to investigate the relationship between metformin exposure, renal clearance (CL R ), and apparent non-renal clearance of metformin (CL NR /F) in patients with varying degrees of kidney function and to develop dosing recommendations. Plasma and urine samples were collected from three studies consisting of patients with varying degrees of kidney function (creatinine clearance, CL CR ; range, 14-112 mL/min). A population pharmacokinetic model was built (NONMEM) in which the oral availability (F) was fixed to 0.55 with an estimated inter-individual variability (IIV). Simulations were performed to estimate AUC 0-τ , CL R , and CL NR /F. The data (66 patients, 327 observations) were best described by a two-compartment model, and CL CR was a covariate for CL R . Mean CL R was 17 L/h (CV 22%) and mean CL NR /F was 1.6 L/h (69%).The median recovery of metformin in urine was 49% (range 19-75%) over a dosage interval. When CL R increased due to improved renal function, AUC 0-τ decreased proportionally, while CL NR /F did not change with kidney function. Target doses (mg/day) of metformin can be reached using CL CR /3 × 100 to obtain median AUC 0-12 of 18-26 mg/L/h for metformin IR and AUC 0-24 of 38-51 mg/L/h for metformin XR, with C max  kidney function to maintain consistent drug exposure. However, there is still marked IIV and therapeutic drug monitoring of metformin plasma concentrations is recommended.

  4. 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

  5. Development of a three component complex to increase isoniazid efficacy against isoniazid resistant and nonresistant Mycobacterium tuberculosis.

    Science.gov (United States)

    Manning, Thomas; Plummer, Sydney; Baker, Tess; Wylie, Greg; Clingenpeel, Amy C; Phillips, Dennis

    2015-10-15

    The bacterium responsible for causing tuberculosis has evolved resistance to antibiotics used to treat the disease, resulting in new multidrug resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug resistant M. tuberculosis (XDR-TB) strains. Analytical techniques (1)H and (13)C Nuclear Magnetic Resonance (NMR), Fourier Transform-Ion Cyclotron Resonance with Electrospray Ionization (FT-ICR/ESI), and Matrix Assisted Laser Desorption Ionization-Mass Spectrometry (MALDI-TOF-MS) were used to study different aspects of the Cu(II)-polyethylene glycol (PEG-3350)-sucrose-isoniazid and Cu(II)-polyethylene glycol (PEG3350)-glucose-isoniazid complexes. The Cu(II) cation, sucrose or glucose, and the aggregate formed by PEG primarily serve as a composite drug delivery agent for the frontline antibiotic, however the improvement in MIC values produced with the CU-PEG-SUC-INH complex suggest an additional effect. Several Cu-PEG-SUC-INH complex variations were tested against INH resistant and nonresistant strains of M. tuberculosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Therapeutic drug monitoring of isoniazid and rifampicin during anti-tuberculosis treatment in Auckland, New Zealand.

    Science.gov (United States)

    Maze, M J; Paynter, J; Chiu, W; Hu, R; Nisbet, M; Lewis, C

    2016-07-01

    There is uncertainty as to the optimal therapeutic concentrations of anti-tuberculosis drugs to achieve cure. To characterise the use of therapeutic drug monitoring (TDM), and identify risk factors and outcomes for those with concentrations below the drug interval. Patients treated for tuberculosis (TB) who had rifampicin (RMP) or isoniazid (INH) concentrations measured between 1 January 2005 and 31 December 2012 were studied retrospectively. Matched concentrations and drug dosing time were assessed according to contemporary regional drug intervals (RMP > 6 μmol/l, INH > 7.5 μmol/l) and current international recommendations (RMP > 10 μmol/l, INH > 22 μmol/l). Outcomes were assessed using World Health Organization criteria. Of 865 patients, 121 had concentrations of either or both medications. RMP concentrations were within the regional drug intervals in 106/114 (93%) and INH in 91/100 (91%). Concentrations were within international drug intervals for RMP in 76/114 (67%) and INH in 53/100 (53%). Low weight-based dose was the only statistically significant risk factor for concentrations below the drug interval. Of the 35 patients with low concentrations, 21 were cured, 9 completed treatment and 5 transferred out. There were no relapses during follow-up (mean 66.5 months). There were no clinically useful characteristics to guide use of TDM. Many patients had concentrations below international therapeutic intervals, but were successfully treated.

  7. PREPARATION OF ISONIAZID AS DRY POWDER FORMULATIONS FOR INHALATION BY PHYSICAL MIXING AND SPRAY DRYING

    Directory of Open Access Journals (Sweden)

    SOMCHAI SAWATDEE

    2006-01-01

    Full Text Available The main purpose of this study is to develop isoniazid as dry powder aerosol for delivery to the lower airways and to study the susceptibility of M. bovis and M. tuberculosis to the formulationsstudied. Isoniazid was formulated with trehalose, mannose and lactose by physical mixing and spray drying techniques. All formulations were evaluated for delivery efficiency and stability.Susceptibility tests of Mycobacterium species to the drug formulations were carried out. Isoniazid mixed with fine trehalose, micronised mannose or fine lactose produced the formulations whichgave fine particle fraction ( 0.05.

  8. Flow-injection system for automated dissolution testing of isoniazid tablets with chemiluminescence detection.

    Science.gov (United States)

    Li, B; Zhang, Z; Liu, W

    2001-05-30

    A simple and sensitive flow-injection chemiluminescence (CL) system for automated dissolution testing is described and evaluated for monitoring of dissolution profiles of isoniazid tablets. The undissolved suspended particles in the dissolved solution were eliminated via on-line filter. The novel CL system of KIO(4)-isoniazid was also investigated. The sampling frequency of the system was 120 h(-1). The dissolution profiles of isoniazid fast-release tablets from three sources were determined, which demonstrates the stability, great sensitivity, large dynamic measuring range and robustness of the system.

  9. A Prospective Study of Tuberculosis Drug Susceptibility in Sabah, Malaysia, and an Algorithm for Management of Isoniazid Resistance

    Science.gov (United States)

    Rashid Ali, Muhammad Redzwan S.; Parameswaran, Uma; William, Timothy; Bird, Elspeth; Wilkes, Christopher S.; Lee, Wai Khew; Yeo, Tsin Wen; Anstey, Nicholas M.; Ralph, Anna P.

    2015-01-01

    Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium tuberculosis drug resistance are poorly defined. Our objectives were to determine M. tuberculosis susceptibility and document management after receipt of susceptibility results. Methods. Prospective study of adult outpatients with smear-positive pulmonary tuberculosis (PTB) in Sabah, Malaysia. Additionally, hospital clinicians accessed the reference laboratory for clinical purposes during the study. Results. 176 outpatients were enrolled; 173 provided sputum samples. Mycobacterial culture yielded M. tuberculosis in 159 (91.9%) and nontuberculous Mycobacterium (NTM) in three (1.7%). Among outpatients there were no instances of multidrug resistant M. tuberculosis (MDR-TB). Seven people (4.5%) had isoniazid resistance (INH-R); all were switched to an appropriate second-line regimen for varying durations (4.5–9 months). Median delay to commencement of the second-line regimen was 13 weeks. Among 15 inpatients with suspected TB, 2 had multidrug resistant TB (one extensively drug resistant), 2 had INH-R, and 4 had NTM. Conclusions. Current community rates of MDR-TB in Sabah are low. However, INH-resistance poses challenges, and NTM is an important differential diagnosis in this setting, where smear microscopy is the usual diagnostic modality. To address INH-R management issues in our setting, we propose an algorithm for the treatment of isoniazid-resistant PTB. PMID:25838829

  10. Effects of varying doses of β-nerve growth factor on the timing of ovulation, plasma progesterone concentration and corpus luteum size in female alpacas (Vicugna pacos).

    Science.gov (United States)

    Stuart, C C; Vaughan, J L; Kershaw-Young, C M; Wilkinson, J; Bathgate, R; de Graaf, S P

    2015-11-01

    Ovulation in camelids is induced by the seminal plasma protein ovulation-inducing factor (OIF), recently identified as β-nerve growth factor (β-NGF). The present study measured the total protein concentration in alpaca seminal plasma using a bicinchoninic acid (BCA) protein quantification assay and found it to be 22.2±2.0mgmL(-1). To measure the effects of varying doses of β-NGF on the incidence and timing of ovulation, corpus luteum (CL) size and plasma progesterone concentration, 24 female alpacas were synchronised and treated with either: (1) 1mL 0.9% saline (n=5); (2) 4µg buserelin (n=5); (3) 1mg β-NGF protein (n=5); (4) 0.1mg β-NGF (n=5); or (5) 0.01mg β-NGF (n=4). Females were examined by transrectal ultrasonography at 1-2-h intervals between 20 and 45h after treatment or until ovulation occurred, as well as on Day 8 to observe the size of the CL, at which time blood was collected to measure plasma progesterone concentrations. Ovulation was detected in 0/5, 5/5, 5/5, 3/5 and 0/4 female alpacas treated with saline, buserelin, 1, 0.1 and 0.01mg β-NGF, respectively. Mean ovulation interval (P=0.76), CL diameter (P=0.96) and plasma progesterone concentration (P=0.96) did not differ between treatments. Mean ovulation interval overall was 26.2±1.0h. In conclusion, buserelin and 1mg β-NGF are equally effective at inducing ovulation in female alpacas, but at doses ≤0.1mg, β-NGF is not a reliable method for the induction of ovulation.

  11. Pregnancy Outcomes in HIV-Infected Women Receiving Long-Term Isoniazid Prophylaxis for Tuberculosis and Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Allan W. Taylor

    2013-01-01

    Full Text Available Objective. While 6- to 12-month courses of isoniazid for tuberculosis prevention are considered safe in pregnant women, the effects of longer-term isoniazid prophylaxis or isoniazid in combination with antiretroviral therapy (ART are not established in human-immunodeficiency-virus-(HIV- infected women who experience pregnancy during the course of therapy. Design. Nested study of pregnancy outcomes among HIV-infected women participating in a placebo-controlled, TB-prevention trial using 36 months daily isoniazid. Pregnancy outcomes were collected by interview and record review. Results. Among 196 pregnant women, 103 (52.6% were exposed to isoniazid during pregnancy; all were exposed to antiretroviral drugs. Prior to pregnancy they had received a median of 341 days (range 1–1095 of isoniazid. We observed no isoniazid-associated hepatitis or other severe isoniazid-associated adverse events in the 103 women. Pregnancy outcomes were 132 term live births, 42 premature births, 11 stillbirths, 8 low birth weight, 6 spontaneous abortions, 4 neonatal deaths, and 1 congenital abnormality. In a multivariable model, neither isoniazid nor ART exposure during pregnancy was significantly associated with adverse pregnancy outcome (adjusted odds ratios 0.6, 95% CI: 0.3–1.1 and 1.8, 95% CI 0.9–3.6, resp.. Conclusions. Long-term isoniazid prophylaxis was not associated with adverse pregnancy outcomes, such as preterm delivery, even in the context of ART exposure.

  12. Effect of single varied doses of UV-C radiation on photosynthesis, traspiration and chlorophyll content in the leaves of two varieties of faba bean and pea

    International Nuclear Information System (INIS)

    Olszewski, J.; Pszczolkowska, A.

    2004-01-01

    The effect of single, varied (75, 120 and 165 min) UV-C radiation on photosynthesis and transpiration in leaves of two morphotypes of faba bean and pea was determined in a pot experiment. The SPAD leaf greenness index, which characterises the a and b chlorophyll contents (as well as changes in its content caused by radiation) were analysed. The experimental results indicated that the intensity of photosynthesis and transpiration in faba bean leaves was higher in the plants treated with the UV-C radiation. In addition, the intensity of photosynthesis and the chlorophyll content were higher in the Neptun variety than in the self-terminating faba bean variety. The Rola pea variety plants showed a significant decrease in photsynthesis intensity under radiation in the 3rd leaf phase and a slight decrease in later developmental phases. Moreover, transpiration was found to decrease at the beginning of the vegetation. In the case of the Ramrod variety, rather ambiguous results were obtained. The chlorophyll content in both pea varieties was high in the 3rd proper leaf phase and in the Rola plants it increased with increasing radiation doses in the stem extension phase

  13. Poly(amidosulfonic acid) modified glassy carbon electrode for determination of isoniazid in pharmaceuticals.

    Science.gov (United States)

    Yang, Gongjun; Wang, Cunxiao; Zhang, Rui; Wang, Chenying; Qu, Qishu; Hu, Xiaoya

    2008-06-01

    Amidosulfonic acid was electropolymerized by cyclic voltammetry onto the surface of glassy carbon electrode (GCE) to fabricate the chemically modified electrode, which showed high stability, good selectivity and reproducibility for determination of isoniazid. The modified electrode showed an excellent electrocatalytical effect on the oxidation of isoniazid. Under the optimum conditions, there was a good linear relationship between anodic peak current and isoniazid concentration in the range of 5.0 x 10(-8)- 1.0 x 10(-5) M, and a detection limit of 1.0 x 10(-8) M (S/N = 3) was obtained after 120 s at the accumulation potential of - 0.2 V (vs. SCE). This developed method had been applied to the direct determination of isoniazid in injection and tablet samples with satisfactory results.

  14. Penetration of isoniazid, rifampicin and pyrazinamide in tuberculous pleural effusion and psoas abscess

    NARCIS (Netherlands)

    Jutte, P.C.; Rutgers, S.R.; Van Altena, R.; Uges, D.R.; van Horn, J.R.

    2004-01-01

    SETTING: Tuberculosis Centre, University Medical Centre, Groningen, The Netherlands. OBJECTIVES: To study intralesional concentrations of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) in tuberculous pleural effusions and psoas abscesses, and to compare these to reference serum values and

  15. Penetration of isoniazid, refampicin and pyrazinamide in tuberculous pleural effusion and psoas abscess

    NARCIS (Netherlands)

    Jutte, PC; Rutgers, [No Value; Van Altena, R; Uges, DR; Van Horn, [No Value

    SETTING: Tuberculosis Centre, University Medical Centre, Groningen, The Netherlands. OBJECTIVES: To study intralesional concentrations of isoniazid (INH), rifampicin (RMP) and pyrazinamide (PZA) in tuberculous pleural effusions and psoas abscesses, and to compare these to reference serum values and

  16. Electrocatalytic Determination of Isoniazid by a Glassy Carbon Electrode Modified with Poly (Eriochrome Black T)

    OpenAIRE

    Karim Asadpour-Zeynali; Venus Baghalabadi

    2017-01-01

    In this work poly eriochrome black T (EBT) was electrochemically synthesized on the glassy carbon electrode as electrode modifier. On the modified electrode, voltammetric behavior of isoniazid (INH) was investigated. The poly (EBT)-modified glassy carbon electrode has excellent electrocatalytic ability for the electrooxidation of isoniazid. This fact was appeared as a reduced overpotential of INH oxidation in a wide operational pH range from 2 to 13. It has been found that the catalytic peak ...

  17. Isoniazid-induced flu-like syndrome: A rare side effect

    Directory of Open Access Journals (Sweden)

    Sudipta Pandit

    2013-01-01

    Full Text Available Drug-induced flu-like syndrome is very rare. It is mainly produced by rifampicin. We report a case of pulmonary tuberculosis (PTB that developed isoniazid-induced flu-like syndrome, but could be cured with a modified regimen replacing isoniazid with levofloxacin. A 10-year-old girl with PTB was treated with isoniazid (H, rifampicin (R, ethambutol (E, and pyrazinamide (Z. She developed features of flu from the sixth day. Symptoms recurred everyday within 1 h of drug ingestion and subsided automatically by next 12 h. After admission, HREZ were continued. She developed symptoms of flu after 1 h of drug ingestion. Antitubercular therapy (ATT was stopped and symptoms subsided automatically. Individual drug was started one by one after three days. Severe symptoms of flu developed after taking isoniazid, while other drugs were tolerated well. Levofloxacin was used as an alternative to isoniazid. She was cured after 6 months of chemotherapy. Isoniazid can possibly cause flu-like syndrome and the treating physician should be aware of this possible side effect when using ATT.

  18. Gastric-resistant isoniazid pellets reduced degradation of rifampicin in acidic medium

    Directory of Open Access Journals (Sweden)

    Fátima Duarte Freire

    2014-12-01

    Full Text Available Isoniazid and rifampicin are considered the first-line medication for preventing and treating tuberculosis. Rifampicin is degraded in the stomach acidic environment, especially when combined with isoniazid, factor contributing to treatment failure. In this study, gastric-resistant isoniazid pellets were obtained to physical contact of this drug with rifampicin and to bypass the stomach´s acidic environment. The pellets were fabricated using the extrusion-spheronization technique. The coating process was conducted in a fluid spray coater using Acrycoat L 100(r solution as the coating agent. The pellets obtained were submitted to a dissolution test in HCl 0.1 N and phosphate buffer media. The results indicated that optimum gastric-resistance was only attained with the highest amount of coating material, with isoniazid almost fully released in phosphate buffer. The amount of rifampicin released from its mixture with non-coated isoniazid pellets in HCl 0.1 N was less than that released from its mixture with the enteric-coated pellets. Acrycoat L 100(r was shown to be an effective enteric/gastric-resistant coating since the stability of rifampicin appeared to be enhanced when physical contact of this drug with isoniazid was prevented at low pH.

  19. Electrocatalytic Determination of Isoniazid by a Glassy Carbon Electrode Modified with Poly (Eriochrome Black T

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    Karim Asadpour-Zeynali

    2017-06-01

    Full Text Available In this work poly eriochrome black T (EBT was electrochemically synthesized on the glassy carbon electrode as electrode modifier. On the modified electrode, voltammetric behavior of isoniazid (INH was investigated. The poly (EBT-modified glassy carbon electrode has excellent electrocatalytic ability for the electrooxidation of isoniazid. This fact was appeared as a reduced overpotential of INH oxidation in a wide operational pH range from 2 to 13. It has been found that the catalytic peak current depends on the concentration of INH and solution pH. The number of electrons involved in the rate determining step was found 1. The diffusion coefficient of isoniazid was also estimated using chronoamperometry technique. The experimental results showed that the mediated oxidation peak current of isoniazid is linearly dependent on the concentration of isoniazid in the ranges of 8.0 × 10-6 – 1.18 × 10-3 M and 2.90 × 10-5 M – 1.67× 10-3 M with differential pulse voltammetry (DPV and amperometry methods, respectively. The detection limits (S/N = 3 were found to be 6.0 μM and 16.4 μM by DPV and amperometry methods, respectively. This developed method was applied to the determination of isoniazid in tablet samples with satisfactory results.

  20. Tailored release drug delivery system for rifampicin and isoniazid for enhanced bioavailability of rifampicin.

    Science.gov (United States)

    Avachat, Amelia M; Bhise, Satish B

    2011-04-01

    The front line antitubercular drugs rifampicin (RMP) and isoniazid (INH), when co-administered, face the problem of reduced bioavailability of RMP. Stabilization of RMP in the presence of INH under acidic environment may improve the bioavailability of RMP. In vitro degradation studies showed around 15-25% degradation of RMP under the aforesaid conditions if the ratio of RMP: INH is above 1:0.5.This degradation is reduced to less than 10% when the ratio of RMP: INH is below 1:0.25. Based on these findings, an innovative drug delivery system was designed with the immediate release of RMP and tailored prolonged release of INH. The bilayer tablets prepared with this concept were subjected to relative bioavailability studies in healthy human volunteers in an open label, balanced, randomized, single-dose, cross-over study under fasted state. A validated LC-MS/MS bioanalytical method was employed for estimation of RMP and INH in plasma. Bioavailability studies revealed that C(max) and AUC for RMP increased by 18 and 20%, respectively, confirming the above innovative concept. Even in the case of INH, AUC increased significantly by around 30% and thus time above minimum inhibitory concentration (MIC) would also increase, which may result in further improved clinical outcome.

  1. Metabolism of isoniazid by neutrophil myeloperoxidase leads to isoniazid-NAD(+) adduct formation: A comparison of the reactivity of isoniazid with its known human metabolites.

    Science.gov (United States)

    Khan, Saifur R; Morgan, Andrew G M; Michail, Karim; Srivastava, Nutan; Whittal, Randy M; Aljuhani, Naif; Siraki, Arno G

    2016-04-15

    The formation of isonicotinyl-nicotinamide adenine dinucleotide (INH-NAD(+)) via the mycobacterial catalase-peroxidase enzyme, KatG, has been described as the major component of the mode of action of isoniazid (INH). However, there are numerous human peroxidases that may catalyze this reaction. The role of neutrophil myeloperoxidase (MPO) in INH-NAD(+) adduct formation has never been explored; this is important, as neutrophils are recruited at the site of tuberculosis infection (granuloma) through infected macrophages' cell death signals. In our studies, we showed that neutrophil MPO is capable of INH metabolism using electron paramagnetic resonance (EPR) spin-trapping and UV-Vis spectroscopy. MPO or activated human neutrophils (by phorbol myristate acetate) catalyzed the oxidation of INH and formed several free radical intermediates; the inclusion of superoxide dismutase revealed a carbon-centered radical which is considered to be the reactive metabolite that binds with NAD(+). Other human metabolites, including N-acetyl-INH, N-acetylhydrazine, and hydrazine did not show formation of carbon-centered radicals, and either produced no detectable free radicals, N-centered free radicals, or superoxide, respectively. A comparison of these free radical products indicated that only the carbon-centered radical from INH is reducing in nature, based on UV-Vis measurement of nitroblue tetrazolium reduction. Furthermore, only INH oxidation by MPO led to a new product (λmax=326nm) in the presence of NAD(+). This adduct was confirmed to be isonicotinyl-NAD(+) using LC-MS analysis where the intact adduct was detected (m/z=769). The findings of this study suggest that neutrophil MPO may also play a role in INH pharmacological activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Bioavailability of rifampicin following concomitant administration of ethambutol or isoniazid or pyrazinamide or a combination of the three drugs.

    Science.gov (United States)

    Immanuel, Chandra; Gurumurthy, Prema; Ramachandran, Geetha; Venkatesan, P; Chandrasekaran, V; Prabhakar, R

    2003-09-01

    Poor bioavailability of rifampicin (R) in combination with other anti-tuberculosis drugs such as isoniazid (H), pyrazinamide (Z), and ethambutol (E) is a subject of much concern for the last few decades. This could be due to an interaction between R and other drugs. An investigation was therefore undertaken to examine the bioavailability of R in the presence of H, Z and E or a combination of the three drugs. The study included eight healthy volunteers, each being investigated on four occasions at weekly intervals once with R alone and with three of the four combinations on the three remaining occasions. A partially balanced incomplete block design was employed and the allocation of R or the drug combinations was random. Plasma concentrations of R at intervals up to 12 h were determined by microbiological assay using Staphylococcus aureus as the test organism. The proportion (%) dose of R as R plus desacetyl R (DR) in urine excreted over the periods 0-8 and 8-12 h was also determined. Bioavailability was expressed as an index (BI) of area under time concentration curve (AUC) calculated from the plasma concentrations or proportion of dose of R excreted as R plus DR in urine with the combinations to that with R alone. The bioavailability indices based on AUC were 0.96 with RE, 0.76 with RH, 1.08 with RZ and 0.65 with REHZ. The indices based on urine estimations (0-8 h) were similar, the values being 0.94, 0.84, 0.94 and 0.75, respectively. A second investigation revealed that the decrease of bioavailability of R with H was not due to the excipients present in H tablets. Isoniazid alone or in combination with E and Z reduces the bioavailability of R. Urinary excretion data offer a simple and non invasive method for the assessment of bioavailability of R.

  3. A novel solid dosage form of rifampicin and isoniazid with improved functionality.

    Science.gov (United States)

    Gohel, Mukesh C; Sarvaiya, Krishnakant G

    2007-08-24

    The aim of the present investigation was to develop a novel dosage form of rifampicin and isoniazid to minimize degradation of rifampicin in acidic medium and to modulate the release of rifampicin in the stomach and isoniazid in the intestine. Gastroretentive tablets of rifampicin (150 mg) were prepared by the wet granulation method using hydroxypropyl methylcellulose, calcium carbonate, and polyethylene glycol 4000. The granules and tablets of rifampicin were characterized. Hard gelatin capsules (size 4) containing a compacted mass of isoniazid (150 mg) and dicalcium phosphate (75 mg) were enteric coated. Two tablets of rifampicin and 1 capsule (size 4) of isoniazid were put into a hard gelatin capsule (size 00). The in vitro drug release and in vitro drug degradation studies were performed. Rifampicin was released over 4 hours by zero-order kinetics from the novel dosage form. More than 90% of isoniazid was released in alkaline medium in 30 minutes. The results of dissolution studies with the US Pharmacopeia XXIII method revealed that a substantial amount of rifampicin was degraded from the immediate release capsule containing rifampicin and isoniazid powder owing to drug accumulation in the dissolution vessel and also to the presence of isoniazid. The degradation of rifampicin to 3-formyl rifampicin SV (3FRSV) was arrested (3.6%-4.8% degradation of rifampicin at 4 hours) because of the minimization of physical contact between the 2 drugs and controlled release of rifampicin in acidic medium in the modified Rossett-Rice apparatus. This study concludes that the problem of rifampicin degradation can be alleviated to a certain extent by this novel dosage form.

  4. Eligibility for isoniazid preventive therapy in South African gold mines.

    Directory of Open Access Journals (Sweden)

    James J Lewis

    Full Text Available The "Thibela TB" cluster randomised trial of community-wide isoniazid preventive therapy (IPT to reduce tuberculosis incidence in the South African gold mines.To determine the proportion of participants eligible for IPT and the reasons and risk factors for ineligibility, to inform the scale-up of IPT.Cross-sectional survey of participants in intervention clusters (mine shafts consenting to tuberculosis screening and assessment for eligibility to start IPT.Among 27,126 consenting participants, 94.7% were male, the median age was 41 years, 12.2% reported previous tuberculosis, 0.6% reported ever taking IPT and 2.5% reported currently taking antiretroviral therapy. There were 24,430 (90.1% assessed as eligible to start IPT, of whom 23,659 started IPT. The most common reasons for ineligibility were having suspected tuberculosis that was subsequently confirmed by a positive smear and/or culture (n=705, excessive alcohol consumption (n=427 and being on tuberculosis treatment at time of initial screen (n=241. Ineligibility was associated with factors including older age, female gender, prior history of tuberculosis and being in "HIV care". However, at least 78% were eligible for IPT in all of these sub-groups.The vast majority of participants in this community-wide intervention were eligible for IPT.

  5. Pyrosequencing for Rapid Detection of Mycobacterium tuberculosis Resistance to Rifampin, Isoniazid, and Fluoroquinolones ▿

    Science.gov (United States)

    Bravo, Lulette Tricia C.; Tuohy, Marion J.; Ang, Concepcion; Destura, Raul V.; Mendoza, Myrna; Procop, Gary W.; Gordon, Steven M.; Hall, Geraldine S.; Shrestha, Nabin K.

    2009-01-01

    After isoniazid and rifampin (rifampicin), the next pivotal drug class in Mycobacterium tuberculosis treatment is the fluoroquinolone class. Mutations in resistance-determining regions (RDR) of the rpoB, katG, and gyrA genes occur with frequencies of 97%, 50%, and 85% among M. tuberculosis isolates resistant to rifampin, isoniazid, and fluoroquinolones, respectively. Sequences are highly conserved, and certain mutations correlate well with phenotypic resistance. We developed a pyrosequencing assay to determine M. tuberculosis genotypic resistance to rifampin, isoniazid, and fluoroquinolones. We characterized 102 M. tuberculosis clinical isolates from the Philippines for susceptibility to rifampin, isoniazid, and ofloxacin by using the conventional submerged-disk proportion method and validated our pyrosequencing assay using these isolates. DNA was extracted and amplified by using PCR primers directed toward the RDR of the rpoB, katG, and gyrA genes, and pyrosequencing was performed on the extracts. The M. tuberculosis H37Rv strain (ATCC 25618) was used as the reference strain. The sensitivities and specificities of pyrosequencing were 96.7% and 97.3%, 63.8% and 100%, and 70.0% and 100% for the detection of resistance to rifampin, isoniazid, and ofloxacin, respectively. Pyrosequencing is thus a rapid and accurate method for detecting M. tuberculosis resistance to these three drugs. PMID:19846642

  6. Barriers in the implementation of isoniazid preventive therapy for people living with HIV in Northern Ethiopia: a mixed quantitative and qualitative study

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    Gebrehiwot Teklay

    2016-08-01

    Full Text Available Abstract Background Isoniazid preventive therapy is a key public health intervention for the prevention of tuberculosis disease among people living with HIV. Despite the confirmed efficacy of isoniazid preventive therapy and global recommendations existing for decades, its implementation remains limited. In resource constrained settings, few have investigated why isoniazid preventive therapy is not implemented on full scale. This study was designed to investigate the level of isoniazid preventive therapy implementation and reasons for suboptimal implementation in Tigray region of Ethiopia. Methods A review of patient records combined with a qualitative study using in-depth interviews and focus group discussions was conducted in 11 hospitals providing isoniazid preventive therapy in the Tigray Region. The study participants were health providers working in the HIV clinics of the 11 hospitals in the province. Health providers were interviewed about their experience of providing isoniazid preventive therapy and challenges faced during its implementation. All conversations were audio-recorded. Record review of 16,443 HIV patients registered for care in these hospitals between September 2011 and April 2014 was done to determine isoniazid preventive therapy utilization. Data were collected from April to August 2014. Results Fifty health providers participated in the study. Overall isoniazid preventive therapy coverage of the region was estimated to be 20 %. Isoniazid stock out, fear of creating isoniazid resistance, problems in patient acceptance, and lack of commitment of health managers to scale up the program were indicated by health providers as the main barriers hindering implementation of isoniazid preventive therapy. Conclusion Implementation of isoniazid preventive therapy in Tigray region of Ethiopia had low coverage. Frequent interruption of isoniazid supplies raises the concern of interrupted therapy resulting in creation of isoniazid

  7. Preparation of labelled antituberculotics for clarifying specific problems in therapy optimization. 1. Preparation of tritiated isoniazid and injectable solutions, investigation of the stability of labelling

    Energy Technology Data Exchange (ETDEWEB)

    Winsel, K.; Iwainsky, H. (Forschungsinstitut fuer Lungenkrankheiten und Tuberkulose, Berlin-Buch (German Democratic Republic)); Mittag, E.; Kiessling, M. (Zentralinstitut fuer Kernforschung, Rossendorf bei Dresden (German Democratic Republic)); Koehler, H. (Zentralklinik fuer Herz- und Lungenkrankheiten, Bad Berka (German Democratic Republic))

    1985-09-01

    The preparation of tritium labelled isoniazid according to the Wilzbach method and by catalytic exchange is described. The purified labelled isoniazid is adjusted to an activity of 37 MBq/300 mg isoniazid. It meets the requirements for an injectable pharmaceutical. The tritium labelling is stable under in vitro conditions and in the macroorganism.

  8. The use of isoniazid as a marker to monitor the self-administration of medicaments.

    Science.gov (United States)

    Stark, J E; Ellard, G A; Gammon, P T; Fox, W

    1975-01-01

    1. Isoniazid was used as a marker to monitor the regularity of drug self-administration in a trial of chemoprophylaxis against natural influenza infection. Two hundred and sixty-two volunteers were treated for five weeks with a synthetic isoquinoline compound (U.K. 2371) or a matching placebo. 2. Five marker tablets containing isoniazid (150 mg) were incorporated into each regimen and their ingestion monitored by testing for acetylisoniazid in the urine. 3. Positive evidence of marker tablet consumption was obtained on 75% of the occasions on which urine samples were requested. The results obtained among the volunteers from each treatment group who returned urine specimens as requested (92%) indicated that they had swallowed at least 81% of their prescribed tablets. 4. The findings of the study suggest that when used in this way isoniazid is a very suitable compound for use on a few occasions for monitoring the self-administration of drugs in clinical trials. PMID:788733

  9. The bystander cell-killing effect mediated by nitric oxide in normal human fibroblasts varies with irradiation dose but not with radiation quality.

    Science.gov (United States)

    Yokota, Yuichiro; Funayama, Tomoo; Mutou-Yoshihara, Yasuko; Ikeda, Hiroko; Kobayashi, Yasuhiko

    2015-05-01

    To investigate the dependence of the bystander cell-killing effect on radiation dose and quality, and to elucidate related molecular mechanisms. Normal human fibroblast WI-38 cells were irradiated with 0.125 - 2 Gy of γ-rays or carbon ions and were co-cultured with non-irradiated cells. Survival rates of bystander cells were investigated using the colony formation assays, and nitrite concentrations in the medium were measured using the modified Saltzman method. Survival rates of bystander cells decreased with doses of γ-rays and carbon ions of ≤ 0.5 Gy. Treatment of the specific nitric oxide (NO) radical scavenger prevented reductions in survival rates of bystander cells. Moreover, nitrite concentrations increased with doses of less than 0.25 Gy (γ-rays) and 1 Gy (carbon ions). The dose responses of increased nitrite concentrations as well as survival reduction were similar between γ-rays and carbon ions. In addition, negative relationships were observed between survival rates and nitrite concentrations. The bystander cell-killing effect mediated by NO radicals in normal human fibroblasts depends on irradiation doses of up to 0.5 Gy, but not on radiation quality. NO radical production appears to be an important determinant of γ-ray- and carbon-ion-induced bystander effects.

  10. [Comparative data regarding two HPLC methods for determination of isoniazid].

    Science.gov (United States)

    Gârbuleţ, Daniela; Spac, A F; Dorneanu, V

    2009-01-01

    For the determination of isoniazide (isonicotinic acid hydrazide - HIN) two different HPLC methods were developed and validated. Both experiments were performed using a Waters 2695 liquid chromatograph and a UV - Waters 2489 detector. The first method (I) used a Nucleosil 100-10 C18 column (250 x 4.6 mm), a mobile phase formed by a mixture of acetonitrile/10(-2) M oxalic acid (80/20) and a flow of 1.5 mL/ min; detection was done at 230 nm. The second method (II) used a Luna 100-5 C18 column (250 x 4.6 mm), a mobile phase formed by a mixture of methanol/acetate buffer, pH = 5.0 (20/ 80), a flow of 1 mL/min; detection was done at 270 nm. Both methods were validated, the correlation coefficients were 0.9998 (I) and 0.9999 (II), the detection limits were 0.6 microg/mL (I) and 0.055 microg/mL (II), the quantitation limits were 1.9 microg/mL (I) and 0.2 microg/ mL (II). There were also studied: the system precision (RSD = 0.1692% (I) and 0.2000% (II)), the method precision (RSD = 1.1844% (I) and 0.6170% (II)) and the intermediate precision (RSD = 1.8058% (I) and 0.5970% (II)). The accuracy was good, the calculated recoveries were 102.66% (I) and 101.36 (II). Both validated methods were applied for HIN determination from tablets with good and comparable results.

  11. Penetapan Kadar Rifampisin dan Isoniazid dalam Sediaan Tablet Secara Multikomponen dengan Metode Spektrofotometri Ultraviolet

    OpenAIRE

    Hastia, Faula

    2011-01-01

    Tuberculosis is the most deadly infectious diseases and the number two cause of death after heart disease. The number of tuberculosis patients in Indonesia as many as 583,000 people, China 2 million and 1.5 million Indians. Combination of rifampicin and isoniazid in the tablet is one of the drugs which is usually use for TBC treatment. The aim of this study is to determination value of rifampicin and isoniazid in the tablet which circulates in the general by ultraviolet spectrophotometry. ...

  12. Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine over a 2-year period.

    Science.gov (United States)

    Lovering, E G; Matsui, F; Curran, N M; Robertson, D L; Sears, R W

    1983-08-01

    Hydrazine levels in formulations of hydralazine, isoniazid, and phenelzine have been measured over a 2-year period under ambient conditions and under temperature and humidity stress. Hydralazine tablets are stable under ambient conditions, but the hydrazine level in an injectable formulation increased from 4.5 to 10 micrograms/ml over a 23-month period. Isoniazid tablets are also stable, but hydrazine levels in an elixir and a pyridoxine combination product doubled to 44 micrograms/ml and 19 micrograms/tablet, respectively. Levels in phenelzine tablets appeared to remain constant at approximately 60 micrograms/tablet, with considerable tablet-to-tablet variation.

  13. Synthesis and antimycobacterial activity of isoniazid derivatives from renewable fatty acids.

    Science.gov (United States)

    Rodrigues, Marieli O; Cantos, Jéssica B; D'Oca, Caroline R Montes; Soares, Karina L; Coelho, Tatiane S; Piovesan, Luciana A; Russowsky, Dennis; da Silva, Pedro A; D'Oca, Marcelo G Montes

    2013-11-15

    This work describes the synthesis of a series of fatty acid hydrazide derivatives of isoniazid (INH). The compounds were tested against Mycobacterium tuberculosis H37Rv (ATCC 27294) as well as INH-resistant (ATCC 35822 and 1896 HF) and rifampicin-resistant (ATCC 35338) M. tuberculosis strains. The fatty acid derivatives of INH showed high antimycobacterial potency against the studied strains, which is desirable for a pharmaceutical compound, suggesting that the increased lipophilicity of isoniazid plays an important role in its antimycobacterial activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Hand rub dose needed for a single disinfection varies according to product: a bias in benchmarking using indirect hand hygiene indicator.

    Science.gov (United States)

    Girard, Raphaële; Aupee, Martine; Erb, Martine; Bettinger, Anne; Jouve, Alice

    2012-12-01

    The 3ml volume currently used as the hand hygiene (HH) measure has been explored as the pertinent dose for an indirect indicator of HH compliance. A multicenter study was conducted in order to ascertain the required dose using different products. The average contact duration before drying was measured and compared with references. Effective hand coverage had to include the whole hand and the wrist. Two durations were chosen as points of reference: 30s, as given by guidelines, and the duration validated by the European standard EN 1500. Each product was to be tested, using standardized procedures, by three nosocomial infection prevention teams, for three different doses (3, 2 and 1.5ml). Data from 27 products and 1706 tests were analyzed. Depending on the product, the dose needed to ensure a 30-s contact duration in 75% of tests ranging from 2ml to more than 3ml, and to ensure a contact duration exceeding the EN 1500 times in 75% of tests ranging from 1.5ml to more than 3ml. The aftermath interpretation is the following: if different products are used, the volume utilized does not give an unbiased estimation of the HH compliance. Other compliance evaluation methods remain necessary for efficient benchmarking. Copyright © 2012 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  15. Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis.

    NARCIS (Netherlands)

    Fregonese, Federica; Ahuja, Shama D; Akkerman, Onno W; Arakaki-Sanchez, Denise; Ayakaka, Irene; Baghaei, Parvaneh; Bang, Didi; Bastos, Mayara; Benedetti, Andrea; Bonnet, Maryline; Cattamanchi, Adithya; Cegielski, Peter; Chien, Jung-Yien; Cox, Helen; Dedicoat, Martin; Erkens, Connie; Escalante, Patricio; Falzon, Dennis; Garcia-Prats, Anthony J; Gegia, Medea; Gillespie, Stephen H; Glynn, Judith R; Goldberg, Stefan; Griffith, David; Jacobson, Karen R; Johnston, James C; Jones-López, Edward C; Khan, Awal; Koh, Won-Jung; Kritski, Afranio; Lan, Zhi Yi; Lee, Jae Ho; Li, Pei Zhi; Maciel, Ethel L; Galliez, Rafael Mello; Merle, Corinne S C; Munang, Melinda; Narendran, Gopalan; Nguyen, Viet Nhung; Nunn, Andrew; Ohkado, Akihiro; Park, Jong Sun; Phillips, Patrick P J; Ponnuraja, Chinnaiyan; Reves, Randall; Romanowski, Kamila; Seung, Kwonjune; Schaaf, H Simon; Skrahina, Alena; Soolingen, Dick van; Tabarsi, Payam; Trajman, Anete; Trieu, Lisa; Banurekha, Velayutham V; Viiklepp, Piret; Wang, Jann-Yuan; Yoshiyama, Takashi; Menzies, Dick

    Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and

  16. Comparison of different treatments for isoniazid-resistant tuberculosis : an individual patient data meta-analysis

    NARCIS (Netherlands)

    Fregonese, Federica; Ahuja, Shama D; Akkerman, Onno W; Arakaki-Sanchez, Denise; Ayakaka, Irene; Baghaei, Parvaneh; Bang, Didi; Bastos, Mayara; Benedetti, Andrea; Bonnet, Maryline; Cattamanchi, Adithya; Cegielski, Peter; Chien, Jung-Yien; Cox, Helen; Dedicoat, Martin; Erkens, Connie; Escalante, Patricio; Falzon, Dennis; Garcia-Prats, Anthony J; Gegia, Medea; Gillespie, Stephen H; Glynn, Judith R; Goldberg, Stefan; Griffith, David; Jacobson, Karen R; Johnston, James C; Jones-López, Edward C; Khan, Awal; Koh, Won-Jung; Kritski, Afranio; Lan, Zhi Yi; Lee, Jae Ho; Li, Pei Zhi; Maciel, Ethel L; Galliez, Rafael Mello; Merle, Corinne S C; Munang, Melinda; Narendran, Gopalan; Nguyen, Viet Nhung; Nunn, Andrew; Ohkado, Akihiro; Park, Jong Sun; Phillips, Patrick P J; Ponnuraja, Chinnaiyan; Reves, Randall; Romanowski, Kamila; Seung, Kwonjune; Schaaf, H Simon; Skrahina, Alena; Soolingen, Dick van; Tabarsi, Payam; Trajman, Anete; Trieu, Lisa; Banurekha, Velayutham V; Viiklepp, Piret; Wang, Jann-Yuan; Yoshiyama, Takashi; Menzies, Dick

    BACKGROUND: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success,

  17. Transient electromyographic findings in serotonergic toxicity due to combination of essitalopram and isoniazid

    Directory of Open Access Journals (Sweden)

    Çagdas Erdogan

    2013-01-01

    Full Text Available Here, we report a case of serotonergic toxicity due to combination of essitalopram and isoniazid, which was rarely reported before. Moreover, we observed transient neurogenic denervation potentials in needle electromyography, which disappeared with the treatment of serotonergic toxicity. As to our best knowledge, this is the first case, reporting transient electromyographic changes probably due to serotonergic toxicity.

  18. A rare case of unilateral gynecomastia during antituberculous chemotherapy with isoniazid.

    Science.gov (United States)

    Goud, B K Manjunatha; Devi, Oinam Sarsina; Nayal, Bhavna; Devaki, R N

    2012-01-01

    Gynecomastia refers to enlargement of male breast (s) due to benign proliferation of glandular tissue and is caused by excessive estrogen. The etiology may be pathological, pharmacological, or idiopathic reasons. The present report describes a case of gynecomastia due to isoniazid therapy.

  19. Isoniazid Toxicity among an Older Veteran Population: A Retrospective Cohort Study.

    Science.gov (United States)

    Vinnard, Christopher; Gopal, Anand; Linkin, Darren R; Maslow, Joel

    2013-01-01

    our objective was to determine the incidence of toxicity among veterans initiating isoniazid therapy for latent tuberculosis infection (LTBI) and determine whether advancing age was a risk factor for toxicity. we performed a retrospective cohort study among all adults initiating isoniazid treatment for LTBI at a Veterans Medical Center from 1999 to 2005. We collected data on patient demographics, co-morbidities, site of initiation, and treatment outcome. 219 patients initiated isoniazid therapy for LTBI during the period of observation, and the completion of therapy was confirmed in 100 patients (46%). Among 18/219 patients (8%) that discontinued therapy due to a documented suspected toxicity, the median time to onset was 3 months (IQR 1-5 months). In an adjusted Cox regression model, there was no association between discontinuation due to suspected toxicity and advancing age (HR 1.03, 95% CI 0.99, 1.07). In contrast, hepatitis C infection was a significant predictor of cessation due to toxicity in the adjusted analysis (HR 3.03, 95% CI 1.08, 8.52). cessation of isoniazid therapy due to suspected toxicity was infrequently observed among a veteran population and was not associated with advancing age. Alternative LTBI treatment approaches should be further examined in the veteran population.

  20. Isoniazid Toxicity among an Older Veteran Population: A Retrospective Cohort Study

    Directory of Open Access Journals (Sweden)

    Christopher Vinnard

    2013-01-01

    Full Text Available Background: our objective was to determine the incidence of toxicity among veterans initiating isoniazid therapy for latent tuberculosis infection (LTBI and determine whether advancing age was a risk factor for toxicity. Methods: we performed a retrospective cohort study among all adults initiating isoniazid treatment for LTBI at a Veterans Medical Center from 1999 to 2005. We collected data on patient demographics, co-morbidities, site of initiation, and treatment outcome. Results: 219 patients initiated isoniazid therapy for LTBI during the period of observation, and the completion of therapy was confirmed in 100 patients (46%. Among 18/219 patients (8% that discontinued therapy due to a documented suspected toxicity, the median time to onset was 3 months (IQR 1–5 months. In an adjusted Cox regression model, there was no association between discontinuation due to suspected toxicity and advancing age (HR 1.03, 95% CI 0.99, 1.07. In contrast, hepatitis C infection was a significant predictor of cessation due to toxicity in the adjusted analysis (HR 3.03, 95% CI 1.08, 8.52. Conclusions: cessation of isoniazid therapy due to suspected toxicity was infrequently observed among a veteran population and was not associated with advancing age. Alternative LTBI treatment approaches should be further examined in the veteran population.

  1. Hand rub dose needed for a single disinfection varies according to product: A bias in benchmarking using indirect hand hygiene indicator

    Directory of Open Access Journals (Sweden)

    Raphaële Girard

    2012-12-01

    Results: Data from 27 products and 1706 tests were analyzed. Depending on the product, the dose needed to ensure a 30-s contact duration in 75% of tests ranging from 2 ml to more than 3 ml, and to ensure a contact duration exceeding the EN 1500 times in 75% of tests ranging from 1.5 ml to more than 3 ml. The aftermath interpretation is the following: if different products are used, the volume utilized does not give an unbiased estimation of the HH compliance. Other compliance evaluation methods remain necessary for efficient benchmarking.

  2. Development and Validation of an HPLC Method for Simultaneous Determination of Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol Hydrochloride in Pharmaceutical Formulations.

    Science.gov (United States)

    Chellini, Paula R; Lages, Eduardo B; Franco, Pedro H C; Nogueira, Fernando H A; César, Isabela C; Pianetti, Gerson A

    2015-01-01

    Tuberculosis treatment consists of a fixed dose combination of rifampicin (RIF), isoniazid (INH), pyrazinamide (PYZ), and ethambutol hydrochloride (EMB). The combined treatment using various drugs is necessary for patient curing, without recrudescence, and for prevention of drug-resistant mutants, which may occur during treatment. An HPLC-diode array detector (DAD) method for the simultaneous determination of RIF, INH, PYZ, and EMB in fixed dose combination tablets was developed and validated. Chromatographic experiments were performed on an Agilent 1200 HPLC system, and the separation was carried out on a Purospher STAR RP18e (250×4.6 mm id, 5 μm, Merck) analytical column. Gradient elution was carried out with a mobile phase of 20 mM monobasic sodium phosphate buffer with 0.2% triethylamine (pH 7.0) and acetonitrile at a flow rate of 1.5 mL/min. The total run time was 12 min, and the re-equilibration time was 5 min. EMB detection was performed at 210 nm, and RIF, INH, and PYZ were detected at 238 nm, using a DAD. The method proved to be specific, linear (r2>0.99), precise (RSD<2%), accurate, and robust and may be applied to the QC analysis of pharmaceutical formulations.

  3. 19-Hydroxyeicosatetraenoic acid and isoniazid protect against angiotensin II-induced cardiac hypertrophy

    Energy Technology Data Exchange (ETDEWEB)

    Elkhatali, Samya; El-Sherbeni, Ahmed A.; Elshenawy, Osama H. [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada); Abdelhamid, Ghada [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada); Department of Pharmacology and Toxicology, Faculty of Pharmacy, Helwan University, Helwan (Egypt); El-Kadi, Ayman O.S., E-mail: aelkadi@ualberta.ca [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1 (Canada)

    2015-12-15

    We have recently demonstrated that 19-hydroxyeicosatetraenoic acid (19-HETE) is the major subterminal-HETE formed in the heart tissue, and its formation was decreased during cardiac hypertrophy. In the current study, we examined whether 19-HETE confers cardioprotection against angiotensin II (Ang II)-induced cardiac hypertrophy. The effect of Ang II, with and without 19-HETE (20 μM), on the development of cellular hypertrophy in cardiomyocyte RL-14 cells was assessed by real-time PCR. Also, cardiac hypertrophy was induced in Sprague–Dawley rats by Ang II, and the effect of increasing 19-HETE by isoniazid (INH; 200 mg/kg/day) was assessed by heart weight and echocardiography. Also, alterations in cardiac cytochrome P450 (CYP) and their associated arachidonic acid (AA) metabolites were determined by real-time PCR, Western blotting and liquid-chromatography–mass-spectrometry. Our results demonstrated that 19-HETE conferred a cardioprotective effect against Ang II-induced cellular hypertrophy in vitro, as indicated by the significant reduction in β/α-myosin heavy chain ratio. In vivo, INH improved heart dimensions, and reversed the increase in heart weight to tibia length ratio caused by Ang II. We found a significant increase in cardiac 19-HETE, as well as a significant reduction in AA and its metabolite, 20-HETE. In conclusion, 19-HETE, incubated with cardiomyocytes in vitro or induced in the heart by INH in vivo, provides cardioprotection against Ang II-induced hypertrophy. This further confirms the role of CYP, and their associated AA metabolites in the development of cardiac hypertrophy. - Highlights: • We found 19-hydroxy arachidonic acid to protect cardiomyocytes from hypertrophy. • We validated the use of isoniazid as a cardiac 19-hydroxy arachidonic acid inducer. • We found isoniazid to increase protective and inhibit toxic eicosanoides. • We found isoniazid to protect against angiotensin-induced cardiac hypertrophy. • This will help to

  4. Rifapentine Pharmacokinetics and Tolerability in Children and Adults Treated Once Weekly With Rifapentine and Isoniazid for Latent Tuberculosis Infection.

    Science.gov (United States)

    Weiner, Marc; Savic, Radojka M; Kenzie, William R Mac; Wing, Diane; Peloquin, Charles A; Engle, Melissa; Bliven, Erin; Prihoda, Thomas J; Gelfond, Jonathan A L; Scott, Nigel A; Abdel-Rahman, Susan M; Kearns, Gregory L; Burman, William J; Sterling, Timothy R; Villarino, M Elsa

    2014-06-01

    In a phase 3, randomized clinical trial (PREVENT TB) of 8053 people with latent tuberculosis infection, 12 once-weekly doses of rifapentine and isoniazid had good efficacy and tolerability. Children received higher rifapentine milligram per kilogram doses than adults. In the present pharmacokinetic study (a component of the PREVENT TB trial), rifapentine exposure was compared between children and adults. Rifapentine doses in children ranged from 300 to 900 mg, and adults received 900 mg. Children who could not swallow tablets received crushed tablets. Sparse pharmacokinetic sampling was performed with 1 rifapentine concentration at 24 hours after drug administration (C24). Rifapentine area under concentration-time curve (AUC) was estimated from a nonlinear, mixed effects regression model (NLME). There were 80 children (age: median, 4.5 years; range, 2-11 years) and 77 adults (age: median, 40 years; all ≥18 years) in the study. The geometric mean rifapentine milligram per kilogram dose was greater in children than in adults (children, 23 mg/kg; adults, 11 mg/kg). Rifapentine geometric mean AUC and C24 were 1.3-fold greater in children (all children combined) than in adults. Children who swallowed whole tablets had 1.3-fold higher geometric mean AUC than children who received crushed tablets, and children who swallowed whole tablets had a 1.6-fold higher geometric mean AUC than adults. The higher rifapentine doses in children were well tolerated. To obtain rifapentine exposures comparable in children to adults, dosing algorithms modeled by NLME were developed. A 2-fold greater rifapentine dose for all children resulted in a 1.3-fold higher AUC compared to adults administered a standard dose. Use of higher weight-adjusted rifapentine doses for young children are warranted to achieve systemic exposures that are associated with successful treatment of latent tuberculosis infection in adults. Published by Oxford University Press on behalf of the Pediatric Infectious

  5. Effect of isoniazid preventive therapy on tuberculosis or death in persons with HIV : a retrospective cohort study

    NARCIS (Netherlands)

    Ayele, Henok Tadesse; van Mourik, Maaike S M; Bonten, Marc J M

    2015-01-01

    Background: Isoniazid preventive therapy (IPT) is a recommended strategy for prevention of tuberculosis (TB) in persons with Human Immunodeficiency Virus (HIV) although the benefits have not been unequivocally demonstrated in routine clinical practice with widespread ART adoption. Therefore, we

  6. PCR-Restriction Fragment Length Polymorphism for Rapid, Low-Cost Identification of Isoniazid-Resistant Mycobacterium tuberculosis▿

    Science.gov (United States)

    Caws, Maxine; Tho, Dau Quang; Duy, Phan Minh; Lan, Nguyen Thi Ngoc; Hoa, Dai Viet; Torok, Mili Estee; Chau, Tran Thi Hong; Van Vinh Chau, Nguyen; Chinh, Nguyen Tran; Farrar, Jeremy

    2007-01-01

    PCR-restriction fragment length poymorphism (PCR-RFLP) is a simple, robust technique for the rapid identification of isoniazid-resistant Mycobacterium tuberculosis. One hundred consecutive isolates from a Vietnamese tuberculosis hospital were tested by MspA1I PCR-RFLP for the detection of isoniazid-resistant katG_315 mutants. The test had a sensitivity of 80% and a specificity of 100% against conventional phenotypic drug susceptibility testing. The positive and negative predictive values were 1 and 0.86, respectively. None of the discrepant isolates had mutant katG_315 codons by sequencing. The test is cheap (less than $1.50 per test), specific, and suitable for the rapid identification of isoniazid resistance in regions with a high prevalence of katG_315 mutants among isoniazid-resistant M. tuberculosis isolates. PMID:17428939

  7. Synthesis, characterization, and efficacy of antituberculosis isoniazid zinc aluminum-layered double hydroxide based nanocomposites

    Directory of Open Access Journals (Sweden)

    Saifullah B

    2016-07-01

    Full Text Available Bullo Saifullah,1 Mohamed Ezzat El Zowalaty,2,3 Palanisamy Arulselvan,3 Sharida Fakurazi,3,4 Thomas J Webster,5–7 Benjamin Mahler Geilich,5,6 Mohd Zobir Hussein1 1Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology, (ITMA, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 2School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, South Africa; 3Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, 4Department of Human Anatomy, Faculty of Medicine and Health Science, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; 5Department of Chemical Engineering, 6Department of Bioengineering, Northeastern University, Boston, MA, USA; 7Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi Arabia Abstract: The chemotherapy for tuberculosis (TB is complicated by its long-term treatment, its frequent drug dosing, and the adverse effects of anti-TB drugs. In this study, we have developed two nanocomposites (A and B by intercalating the anti-TB drug isoniazid (INH into Zn/Al-layered double hydroxides. The average size of the nanocomposites was found to be ~164 nm. The efficacy of the Zn/Al-layered double hydroxides intercalated INH against Mycobacterium tuberculosis was increased by approximately three times more than free INH. The nanocomposites were also found to be active against Gram-positive and -negative bacteria. Compared to the free INH, the nanodelivery formulation was determined to be three times more biocompatible with human normal lung fibroblast MRC-5 cells and 3T3 fibroblast cells at a very high concentration of 50 µg/mL for up to 72 hours. The in vitro release of INH from the Zn/Al-layered double hydroxides was found to be sustained in human body-simulated buffer solutions of pH 4.8 and 7.4. This research is a step forward in making the TB chemotherapy patient friendly. Keywords: tuberculosis, Zn/Al-LDHs, drug

  8. Localized surface plasmon resonance of gold nanoparticles as colorimetric probes for determination of Isoniazid in pharmacological formulation

    Science.gov (United States)

    Zargar, Behrooz; Hatamie, Amir

    2013-04-01

    Isoniazid is an important antibiotic, which is widely used to treat tuberculosis. This study presents a colorimetric method for the determination of Isoniazid based on localized surface plasmon resonance (LSPR) property of gold nanoparticles. An LSPR band is produced by reducing gold ions in solution using Isoniazid as the reducing agent. Influences of the following relevant variables were examined and optimized in the experiment, formation time of gold nanoparticles, pH, buffer and stabilizer. These tests demonstrated that under optimum conditions the absorbance of Au nanoparticles at 530 nm related linearly to the concentration of Isoniazid in the range of 1.0-8.0 μg mL-1 with a detection limit of 0.98 μg mL-1. This colorimetric method has been successfully applied to the determine Isoniazid in tablets and spiked serum samples. The proposed colorimetric assay exhibits good reproducibility and accuracy, providing a simple and rapid method for analysis of Isoniazid.

  9. Spectroscopic and theoretical study of the o-vanillin hydrazone of the mycobactericidal drug isoniazid

    Science.gov (United States)

    González-Baró, Ana C.; Pis-Diez, Reinaldo; Parajón-Costa, Beatriz S.; Rey, Nicolás A.

    2012-01-01

    A complete and detailed study of the hydrazone obtained from condensation of antituberculous isoniazid (hydrazide of the isonicotinic acid, INH) and o-vanillin (2-hydroxy-3-methoxybenzaldehyde, o-HVa) is performed. It includes structural and spectroscopic analyses, comparing experimental and theoretical results. The compound was obtained as a chloride of the pyridinic salt (INHOVA +Cl -) but it will be referred as INHOVA for the sake of simplicity. The conformational space was searched and optimized geometries were determined both in gas phase and including solvent effects. Vibrational (IR and Raman), electronic and NMR spectra were registered and assigned with the help of computational methods based on the Density Functional Theory. Isoniazid hydrazones are good candidates for therapeutic agents against tuberculosis with conserved efficiency and lower toxicity and resistance than parent INH.

  10. Simultaneous determination of rifampicin, isoniazid and pyrazinamide in tablet preparations by multivariate spectrophotometric calibration.

    Science.gov (United States)

    Goicoechea, H C; Olivieri, A C

    1999-08-01

    The use of multivariate spectrophotometric calibration is presented for the simultaneous determination of the active components of tablets used in the treatment of pulmonary tuberculosis. The resolution of ternary mixtures of rifampicin, isoniazid and pyrazinamide has been accomplished by using partial least squares (PLS-1) regression analysis. Although the components show an important degree of spectral overlap, they have been simultaneously determined with high accuracy and precision, rapidly and with no need of nonaqueous solvents for dissolving the samples. No interference has been observed from the tablet excipients. A comparison is presented with the related multivariate method of classical least squares (CLS) analysis, which is shown to yield less reliable results due to the severe spectral overlap among the studied compounds. This is highlighted in the case of isoniazid, due to the small absorbances measured for this component.

  11. Isoniazid concentrations in hair and plasma area-under-the-curve exposure among children with tuberculosis.

    Directory of Open Access Journals (Sweden)

    Vidya Mave

    Full Text Available We measured hair and plasma concentrations of isoniazid among sixteen children with tuberculosis who underwent personal or video-assisted directly observed therapy and thus had 100% adherence. This study therefore defined typical isoniazid exposure parameters after two months of treatment among fully-adherent patients in both hair and plasma (plasma area under the concentration-time curve, AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after drug administration. We found that INH levels in hair among highly-adherent individuals did not correlate well with plasma AUC or trough concentrations, suggesting that each measure may provide incremental and complementary information regarding drug exposure in the context of TB treatment.

  12. Characterization of mutations causing rifampicin and isoniazid resistance of Mycobacterium tuberculosis in Syria.

    Science.gov (United States)

    Madania, Ammar; Habous, Maya; Zarzour, Hana; Ghoury, Ifad; Hebbo, Barea

    2012-01-01

    In order to characterize mutations causing rifampicin and isoniazid resistance of M. tuberculosis in Syria, 69 rifampicin resistant (Rif(r)) and 72 isoniazid resistant (Inh(r)) isolates were screened for point mutations in hot spots of the rpoB, katG and inhA genes by DNA sequencing and real time PCR. Of 69 Rif(r) isolates, 62 (90%) had mutations in the rifampin resistance determining region (RRDR) of the rpoB gene, with codons 531 (61%), 526 (13%), and 516 (8.7%) being the most commonly mutated. We found two new mutations (Asp516Thr and Ser531Gly) described for the first time in the rpoB-RRDR in association with rifampicin resistance. Only one mutation (Ile572Phe) was found outside the rpoB-RRDR. Of 72 Inh(r) strains, 30 (41.6%) had a mutation in katGcodon315 (with Ser315Thr being the predominant alteration), and 23 (32%) harbored the inhA(-15C-->T) mutation. While the general pattern of rpoB-RRDR and katG mutations reflected those found worldwide, the prevalence of the inhA(-15C-->T mutation was above the value found in most other countries, emphasizing the great importance of testing the inhA(-15C-->T) mutation for prediction of isoniazid resistance in Syria. Sensitivity of a rapid test using real time PCR and 3'-Minor groove binder (MGB) probes in detecting Rif(r) and Inh(r) isolates was 90% and 69.4%, respectively. This demonstrates that a small set of MGB-probes can be used in real time PCR in order to detect most mutations causing resistance to rifampicin and isoniazid.

  13. Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes

    International Nuclear Information System (INIS)

    Chen, Yanyan; Xue, Peng; Hou, Yongyong; Zhang, Hao; Zheng, Hongzhi; Zhou, Tong; Qu, Weidong; Teng, Weiping; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2013-01-01

    Transcriptional signaling through the antioxidant response element (ARE), orchestrated by the Nuclear factor E2-related factor 2 (Nrf2), is a major cellular defense mechanism against oxidative or electrophilic stress. Here, we reported that isoniazid (INH), a widely used antitubercular drug, displays a substantial inhibitory property against ARE activities in diverse mouse and human cells. In 3T3-L1 preadipocytes, INH concentration-dependently suppressed the ARE-luciferase reporter activity and mRNA expression of various ARE-dependent antioxidant genes under basal and oxidative stressed conditions. In keeping with our previous findings that Nrf2-ARE plays a critical role in adipogenesis by regulating expression of CCAAT/enhancer-binding protein β (C/EBPβ) and peroxisome proliferator-activated receptor γ (PPARγ), suppression of ARE signaling by INH hampered adipogenic differentiation of 3T3-L1 cells and human adipose-derived stem cells (ADSCs). Following adipogenesis induced by hormonal cocktails, INH-treated 3T3-L1 cells and ADSCs displayed significantly reduced levels of lipid accumulation and attenuated expression of C/EBPα and PPARγ. Time-course studies in 3T3-L1 cells revealed that inhibition of adipogenesis by INH occurred in the early stage of terminal adipogenic differentiation, where reduced expression of C/EBPβ and C/EBPδ was observed. To our knowledge, the present study is the first to demonstrate that INH suppresses ARE signaling and interrupts with the transcriptional network of adipogenesis, leading to impaired adipogenic differentiation. The inhibition of ARE signaling may be a potential underlying mechanism by which INH attenuates cellular antioxidant response contributing to various complications. - Highlights: • Isoniazid suppresses ARE-mediated transcriptional activity. • Isoniazid inhibits adipogenesis in preadipocytes. • Isoniazid suppresses adipogenic gene expression during adipogenesis

  14. Polymorphisms in Isoniazid and Prothionamide Resistance Genes of the Mycobacterium tuberculosis Complex

    KAUST Repository

    Projahn, M.; Koser, C. U.; Homolka, S.; Summers, D. K.; Archer, John A.C.; Niemann, S.

    2011-01-01

    Sequence analyses of 74 strains that encompassed major phylogenetic lineages of the Mycobacterium tuberculosis complex revealed 10 polymorphisms in mshA (Rv0486) and four polymorphisms in inhA (Rv1484) that were not responsible for isoniazid or prothionamide resistance. Instead, some of these mutations were phylogenetically informative. This genetic diversity must be taken into consideration for drug development and for the design of molecular tests for drug resistance.

  15. Polymorphisms in Isoniazid and Prothionamide Resistance Genes of the Mycobacterium tuberculosis Complex

    KAUST Repository

    Projahn, M.

    2011-06-27

    Sequence analyses of 74 strains that encompassed major phylogenetic lineages of the Mycobacterium tuberculosis complex revealed 10 polymorphisms in mshA (Rv0486) and four polymorphisms in inhA (Rv1484) that were not responsible for isoniazid or prothionamide resistance. Instead, some of these mutations were phylogenetically informative. This genetic diversity must be taken into consideration for drug development and for the design of molecular tests for drug resistance.

  16. Sonocrystallization—Case Studies of Salicylamide Particle Size Reduction and Isoniazid Derivative Synthesis and Crystallization

    Directory of Open Access Journals (Sweden)

    Zhen-Yu Yang

    2018-06-01

    Full Text Available Two case studies of salicylamide particle size reduction and isoniazid derivative synthesis and crystallization realized using sonocrystallization were investigated. The size, habit, structure, thermal behavior, and spectrometric properties of sonocrystallized crystals were analyzed through scanning electron microscopy (SEM, powder X-ray diffractometry (PXRD, differential scanning calorimetry (DSC, and Fourier transform infrared (FTIR spectroscopy. The effects of the operating parameters, such as sonication intensity, sonication duration, and solution concentration, on sonocrystallization were compared. The crystal size of salicylamide was reduced from 595 μm (the original size and was efficiently manipulated to be between 40 and 80 μm. Moreover, compared with the crystal habits of unprocessed crystals and recrystallized crystals fabricated through conventional methods, the crystal habit of salicylamide could be modified to present a regular shape. The structure, thermal behavior, and spectrometric properties of sonocrystallized salicylamide were found to be in agreement with those of an unprocessed sample. For producing isoniazid derivative crystals, N′-(propan-2-ylidene-isonicotinohydrazide was synthesized using isoniazid in acetone at 318 K. The resulting solution was then cooled by applying power ultrasound to isolate N′-(propan-2-ylidene-isonicotinohydrazide crystals. The solid-state properties of the synthesized N′-(propan-2-ylidene-isonicotinohydrazide was verified through PXRD, DSC, and FTIR spectroscopy. The feasibility of particle size manipulation was then demonstrated through sonocrystallization.

  17. A patient on RIPE therapy presenting with recurrent isoniazid-associated pleural effusions: a case report

    Directory of Open Access Journals (Sweden)

    Varenika Vanja

    2011-11-01

    Full Text Available Abstract Introduction The clinical scenario of a new or worsening pleural effusion following the initiation of antituberculous therapy has been classically referred to as a 'paradoxical' pleural response, presumably explained by an immunological rebound phenomenon. Emerging evidence suggests that there also may be a role for a lupus-related reaction in the pathophysiology of this disorder. Case presentation An 84-year-old Asian man treated with isoniazid, along with rifampin, pyrazinamide and ethambutol for suspected extrapulmonary tuberculosis, presented with a recurrent pleural effusion, his third episode since the initiation of this therapy. The first effusion occurred one month after the start of treatment, without any prior evidence of pulmonary tuberculosis involvement. Follow-up testing, including thoracoscopic pleural biopsies, never confirmed tuberculosis infection. Further evaluation yielded serological evidence suggesting drug-induced lupus. No effusions recurred following the discontinuation of isoniazid, although other antituberculosis medications were continued. Conclusion The immunological rebound construct is inconsistent with the evolution of this case, which indicates rather that drug-induced lupus may explain at least some cases of new pleural effusions following the initiation of isoniazid.

  18. Prevalence, Risk Factors, and Treatment Outcomes of Isoniazid- and Rifampicin-Mono-Resistant Pulmonary Tuberculosis in Lima, Peru.

    Directory of Open Access Journals (Sweden)

    Leonela Villegas

    Full Text Available Isoniazid and rifampicin are the two most efficacious first-line agents for tuberculosis (TB treatment. We assessed the prevalence of isoniazid and rifampicin mono-resistance, associated risk factors, and the association of mono-resistance on treatment outcomes.A prospective, observational cohort study enrolled adults with a first episode of smear-positive pulmonary TB from 34 health facilities in a northern district of Lima, Peru, from March 2010 through December 2011. Participants were interviewed and a sputum sample was cultured on Löwenstein-Jensen (LJ media. Drug susceptibility testing was performed using the proportion method. Medication regimens were documented for each patient. Our primary outcomes were treatment outcome at the end of treatment. The secondary outcome included recurrent episodes among cured patients within two years after completion of the treatment.Of 1292 patients enrolled, 1039 (80% were culture-positive. From this subpopulation, isoniazid mono-resistance was present in 85 (8% patients and rifampicin mono-resistance was present in 24 (2% patients. In the multivariate logistic regression model, isoniazid mono-resistance was associated with illicit drug use (adjusted odds ratio (aOR = 2.10; 95% confidence interval (CI: 1.1-4.1, and rifampicin mono-resistance was associated with HIV infection (aOR = 9.43; 95%CI: 1.9-47.8. Isoniazid mono-resistant patients had a higher risk of poor treatment outcomes including treatment failure (2/85, 2%, p-value<0.01 and death (4/85, 5%, p<0.02. Rifampicin mono-resistant patients had a higher risk of death (2/24, 8%, p<0.01.A high prevalence of isoniazid and rifampicin mono-resistance was found among TB patients in our low HIV burden setting which were similar to regions with high HIV burden. Patients with isoniazid and rifampicin mono-resistance had an increased risk of poor treatment outcomes.

  19. [Application of wavelet transform-radial basis function neural network in NIRS for determination of rifampicin and isoniazide tablets].

    Science.gov (United States)

    Lu, Jia-hui; Zhang, Yi-bo; Zhang, Zhuo-yong; Meng, Qing-fan; Guo, Wei-liang; Teng, Li-rong

    2008-06-01

    A calibration model (WT-RBFNN) combination of wavelet transform (WT) and radial basis function neural network (RBFNN) was proposed for synchronous and rapid determination of rifampicin and isoniazide in Rifampicin and Isoniazide tablets by near infrared reflectance spectroscopy (NIRS). The approximation coefficients were used for input data in RBFNN. The network parameters including the number of hidden layer neurons and spread constant (SC) were investigated. WT-RBFNN model which compressed the original spectra data, removed the noise and the interference of background, and reduced the randomness, the capabilities of prediction were well optimized. The root mean square errors of prediction (RMSEP) for the determination of rifampicin and isoniazide obtained from the optimum WT-RBFNN model are 0.00639 and 0.00587, and the root mean square errors of cross-calibration (RMSECV) for them are 0.00604 and 0.00457, respectively which are superior to those obtained by the optimum RBFNN and PLS models. Regression coefficient (R) between NIRS predicted values and RP-HPLC values for rifampicin and isoniazide are 0.99522 and 0.99392, respectively and the relative error is lower than 2.300%. It was verified that WT-RBFNN model is a suitable approach to dealing with NIRS. The proposed WT-RBFNN model is convenient, and rapid and with no pollution for the determination of rifampicin and isoniazide tablets.

  20. Ternary mutual diffusion of isoniazid in aqueous sodium chloride, sodium hydroxide, and hydrochloric acid at T = 298.15 K

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Ana C.F., E-mail: anacfrib@ci.uc.p [Department of Chemistry, University of Coimbra, 3004-535 Coimbra (Portugal); Santos, Ana C.G., E-mail: anacatarinasantos123@gmail.co [Department of Chemistry, University of Coimbra, 3004-535 Coimbra (Portugal); Lobo, Victor M.M., E-mail: vlobo@ci.uc.p [Department of Chemistry, University of Coimbra, 3004-535 Coimbra (Portugal); Sobral, Abilio J.F.N., E-mail: asobral@ci.uc.p [Department of Chemistry, University of Coimbra, 3004-535 Coimbra (Portugal); Cabral, Ana M.T.D.P.V., E-mail: acabral@ff.uc.p [Faculty of Pharmacy, University of Coimbra, 3000-295 Coimbra (Portugal); Esteso, Miguel A., E-mail: miguel.esteso@uah.e [Departamento de Quimica Fisica, Facultad de Farmacia, Universidad de Alcala, 28871 Alcala de Henares, Madrid (Spain)

    2010-07-15

    Ternary mutual diffusion coefficients measured by Taylor dispersion method (D{sub 11}, D{sub 22}, D{sub 12}, and D{sub 21}) are reported for aqueous solutions containing isoniazid and different electrolytes (NaCl, NaOH, or HCl) at T = 298.15 K at different carrier concentrations. These diffusion coefficients have been measured having in mind a better understanding of the structure of these systems and the thermodynamic behaviour of isoniazid in different media. For example, it is possible to make conclusions about the influence of these electrolytes in diffusion of isoniazid, and to obtain information concerning the number of moles of each component transported per mole of the other component driven by its own concentration gradient.

  1. Controlled release hydrophilic matrix tablet formulations of isoniazid: design and in vitro studies.

    Science.gov (United States)

    Hiremath, Praveen S; Saha, Ranendra N

    2008-01-01

    The aim of the present investigation was to develop oral controlled release matrix tablet formulations of isoniazid using hydroxypropyl methylcellulose (HPMC) as a hydrophilic release retardant polymer and to study the influence of various formulation factors like proportion of the polymer, polymer viscosity grade, compression force, and release media on the in vitro release characteristics of the drug. The formulations were developed using wet granulation technology. The in vitro release studies were performed using US Pharmacopoeia type 1 apparatus (basket method) in 900 ml of pH 7.4 phosphate buffer at 100 rpm. The release kinetics was analyzed using Korsmeyer-Peppas model. The release profiles were also analyzed using statistical method (one-way analysis of variance) and f (2) metric values. The release profiles found to follow Higuchi's square root kinetics model irrespective of the polymer ratio and the viscosity grade used. The results in the present investigation confirm that the release rate of the drug from the HPMC matrices is highly influenced by the drug/HPMC ratio and viscosity grade of the HPMC. Also, the effect of compression force and release media was found to be significant on the release profiles of isoniazid from HPMC matrix tablets. The release mechanism was found to be anomalous non-Fickian diffusion in all the cases. In the present investigation, a series of controlled release formulations of isoniazid were developed with different release rates and duration so that these formulations could further be assessed from the in vivo bioavailability studies. The formulations were found to be stable and reproducible.

  2. Ginecomastia: um efeito colateral raro da isoniazida Gynecomastia: a rare adverse effect of isoniazid

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    Nelson Morrone

    2008-11-01

    Full Text Available Relata-se o caso de um paciente que desenvolveu ginecomastia duas vezes após tratamento para tuberculose. Homem de 18 anos de idade foi tratado com o esquema isoniazida-rifampicina-pirazinamida; no terceiro mês desenvolveu ginecomastia bilateral, dolorosa, com regressão parcial ao final do tratamento. Foi retratado oito anos após com o mesmo regime, e a ginecomastia recorreu após seis meses de tratamento. Dosagens hormonais foram normais, e a mamografia revelou ginecomastia bilateral. A isoniazida foi suspensa, tendo a ginecomastia regredido parcialmente no final do tratamento. Quatro anos após, não foi constatada ginecomastia. Conclui-se que a ginecomastia relacionada à isoniazida regride totalmente após a suspensão da droga e, portanto, o tratamento cirúrgico ou medicamentoso deve ser evitado.We report the case of a patient who twice developed gynecomastia following tuberculosis treatment. An 18-year-old male developed painful bilateral gynecomastia after three months of treatment with the isoniazid-rifampin-pyrazinamide regimen. Partial resolution of gynecomastia was achieved at the end of treatment. The patient was retreated with the same regimen eight years later, and gynecomastia recurred after six months of treatment. Hormone levels were normal, and a mammogram revealed bilateral gynecomastia. The isoniazid was discontinued, and the gynecomastia was partially resolved by the end of treatment. Four years later, gynecomastia was not detected. We conclude that isoniazid-related gynecomastia completely resolves when the medication is discontinued. Therefore, pharmacological and surgical treatment should be avoided.

  3. Therapeutic analysis of high-dose-rate "1"9"2Ir vaginal cuff brachytherapy for endometrial cancer using a cylindrical target volume model and varied cancer cell distributions

    International Nuclear Information System (INIS)

    Zhang, Hualin; Donnelly, Eric D.; Strauss, Jonathan B.; Qi, Yujin

    2016-01-01

    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)"4 to (13.4)"4 for

  4. Notes from the field: national shortage of isoniazid 300 mg tablets.

    Science.gov (United States)

    2012-12-21

    On November 16, 2012, the Illinois State tuberculosis (TB) program notified CDC's Division of Tuberculosis Elimination of a national shortage of 300 mg tablets of the antituberculosis medication isoniazid (INH). Subsequently, other state TB programs (e.g., California, Indiana, Maryland, New York, Virginia, and Wisconsin) reported difficulty obtaining INH 300 mg tablets. Other programs (e.g., San Diego) have experienced difficulties obtaining at least one of the commercially available anti-TB preparations containing the combination of rifampin and INH (IsonaRif [VersaPharm]).

  5. Structure and function of the liver in conditions of chrome-isoniazid-rifampicin affection of rats after applying of sorbex

    OpenAIRE

    N. I. Burmas; L. S. Fira

    2014-01-01

    The aim of this research was to assess the activity of marker enzymes of the liver and its biliary formation function in conditions of the affection of animals by hexavalent chromium compounds, isoniazid and rifampicin, after applying of sorbex. The experimental affection of rats of different age was carried in the conditions of combined injection of hexavalent chromium compounds (solution of potassium dichromate, 3 mg/kg), isoniazid (0.05 g/kg) and rifampicin (0.25 g/kg) during the 7th and 1...

  6. Short-course chemotherapy for pulmonary tuberculosis with a rifampicin-isoniazid-pyrazinamide combination tablet.

    Science.gov (United States)

    Cowie, R L; Brink, B A

    1990-04-21

    The effectiveness of a tablet containing a combination of rifampicin, isoniazid and pyrazinamide (Rifater; Mer-National) in the treatment of pulmonary tuberculosis was examined by comparing it with a previously evaluated four-drug regimen. Of 150 black goldminers with a first case of pulmonary tuberculosis, 69 were randomly allocated to receive the combination tablet (RHZ), 5 tablets per day on weekdays for 100 treatment-days, and 81 the four-drug regimen (streptomycin, rifampicin, isoniazid and pyrazinamide) (RHZS). Non-compliance was detected in 42% of the RHZ group and in 16% of the RHZS group. Two patients in the RHZ group and 4 in the RHZS group had to have their treatment altered because routine investigations revealed drug-resistant mycobacteria. Treatment was unsuccessful in 10 patients in the RHZ group, with 4 men failing to complete the regimen and being lost to follow-up, 3 cases of failure of conversion of sputum on the regimen, and 3 relapses. The results for the RHZS group were similar, with 4 failures to complete the regimen, 2 treatment failures and 4 relapses. Evaluation of RHZ showed it to be comparable with a previously evaluated, successful short-course regimen (RHZS). The high incidence of non-compliance probably reflects reduced supervision of this wholly oral regimen.

  7. Simultaneous chemometric determination of pyridoxine hydrochloride and isoniazid in tablets by multivariate regression methods.

    Science.gov (United States)

    Dinç, Erdal; Ustündağ, Ozgür; Baleanu, Dumitru

    2010-08-01

    The sole use of pyridoxine hydrochloride during treatment of tuberculosis gives rise to pyridoxine deficiency. Therefore, a combination of pyridoxine hydrochloride and isoniazid is used in pharmaceutical dosage form in tuberculosis treatment to reduce this side effect. In this study, two chemometric methods, partial least squares (PLS) and principal component regression (PCR), were applied to the simultaneous determination of pyridoxine (PYR) and isoniazid (ISO) in their tablets. A concentration training set comprising binary mixtures of PYR and ISO consisting of 20 different combinations were randomly prepared in 0.1 M HCl. Both multivariate calibration models were constructed using the relationships between the concentration data set (concentration data matrix) and absorbance data matrix in the spectral region 200-330 nm. The accuracy and the precision of the proposed chemometric methods were validated by analyzing synthetic mixtures containing the investigated drugs. The recovery results obtained by applying PCR and PLS calibrations to the artificial mixtures were found between 100.0 and 100.7%. Satisfactory results obtained by applying the PLS and PCR methods to both artificial and commercial samples were obtained. The results obtained in this manuscript strongly encourage us to use them for the quality control and the routine analysis of the marketing tablets containing PYR and ISO drugs. Copyright © 2010 John Wiley & Sons, Ltd.

  8. Antioxidant activity of Green tea extract against Isoniazid induced hepatotoxicity in the rats

    Directory of Open Access Journals (Sweden)

    2011-08-01

    Full Text Available Tuberculosis continues to be a common health problem worldwide. Isoniazid, an antibiotic used routinely for tuberculosis chemotherapy is documented to be a potent hepatotoxicant. The aim of the present study was to assess the antioxidant activity of Green tea extract (GTE against Isoniazid induced hepatotoxicity in the rats. Male Wistar rats were randomly assigned into 4 groups of 10 animals each including 1- normal healthy control rats, 2- healthy rats receiving (GTE 3- toxicant control, and 4- toxicant drug+ GTE treatment group. In groups 2 and 4 GTE (1.5%, w/v was given as only source of drinking for 8 weeks. In the midst stage of experiment (4th and 5th weeks, Isonizid (50 mg/kg b.w./day, i.p. was administrated for groups 3 and 4 for a period of 2 weeks. At the end of experiment, product of lipid peroxidation (MDA, activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPX and glutathione reductase (GR were assayed in liver homogenates to evaluate antioxidant activity. Significant differences among the groups were determined by one-way analysis of variance followed by Tukey post-test. Statistical significance was considered at p

  9. Solution thermodynamics of pyrazinamide, isoniazid, and p-aminobenzoic acid in buffers and octanol

    International Nuclear Information System (INIS)

    Blokhina, Svetlana V.; Ol’khovich, Marina V.; Sharapova, Angelica V.; Volkova, Tatyana V.; Perlovich, German L.

    2015-01-01

    Highlights: • Solubility of pyrazinamide, isoniazid, p-aminobenzoic acid were measured. • The activity coefficients of the compounds at infinite dilution were determined. • Thermodynamic functions of dissolution and solvation were calculated. - Abstract: The solubility values of pyrazinamide, isoniazid, and p-aminobenzoic acid in buffers (pH 2.0 and 7.4) and octanol were measured in the temperature range of 293.15 to 313.15 K. The dissolution Gibbs energy, enthalpy, and entropy were calculated. The dissolving process was endothermic and enthalpy-determined. The activity coefficients of the compounds at infinite dilution were determined based on the solubility data and thermophysical parameters. A positive deviation from the ideality was observed in all the solutions. A common tendency of the solubility increase with a decrease in the activity coefficients at T = 298.15 K was revealed for the investigated solute-solvent systems. The excess thermodynamic solubility functions were calculated from the temperature dependences of the activity coefficients. The solvation processes were found to have a considerable influence on the solubility of the substances in solutions studied.

  10. Detection of mutation in isoniazid-resistant Mycobacterium tuberculosis isolates from tuberculosis patients in Belarus

    Directory of Open Access Journals (Sweden)

    Bostanabad S

    2008-01-01

    Full Text Available The aim of this study was to investigate the frequency, location and type of katG mutations in Mycobacterium tuberculosis strains isolated from patients in Belarus. Forty two isoniazid-resistant isolates were identified from sputum of 163 patients with active pulmonary tuberculosis. Drug susceptibility testing was determined by using CDC standard conventional proportional method and BACTEC system. Standard PCR method for detection of isoniazid resistance associated mutations was performed by katG gene amplification and DNA sequencing. Most mutations were found in katG gene codons 315, 316 and 309. Four types of mutations were identified in codon 315: AGC→ACC ( n = 36 85%, AGC→AGG ( n = 1 2.3%, AGC→AAC ( n = 2 4.7%, AGC→GGC ( n = 1 2.3%. One type of mutation was found in codon 316: GGC→AGC ( n = 1841.4%, four types of mutations were detected in codon 309: GGT→GGT ( n = 716.1%, GGT→GCT ( n = 49.2%, GGT→GTC ( n = 36.9%, GGT→GGG ( n = 12.7%. The highest frequency of mutations sharing between primary and secondary infections was found in codon 315.

  11. The Non-Linear Child: Ontogeny, Isoniazid Concentration, and NAT2 Genotype Modulate Enzyme Reaction Kinetics and Metabolism.

    Science.gov (United States)

    Rogers, Zoe; Hiruy, Hiwot; Pasipanodya, Jotam G; Mbowane, Chris; Adamson, John; Ngotho, Lihle; Karim, Farina; Jeena, Prakash; Bishai, William; Gumbo, Tawanda

    2016-09-01

    N-acetyltransferase 2 (NAT2) catalyzes the acetylation of isoniazid to N-acetylisoniazid. NAT2 polymorphism explains 88% of isoniazid clearance variability in adults. We examined the effects of clinical and genetic factors on Michaelis-Menten reaction kinetic constants of maximum velocity (V max ) and affinity (K m ) in children 0-10years old. We measured the rates of isoniazid elimination and N-acetylisoniazid production in the blood of 30 children. Since maturation effects could be non-linear, we utilized a pharmacometric approach and the artificial intelligence method, multivariate adaptive regression splines (MARS), to identify factors predicting NAT2 V max and K m by examining clinical, genetic, and laboratory factors in toto. Isoniazid concentration predicted both V max and K m and superseded the contribution of NAT2 genotype. Age non-linearly modified the NAT2 genotype contribution until maturation at ≥5.3years. Thus, enzyme efficiency was constrained by substrate concentration, genes, and age. Since MARS output is in the form of basis functions and equations, it allows multiscale systems modeling from the level of cellular chemical reactions to whole body physiological parameters, by automatic selection of significant predictors by the algorithm. Copyright © 2016 Forschungsgesellschaft für Arbeitsphysiologie und Arbeitschutz e.V. Published by Elsevier B.V. All rights reserved.

  12. The Non-Linear Child: Ontogeny, Isoniazid Concentration, and NAT2 Genotype Modulate Enzyme Reaction Kinetics and Metabolism

    Directory of Open Access Journals (Sweden)

    Zoe Rogers

    2016-09-01

    Full Text Available N-acetyltransferase 2 (NAT2 catalyzes the acetylation of isoniazid to N-acetylisoniazid. NAT2 polymorphism explains 88% of isoniazid clearance variability in adults. We examined the effects of clinical and genetic factors on Michaelis-Menten reaction kinetic constants of maximum velocity (Vmax and affinity (Km in children 0–10 years old. We measured the rates of isoniazid elimination and N-acetylisoniazid production in the blood of 30 children. Since maturation effects could be non-linear, we utilized a pharmacometric approach and the artificial intelligence method, multivariate adaptive regression splines (MARS, to identify factors predicting NAT2 Vmax and Km by examining clinical, genetic, and laboratory factors in toto. Isoniazid concentration predicted both Vmax and Km and superseded the contribution of NAT2 genotype. Age non-linearly modified the NAT2 genotype contribution until maturation at ≥5.3 years. Thus, enzyme efficiency was constrained by substrate concentration, genes, and age. Since MARS output is in the form of basis functions and equations, it allows multiscale systems modeling from the level of cellular chemical reactions to whole body physiological parameters, by automatic selection of significant predictors by the algorithm.

  13. Evaluation of the isoniazid preventive therapy (IPT) program in Shurugwi District, Midlands Province, Zimbabwe, January 2013 to August 2014.

    Science.gov (United States)

    Makoni, Annamercy; Chemhuru, Milton; Tshimanga, Mufuta; Gombe, Notion Tafara; Mungati, More; Bangure, Donewell

    2015-09-25

    Midlands Province started implementing the Isoniazid (INH) preventive therapy (IPT) program in January 2013. Shurugwi and Gokwe North were the piloting district hospitals. In May 2014, four more districts hospitals (Gokwe South, Gweru, Kwekwe and Zvishavane) started implementing IPT. Shurugwi District decentralized the program to its rural health facilities in January 2014. A review of the Shurugwi IPT program, 2013 data, indicated that the majority of eligible clients were not started on IPT. None out of the 400 eligible clients were started on IPT in November against the 100% target according to the World Health Organization and the National Tuberculosis (TB) Program. We conducted a study to evaluate the IPT program in Shurugwi District from January 2013 to August 2014. The logical framework approach was used to evaluate inputs, processes, outputs and outcomes of the IPT program. An interviewer administered questionnaire was used to collect data from key informants. Checklists were used to collect data from IPT program records. Sixteen health facilities were implementing IPT in Shurugwi District. All the facilities had TB screening tools and three did not have TB screening algorithms. The district experienced medicine stock outs in 2013. One formal training at district level and on job trainings in implementing health facilities were done. From January 2013 to August 2014, Shurugwi District screened 6794 antiretroviral (ART) clients for TB. Out of those screened, 5255 were eligible for IPT and 2831 (54%) were started on IPT. A total of 700 clients had completed the IPT 6 month's course by August 2014. The dropout rate due to INH toxicity and TB was 0.6% (n = 18) and 0.3% (n = 8) respectively. Fifty-three advocacy and community sensitization meetings were done. The program had no Information Education and Communication (IEC) materials. The IPT program in Shurugwi District achieved half its target. This could be due to inadequate formally trained staff, lack of IEC

  14. Isoniazid completion rates for latent tuberculosis infection among college students managed by a community pharmacist.

    Science.gov (United States)

    Hess, Karl; Goad, Jeffery; Wu, Joanne; Johnson, Kathleen

    2009-01-01

    The authors' objective was to document 9-month and previously recommended 6-month treatment completion rates for latent tuberculosis infection (LTBI) in a pharmacist-managed LTBI clinic in a community pharmacy on a college campus, and to describe patient characteristics. Participants were university students diagnosed with LTBI. The authors conducted a retrospective review of pharmacy records from 2000 to 2006. Main outcome measures included 6-month and 9-month LTBI treatment completion rates, total isoniazid (INH) tablets taken, characteristics of completers versus noncompleters, average time to treatment completion, and reported adverse drug events. The 9-month completion rate was 59%, and the 6-month completion rate was 67%. Among those not completing treatment, 15.2% experienced fatigue and 2.2% experienced a rash (p=.04 and p=.03, respectively). LTBI clinics are a unique niche for community pharmacies and can provide individualized patient care to ensure LTBI treatment adherence, monitoring for disease progression, and safety of INH.

  15. [DNA mutations associated to rifampicin or isoniazid resistance in M. tuberculosis clinical isolates from Sonora, Mexico].

    Science.gov (United States)

    Bolado-Martínez, Enrique; Pérez-Mendoza, Ansix; Alegría-Morquecho, Francisco Monserrat; Candia-Plata, María del Carmen; Aguayo-Verdugo, María del Rosario; Alvarez-Hernández, Gerardo

    2012-01-01

    To perform the analysis of specific regions of the major genes associated with resistance to isoniazid or rifampin. Twenty two M. tuberculosis strains, isolated from human samples obtained in Sonora, Mexico. Specific primers for hotspots of the rpoB, katG, inhA genes and the ahpC-oxyR intergenic region were used. The purified PCR products were sequenced. Mutations in the promoter of inhA, the ahpC-oxyR region, and codon 315 of katG and in 451 or 456 codons of rpoB, were identified. Detection of mutations not previously reported requires further genotypic analysis of Mycobacterium tuberculosis isolates in Sonora.

  16. Pengembangan Metode Kromatografi Cair Kinerja Tinggi Spektrometri Massa untuk Penetapan Kadar Rifampisin, Isoniazid dan Pirazinamid dari Plasma Manusia dan Sediaan Tablet

    OpenAIRE

    Nerdy

    2012-01-01

    The drugs used in the treatment of tuberculosis can be divided into two categories, i.e.: primary anti-tuberculosis and secondary anti-tuberculosis. The primary anti-tuberculosis have a higher efficacy and better safety than those of secondary anti-tuberculosis drugs. Primary anti-tuberculosis drugs are rifampicin, isoniazid, pyrazinamide and ethambutol. In their use rifampicin, isoniazid and pyrazinamide are usually combined. According to the Law of the Republic of Indonesia number 36 yea...

  17. Novel pH- and temperature-responsive blend hydrogel microspheres of sodium alginate and PNIPAAm-g-GG for controlled release of isoniazid.

    Science.gov (United States)

    Kajjari, Praveen B; Manjeshwar, Lata S; Aminabhavi, Tejraj M

    2012-12-01

    This paper reports the preparation and characterization of novel pH- and thermo-responsive blend hydrogel microspheres of sodium alginate (NaAlg) and poly(N-isopropylacrylamide)(PNIPAAm)-grafted-guar gum (GG) i.e., PNIPAAm-g-GG by emulsion cross-linking method using glutaraldehyde (GA) as a cross-linker. Isoniazid (INZ) was chosen as the model antituberculosis drug to achieve encapsulation up to 62%. INZ has a plasma half-life of 1.5 h, whose release was extended up to 12 h. Fourier transform infrared spectroscopy was used to confirm the grafting reaction and chemical stability of INZ during the encapsulation. Differential scanning calorimetry was used to investigate the drug's physical state, while powder X-ray diffraction confirmed the molecular level dispersion of INZ in the matrix. Scanning electron microscopy confirmed varying surface morphologies of the drug-loaded microspheres. Temperature- and pH-responsive nature of the blend hydrogel microspheres were investigated by equilibrium swelling, and in vitro release experiments were performed in pH 1.2 and pH 7.4 buffer media at 37°C as well as at 25°C. Kinetics of INZ release was analyzed by Ritger-Peppas empirical equation to compute the diffusional exponent parameter (n), whose value ranged between 0.27 and 0.58, indicating the release of INZ follows a diffusion swelling controlled release mechanism.

  18. Implications of the 2015 World Health Organization isoniazid preventive therapy recommendations on tuberculosis prevention efforts in Namibia.

    Science.gov (United States)

    Oloo, Stella Anne

    2016-07-01

    The World Health Organization recently released guidelines recommending 36-month use of isoniazid preventive therapy in adults and adolescents living with HIV in resource-limited settings. Namibia continues to grapple with one of the highest incidences of tuberculosis (TB) worldwide. Implementation of these guidelines requires considerations of TB epidemiology, health infrastructure, programmatic priorities and patient adherence. This article explores the challenges Namibia currently faces in its fight against TB and the implications of the new guidelines on Namibian TB prevention efforts.

  19. MicroRNA-122 is involved in oxidative stress in isoniazid-induced liver injury in mice.

    Science.gov (United States)

    Song, L; Zhang, Z R; Zhang, J L; Zhu, X B; He, L; Shi, Z; Gao, L; Li, Y; Hu, B; Feng, F M

    2015-10-27

    Many studies have shown that the pathogenesis of liver injury includes oxidative stress. MicroRNA-122 may be a marker for the early diagnosis of drug-induced liver injury. However, the relationship between microRNA-122 and oxidative stress in anti-tuberculosis drug-induced liver injury remains unknown. We measured changes in tissue microRNA-122 levels and indices of oxidative stress during liver injury in mice after administration of isoniazid, a first-line anti-tuberculosis drug. We quantified microRNA-122 expression and indices of oxidative stress at 7 time points, including 1, 3, and 5 days and 1, 2, 3, and 4 weeks. The tissue microRNA-122 levels and oxidative stress significantly changed at 3 and 5 days, suggesting that isoniazid-induced liver injury reduces oxidative stress and microRNA-122 expression compared to in the control group (P microRNA-122, began to change at 5 days (P microRNA-122 profile may affect oxidative stress by regulating mitochondrial ribosome protein S11 gene during isoniazid-induced liver injury, which may contribute to the response mechanisms of microRNA-122 and oxidative stress.

  20. Assessment of the Isoniazid Preventive Therapy Uptake and Associated Characteristics: A Cross-Sectional Study

    Directory of Open Access Journals (Sweden)

    Francine Mwayuma Birungi

    2018-01-01

    Full Text Available Objective. To assess the uptake of isoniazid preventive therapy (IPT by eligible children in Kigali, Rwanda, and associated individual, households, and healthcare systems characteristics. Methods. A cross-sectional study was conducted among child contacts of index cases having sputum smear-positive pulmonary tuberculosis. Data were collected from 13 selected primary health centres. Descriptive statistics were used to generate frequency tables and figures. Logistic regression models were performed to determine characteristics associated with IPT uptake. Results. Of 270 children (under 15 years, who were household contacts of 136 index cases, 94 (35% children were less than 5 years old and eligible for IPT; and 84 (89%, 95% CI 81–94 were initiated on IPT. The reasons for not initiating IPT in the remaining 10 children were parents/caregivers’ lack of information on the need for IPT, refusal to give IPT to their children, and poor quality services offered at health centres. Factors associated with no uptake of IPT included children older than 3 years, unfriendly healthcare providers, HIV infected index cases, and the index case not being the child’s parent. Conclusion. The National Tuberculosis Program’s policy on IPT delivery was effectively implemented. Future interventions should find strategies to manage factors associated with IPT uptake.

  1. Preparation and characterization of isoniazid-loaded crude soybean lecithin liposomes.

    Science.gov (United States)

    Nkanga, Christian Isalomboto; Krause, Rui Werner; Noundou, Xavier Siwe; Walker, Roderick Bryan

    2017-06-30

    Tuberculosis (TB) is a poverty related infectious disease that is rapidly giving rise to public health concerns. Lengthy drug administration and frequent adverse side-effects associated with TB treatment make anti-tubercular drugs (ATDs) good candidates for drug delivery studies. This work aimed to formulate and prepare liposomes as a cost-effective option for ATD delivery. Liposomes were prepared by film hydration using crude soybean lecithin (CL) and not pure phospholipids as in the normal practice. Cholesterol was also used (up to 25% mass ratio), and isoniazid (INH) was encapsulated as model drug using a freeze-thaw loading technique. Purified soybean lecithin (PL) was also used for comparative purposes, under the same conditions. INH-loaded liposomes were characterized for particle size, Zeta Potential (ZP), encapsulation efficiency (EE) and drug release. Physicochemical properties were investigated using thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction and Fourier transform infrared. INH-loaded CL-based liposomes showed high EE (79±2.45%). The average particle size (813.00±9.21nm) and ZP (-42.80±4.31mV) of this formulation are promising for the treatment of TB by pulmonary delivery. These findings suggest the possibility of encapsulating ATDs in liposomes made of crude soybean lecithin that is cheap and readily available. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Design and evaluation of enteric-coated tablets for rifampicin and isoniazid combinations.

    Science.gov (United States)

    Wang, Yongjun; Liu, Hongzhuo; Liu, Kai; Sun, Jin; He, Zhonggui

    2013-01-01

    In order to improve the bioavailability of rifampicin (RIF) from rifampicin and isoniazid (INH) combination formulations, the physicochemical characteristics of RIF, stability of RIF in different pH buffers in the presence of INH, as well as the effect of particle size of RIF materials on the dissolution rate were investigated. On the basis of the above examinations, enteric-coated tablets for RIF and INH combinations were designed and prepared. RIF showed low solubility and high apparent distribution coefficient in the intestinal pH (pH 4.0-7.4). With the decrease in pH, the degradation of RIF increase and the presence of INH deepen the degradation. Enteric-coated tablets were prepared after grinding the RIF materials by dry granulation technique. The pharmacokinetics of RIF and INH of self-made enteric-coated tablets in dogs were studied by comparing with the reference tablets. The AUC(0-48) of RIF in both reference and test tablets were 304.77 ± 42.27 and 353.79 ± 31.63 µg·h·mL(-1), respectively. The AUC(0-48) of INH in both reference and test tablets were 17.14 ± 8.59 and 19.62 ± 10.57 µg·h·mL(-1), respectively. Enteric-coated tablets may minimize the decomposition of RIF in gastrointestinal tract and improve the bioavailability.

  3. [Considerations about the efficiency of treatment regimens with fixed Rifampicin-Isoniazid combinations in pulmonary tuberculosis].

    Science.gov (United States)

    Munteanu, Ioana; Husar, Iulia; Didilescu, C; Stoicescu, I P

    2004-01-01

    Here are presented the results of a prospective, randomized study regarding the efficiency of regimens with fixed drug combination Rifampicin-Isoniazide manufactured by Antibiotics S.A. of Iasi in comparison with single drugs routinely used in treatment of patients with pulmonary tuberculosis. Newly diagnosed (confirmed by smear and culture) pulmonary tuberculosis patients were selected, and those who accepted to be included in the study, were admitted to the National Institute of Pneumology "Marius Nasta" between August 2001 and September 2002. At the time of admission, they were randomized into two groups: 20 patients received fixed drug combination RMP300 HIN150, and 18 patients received RMP and HIN in single drug tablets (2 patients were excluded). The follow-up of the patients was for one year from the date of enclosure. The smear conversion rate was 83,3% for the patients using single drug tablets, and 70% for those using fixed drug combination, motivated with some more severe TB patterns. The success rate was 100% for all TB patients. Although the present study was done for few patients, we can say that it demonstrated the same efficiency of fixed drug combination produced in Romania, with the single drug tablets, and it suggests a better compliance to treatment with a lower price.

  4. Enhanced electrocatalytic oxidation of isoniazid at electrochemically modified rhodium electrode for biological and pharmaceutical analysis.

    Science.gov (United States)

    Cheemalapati, Srikanth; Chen, Shen-Ming; Ali, M Ajmal; Al-Hemaid, Fahad M A

    2014-09-01

    A simple and sensitive electrochemical method has been proposed for the determination of isoniazid (INZ). For the first time, rhodium (Rh) modified glassy carbon electrode (GCE) has been employed for the determination of INZ by linear sweep voltammetry technique (LSV). Compared with the unmodified electrode, the proposed Rh modified electrode provides strong electrocatalytic activity toward INZ with significant enhancement in the anodic peak current. Scanning electron microscopy (SEM) and field emission scanning electron microscopy (FESEM) results reveal the morphology of Rh particles. With the advantages of wide linearity (70-1300μM), good sensitivity (0.139μAμM(-1)cm(-2)) and low detection limit (13μM), this proposed sensor holds great potential for the determination of INZ in real samples. The practicality of the proposed electrode for the detection of INZ in human urine and blood plasma samples has been successfully demonstrated using LSV technique. Through the determination of INZ in commercially available pharmaceutical tablets, the practical applicability of the proposed method has been validated. The recovery results are found to be in good agreement with the labeled amounts of INZ in tablets, thus showing its great potential for use in clinical and pharmaceutical analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Simultaneous determination of isoniazid and p-aminosalicylic acid by capillary electrophoresis using chemiluminescence detection.

    Science.gov (United States)

    Zhang, Xinfeng; Xuan, Yuelan; Sun, Aimin; Lv, Yi; Hou, Xiandeng

    2009-01-01

    It was found that isoniazid (ISO) or p-aminosalicylic acid (PAS) could enhance the chemiluminescence (CL) emission from Cu (II)-luminol-hydrogen peroxide system, and the increased chemiluminescence signals were proportional to their concentrations, respectively. Based on this phenomenon, a chemiluminescence method coupled to capillary electrophoresis (CE) was established for simultaneous determination of ISO and PAS. The CE conditions including running buffer and running voltage were investigated in detail. The effects of the pH of H(2)O(2) solution and the concentrations of luminol, H(2)O(2) and Cu (II) on the CL signal were also investigated carefully. Under the optimized conditions, the analysis could be accomplished within 10 min, with the limits of detection of 0.3 microg mL(-1) for ISO and 1.1 microg mL(-1) for PAS, corresponding to 7.2 and 26.4 pg per injection (24 nL), respectively. Finally, the method was validated by determining the two analytes in pharmaceutical preparation and spiked human serum samples. The results of pharmaceutical tablet analysis were in good agreement with the labeled amounts. The recoveries for ISO and PAS in human serum were in the range of 92-104% and 90-113%, respectively. Copyright 2008 John Wiley & Sons, Ltd.

  6. PROPOSAL OF ANTI-TUBERCULOSIS REGIMENS BASED ON SUSCEPTIBILITY TO ISONIAZID AND RIFAMPICIN

    Science.gov (United States)

    Mendoza-Ticona, Alberto; Moore, David AJ; Alarcón, Valentina; Samalvides, Frine; Seas, Carlos

    2014-01-01

    Objective To elaborate optimal anti-tuberculosis regimens following drug susceptibility testing (DST) to isoniazid (H) and rifampicin (R). Design 12 311 M. tuberculosis strains (National Health Institute of Peru 2007-2009) were classified in four groups according H and R resistance. In each group the sensitivity to ethambutol (E), pirazinamide (Z), streptomycin (S), kanamycin (Km), capreomycin (Cm), ciprofloxacin (Cfx), ethionamide (Eto), cicloserine (Cs) and p-amino salicilic acid (PAS) was determined. Based on resistance profiles, domestic costs, and following WHO guidelines, we elaborated and selected optimal putative regimens for each group. The potential efficacy (PE) variable was defined as the proportion of strains sensitive to at least three or four drugs for each regimen evaluated. Results Selected regimes with the lowest cost, and highest PE of containing 3 and 4 effective drugs for TB sensitive to H and R were: HRZ (99,5%) and HREZ (99,1%), respectively; RZECfx (PE=98,9%) and RZECfxKm (PE=97,7%) for TB resistant to H; HZECfx (96,8%) and HZECfxKm (95,4%) for TB resistant to R; and EZCfxKmEtoCs (82.9%) for MDR-TB. Conclusion Based on resistance to H and R it was possible to select anti-tuberculosis regimens with high probability of success. This proposal is a feasible alternative to tackle tuberculosis in Peru where the access to rapid DST to H and R is improving progressively. PMID:23949502

  7. Novel Isoniazid cocrystals with aromatic carboxylic acids: Crystal engineering, spectroscopy and thermochemical investigations

    Science.gov (United States)

    Diniz, Luan F.; Souza, Matheus S.; Carvalho, Paulo S.; da Silva, Cecilia C. P.; D'Vries, Richard F.; Ellena, Javier

    2018-02-01

    Four novel cocrystals of the anti-tuberculosis drug Isoniazid (INH), including two polymorphs, with the aromatic carboxylic acids p-nitrobenzoic (PNBA), p-cyanobenzoic (PCNBA) and p-aminobenzoic (PABA) were rationally designed and synthesized by solvent evaporation. Aiming to explore the possible supramolecular synthons of this API, these cocrystals were fully characterized by X-ray diffraction (SCXRD, PXRD), spectroscopic (FT-IR) and thermal (TGA, DSC, HSM) techniques. The cocrystal formation was found to be mainly driven by the synthons formed by the pyridine and hydrazide moieties. In both INH-PABA polymorphs, the COOH acid groups are H-bonded to pyridine and hydrazide groups giving rise to the acid⋯pyridine and acid⋯hydrazide heterosynthons. In INH-PNBA and INH-PCNBA cocrystals these acid groups are only related to the pyridine moiety. In addition to the structural study, supramolecular and Hirshfeld surface analysis were also performed based on the structural data. The cocrystals were identified from the FT-IR spectra and their thermal behaviors were studied by a combination of DSC, TGA and HSM techniques.

  8. Determination of isoniazid concentration in rabbit vertebrae by isotope tracing technique in conjunction with HPLC.

    Science.gov (United States)

    Liu, Peng; Fu, Zhaozong; Jiang, Jianming; Yuan, Liang; Lin, Zhen

    2013-09-01

    Medications compounded with isoniazid (INH) are usually applied to surgical sites at the completion of surgery to locally kill postoperative residual tubercle bacilli. However, the distribution and elimination of INH in the vertebrae in vivo are not known. In this study, isotope tracing was used in conjunction with high-pressure liquid chromatography (HPLC) to address this. INH and technetium-99 m-labeled INH were applied to the vertebrae of rabbits. After 2 and 6 h, osseous tissues containing INH, as determined by radionuclide imaging, were collected for detection with HPLC. The results showed that INH mainly stayed around the vertebrae 6 h after its application and did not permeate widely into the blood or other organs, except for the kidneys. The standard deviations of INH concentrations in the technetium-99 m-INH group were approximately four-fold smaller than those in the INH group. This method of coupling isotope tracing and HPLC can effectively limit experimental error during sample collection, allowing accurate and reliable identification of the concentration levels of INH in osseous tissues in vivo. Copyright © 2013 John Wiley & Sons, Ltd.

  9. Isoniazid Prophylaxis of Latent Tuberculous Infection among Healthcare Workers in Bamrasnaradura Infectious Diseases Institute

    Directory of Open Access Journals (Sweden)

    Patama Suttha

    2016-07-01

    Full Text Available Background: Treatment of latent tuberculosis infection (LTBI is one of the essential measures for tuberculosis (TB control. The tuberculin skin test (TST is an important tool for the detection of LTBI and the identification of healthcare workers (HCWs who require chemoprophylaxis. Also, the rate of active TB should be evaluated among HCWs with and without isoniazid (INH prophylactic treatment for LTBI. Objective: To evaluate the rate of active TB disease among HCWs with or without INH prophylaxis for LTBI. Methods: We retrospectively studied the clinical records of HCWs with LTBI at the employee TB screening clinic in Bamrasnaradura Infectious Diseases Institute from January 2008 to December 2010. Voluntary INH prophylaxis was recommended by physicians and nurses at the TB clinic in case of recent positive 2-step TST. The rate of active TB disease in HCWs with and without INH prophylaxis for LTBI was evaluated and followed during a period of 5 years. As well, the compliance and adverse effects of INH prophylaxis were identified by history taking. Results: There were 29 from 113 HCWS (25.7% receiving INH prophylaxis for 6 months (23 HCWs and 9 months (6 HCWs. 2 HCWs in each 6- and 9-month group did not complete INH prophylaxis for LTBI. After 5 years of TST, no case of active TB disease was found in HCWS with or without INH prophylaxis. Moreover, no adverse drug reactions were reported. Conclusion: No active tuberculosis disease was noted between the INH treatment and the control groups.

  10. Significance of Coexisting Mutations on Determination of the Degree of Isoniazid Resistance in Mycobacterium tuberculosis Strains.

    Science.gov (United States)

    Karunaratne, Galbokka Hewage Roshanthi Eranga; Wijesundera, Sandhya Sulochana; Vidanagama, Dhammika; Adikaram, Chamila Priyangani; Perera, Jennifer

    2018-04-23

    The emergence and spread of drug-resistant tuberculosis (TB) pose a threat to TB control in Sri Lanka. Isoniazid (INH) is a key element of the first-line anti-TB treatment regimen. Resistance to INH is mainly associated with point mutations in katG, inhA, and ahpC genes. The objective of this study was to determine mutations of these three genes in INH-resistant Mycobacterium tuberculosis (MTb) strains in Sri Lanka. Complete nucleotide sequence of the three genes was amplified by polymerase chain reaction and subjected to DNA sequencing. Point mutations in the katG gene were identified in 93% isolates, of which the majority (78.6%) were at codon 315. Mutations at codons 212 and 293 of the katG gene have not been reported previously. Novel mutations were recognized in the promoter region of the inhA gene (C deletion at -34), fabG1 gene (codon 27), and ahpC gene (codon 39). Single S315T mutation in the katG gene led to a high level of resistance, while a low level of resistance with high frequency (41%) was observed when katG codon 315 coexisted with the mutation at codon 463. Since most of the observed mutations of all three genes coexisted with the katG315 mutation, screening of katG315 mutations will be a useful marker for molecular detection of INH resistance of MTb in Sri Lanka.

  11. Public health impact of isoniazid-resistant Mycobacterium tuberculosis strains with a mutation at amino-acid position 315 of katG: a decade of experience in The Netherlands

    NARCIS (Netherlands)

    van Doorn, H. R.; de Haas, P. E. W.; Kremer, K.; Vandenbroucke-Grauls, C. M. J. E.; Borgdorff, M. W.; van Soolingen, D.

    2006-01-01

    A previous limited study demonstrated that Mycobacterium tuberculosis isolates with a mutation at amino-acid position 315 of katG (Delta315) exhibited high-level resistance to isoniazid and were more frequently resistant to streptomycin. In the present study, isoniazid-resistant M. tuberculosis

  12. Characterisation of the membrane affinity of an isoniazide peptide conjugate by tensiometry, atomic force microscopy and sum-frequency vibrational spectroscopy, using a phospholipid Langmuir monolayer model.

    Science.gov (United States)

    Hill, Katalin; Pénzes, Csanád Botond; Schnöller, Donát; Horváti, Kata; Bosze, Szilvia; Hudecz, Ferenc; Keszthelyi, Tamás; Kiss, Eva

    2010-10-07

    Tensiometry, sum-frequency vibrational spectroscopy, and atomic force microscopy were employed to assess the cell penetration ability of a peptide conjugate of the antituberculotic agent isoniazide. Isoniazide was conjugated to peptide (91)SEFAYGSFVRTVSLPV(106), a functional T-cell epitope of the immunodominant 16 kDa protein of Mycobacterium tuberculosis. As a simple but versatile model of the cell membrane a phospholipid Langmuir monolayer at the liquid/air interface was used. Changes induced in the structure of the phospholipid monolayer by injection of the peptide conjugate into the subphase were followed by tensiometry and sum-frequency vibrational spectroscopy. The drug penetrated lipid films were transferred to a solid support by the Langmuir-Blodgett technique, and their structures were characterized by atomic force microscopy. Peptide conjugation was found to strongly enhance the cell penetration ability of isoniazide.

  13. Comparative bioequivalence study of rifampicin and isoniazid combinations in healthy volunteers.

    Science.gov (United States)

    Padgaonkar, K A; Revankar, S N; Bhatt, A D; Vaz, J A; Desai, N D; D'Sa, S; Shah, V; Gandewar, K

    1999-07-01

    To assess the bioavailability of rifampicin (RMP) in three brands of combination formulations of anti-tuberculosis drugs. A three-way double-blind, cross-over bioavailability study of RMP and isoniazid (INH), consisting of a comparison of a two-drug combination of tablets of RMP and INH each separately (reference brand R) and a tablet of RMP + INH (brand N), and a capsule of RMP + INH (brand L) was carried out in 12 healthy male volunteers. Coded plasma samples were analysed for levels of RMP as well as INH and acetylisoniazid (ACINH) by two high performance liquid chromatography (HPLC) methods. The mean values of RMP in brand N (Cmax 6.49+/-0.52 microg/mL, Tmax 2.33+/-0.18 h, AUC(0-24h) 39.83+/-3.44 microg/mL.h) were comparable with those obtained with brand R (Cmax 5.22+/-0.59 microg/mL, Tmax 2.50+/-0.12 h, AUC(0-24h) 33.33+/-3.47 microg/mL.h). The mean values of RMP in brand L (Cmax 3.05+/-0.52 microg/ mL, Tmax 3.79+/-0.57 h and AUC(0-24h) 21.78+/-3.67 microg/ mL.h) were significantly different from those in brand R. Nevertheless, all of the pharmacokinetic parameters obtained for INH and ACINH in all three brands were comparable. Using brand R as a comparison, brand N was bioequivalent and brand L was not bioequivalent.

  14. Treatment outcomes for isoniazid-resistant tuberculosis under program conditions in British Columbia, Canada.

    Science.gov (United States)

    Romanowski, Kamila; Chiang, Leslie Y; Roth, David Z; Krajden, Mel; Tang, Patrick; Cook, Victoria J; Johnston, James C

    2017-09-04

    Every year, over 1 million people develop isoniazid (INH) resistant tuberculosis (TB). Yet, the optimal treatment regimen remains unclear. Given increasing prevalence, the clinical efficacy of regimens used by physicians is of interest. This study aims to examine treatment outcomes of INH resistant TB patients, treated under programmatic conditions in British Columbia, Canada. Medical charts were retrospectively reviewed for cases of culture-confirmed INH mono-resistant TB reported to the BC Centre for Disease Control (BCCDC) from 2002 to 2014. Treatment regimens, patient and strain characteristics, and clinical outcomes were analysed. One hundred sixty five cases of INH mono-resistant TB were included in analysis and over 30 different treatment regimens were prescribed. Median treatment duration was 10.5 months (IQR 9-12 months) and treatment was extended beyond 12 months for 26 patients (15.8%). Fifty six patients (22.6%) experienced an adverse event that resulted in a drug regimen modification. Overall, 140 patients (84.8%) had a successful treatment outcome while 12 (7.2%) had an unsuccessful treatment outcome of failure (n = 2; 1.2%), relapse (n = 4; 2.4%) or all cause mortality (n = 6; 3.6%). Our treatment outcomes, while consistent with findings reported from other studies in high resource settings, raise concerns about current recommendations for INH resistant TB treatment. Only a small proportion of patients completed the recommended treatment regimens. High quality studies to confirm the effectiveness of standardized regimens are urgently needed, with special consideration given to trials utilizing fluoroquinolones.

  15. Tuberculosis Prevention in the Private Sector: Using Claims-Based Methods to Identify and Evaluate Latent Tuberculosis Infection Treatment With Isoniazid Among the Commercially Insured.

    Science.gov (United States)

    Stockbridge, Erica L; Miller, Thaddeus L; Carlson, Erin K; Ho, Christine

    Targeted identification and treatment of people with latent tuberculosis infection (LTBI) are key components of the US tuberculosis elimination strategy. Because of recent policy changes, some LTBI treatment may shift from public health departments to the private sector. To (1) develop methodology to estimate initiation and completion of treatment with isoniazid for LTBI using claims data, and (2) estimate treatment completion rates for isoniazid regimens from commercial insurance claims. Medical and pharmacy claims data representing insurance-paid services rendered and prescriptions filled between January 2011 and March 2015 were analyzed. Four million commercially insured individuals 0 to 64 years of age. Six-month and 9-month treatment completion rates for isoniazid LTBI regimens. There was an annual isoniazid LTBI treatment initiation rate of 12.5/100 000 insured persons. Of 1074 unique courses of treatment with isoniazid for which treatment completion could be assessed, almost half (46.3%; confidence interval, 43.3-49.3) completed 6 or more months of therapy. Of those, approximately half (48.9%; confidence interval, 44.5-53.3) completed 9 months or more. Claims data can be used to identify and evaluate LTBI treatment with isoniazid occurring in the commercial sector. Completion rates were in the range of those found in public health settings. These findings suggest that the commercial sector may be a valuable adjunct to more traditional venues for tuberculosis prevention. In addition, these newly developed claims-based methods offer a means to gain important insights and open new avenues to monitor, evaluate, and coordinate tuberculosis prevention.

  16. Routine implementation of isoniazid preventive therapy in HIV-infected patients in seven pilot sites in Zimbabwe

    Science.gov (United States)

    Choto, R. C.; Harries, A. D.; Mutasa-Apollo, T.; Chakanyuka-Musanhu, C.

    2017-01-01

    Setting: Seven pilot sites in Zimbabwe implementing 6 months of isoniazid preventive therapy (IPT) for people living with the human immunodeficiency virus (PLHIV). Objectives: To determine, among PLHIV started on IPT, the completion rates for a 6-month course of IPT and factors associated with non-adherence. Design: A retrospective cohort study. Results: Of 578 patients, 466 (81%) completed IPT. Of the 112 patients who failed to complete IPT, 69 (60%) were lost to follow-up, 30 (27%) stopped treatment with no documented reasons, 8 (7%) developed toxicity/adverse reactions, 5 (5%) were documented as having drug stock-outs and the remainder transferred out or refused to continue treatment. Currently being on antiretroviral therapy (ART) (aOR 0.09, 95%CI 0.03–0.28) and receiving a ⩾2 month supply of isoniazid at the start of treatment were associated with a lower risk of not completing IPT, while missing clinic visits prior to starting IPT (aOR 5.25, 95%CI 2.10–13.14) was associated with a higher risk of non-completion. Conclusion: IPT completion rates in seven pilot sites of Zimbabwe were comparatively high, showing that IPT roll-out in public health facilities is feasible. Enhanced adherence counselling or active tracing among pre-ART patients and those with a history of loss to follow-up may improve IPT completion rates, along with synchronising IPT and ART resupplies. PMID:28775944

  17. Phosphodiesterase-4 inhibition combined with isoniazid treatment of rabbits with pulmonary tuberculosis reduces macrophage activation and lung pathology.

    Science.gov (United States)

    Subbian, Selvakumar; Tsenova, Liana; O'Brien, Paul; Yang, Guibin; Koo, Mi-Sun; Peixoto, Blas; Fallows, Dorothy; Zeldis, Jerome B; Muller, George; Kaplan, Gilla

    2011-07-01

    Tuberculosis (TB) is responsible for significant morbidity and mortality worldwide. Even after successful microbiological cure of TB, many patients are left with residual pulmonary damage that can lead to chronic respiratory impairment and greater risk of additional TB episodes due to reinfection with Mycobacterium tuberculosis. Elevated levels of the proinflammatory cytokine tumor necrosis factor-α and several other markers of inflammation, together with expression of matrix metalloproteinases, have been associated with increased risk of pulmonary fibrosis, tissue damage, and poor treatment outcomes in TB patients. In this study, we used a rabbit model of pulmonary TB to evaluate the impact of adjunctive immune modulation, using a phosphodiesterase-4 inhibitor that dampens the innate immune response, on the outcome of treatment with the antibiotic isoniazid. Our data show that cotreatment of M. tuberculosis infected rabbits with the phosphodiesterase-4 inhibitor CC-3052 plus isoniazid significantly reduced the extent of immune pathogenesis, compared with antibiotic alone, as determined by histologic analysis of infected tissues and the expression of genes involved in inflammation, fibrosis, and wound healing in the lungs. Combined treatment with an antibiotic and CC-3052 not only lessened disease but also improved bacterial clearance from the lungs. These findings support the potential for adjunctive immune modulation to improve the treatment of pulmonary TB and reduce the risk of chronic respiratory impairment. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  18. Risk Factors for Acquired Rifamycin and Isoniazid Resistance: A Systematic Review and Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Neesha Rockwood

    Full Text Available Studies looking at acquired drug resistance (ADR are diverse with respect to geographical distribution, HIV co-infection rates, retreatment status and programmatic factors such as regimens administered and directly observed therapy. Our objective was to examine and consolidate evidence from clinical studies of the multifactorial aetiology of acquired rifamycin and/or isoniazid resistance within the scope of a single systematic review. This is important to inform policy and identify key areas for further studies.Case-control and cohort studies and randomised controlled trials that reported ADR as an outcome during antitubercular treatment regimens including a rifamycin and examined the association of at least 1 risk factor were included. Post hoc, we carried out random effects Mantel-Haenszel weighted meta-analyses of the impact of 2 key risk factors 1 HIV and 2 baseline drug resistance on the binary outcome of ADR. Heterogeneity was assessed used I2 statistic. As a secondary outcome, we calculated median cumulative incidence of ADR, weighted by the sample size of the studies.Meta-analysis of 15 studies showed increased risk of ADR with baseline mono- or polyresistance (RR 4.85 95% CI 3.26 to 7.23, heterogeneity I2 58%, 95% CI 26 to 76%. Meta-analysis of 8 studies showed that HIV co-infection was associated with increased risk of ADR (RR 3.02, 95% CI 1.28 to 7.11; there was considerable heterogeneity amongst these studies (I2 81%, 95% CI 64 to 90%. Non-adherence, extrapulmonary/disseminated disease and advanced immunosuppression in HIV co-infection were other risk factors noted. The weighted median cumulative incidence of acquired multi drug resistance calculated in 24 studies (assuming whole cohort as denominator, regardless of follow up DST was 0.1% (5th to 95th percentile 0.07 to 3.2%.Baseline drug resistance and HIV co-infection were significant risk factors for ADR. There was a trend of positive association with non-adherence which is likely

  19. The Genotype MTBDRplus ver. 2.0 test as a quick indicator of resistance to rifampicin and isoniazid in Mycobacterium tuberculosis strains

    Directory of Open Access Journals (Sweden)

    Salvatore Nisticò

    2013-08-01

    Full Text Available Tuberculosis is still a global emergency and a major public health problem, in some cases related to the appearance of strains of multi drug resistance (MDR and extensive drug resistance (XDR Mycobacterium tuberculosis complex.The correct determination of antibiotic sensitivity profiles is therefore crucial to carry out appropriate treatment aimed to decrease the infectivity of each patient and to reduce mortality. The poor adherence to treatment by the patient or the use of therapies based on a single drug, as a result of incorrect requirements, promote the development of drug-resistance. Have some time on the market of molecular diagnostic tests that allow, quickly and directly from biological sample to search for resistance genes some key drugs of anti-TB therapy (Rifampicin and Isoniazid. One of the tests in question is the Genotype MTBDRplus ver 2.0 which can reveal the presence of genes for resistance to Isoniazid (INH and Rifampin (RMP.The loci analyzed are those corresponding to the rpoB gene for rifampicin, katG and inhA for isoniazid. Our study is based on the analysis of 83 strains of tubercular Mycobacteria identified and isolated from patients with tuberculosis disease and subjected to the tests sensitivity, searching for mutations and phenotypic susceptibility testing for Rifampicin and Isoniazid.The comparison of the results has shown that the results obtained using the Genotype MTBDRplus ver 2.0 test, were similar to the results obtained by the traditional susceptibility testing.

  20. Canine generalized demodicosis treated with varying doses of a 2.5% moxidectin+10% imidacloprid spot-on and oral ivermectin: parasiticidal effects and long-term treatment outcomes.

    Science.gov (United States)

    Paterson, Tara E; Halliwell, Richard E; Fields, Paul J; Louw, Marta Lanza; Ball, Geoff; Louw, Jakobus; Pinckney, Rhonda

    2014-10-15

    Advocate(®) (2.5% moxidectin+10% imidacloprid) (Bayer HealthCare, Leverkusen, Germany) is a multiparasiticidal spot-on authorized for treating canine demodicosis in many countries. This blinded, randomized three-phase clinical trial compared its efficacy employing different dosing regimens with that of ivermectin. In the blinded first phase, 58 dogs suffering from generalized demodicosis were randomly assigned to one of four groups and treated with monthly, biweekly or weekly applications of Advocate(®), or with oral ivermectin (IVR) at 500 μg/kg daily. Dogs were evaluated clinically and multiple skin scrapings undertaken every 4 weeks until parasitological cure was achieved (defined as two consecutive series of deep skin scrapings at monthly intervals negative for all life forms). Forty dogs completed the 16-week initial blinded phase, with 5 cases achieving parasitological cure. Five dogs were deemed treatment failures and subsequently treated with ivermectin. The treatment protocol was then changed for the remaining 35 dogs and this cross-over phase (Phase 2) was maintained for a further 8 weeks with an additional 9 dogs achieving parasitological cure. Thereafter, all remaining animals were treated with IVR until cured (Phase 3). Overall, 26 dogs achieved parasitological cure during the clinical investigation. Of these, 23 remained disease-free for at least 12 months while two were lost to follow up and one died of unrelated causes. A total of 32 (55.2%) dogs were withdrawn at various stages of the investigation including the 5 dogs that were judged treatment failures. Other reasons for withdrawal included: non-compliance, lost to follow-up, ivermectin toxicity or reasons unrelated to the investigation. No adverse effects were attributable to the use of Advocate(®). Parasiticidal efficacy was assessed by changes in mite counts (live adult, juvenile and egg) and skin lesion extent & severity scores. Statistical significance was assessed using ANCOVA with

  1. Production and accumulation of UV-B [ultra violet] absorbing compounds in UV-B irradiated leaves of rice, Oryza SativaL.: effects of varying UV-B doses on leaf damage, phenolic content and HPLC [high performance liquid chromatography] peak I area

    International Nuclear Information System (INIS)

    Caasi-Lit, M.T.

    2005-01-01

    The effects of varying UV-B doses on leaf damage, phenolic content and HPLC peak 1 area were studied using 65-d-old plants of the UV-B tolerant rice cultivar, M202, and the UV-B susceptible rice cultivar, Dular. Results showed that the production and accumulation of UV-B- absorbing compounds in rice leaves were affected by leaf position and levels (dose) of UV-B and time or duration of UV-B irradiation or exposure. The youngest terminal leaves showed the least damage when exposed to medium and high UV-B doses. The production of these absorptive compounds as represented by relative phenolic and HPLC peak 1 were significantly higher in younger leaves and lower in older or senescing leaves. M202 showed significantly higher amounts of peak 1 area and relative phenolic compared to UV-B susceptible rice cultivar, Dular. The results also confirmed the strong relationship of overall damage rating and area of HPLC peak 1. The development of UV-B symptoms in the susceptible cultivar was hastened when a high UV-B treatment was applied. Peak 1 area did not accumulate in the UV-B susceptible Dular at any given UV-B dose

  2. Time-varying BRDFs.

    Science.gov (United States)

    Sun, Bo; Sunkavalli, Kalyan; Ramamoorthi, Ravi; Belhumeur, Peter N; Nayar, Shree K

    2007-01-01

    The properties of virtually all real-world materials change with time, causing their bidirectional reflectance distribution functions (BRDFs) to be time varying. However, none of the existing BRDF models and databases take time variation into consideration; they represent the appearance of a material at a single time instance. In this paper, we address the acquisition, analysis, modeling, and rendering of a wide range of time-varying BRDFs (TVBRDFs). We have developed an acquisition system that is capable of sampling a material's BRDF at multiple time instances, with each time sample acquired within 36 sec. We have used this acquisition system to measure the BRDFs of a wide range of time-varying phenomena, which include the drying of various types of paints (watercolor, spray, and oil), the drying of wet rough surfaces (cement, plaster, and fabrics), the accumulation of dusts (household and joint compound) on surfaces, and the melting of materials (chocolate). Analytic BRDF functions are fit to these measurements and the model parameters' variations with time are analyzed. Each category exhibits interesting and sometimes nonintuitive parameter trends. These parameter trends are then used to develop analytic TVBRDF models. The analytic TVBRDF models enable us to apply effects such as paint drying and dust accumulation to arbitrary surfaces and novel materials.

  3. Tuberculosis contact screening and isoniazid preventive therapy in a South Indian district: operational issues for programmatic consideration.

    Science.gov (United States)

    Pothukuchi, Madhavi; Nagaraja, Sharath Burugina; Kelamane, Santosha; Satyanarayana, Srinath; Shashidhar; Babu, Sai; Dewan, Puneet; Wares, Fraser

    2011-01-01

    Under India's Revised National Tuberculosis Control Programme (RNTCP), all household contacts of sputum smear positive Pulmonary Tuberculosis (PTB) patients are screened for TB. In the absence of active TB disease, household contacts aged Isoniazid Preventive Therapy (IPT) (5 milligrams/kilogram body weight/day) for 6 months. To estimate the number of household contacts aged tablets in peripheral health centers. The reasons for non-evaluation of the remaining eligible children (n = 56, 33%) include no home visit by the health staff in 25 contacts, home visit done but not evaluated in 31 contacts. House-hold contacts in rural areas were less likely to be evaluated and initiated on IPT [risk ratio 6.65 (95% CI; 3.06-14.42)]. Contact screening and IPT implementation under routine programmatic conditions is sub-optimal. There is an urgent need to sensitize all concerned programme staff on its importance and establishment of mechanisms for rigorous monitoring.

  4. The effect of partner HIV status on motivation to take antiretroviral and isoniazid preventive therapies: a conjoint analysis.

    Science.gov (United States)

    Kim, Hae-Young; Hanrahan, Colleen F; Dowdy, David W; Martinson, Neil; Golub, Jonathan; Bridges, John F P

    2018-03-29

    Antiretroviral therapy (ART) and isoniazid preventive therapy (IPT) are important to reduce morbidity and mortality among people newly diagnosed of HIV. The successful uptake of ART and IPT requires a comprehensive understanding of patients' motivation to take such therapies. Partners also play an important role in the decision to be initiated and retained in care. We quantified patients' motivation to take preventive therapies (ART and IPT) and compared by partner HIV status among people newly diagnosed of HIV. We enrolled and surveyed adults (≥18 years) with a recent HIV diagnosis (ART and 334 (79%) had a partner or spouse. Keeping themselves healthy for their family was the most important motivator to take preventive therapies (p motivation for ART and IPT initiation and adherence compared to individual health benefits. These messages should be emphasized to provide effective patient-centered care and counseling.

  5. Dissolution testing of isoniazid, rifampicin, pyrazinamide and ethambutol tablets using near-infrared spectroscopy (NIRS) and multivariate calibration.

    Science.gov (United States)

    de Oliveira Neves, Ana Carolina; Soares, Gustavo Mesquita; de Morais, Stéphanie Cavalcante; da Costa, Fernanda Saadna Lopes; Porto, Dayanne Lopes; de Lima, Kássio Michell Gomes

    2012-01-05

    This work utilized the near-infrared spectroscopy (NIRS) and multivariate calibration to measure the percentage drug dissolution of four active pharmaceutical ingredients (APIs) (isoniazid, rifampicin, pyrazinamide and ethambutol) in finished pharmaceutical products produced in the Federal University of Rio Grande do Norte (Brazil). The conventional analytical method employed in quality control tests of the dissolution by the pharmaceutical industry is high-performance liquid chromatography (HPLC). The NIRS is a reliable method that offers important advantages for the large-scale production of tablets and for non-destructive analysis. NIR spectra of 38 samples (in triplicate) were measured using a Bomen FT-NIR 160 MB in the range 1100-2500nm. Each spectrum was the average of 50 scans obtained in the diffuse reflectance mode. The dissolution test, which was initially carried out in 900mL of 0.1N hydrochloric acid at 37±0.5°C, was used to determine the percentage a drug that dissolved from each tablet measured at the same time interval (45min) at pH 6.8. The measurement of the four API was performed by HPLC (Shimadzu, Japan) in the gradiente mode. The influence of various spectral pretreatments (Savitzky-Golay smoothing, Multiplicative Scatter Correction (MSC), and Savitzky-Golay derivatives) and multivariate analysis using the partial least squares (PLS) regression algorithm was calculated by the Unscrambler 9.8 (Camo) software. The correlation coefficient (R(2)) for the HPLC determination versus predicted values (NIRS) ranged from 0.88 to 0.98. The root-mean-square error of prediction (RMSEP) obtained from PLS models were 9.99%, 8.63%, 8.57% and 9.97% for isoniazid, rifampicin, ethambutol and pyrazinamide, respectively, indicating that the NIR method is an effective and non-destructive tool for measurement of drug dissolution from tablets. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  6. Evaluation of rapid MTT tube method for detection of drug susceptibility of mycobacterium tuberculosis to rifampicin and isoniazid

    Directory of Open Access Journals (Sweden)

    Raut U

    2008-01-01

    Full Text Available Purpose: To evaluate MTT method for detection of drug resistance to rifampicin and isoniazid in M.tuberculosis . This method utilises the ability of viable mycobacterial cells to reduce MTT( 3-4,5-dimethylthiazol-2-yl-2, 5-diphenyl tetrazolium bromide. Methods: The method was standardised with known resistant and sensitive strains of M.tuberculosis and was then extended to 50 clinical isolates. An inoculum of 10 7 cfu/mL was prepared in Middlebrook 7H9 medium supplemented with oleic acid, albumin, dextrose and catalase. For each drug three tubes were used, one with INH(0.2μg/mL or RIF(1μg/mL, another as inoculum control and third as blank control. These were incubated at 37°C for four and seven days respectively for RIF and INH after which MTT assay was performed. Results were read visually and by colorimeter at 570 nm. Relative optical density unit (RODU of 0.2 was taken as cut off. Results were compared with drug sensitivity obtained by proportion method using LJ medium. Results: For rifampicin, concordance with proportion method was 90% by visual and 94% by RODU. Sensitivity and specificity was 86.8% and 100% respectively by visual method and 95.2% and 87.5% respectively by RODU. For Isoniazid, concordance was 94% and sensitivity and specificity was 94.7 and 91.7% respectively by both visual and RODU. Conclusions: MTT assay proved to be rapid and cheap method for performing drug sensitivity of M.tuberculosis

  7. Diagnostic moléculaire du complexe Mycobacterium tuberculosis résistant à l'isoniazide et à la rifampicine au Burkina Faso

    Science.gov (United States)

    Désire, Ilboudo; Cyrille, Bisseye; Florencia, Djigma; Souba, Diande; Albert, Yonli; Valerie, Bazie Jean Telesphore; Rebecca, Compaore; Charlemagne, Gnoula; Tamboura, Djibril; Rémy, Moret; Virginio, Pietra; Simplice, Karou Damintoti; Martial, Ouedraogo; Jacques, Simpore

    2015-01-01

    Introduction Cette étude a eu pour objectifs de diagnostiquer la tuberculose pulmonaire par l'examen microscopique et par la PCR des crachats et de déterminer les bases moléculaires de la résistance à la rifampicine et à l'isoniazide. Méthodes Le diagnostic du Complexe Mycobacterium Tuberculosis (CMTB) a été effectué par microscopie après coloration au Ziehl Nielsen et par PCR en temps réel en utilisant le kit d'identification du complexe MTB (Sacace Biotechnologie, Italie). Les résistances à la Rifampicine et à l'Isoniazide ont été étudiées par la technique de la PCR en utilisant le kit MTB résistance 8 (Sacace, Biotechnologie). Résultats Sur les 59 patients diagnostiqués pour la tuberculose pulmonaire, 59,3% étaient positifs en microscopie optique et 44,1% étaient positifs par PCR en Temps réel. Les résistances à la rifampicine (rpoB) et à l'isoniazide (katG et inhA) ont été observées chez 9 patients. La résistance à la rifampicine était due aux mutations (Asp516Val, Ser531Trp, Leu533Pro) et celle à l'isoniazide par les substitutions Ser315Thr du gène katG et C209T du gène inhA. Les multi résistances à la rifampicine et à l'isoniazide ont été observées dans 55,5% des échantillons et concernaient les associations: ropBAsp513Val + inhAC209T et rpoBLeu533Pro + katGSer315Thr. Conclusion La PCR en temps réel qui permet l'identification des allèles mutants rpoB, katG et inhA de M. tuberculosis est un outil de diagnostic épidémiologique de grande importance car elle permet de déterminer le niveau de résistance à la rifampicine et à l'isoniazide. PMID:26491516

  8. varying elastic parameters distributions

    KAUST Repository

    Moussawi, Ali

    2014-12-01

    The experimental identication of mechanical properties is crucial in mechanics for understanding material behavior and for the development of numerical models. Classical identi cation procedures employ standard shaped specimens, assume that the mechanical elds in the object are homogeneous, and recover global properties. Thus, multiple tests are required for full characterization of a heterogeneous object, leading to a time consuming and costly process. The development of non-contact, full- eld measurement techniques from which complex kinematic elds can be recorded has opened the door to a new way of thinking. From the identi cation point of view, suitable methods can be used to process these complex kinematic elds in order to recover multiple spatially varying parameters through one test or a few tests. The requirement is the development of identi cation techniques that can process these complex experimental data. This thesis introduces a novel identi cation technique called the constitutive compatibility method. The key idea is to de ne stresses as compatible with the observed kinematic eld through the chosen class of constitutive equation, making possible the uncoupling of the identi cation of stress from the identi cation of the material parameters. This uncoupling leads to parametrized solutions in cases where 5 the solution is non-unique (due to unknown traction boundary conditions) as demonstrated on 2D numerical examples. First the theory is outlined and the method is demonstrated in 2D applications. Second, the method is implemented within a domain decomposition framework in order to reduce the cost for processing very large problems. Finally, it is extended to 3D numerical examples. Promising results are shown for 2D and 3D problems.

  9. One-year mortality of HIV-positive patients treated for rifampicin- and isoniazid-susceptible tuberculosis in Eastern Europe, Western Europe, and Latin America

    DEFF Research Database (Denmark)

    Podlekareva, DN; Schultze, A; Panteleev, A

    2017-01-01

    in Western Europe or Latin America. METHODS: One-year mortality of HIV-positive patients with rifampicin/isoniazid-susceptible TB in Eastern Europe, Western Europe, and Latin America was analysed and compared in a prospective observational cohort study. Factors associated with death were analysed using Cox......OBJECTIVES: The high mortality among HIV/tuberculosis (TB) coinfected patients in Eastern Europe is partly explained by the high prevalence of drug-resistant TB. It remains unclear whether outcomes of HIV/TB patients with rifampicin/isoniazid-susceptible TB in Eastern Europe differ from those...... cell count. These results call for improvement of care for TB/HIV patients in Eastern Europe....

  10. Effect of medium acidity on the thermodynamics and kinetics of the reaction of pyridoxal 5'-phosphate with isoniazid in an aqueous solution

    Science.gov (United States)

    Gamov, G. A.; Zavalishin, M. N.; Usacheva, T. R.; Sharnin, V. A.

    2017-05-01

    Thermodynamic characteristics of the formation of the Schiff base between isoniazid and pyridoxal 5'-phosphate in an aqueous solution at different pH values of a medium are determined by means of spectrophotometry and calorimetric titration. The process kinetics is studied spectrophotometrically, and the reaction rate constants for the formation of the imine at different acidities of a medium are determined. Biochemical aspects of the binding of pyridoxal 5'-phosphate into stable compounds are discussed.

  11. Electrochemical behavior of the antituberculosis drug isoniazid and its square-wave adsorptive stripping voltammetric estimation in bulk form, tablets and biological fluids at a mercury electrode.

    Science.gov (United States)

    Ghoneim, M M; el-Baradie, K Y; Tawfik, A

    2003-11-24

    Isoniazid, pyridine-4-carboxylic acid hydrazide, is an antituberculosis-agent, which is used to prevent the development of clinical tuberculosis. A validated square-wave adsorptive cathodic stripping voltammetric procedure for the trace determination of the bulk drug at the hanging mercury drop electrode (HMDE) has been developed. Under the optimized conditions, (accumulation potential=-0.9 V, accumulation time=50-300 s, scan increment=8 mV, pulse-amplitude=25 mV, frequency=120 Hz and acetate buffer at pH 5.5) isoniazed generated two irreversible cathodic peaks. The first peak current showed a linear dependence with the drug concentration over the range 5 x 10(-10)-21 x 0(-6) M. The mean percentage recoveries, based on the average of five replicate measurements, for 7 x 10(-9) and 5 x 10(-8) M isoniazid were 97.71+/-2.93 and 99.76+/-0.77, respectively. The achieved limits of detection (LOD) and quantitation (LOQ) were 1.18 x 10(-10) and 3.93 x 10(-10) M isoniazid, respectively. The procedure was applied to the assay of the drug in tablets (Isocid and T.B. Zide), spiked human serum and urine with mean percentage recoveries of 97.81+/-1.49, 97.45+/-2.09, and 97.08+/-1.06, respectively. The limits of detection of 1.47 x 10(-9) and 2.4 x 10(-8) M, and quantitation of 4.9 x 10(-9) and 8 x 10(-8) M drug in human serum and urine, respectively, were achieved. The mean values of the various pharmackinetic parameters of isoniazid (C(max), T(max), t(1/2), AUC, and K(e)), estimated from analysis of plasma of two volunteers by means of the proposed procedure were similar to literature values.

  12. Structure and function of the liver in conditions of chrome-isoniazid-rifampicin affection of rats after applying of sorbex

    Directory of Open Access Journals (Sweden)

    N. I. Burmas

    2014-09-01

    Full Text Available The aim of this research was to assess the activity of marker enzymes of the liver and its biliary formation function in conditions of the affection of animals by hexavalent chromium compounds, isoniazid and rifampicin, after applying of sorbex. The experimental affection of rats of different age was carried in the conditions of combined injection of hexavalent chromium compounds (solution of potassium dichromate, 3 mg/kg, isoniazid (0.05 g/kg and rifampicin (0.25 g/kg during the 7th and 14th days, and sorbex enterosorbent was introduced in quantity of 150 mg/kg. The activity of marker enzymes of the liver was evaluated by the activity of alanine and aspartate aminotransferases (ALT and AST and alkaline phosphatase (ALP. The state of biliary formation function of the liver was evaluated by the content of total bilirubin (TB and bile acids (BA in blood. The most significant changes in ALT activity were observed in the liver of old animals by the combined effects of the abovementioned xenobiotics – the activity of ALT was decreased by the end of the experiment by 58% compared with the animals of intact control. Using of sorbex led to decreasing in blood serum and increasing in the liver of affected animals of the different age of ALT activity throughout the experiment. AST activity in blood serum increased, and it was the highest in old animals upon chrome-isoniazid-rifampicin affection on the 14th day of the research. With the use of sorbex, there was a tendency to normalization of this index in blood serum and liver of affected animals on the 7th day from the beginning of the experiment. It was found that the largest increase in ALP took place in blood serum of immature animals by the combined effects of toxicants. In the liver of affected animals the activity of ALP decreased throughout the experiment in all age groups of animals. Maximum corrective effect on the activity of ALP was shown by the enterosorbent in the liver of mature animals on

  13. The implementation of isoniazid preventive therapy in HIV clinics: the experience from the TB/HIV in Rio (THRio) study.

    Science.gov (United States)

    Durovni, Betina; Cavalcante, Solange C; Saraceni, Valeria; Vellozo, Vitoria; Israel, Giselle; King, Bonnie S; Cohn, Silvia; Efron, Anne; Pacheco, Antonio G; Moulton, Lawrence H; Chaisson, Richard E; Golub, Jonathan E

    2010-11-01

    The TB/HIV in Rio (THRio) study was launched in September 2005 to assess the impact of integrated tuberculosis (TB) and HIV treatment strategies in 29 HIV clinics in Rio de Janeiro, Brazil. THRio is a cluster-randomized trial (CRT) to determine whether routine screening for and treatment of latent TB in HIV clinic patients with access to antiretroviral therapy will reduce TB incidence at the clinic level. THRio is part of the Consortium to Respond Effectively to AIDS/TB Epidemic that is implementing research studies to assess the impact of bold, new public health paradigms for controlling the AIDS/TB epidemic. Twenty-nine public primary HIV clinics were randomly assigned a date to begin implementing TB screening procedures and provision of isoniazid preventive therapy (IPT) for TB/HIV coinfected patients. Final analysis of the CRT is expected in 2011. Starting at date of tuberculin skin test (TST)/IPT implementation at each clinic through August 2010, 1670 HIV-infected patients initiated IPT, of which 215 are still receiving treatment. Of the remaining 1455 patients, 1230 (85%) completed therapy and only 20 (1.2%) patients initiating IPT reported adverse reactions leading to discontinuation of therapy. IPT completion was higher among HIV-infected patients receiving HAART (87%) than those not yet receiving HAART (79%, P effort requires a package of activities including training, advocacy and reorganization of services.

  14. It's hard work, but it's worth it: the task of keeping children adherent to isoniazid preventive therapy.

    Science.gov (United States)

    Skinner, D; Hesseling, A C; Francis, C; Mandalakas, A M

    2013-09-21

    Isoniazid preventive therapy (IPT) offers children protection against tuberculosis (TB), but it has been difficult to implement, particularly in developing countries. To understand what encourages or inhibits children from adhering to IPT. In-depth interviews were conducted with two parents of children adherent to IPT and two staff members from three primary health care clinics in high TB prevalence communities. Themes explored were knowledge and attitudes towards IPT, problems in accessing and adhering to treatment, and community responses. Parents administering treatment valued it positively, realised their children's risk of TB, and were positive about the clinic. Nurses acknowledged that resistance to treatment remained, with some parents not wanting to acknowledge risk nor willing to make the effort for their children; there was also considerable misinformation about IPT. Clinic nurses acknowledged problems of staff shortages, lengthy waiting times and conflict between staff and community members. Adherence was affected by social problems, stigma about TB and its link to the human immunodeficiency virus, and the extended treatment period. Parents who maintained adherence to the IPT regimen showed that it was possible even in very difficult circumstances. Further effort is required to improve some of the clinic services, correct misinformation, reduce stigma and provide support to parents.

  15. Wild-type catalase peroxidase vs G279D mutant type: Molecular basis of Isoniazid drug resistance in Mycobacterium tuberculosis.

    Science.gov (United States)

    Singh, Aishwarya; Singh, Aditi; Grover, Sonam; Pandey, Bharati; Kumari, Anchala; Grover, Abhinav

    2018-01-30

    Mycobacterium tuberculosis katG gene is responsible for production of an enzyme catalase peroxidase that peroxidises and activates the prodrug Isoniazid (INH), a first-line antitubercular agent. INH interacts with catalase peroxidase enzyme within its heme pocket and gets converted to an active form. Mutations occurring in katG gene are often linked to reduced conversion rates for INH. This study is focussed on one such mutation occurring at residue 279, where glycine often mutates to aspartic acid (G279D). In the present study, several structural analyses were performed to study the effect of this mutation on functionality of KatG protein. On comparison, mutant protein exhibited a lower docking score, smaller binding cavity and reduced affinity towards INH. Molecular dynamics analysis revealed the mutant to be more rigid and less compact than the native protein. Essential dynamics analysis determined correlated motions of residues within the protein structure. G279D mutant was found to have many residues that showed related motions and an undesirable effect on the functionality of protein. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. NANOBIOCATALYTIC SYSTEMS BASED ON LIPASE-Fe3O4 AND CONVENTIONAL SYSTEMS FOR ISONIAZID SYNTHESIS: A COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    V. M. Costa

    Full Text Available Abstract Superparamagnetic nanomaterials have attracted interest in many areas due to the high saturation magnetization and surface area. For enzyme immobilization, these properties favor the enzyme-support contact during the immobilization reaction and easy separation from the reaction mixture by use of low-cost magnetic processes. Iron oxide magnetic nanoparticles (Fe3O4, MNPs, produced by the co-precipitation method, functionalized with 3-aminopropyltriethoxysilane (APTES and glutaraldehyde (GLU, were evaluated as a solid support for Candida antarctica lipase B (CALB immobilization. The nanomagnetic derivative (11nm obtained after CALB immobilization (MNPs/APTES/GLU/CALB was evaluated as biocatalyst in isoniazide (INH synthesis using ethyl isonicotinate (INE and hydrazine hydrate (HID as substrates, in 1,4-dioxane. The results showed that MNPs/APTES/CALB had a similar performance when compared to a commercial enzyme Novozym 435, showing significant advantages over other biocatalysts, such as Rhizhomucor miehei lipase (RML and CALB immobilized on non-conventional, low-cost, chitosan-based supports.

  17. A new rapid colourimetric method for testing Mycobacterium tuberculosis susceptibility to isoniazid and rifampicin: a crystal violet decolourisation assay

    Directory of Open Access Journals (Sweden)

    Ahmet Yilmaz Coban

    2014-04-01

    Full Text Available The aim of this study was to investigate the performance of a new and accurate method for the detection of isoniazid (INH and rifampicin (RIF resistance among Mycobacterium tuberculosis isolates using a crystal violet decolourisation assay (CVDA. Fifty-five M. tuberculosis isolates obtained from culture stocks stored at -80ºC were tested. After bacterial inoculation, the samples were incubated at 37ºC for seven days and 100 µL of CV (25 mg/L stock solution was then added to the control and sample tubes. The tubes were incubated for an additional 24-48 h. CV (blue/purple was decolourised in the presence of bacterial growth; thus, if CV lost its colour in a sample containing a drug, the tested isolate was reported as resistant. The sensitivity, specificity, positive predictive value, negative predictive value and agreement for INH were 92.5%, 96.4%, 96.1%, 93.1% and 94.5%, respectively, and 88.8%, 100%, 100%, 94.8% and 96.3%, respectively, for RIF. The results were obtained within eight-nine days. This study shows that CVDA is an effective method to detect M. tuberculosis resistance to INH and RIF in developing countries. This method is rapid, simple and inexpensive. Nonetheless, further studies are necessary before routine laboratory implementation.

  18. Effect of isoniazid preventive therapy on tuberculosis incidence in people living with HIV-AIDS at Hasan Sadikin hospital

    Science.gov (United States)

    Satiavan, I.; Hartantri, Y.; Werry, B.; Nababan, Y.; Wisaksana, R.; Alisjahban, B.

    2018-03-01

    Indonesia is the second largest number of tuberculosis (TB) in the world. Isoniazid Preventive Therapy (IPT) as one of the three I’s TB-HIV collaboration to manage TB in people living with HIV / AIDS (PLHIV) has not been fully performed. It is related to doubt to get rid of TB in PLHIV. This study aims to see the effect of IPT on the incidence of TB in PLHIV. This issue is a retrospective cohort study based on medical record data in HIV clinic. Inclusion criteria are PLHIV ≥ 15 years of age who were registered to visit the CST service and obtain IPT with good adherence if they were receiving ART. Of 462 patients, HIV- infected patients receiving IPT were 154 (33.3%). IPT administration has a protective effect on PLHIV where the rate of TB incidence in PLHIV who received IPT were 0.21 times lower than those who did not receive IPT (IRR = 0.21, 95% CI 0.023-0.881, p 0.008). In this population, IPT administration reduces 79% risk of PLHIV to suffer TB.IPT administration reduces the incidence of TB.

  19. Dose measurements in mammography

    International Nuclear Information System (INIS)

    Kainberger, F.; Kallinger, W.

    1977-01-01

    Dose measurements at the mamma during mammography were carried out in the form of direct measurement with thermoluminescent dosimetry. Measurement was done for the in- and outcoming doses at the mamma, the dose exposure of the sternal region and the scattered rays above the symphysis, the latter as parameter for the genetic radiation exposure. As expected, the dose of the smooth radiation used for mammography showed a strong decrease at the outcome point in comparison with the income point. Surprisingly high was the scattered radiation in the sternal region. A corresponding protection by lead plates could be taken into consideration. Extremely low is the scattered radiation above the symphysis. Even measurements with the very sensitive calcium fluoride dosimeters did not reveal any practically important dose in the symphysis region. Most measurement values remained below the determinable dose of 0.3mR. Some maximal values varied in the range of 3-1 mR. (orig.) [de

  20. Phosphodiesterase-4 inhibition alters gene expression and improves isoniazid-mediated clearance of Mycobacterium tuberculosis in rabbit lungs.

    Directory of Open Access Journals (Sweden)

    Selvakumar Subbian

    2011-09-01

    Full Text Available Tuberculosis (TB treatment is hampered by the long duration of antibiotic therapy required to achieve cure. This indolent response has been partly attributed to the ability of subpopulations of less metabolically active Mycobacterium tuberculosis (Mtb to withstand killing by current anti-TB drugs. We have used immune modulation with a phosphodiesterase-4 (PDE4 inhibitor, CC-3052, that reduces tumor necrosis factor alpha (TNF-α production by increasing intracellular cAMP in macrophages, to examine the crosstalk between host and pathogen in rabbits with pulmonary TB during treatment with isoniazid (INH. Based on DNA microarray, changes in host gene expression during CC-3052 treatment of Mtb infected rabbits support a link between PDE4 inhibition and specific down-regulation of the innate immune response. The overall pattern of host gene expression in the lungs of infected rabbits treated with CC-3052, compared to untreated rabbits, was similar to that described in vitro in resting Mtb infected macrophages, suggesting suboptimal macrophage activation. These alterations in host immunity were associated with corresponding down-regulation of a number of Mtb genes that have been associated with a metabolic shift towards dormancy. Moreover, treatment with CC-3052 and INH resulted in reduced expression of those genes associated with the bacterial response to INH. Importantly, CC-3052 treatment of infected rabbits was associated with reduced ability of Mtb to withstand INH killing, shown by improved bacillary clearance, from the lungs of co-treated animals compared to rabbits treated with INH alone. The results of our study suggest that changes in Mtb gene expression, in response to changes in the host immune response, can alter the responsiveness of the bacteria to antimicrobial agents. These findings provide a basis for exploring the potential use of adjunctive immune modulation with PDE4 inhibitors to enhance the efficacy of existing anti-TB treatment.

  1. Conjugation of isoniazid to a zinc phthalocyanine via hydrazone linkage for pH-dependent liposomal controlled release

    Science.gov (United States)

    Nkanga, Christian Isalomboto; Krause, Rui Werner Maçedo

    2018-05-01

    Tuberculosis (TB) remains the leading cause of mortality from infectious diseases. Extended TB treatment and frequent adverse effects, due to poor bioavailability of anti-tubercular drugs (ATBDs), represent the main rationales behind liposomal encapsulation for controlled delivery. Liposomes have been reported as potential vehicles for targeted delivery of ATBDs due to their rapid uptake by macrophages, which are known as the main host cells for TB causative agent (Mycobacterium tuberculosis). Additionally, the need for controlled release of ATBDs arises because leakage is part of the key liposome challenges for hydrophilic compounds like isoniazid (INH). In this study, INH was conjugated to a highly hydrophobic photosensitizer, zinc (II) phthalocyanine (PC), through hydrazone bonding. The obtained conjugate (PC-INH) was encapsulated in liposomes by film hydration method. PC-INH loaded liposomes (PILs) were characterized using dynamic light scattering, transmission electron microscopy, energy-dispersive X-ray spectrometry and UV-Vis absorption spectrometry, which was used also for estimation of encapsulation efficiency (%EE). INH release was evaluated in different pH media using dialysis. Particle size, zeta potential and %EE of PILs were about 506 nm, - 55 mV and 72%, respectively. Over 12 h, PILs exhibited 22, 41, 97 and 100% of INH, respectively, released in pH 7.4, 6.4, 5.4 and 4.4 media. This pH-dependent behavior is attractive for site-specific delivery. These findings suggest the conjugation of chemotherapeutics to phthalocyanines using pH-labile linkages as a potential strategy for liposomal controlled release.

  2. Clinical characteristics and treatment outcomes of patients with low- and high-concentration isoniazid-monoresistant tuberculosis.

    Directory of Open Access Journals (Sweden)

    Tsai-Yu Wang

    Full Text Available BACKGROUND: Isoniazid (INH resistance is now the most common type of tuberculosis (TB infection resistance worldwide. The aim of this study was to evaluate the clinical characteristics and treatment outcomes of patients with low- and high-concentration INH-monoresistant TB. METHODS: One hundred and thirty-four patients with culture-confirmed INH-monoresistant TB during 2006 January to 2007 December were retrospectively enrolled. INH resistance was classified as either low-concentration or high-concentration resistance according to the critical concentrations of 0.2 µg/mL or 1 µg/mL of INH, respectively. The patients' clinical outcomes, treatment regimens, and treatment duration were analyzed. RESULTS: The treatment success rates between low- and high-concentration INH-resistant TB were similar (81.8% vs. 86.7%. The treatment regimens and treatment duration were similar between both groups. Only a minor percentage of the patients in both groups received 6-month treatment regimens (low vs. high concentration resistance, 9.1% vs. 13.3%; respectively, p = 0.447 The most common reason for treatment duration longer than 6 months was pyrazinamide given for less than 6 months, followed by a delay in clinical response to treatment. Multivariable analysis showed that prior tuberculosis treatment (Odds ratio, 2.82, 95% C.I., 1.02-7.77, p = 0.045 was the only independent risk factor for unsuccessful treatment outcome. CONCLUSION: Different levels of INH resistance did not affect the treatment outcomes of patients with INH-monoresistant tuberculosis. Prolonged Rifampin-containing regimens may achieve those good outcomes in patients with low- and high-concentration INH-monoresistant TB.

  3. Mutation of katG in a clinical isolate of Mycobacterium tuberculosis: effects on catalase-peroxidase for isoniazid activation.

    Science.gov (United States)

    Purkan; Ihsanawati; Natalia, D; Syah, Y M; Retnoningrum, D S; Kusuma, H S

    2016-01-01

    Mutations in katG gene are often associated with isoniazid (INH) resistance in Mycobacterium tuberculosis strain. This research was perfomed to identify the katG mutation in clinical isolate (L8) that is resistant to INH at 1 μg/ml. In addition to characterize the catalase-peroxidase of KatG L8 and perform the ab initio structural study of the protein to get a more complete understanding in drug activation and the resistan­ce mechanism. The katG gene was cloned and expressed in Escherichia coli, then followed by characterization of catalase-peroxidase of KatG. The structure modelling was performed to know a basis of alterations in enzyme activity. A substitution of A713G that correspond to Asn238Ser replacement was found in the L8 katG. The Asn238Ser modification leads to a decline in the activity of catalase-peroxidase and INH oxidation of the L8 KatG protein. The catalytic efficiency (Kcat/KM) of mutant KatGAsn238Ser respectively decreases to 41 and 52% for catalase and peroxidase. The mutant KatGAsn238Ser also shows a decrease of 62% in INH oxidation if compared to a wild type KatG (KatGwt). The mutant Asn238Ser might cause instability in the substrate binding­ site of KatG, because of removal of a salt bridge connecting the amine group of Asn238 to the carbo­xyl group of Glu233, which presents in KatGwt. The lost of the salt bridge in the substrate binding site in mutant KatGAsn238Ser created changes unfavorable for enzyme activities, which in turn emerge as INH resistan­ce in the L8 isolate of M. tuberculosis.

  4. Inhibitory activity of pentacyano(isoniazid)ferrate(II), IQG-607, against promastigotes and amastigotes forms of Leishmania braziliensis

    Science.gov (United States)

    Amorim, Camila F.; Galina, Luiza; Carvalho, Natália B.; Sperotto, Nathalia D. M.; Pissinate, Kenia; Machado, Pablo; Campos, Maria M.; Basso, Luiz A.; Carvalho, Edgar M.; Santos, Diógenes Santiago

    2017-01-01

    M. tuberculosis and parasites of the genus Leishmania present the type II fatty acid biosynthesis system (FASII). The pentacyano(isoniazid)ferrate(II) compound, named IQG-607, inhibits the enzyme 2-trans-enoyl-ACP(CoA) reductase from M. tuberculosis, a key component in the FASII system. Here, we aimed to evaluate the inhibitory activity of IQG-607 against promastigote and amastigote forms of Leishmania (Viannia) braziliensis isolated from patients with different clinical forms of L. braziliensis infection, including cutaneous, mucosal and disseminated leishmaniasis. Importantly, IQG-607 inhibited the proliferation of three different isolates of L. braziliensis promastigotes associated with cutaneous, mucosal and disseminated leishmaniasis. The IC50 values for IQG-607 ranged from 32 to 75 μM, for these forms. Additionally, IQG-607 treatment decreased the proliferation of intracellular amastigotes in infected macrophages, after an analysis of the percentage of infected cells and the number of intracellular parasites/100 cells. IQG-607 reduced from 58% to 98% the proliferation of L. braziliensis from cutaneous, mucosal and disseminated strains. Moreover, IQG-607 was also evaluated regarding its potential toxic profile, by using different cell lines. Cell viability of the lineages Vero, HaCat and HepG2 was significantly reduced after incubation with concentrations of IQG-607 higher than 2 mM. Importantly, IQG-607, in a concentration of 1 mM, did not induce DNA damage in HepG2 cells, when compared to the untreated control group. Future studies will confirm the mechanism of action of IQG-607 against L. braziliensis. PMID:29281707

  5. Mycobacterium tuberculosis Is Resistant to Isoniazid at a Slow Growth Rate by Single Nucleotide Polymorphisms in katG Codon Ser315.

    Directory of Open Access Journals (Sweden)

    Rose E Jeeves

    Full Text Available An important aim for improving TB treatment is to shorten the period of antibiotic therapy without increasing relapse rates or encouraging the development of antibiotic-resistant strains. In any M. tuberculosis population there is a proportion of bacteria that are drug-tolerant; this might be because of pre-existing populations of slow growing/non replicating bacteria that are protected from antibiotic action due to the expression of a phenotype that limits drug activity. We addressed this question by observing populations of either slow growing (constant 69.3h mean generation time or fast growing bacilli (constant 23.1h mean generation time in their response to the effects of isoniazid exposure, using controlled and defined growth in chemostats. Phenotypic differences were detected between the populations at the two growth rates including expression of efflux mechanisms and the involvement of antisense RNA/small RNA in the regulation of a drug-tolerant phenotype, which has not been explored previously for M. tuberculosis. Genotypic analyses showed that slow growing bacilli develop resistance to isoniazid through mutations specifically in katG codon Ser315 which are present in approximately 50-90% of all isoniazid-resistant clinical isolates. The fast growing bacilli persisted as a mixed population with katG mutations distributed throughout the gene. Mutations in katG codon Ser315 appear to have a fitness cost in vitro and particularly in fast growing cultures. Our results suggest a requirement for functional katG-encoded catalase-peroxide in the slow growers but not the fast-growing bacteria, which may explain why katG codon Ser315 mutations are favoured in the slow growing cultures.

  6. One-year mortality of HIV-positive patients treated for rifampicin- and isoniazid-susceptible tuberculosis in Eastern Europe, Western Europe, and Latin America.

    Science.gov (United States)

    2017-01-28

    The high mortality among HIV/tuberculosis (TB) coinfected patients in Eastern Europe is partly explained by the high prevalence of drug-resistant TB. It remains unclear whether outcomes of HIV/TB patients with rifampicin/isoniazid-susceptible TB in Eastern Europe differ from those in Western Europe or Latin America. One-year mortality of HIV-positive patients with rifampicin/isoniazid-susceptible TB in Eastern Europe, Western Europe, and Latin America was analysed and compared in a prospective observational cohort study. Factors associated with death were analysed using Cox regression modelsRESULTS:: Three hundred and forty-one patients were included (Eastern Europe 127, Western Europe 165, Latin America 49). Proportions of patients with disseminated TB (50, 58, 59%) and initiating rifampicin + isoniazid + pyrazinamide-based treatment (93, 94, 94%) were similar in Eastern Europe, Western Europe, and Latin America respectively, whereas receipt of antiretroviral therapy at baseline and after 12 months was lower in Eastern Europe (17, 39, 39%, and 69, 94, 89%). The 1-year probability of death was 16% (95% confidence interval 11-24%) in Eastern Europe, vs. 4% (2-9%) in Western Europe and 9% (3-21%) in Latin America; P Eastern Europe were at nearly 3-fold increased risk of death compared with those in Western Europe/Latin America (aHR 2.79 (1.15-6.76); P = 0.023). Despite comparable use of recommended anti-TB treatment, mortality of patients with rifampicin/isoniazid-susceptible TB remained higher in Eastern Europe when compared with Western Europe/Latin America. The high mortality in Eastern Europe was only partially explained by IDU, use of ART and CD4 cell count. These results call for improvement of care for TB/HIV patients in Eastern Europe.

  7. Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg) demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study.

    Science.gov (United States)

    Daher, André; Pitta, Luciana; Santos, Tereza; Barreira, Draurio; Pinto, Douglas

    2015-06-01

    The recommended treatment for latent tuberculosis (TB) infection in adults is a daily dose of isoniazid (INH) 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration "time t" was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients' adherence to the treatment and quality of life.

  8. Using a single tablet daily to treat latent tuberculosis infection in Brazil: bioequivalence of two different isoniazid formulations (300 mg and 100 mg demonstrated by a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry method in a randomised, crossover study

    Directory of Open Access Journals (Sweden)

    André Daher

    2015-06-01

    Full Text Available The recommended treatment for latent tuberculosis (TB infection in adults is a daily dose of isoniazid (INH 300 mg for six months. In Brazil, INH was formulated as 100 mg tablets. The treatment duration and the high pill burden compromised patient adherence to the treatment. The Brazilian National Programme for Tuberculosis requested a new 300 mg INH formulation. The aim of our study was to compare the bioavailability of the new INH 300 mg formulation and three 100 mg tablets of the reference formulation. We conducted a randomised, single dose, open label, two-phase crossover bioequivalence study in 28 healthy human volunteers. The 90% confidence interval for the INH maximum concentration of drug observed in plasma and area under the plasma concentration vs. time curve from time zero to the last measurable concentration “time t” was 89.61-115.92 and 94.82-119.44, respectively. The main limitation of our study was that neither adherence nor the safety profile of multiple doses was evaluated. To determine the level of INH in human plasma, we developed and validated a sensitive, simple and rapid high-performance liquid chromatography-tandem mass spectrometry method. Our results showed that the new formulation was bioequivalent to the 100 mg reference product. This finding supports the use of a single 300 mg tablet daily strategy to treat latent TB. This new formulation may increase patients’ adherence to the treatment and quality of life.

  9. [Description of Mycobacterium tuberculosis mutations conferring resistance to rifampicin and isoniazid detected by GenoType® MTBDRplus V.2 in Colombia].

    Science.gov (United States)

    Llerena, Claudia; Medina, Raquel

    2017-01-24

    The GenoType®MTBDRplusV.2 assay is a molecular technique endorsed by the World Health Organization and the Pan American Health Organization that allows for the identification of the Mycobacterium tuberculosis complex and the detection of mutations in the rpoβ gene for rifampicin resistance, and katG and inhA genes for isoniazid resistance. Due to the genetic variability in the circulating strains around the world, the national tuberculosis control programs should assess the performance of these new diagnostic technologies and their use under program conditions as rapid tests. To describe the mutations identified by the GenoType®MTBDRplusV.2 assay in pulmonary samples and Mycobacterium tuberculosis isolates in the Laboratorio Nacional de Referencia of the Instituto Nacional de Salud in 2014. We conducted a retrospective, descriptive study to detect the expression of inhA, KatG and rpoβ genes, responsible for resistence against isoniazid and rifampicin using the GenoType® MTBDRplus V.2 assay in 837 samples and isolates from tuberculosis cases. Several mutations in the rpoβ gene were identified. Ser531Leu was the most frequent (36.6%) followed by Asp516Val (21.6%), while Ser315Thr1 was the most frequent mutation in the katG gene (91.9%). We were able to identify different mutations present in MDR-TB strains in the country, with frequencies similar to those reported in other countries in the South American region.

  10. [The effects of various factors on the in vitro velocity of drug release from repository tablets. Part 4: Isoniazid (Rimicid) respository tablets (author's transl)].

    Science.gov (United States)

    Tomassini, L; Michailova, D; Naplatanova, D; Slavtschev, P

    1979-12-01

    The authors investigated the release of isoniazid from repository tablets as related to form, processing technology, strength constant and storage for 5 years. On determining the diffusion coefficient (D), the initial dissolution rate (Vo) and the time required for the diffusion of the releasing medium to the middle of the tablet (t1/2), it was found that the difference in release rate between the flat and the biconvex tablets is small. Furthermore, it was stated that the three-layer tablets have very high D and Vo values and very low t1/2 values, for what reason they are unsuited for repository tablets of the composition under investigation. Moreover, it was found that an increase of the strength constant does not affect the D, t1/2 and Vo values, and that the release of isoniazid is retarded only in flat tablets with the highest strength constant. Storage exerts no effect on the drug release from these tablets. The industrial production of these tablets is under way.

  11. Quality specifications for antituberculosis fixed dose combination products / A-M. Redelinghuys

    OpenAIRE

    Redelinghuys, Anne-Marie

    2006-01-01

    Objective: The World Health Organization (WHO) requested the Research Institute for Industrial Pharmacy, at the North-West University, Potchefstroom, South Africa, to develop monographs for anti-tuberculosis products for The International Pharmacopoeia (IntPh). These included monographs for rifampicin capsules; rifampicin tablets; isoniazid and ethambutol hydrochloride tablets; rifampicin and isoniazid tablets; rifampicin, isoniazid and pyrazinamide tablets; and rifampicin, iso...

  12. Systematic review of TST responses in people living with HIV in under-resourced settings: implications for isoniazid preventive therapy.

    Directory of Open Access Journals (Sweden)

    Andrew D Kerkhoff

    Full Text Available People living with HIV (PLWH who have positive tuberculin skin tests (TST benefit from isoniazid preventive therapy (IPT whereas those testing TST-negative do not. Revised World Health Organization guidelines explicitly state that assessment of TST is not a requirement for initiation of IPT. However, it is not known what proportions of patients will benefit from IPT if implemented without targeting according to TST status. We therefore determined the proportions of PLWH who test TST-positive.We systematically reviewed the literature published between January 1990 and February 2012 to determine the proportions of patients without active tuberculosis attending HIV care services in low and middle-income countries who tested TST-positive (≥5 mm induration. Proportions were also determined for different CD4 count strata. Data from 19 studies with 9,478 PLWH from sub-Saharan Africa, Asia and Central and South America were summarized. The vast majority were not receiving antiretroviral therapy (ART. A sub-analysis was conducted of 5 studies (5,567 subjects from high TB prevalence countries of PLWH with negative TB screens attending HIV care and treatment settings for whom CD4 stratified data were available. The median proportion of PLWH testing TST-positive overall was 22.8% (range, 19.5-32.6%. The median (range proportions with CD4 cell counts of <200, 200-499 or ≥500 cells/µL who tested positive were 12.4% (8.2-15.3%, 28.4% (20.1-36.9% and 37.4% (31.3-56.3%, respectively. Heterogeneity in the data precluded calculation of pooled summary estimates.In most settings, if IPT is administered to PLWH pre-ART without assessment of TST status, only a minority of those treated are likely to benefit, especially among those with the lowest CD4 cell counts. This may be inefficient use of resources and cost-effectiveness analyses should take this into account. Local knowledge of TST response rates may help inform policies. New simple means of identifying

  13. Variáveis fisiológicas em cães submetidos à infusão contínua de diferentes doses de propofol Physiologic parameters in dogs anesthetized with different rates of continuous infusion of propofol

    Directory of Open Access Journals (Sweden)

    Patrícia Cristina Ferro

    2005-10-01

    Full Text Available A fim de determinar possíveis alterações nos principais parâmetros fisiológicos determinados pela infusão contínua de propofol, em diferentes doses, foram utilizados 24 cães adultos distribuídos aleatoriamente em 3 grupos (P2, P4 e P8. Os animais foram induzidos à anestesia pela administração intravenosa de propofol (10mg/kg e, ato contínuo, os cães receberam o anestésico, em infusão contínua nas doses de 0,2mg/kg/min (P2, 0,4mg/kg/min (P4 e 0,8mg/kg/min (P8. As mensurações dos valores das variáveis cardiorrespiratórias [freqüência cardíaca (FC; pressões arteriais sistólica, diastólica e média (PAS, PAD e PAM, respectivamente; eletrocardiografia e freqüência respiratória (f] e temperatura retal (T foram realizadas antes da aplicação do fármaco (M0 e após 10, 20, 30, 40 e 50 minutos do início da infusão contínua. Os dados numéricos das variáveis estudadas foram submetidos à Análise de Variância (ANOVA seguida pelo Teste F (PThe aim of this article was to establish the correlation between different rates of continuous infusion of propofol and the alterations that might occur with the physiologic parameters most commonly measured by the anesthesiologists. Twenty four adult dogs were randomly divided into 3 groups (P2, P4, P8. All the animals were induced with propofol (10mg/kg, followed immediately by the continuous infusion of the agent: 0.2mg/kg/min (P2, 0.4mg/kg/min (P4 and 0.8mg/kg/min (P8. The heart rate (HR, systolic, diastolic and mean arterial pressures (SAP, DAP and MAP, electrocardiography (ECG, respiratory rate (RR, and body temperature (T were measured before any drug administration (M0 and 10, 20, 30, 40 and 50 minutes after the start of the continuous infusion of propofol. The numerical data were submitted to Profile of Variance followed by F Test (P<0.05. The HR showed differences among groups at M20 (P2: 91 ± 14,92; P4: 113 ± 17,18; P8: 120 ± 14,84, M30 (P2: 89 ± 13,79; P4: 110 ± 14

  14. Time-varying Crash Risk

    DEFF Research Database (Denmark)

    Christoffersen, Peter; Feunoua, Bruno; Jeon, Yoontae

    We estimate a continuous-time model with stochastic volatility and dynamic crash probability for the S&P 500 index and find that market illiquidity dominates other factors in explaining the stock market crash risk. While the crash probability is time-varying, its dynamic depends only weakly on re...

  15. Eestlased Karlovy Varys / J. R.

    Index Scriptorium Estoniae

    J. R.

    2007-01-01

    Ilmar Raagi mängufilm "Klass" osaleb 42. Karlovy Vary rahvusvahelise filmifestivali võistlusprogrammis "East of the West" ja Asko Kase lühimängufilm "Zen läbi prügi" on valitud festivali kõrvalprogrammi "Forum of Independents"

  16. Esmaklassiline Karlovy Vary / Jaanus Noormets

    Index Scriptorium Estoniae

    Noormets, Jaanus

    2007-01-01

    Ilmar Raagi mängufilm "Klass" võitis 42. Karlovy Vary rahvusvahelise filmifestivalil kaks auhinda - ametliku kõrvalvõistlusprogrammi "East of the West" eripreemia "Special mention" ja Euroopa väärtfilmikinode keti Europa Cinemas preemia. Ka Asko Kase lühifilmi "Zen läbi prügi linastumisest ning teistest auhinnasaajatest ning osalejatest

  17. Optimistlik Karlovy Vary / Jaan Ruus

    Index Scriptorium Estoniae

    Ruus, Jaan, 1938-2017

    2007-01-01

    42. Karlovy Vary rahvusvahelise filmifestivali auhinnatud filmidest (žürii esimees Peter Bart). Kristallgloobuse sai Islandi-Saksamaa "Katseklaasilinn" (režii Baltasar Kormakur), parimaks režissööriks tunnistati norralane Bard Breien ("Negatiivse mõtlemise kunst"). Austraallase Michael James Rowlandi "Hea õnne teekond" sai žürii eripreemia

  18. Isoniazid Mono-Resistant Tuberculosis: Impact on Treatment Outcome and Survival of Pulmonary Tuberculosis Patients in Southern Mexico 1995-2010.

    Science.gov (United States)

    Báez-Saldaña, Renata; Delgado-Sánchez, Guadalupe; García-García, Lourdes; Cruz-Hervert, Luis Pablo; Montesinos-Castillo, Marlene; Ferreyra-Reyes, Leticia; Bobadilla-Del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Téllez-Vázquez, Norma; Montero-Campos, Rogelio; Yanes-Lane, Mercedes; Mongua-Rodriguez, Norma; Martínez-Gamboa, Rosa Areli; Sifuentes-Osornio, José; Ponce-de-León, Alfredo

    2016-01-01

    Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated. To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico. We conducted a prospective cohort study of pulmonary TB patients in Southern Mexico. From 1995 to 2010 patients with acid-fast bacilli or culture proven Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. We included patients who harbored isoniazid mono-resistant (IMR) strains and patients with strains susceptible to isoniazid, rifampicin, ethambutol and streptomycin. All patients were treated following Mexican TB Program guidelines. We performed annual follow-up to ascertain treatment outcome, recurrence, relapse and mortality. Between 1995 and 2010 1,243 patients with pulmonary TB were recruited; 902/1,243 (72.57%) had drug susceptibility testing; 716 (79.38%) harbored pan-susceptible and 88 (9.75%) IMR strains. Having any contact with a person with TB (adjusted odds ratio (aOR)) 1.85, 95% Confidence interval (CI) 1.15-2.96) and homelessness (adjusted odds ratio (aOR) 2.76, 95% CI 1.08-6.99) were associated with IMR. IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38-45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00-10.84). All the models were adjusted for socio-demographic and clinical variables. The results from our study provide evidence that the standardized treatment schedule with first line drugs in new and previously treated cases with pulmonary TB and IMR produces a high frequency of treatment failure and death due to tuberculosis. We recommend re-evaluating the optimal schedule for patients harboring IMR. It is necessary to strengthen

  19. Genetic polymorphisms in varied environments.

    Science.gov (United States)

    Powell, J R

    1971-12-03

    Thirteen experimenital populationis of Drosophila willistoni were maintained in cages, in some of which the environments were relatively constant and in others varied. After 45 weeks, the populations were assayed by gel electrophoresis for polymorphisms at 22 protein loci. The average heterozygosity per individual and the average unmber of alleles per locus were higher in populations maintained in heterogeneous environments than in populations in more constant enviroments.

  20. Adherence to and outcome of isoniazid chemoprophylaxis among household contact children of adults having pulmonary tuberculosis in Alexandria, Egypt.

    Science.gov (United States)

    Mohamed, Aida M

    2012-08-01

    Current international guidelines recommend 6-9 months of isoniazid (INH) preventive chemotherapy to prevent the development of active tuberculosis (TB) in susceptible children exposed to Mycobacterium tuberculosis. However, this is dependent on good adherence, as shown by previous studies. This study was conducted to describe the outcome of screening of contact children aged 5 years or less with household exposure to an adult pulmonary TB index case to determine the prevalence and possible risk factors of infection among contact children and to determine the extent and outcome of adherence of contact children to unsupervised INH chemoprophylaxis for 6 months. A descriptive facility-based cross-sectional study was conducted from March 2009 to August 2010. Research settings were three of the National TB control program chest dispensaries (primary care facilities) in Alexandria, Egypt. Facility-based TB treatment registers of the previous 3 months were used to identify all new adult pulmonary TB cases. All children aged 5 years or less living in the same house as the index cases were identified and screened for TB. The contact children were given unsupervised INH preventive chemotherapy once active TB was excluded. Adherence to and outcome of preventive chemotherapy were followed up. Preventive chemotherapy consisted of unsupervised INH monotherapy for 6 months with monthly collection of tablets from the clinic. Adherence was documented after completion of the 6-month preventive treatment period. Adherence was considered reasonable if tablets were collected for more than 4 months, poor if collected for 2-4 months, and very poor if collected for less than 2 months. (a) Prevalence of infection and disease and the possible risk factors among contacts. (b) The extent and outcome of adherence to unsupervised INH chemoprophylaxis among contact children. (c) Factors behind poor adherence. In total, 197 adult TB index cases from 187 households were identified. In all, 297

  1. Dose limits

    International Nuclear Information System (INIS)

    Fitoussi, L.

    1987-12-01

    The dose limit is defined to be the level of harmfulness which must not be exceeded, so that an activity can be exercised in a regular manner without running a risk unacceptable to man and the society. The paper examines the effects of radiation categorised into stochastic and non-stochastic. Dose limits for workers and the public are discussed

  2. Perceived barriers to the implementation of Isoniazid preventive therapy for people living with HIV in resource constrained settings: a qualitative study.

    Science.gov (United States)

    Mindachew, Mesele; Deribew, Amare; Memiah, Peter; Biadgilign, Sibhatu

    2014-01-01

    Isoniazid preventive therapy (IPT) reduces the risk of active TB. IPT is a key public health intervention for the prevention of TB among people living with HIV and has been recommended as part of a comprehensive HIV and AIDS care strategy. However, its implementation has been very slow and has been impeded by several barriers. The Objective of the study is to assess the perceived barriers to the implementation of Isoniazid preventive therapy for people living with HIV in resource constrained settings in Addis Ababa, Ethiopia in 2010. A qualitative study using a semi-structured interviewed guide was used for the in-depth interview. A total of 12 key informants including ART Nurse, counselors and coordinators found in four hospitals were included in the interview. Each session of the in-depth interview was recorded via audio tape and detailed notes. The interview was transcribed verbatim. The data was analyzed manually. The findings revealed that poor patient adherence was a major factor; with the following issues cited as the reasons for poor adherence; forgetfulness; lack of understanding of condition and patient non- disclosure of HIV sero-status leading to insubstantial social support; underlying mental health issues resulting in missed or irregular patient appointments; weak patient/healthcare provider relationship due to limited quality interaction; lack of patient information, patient empowerment and proper counseling on IPT; and the deficient reinforcement by health officials and other stakeholders on the significance of IPT medication adherence as a critical for positive health outcomes. Uptake of the implementation of IPT is facing a challenge in resource limited settings. This recalled provision of training/capacity building and awareness creation mechanism for the health workers, facilitating disclosure and social support for the patients is recommended.

  3. Varying Constants, Gravitation and Cosmology

    Directory of Open Access Journals (Sweden)

    Jean-Philippe Uzan

    2011-03-01

    Full Text Available Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. Thus, it is of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, solar system observations, meteorite dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.

  4. Weighted approximation with varying weight

    CERN Document Server

    Totik, Vilmos

    1994-01-01

    A new construction is given for approximating a logarithmic potential by a discrete one. This yields a new approach to approximation with weighted polynomials of the form w"n"(" "= uppercase)P"n"(" "= uppercase). The new technique settles several open problems, and it leads to a simple proof for the strong asymptotics on some L p(uppercase) extremal problems on the real line with exponential weights, which, for the case p=2, are equivalent to power- type asymptotics for the leading coefficients of the corresponding orthogonal polynomials. The method is also modified toyield (in a sense) uniformly good approximation on the whole support. This allows one to deduce strong asymptotics in some L p(uppercase) extremal problems with varying weights. Applications are given, relating to fast decreasing polynomials, asymptotic behavior of orthogonal polynomials and multipoint Pade approximation. The approach is potential-theoretic, but the text is self-contained.

  5. Estrelas variáveis

    OpenAIRE

    Viana, Sérgio Manuel de Oliveira

    2001-01-01

    A observação do céu nocturno é uma prática que vem da Antiguidade. Desde então e durante muito tempo pensou-se que as estrelas mantinham o brilho constante. Assim foi até ao século XVI, quando David Fabricius observou uma estrela cujo brilho variava periodicamente. Dois séculos mais tarde, Jonh Goodricke descobriu uma segunda estrela e com o desenvolvimento de instrumentos de observação este conjunto foi muito alargado e hoje inclui o Sol.A variação do brilho das estrelas variáveis permite d...

  6. Controllable dose

    International Nuclear Information System (INIS)

    Alvarez R, J.T.; Anaya M, R.A.

    2004-01-01

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

  7. Randomized pharmacokinetic evaluation of different rifabutin doses in African HIV- infected tuberculosis patients on lopinavir/ritonavir-based antiretroviral therapy.

    Science.gov (United States)

    Naiker, Suhashni; Connolly, Cathy; Wiesner, Lubbe; Kellerman, Tracey; Reddy, Tarylee; Harries, Anthony; McIlleron, Helen; Lienhardt, Christian; Pym, Alexander

    2014-11-19

    Pharmacokinetic interactions between rifampicin and protease inhibitors (PIs) complicate the management of HIV-associated tuberculosis. Rifabutin is an alternative rifamycin, for patients requiring PIs. Recently some international guidelines have recommended a higher dose of rifabutin (150 mg daily) in combination with boosted lopinavir (LPV/r), than the previous dose of rifabutin (150 mg three times weekly {tiw}). But there are limited pharmacokinetic data evaluating the higher dose of rifabutin in combination with LPV/r. Sub-optimal dosing can lead to acquired rifamycin resistance (ARR). The plasma concentration of 25-O-desacetylrifabutin (d-RBT), the metabolite of rifabutin, increases in the presence of PIs and may lead to toxicity. Sixteen patients with TB-HIV co-infection received rifabutin 300 mg QD in combination with tuberculosis chemotherapy (initially pyrazinamide, isoniazid and ethambutol then only isoniazid), and were then randomized to receive isoniazid and LPV/r based ART with rifabutin 150 mg tiw or rifabutin 150 mg daily. The rifabutin dose with ART was switched after 1 month. Serial rifabutin and d-RBT concentrations were measured after 4 weeks of each treatment. The median AUC0-48 and Cmax of rifabutin in patients taking 150 mg rifabutin tiw was significantly reduced compared to the other treatment arms. Geometric mean ratio (90% CI) for AUC0-48 and Cmax was 0.6 (0.5-0.7) and 0.5 (0.4-0.6) for RBT 150 mg tiw compared with RBT 300 mg and 0.4 (0.4-0.4) and 0.5 (0.5-0.6) for RBT 150 mg tiw compared with 150 mg daily. 86% of patients on the tiw rifabutin arm had an AUC0-24 ART, and grade 3 neutropenia (asymptomatic) was reported in 4 patients. These events were not associated with increases in rifabutin or metabolite concentrations. A daily 150 mg dose of rifabutin in combination with LPV/r safely maintained rifabutin plasma concentrations in line with those shown to prevent ARR. ClinicalTrials.gov Identifier: NCT00640887.

  8. Analytical and clinical performance characteristics of the Abbott RealTime MTB RIF/INH Resistance, an assay for the detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis in pulmonary specimens.

    Science.gov (United States)

    Kostera, Joshua; Leckie, Gregor; Tang, Ning; Lampinen, John; Szostak, Magdalena; Abravaya, Klara; Wang, Hong

    2016-12-01

    Clinical management of drug-resistant tuberculosis patients continues to present significant challenges to global health. To tackle these challenges, the Abbott RealTime MTB RIF/INH Resistance assay was developed to accelerate the diagnosis of rifampicin and/or isoniazid resistant tuberculosis to within a day. This article summarizes the performance of the Abbott RealTime MTB RIF/INH Resistance assay; including reliability, analytical sensitivity, and clinical sensitivity/specificity as compared to Cepheid GeneXpert MTB/RIF version 1.0 and Hain MTBDRplus version 2.0. The limit of detection (LOD) of the Abbott RealTime MTB RIF/INH Resistance assay was determined to be 32 colony forming units/milliliter (cfu/mL) using the Mycobacterium tuberculosis (MTB) strain H37Rv cell line. For rifampicin resistance detection, the Abbott RealTime MTB RIF/INH Resistance assay demonstrated statistically equivalent clinical sensitivity and specificity as compared to Cepheid GeneXpert MTB/RIF. For isoniazid resistance detection, the assay demonstrated statistically equivalent clinical sensitivity and specificity as compared to Hain MTBDRplus. The performance data presented herein demonstrate that the Abbott RealTime MTB RIF/INH Resistance assay is a sensitive, robust, and reliable test for realtime simultaneous detection of first line anti-tuberculosis antibiotics rifampicin and isoniazid in patient specimens. Copyright © 2016 The Author. Published by Elsevier Ltd.. All rights reserved.

  9. One-tube loop-mediated isothermal amplification combined with restriction endonuclease digestion and ELISA for colorimetric detection of resistance to isoniazid, ethambutol and streptomycin in Mycobacterium tuberculosis isolates.

    Science.gov (United States)

    Lee, Mei-Feng; Chen, Yen-Hsu; Hsu, Hui-Jine; Peng, Chien-Fang

    2010-10-01

    In this study, we designed a simple and rapid colorimetric detection method, a one-tube loop-mediated isothermal amplification (LAMP)-PCR-hybridization-restriction endonuclease-ELISA [one-tube LAMP-PCR-HY-RE-ELISA] system, to detect resistance to isoniazid, ethambutol and streptomycin in strains of Mycobacterium tuberculosis isolated from clinical specimens. The clinical performance of this method for detecting isoniazid-resistant, ethambutol-resistant and streptomycin-resistant isolates of M. tuberculosis showed 98.9%, 94.3% and 93.8%, respectively. This assay is rapid and convenient that can be performed within one working day. One-tube LAMP-PCR-HY-RE-ELISA system was designed based on hot spot point mutations in target drug-resistant genes, using LAMP-PCR, hybridization, digestion with restriction endonuclease and colorimetric method of ELISA. In this study, LAMP assay was used to amplify DNA from drug-resistant M. tuberculosis, and ELISA was used for colorimetrical determination. This assay will be a useful tool for rapid diagnosis of mutant codons in strains of M. tuberculosis for isoniazid at katG 315 and katG 463, ethambutol at embB 306 and embB 497, and streptomycin at rpsL 43. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  10. Dose and dose rate monitor

    International Nuclear Information System (INIS)

    Novakova, O.; Ryba, J.; Slezak, V.; Svobodova, B.; Viererbl, L.

    1984-10-01

    The methods are discussea of measuring dose rate or dose using a scintillation counte. A plastic scintillator based on polystyrene with PBD and POPOP activators and coated with ZnS(Ag) was chosen for the projected monitor. The scintillators were cylindrical and spherical in shape and of different sizes; black polypropylene tubes were chosen as the best case for the probs. For the counter with different plastic scintillators, the statistical error 2σ for natural background was determined. For determining the suitable thickness of the ZnS(Ag) layer the energy dependence of the counter was measured. Radioisotopes 137 Cs, 241 Am and 109 Cd were chosen as radiation sources. The best suited ZnS(Ag) thickness was found to be 0.5 μm. Experiments were carried out to determine the directional dependence of the detector response and the signal to noise ratio. The temperature dependence of the detector response and its compensation were studied, as were the time stability and fatigue manifestations of the photomultiplier. The design of a laboratory prototype of a dose rate and dose monitor is described. Block diagrams are given of the various functional parts of the instrument. The designed instrument is easiiy portable, battery powered, measures dose rates from natural background in the range of five orders, i.e., 10 -2 to 10 3 nGy/s, and allows to determine a dose of up to 10 mGy. Accouracy of measurement in the energy range of 50 keV to 1 MeV is better than +-20%. (E.S.)

  11. Interpreting meta-analysis according to the adequacy of sample size. An example using isoniazid chemoprophylaxis for tuberculosis in purified protein derivative negative HIV-infected individuals

    Directory of Open Access Journals (Sweden)

    Kristian Thorlund

    2010-04-01

    Full Text Available Kristian Thorlund1,2, Aranka Anema3, Edward Mills41Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada; 2The Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 3British Columbia Centre for Excellence in HIV/AIDS, University of British Columbia, Vancouver, British Columbia, Canada; 4Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, CanadaObjective: To illustrate the utility of statistical monitoring boundaries in meta-analysis, and provide a framework in which meta-analysis can be interpreted according to the adequacy of sample size. To propose a simple method for determining how many patients need to be randomized in a future trial before a meta-analysis can be deemed conclusive.Study design and setting: Prospective meta-analysis of randomized clinical trials (RCTs that evaluated the effectiveness of isoniazid chemoprophylaxis versus placebo for preventing the incidence of tuberculosis disease among human immunodeficiency virus (HIV-positive individuals testing purified protein derivative negative. Assessment of meta-analysis precision using trial sequential analysis (TSA with LanDeMets monitoring boundaries. Sample size determination for a future trials to make the meta-analysis conclusive according to the thresholds set by the monitoring boundaries.Results: The meta-analysis included nine trials comprising 2,911 trial participants and yielded a relative risk of 0.74 (95% CI, 0.53–1.04, P = 0.082, I2 = 0%. To deem the meta-analysis conclusive according to the thresholds set by the monitoring boundaries, a future RCT would need to randomize 3,800 participants.Conclusion: Statistical monitoring boundaries provide a framework for interpreting meta-analysis according to the adequacy of sample size and project the required sample size for a future RCT to make a meta-analysis conclusive

  12. Evidence-Based Design of Fixed-Dose Combinations: Principles and Application to Pediatric Anti-Tuberculosis Therapy.

    Science.gov (United States)

    Svensson, Elin M; Yngman, Gunnar; Denti, Paolo; McIlleron, Helen; Kjellsson, Maria C; Karlsson, Mats O

    2018-05-01

    Fixed-dose combination formulations where several drugs are included in one tablet are important for the implementation of many long-term multidrug therapies. The selection of optimal dose ratios and tablet content of a fixed-dose combination and the design of individualized dosing regimens is a complex task, requiring multiple simultaneous considerations. In this work, a methodology for the rational design of a fixed-dose combination was developed and applied to the case of a three-drug pediatric anti-tuberculosis formulation individualized on body weight. The optimization methodology synthesizes information about the intended use population, the pharmacokinetic properties of the drugs, therapeutic targets, and practical constraints. A utility function is included to penalize deviations from the targets; a sequential estimation procedure was developed for stable estimation of break-points for individualized dosing. The suggested optimized pediatric anti-tuberculosis fixed-dose combination was compared with the recently launched World Health Organization-endorsed formulation. The optimized fixed-dose combination included 15, 36, and 16% higher amounts of rifampicin, isoniazid, and pyrazinamide, respectively. The optimized fixed-dose combination is expected to result in overall less deviation from the therapeutic targets based on adult exposure and substantially fewer children with underexposure (below half the target). The development of this design tool can aid the implementation of evidence-based formulations, integrating available knowledge and practical considerations, to optimize drug exposures and thereby treatment outcomes.

  13. Dose/dose-rate responses of shrimp larvae to UV-B radiation

    International Nuclear Information System (INIS)

    Damkaer, D.M.

    1981-01-01

    Previous work indicated dose-rate thresholds in the effects of UV-B on the near-surface larvae of three shrimp species. Additional observations suggest that the total dose response varies with dose-rate. Below 0.002 Wm -2 sub([DNA]) irradiance no significant effect is noted in activity, development, or survival. Beyond that dose-rate threshold, shrimp larvae are significantly affected if the total dose exceeds about 85 Jm -2 sub([DNA]). Predictions cannot be made without both the dose-rate and the dose. These dose/dose-rate thresholds are compared to four-year mean dose/dose-rate solar UV-B irradiances at the experimental site, measured at the surface and calculated for 1 m depth. The probability that the shrimp larvae would receive lethal irradiance is low for the first half of the season of surface occurrence, even with a 44% increase in damaging UV radiation. (orig.)

  14. Isoniazid-resistant Mycobacterium kansasii in an HIV-positive patient, and possible development of immune reconstitution inflammatory syndrome after initiation of highly active antiretroviral therapy: case report

    Directory of Open Access Journals (Sweden)

    A. Despotovic

    2016-01-01

    Full Text Available Non-tuberculous mycobacteria are rare but important causes of infection in HIV-positive individuals. A 28-year-old HIV-positive male presented with a high fever, non-productive cough, right subcostal pain, splenomegaly, a very low CD4 count, elevated C-reactive protein and erythrocyte sedimentation rate, and a normal white blood cell count. The suspicion of tuberculosis (TB was very high, and sputum samples were positive for acid-fast bacilli. Standard quadruple anti-TB therapy was initiated, but once culture of the sample revealed Mycobacterium kansasii, pyrazinamide was withdrawn. Highly active antiretroviral therapy (HAART was initiated soon after, consisting of abacavir/lamivudine and efavirenz. The patient's general condition deteriorated 2 weeks after HAART initiation, which could have been due to the development of immune reconstitution inflammatory syndrome (IRIS. The patient recovered and was discharged in good condition. However, the results of resistance testing of the isolated organism arrived after discharge, and showed isoniazid and streptomycin resistance. This is the first case report of M. kansasii infection from Serbia and shows the difficulties encountered during the course of treatment.

  15. Tumor significant dose

    International Nuclear Information System (INIS)

    Supe, S.J.; Nagalaxmi, K.V.; Meenakshi, L.

    1983-01-01

    In the practice of radiotherapy, various concepts like NSD, CRE, TDF, and BIR are being used to evaluate the biological effectiveness of the treatment schedules on the normal tissues. This has been accepted as the tolerance of the normal tissue is the limiting factor in the treatment of cancers. At present when various schedules are tried, attention is therefore paid to the biological damage of the normal tissues only and it is expected that the damage to the cancerous tissues would be extensive enough to control the cancer. Attempt is made in the present work to evaluate the concent of tumor significant dose (TSD) which will represent the damage to the cancerous tissue. Strandquist in the analysis of a large number of cases of squamous cell carcinoma found that for the 5 fraction/week treatment, the total dose required to bring about the same damage for the cancerous tissue is proportional to T/sup -0.22/, where T is the overall time over which the dose is delivered. Using this finding the TSD was defined as DxN/sup -p/xT/sup -q/, where D is the total dose, N the number of fractions, T the overall time p and q are the exponents to be suitably chosen. The values of p and q are adjusted such that p+q< or =0.24, and p varies from 0.0 to 0.24 and q varies from 0.0 to 0.22. Cases of cancer of cervix uteri treated between 1978 and 1980 in the V. N. Cancer Centre, Kuppuswamy Naidu Memorial Hospital, Coimbatore, India were analyzed on the basis of these formulations. These data, coupled with the clinical experience, were used for choice of a formula for the TSD. Further, the dose schedules used in the British Institute of Radiology fraction- ation studies were also used to propose that the tumor significant dose is represented by DxN/sup -0.18/xT/sup -0.06/

  16. Cost-effectiveness of a 12-dose regimen for treating latent tuberculous infection in the United States

    Science.gov (United States)

    Shepardson, D.; Marks, S. M.; Chesson, H.; Kerrigan, A.; Holland, D. P.; Scott, N.; Tian, X.; Borisov, A. S.; Shang, N.; Heilig, C. M.; Sterling, T. R.; Villarino, M. E.; Mac Kenzie, W. R.

    2017-01-01

    SUMMARY SETTING A large randomized controlled trial recently showed that for treating latent tuberculous infection (LTBI) in persons at high risk of progression to tuberculosis (TB) disease, a 12-dose regimen of weekly rifapentine plus isoniazid (3HP) administered as directly observed treatment (DOT) can be as effective as 9 months of daily self-administered isoniazid (9H). OBJECTIVES To assess the cost-effectiveness of 3HP compared to 9H. DESIGN A computational model was designed to simulate individuals with LTBI treated with 9H or 3HP. Costs and health outcomes were estimated to determine the incremental costs per active TB case prevented and per quality-adjusted life year (QALY) gained by 3HP compared to 9H. RESULTS Over a 20-year period, treatment of LTBI with 3HP rather than 9H resulted in 5.2 fewer cases of TB and 25 fewer lost QALYs per 1000 individuals treated. From the health system and societal perspectives, 3HP would cost respectively US$21 525 and $4294 more per TB case prevented, and respectively $4565 and $911 more per QALY gained. CONCLUSIONS 3HP may be a cost-effective alternative to 9H, particularly if the cost of rifapentine decreases, the effectiveness of 3HP can be maintained without DOT, and 3HP treatment is limited to those with a high risk of progression to TB disease. PMID:24200264

  17. Dose rate constants for new dose quantities

    International Nuclear Information System (INIS)

    Tschurlovits, M.; Daverda, G.; Leitner, A.

    1992-01-01

    Conceptual changes and new quantities made is necessary to reassess dose rate quantities. Calculations of the dose rate constant were done for air kerma, ambient dose equivalent and directional dose equivalent. The number of radionuclides is more than 200. The threshold energy is selected as 20 keV for the dose equivalent constants. The dose rate constant for the photon equivalent dose as used mainly in German speaking countries as a temporary quantity is also included. (Author)

  18. Comparative study of eye dose and chest dose received during radiopharmaceutical production processes

    International Nuclear Information System (INIS)

    Chindarkar, A.S.; Chavan, S.V.; Sawant, D.K.; Sahoo, L.; Gopalakrishnan, R.K.; Sneha, C.; Sachdev, S.S.; Dey, A.C.

    2018-01-01

    Radiopharmaceutical laboratory, BRIT, Vashi produces different radiopharmaceuticals of 131 I, 153 Sm, 99 Mo/ 99m Tc and 177 Lu. Principle gamma energies of these isotopes vary from 103 to 740 KeV and their maximum beta energies vary from 384 to 1214 KeV. In the light of the revised eye lens dose limit recommended in IAEA Basic Safety Standard Interim Edition No. GSR Part 3 (IAEA-2011), the study of radiation dose for eye lens was carried out using CaSO 4 : Dy based Thermo luminescence dosimeter (TLD). This TLD was worn at center of the forehead to measure eye lens dose. This TLD dose was then compared with chest TLD dose to deduce any correlation between these TLD doses. These TLD doses were assessed on quarterly basis. Eight quarter data of these TLD doses were compared

  19. A varying-α brane world cosmology

    International Nuclear Information System (INIS)

    Youm, Donam

    2001-08-01

    We study the brane world cosmology in the RS2 model where the electric charge varies with time in the manner described by the varying fine-structure constant theory of Bekenstein. We map such varying electric charge cosmology to the dual variable-speed-of-light cosmology by changing system of units. We comment on cosmological implications for such cosmological models. (author)

  20. Bioequivalence of fixed-dose combination RIN®-150 to each reference drug in loose combination.

    Science.gov (United States)

    Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Damle, B

    2015-03-01

    RIN(®)-150 is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg) and isoniazid (INH, 75 mg) developed for the treatment of tuberculosis. This study was conducted at a single center: the Pfizer Clinical Research Unit in Singapore. To demonstrate bioequivalence of each drug component between RIN-150 and individual products in a loose combination. This was a randomized, open-label, single-dose, two-way crossover study. Subjects received single doses of RIN-150 or two individual reference products under fasting conditions in a crossover fashion, with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC). Of 28 subjects enrolled, 26 completed the study. The adjusted geometric mean ratios of Cmax and AUClast between the FDC and single-drug references and 90% confidence intervals were respectively 91.63% (90%CI 83.13-101.01) and 95.45% (90%CI 92.07-98.94) for RMP, and 107.58% (90%CI 96.07-120.47) and 103.45% (90%CI 99.33-107.75) for INH. Both formulations were generally well tolerated in this study. The RIN-150 FDC tablet formulation is bioequivalent to the two single-drug references for RMP and INH at equivalent doses.

  1. Marijuana smoking: effects of varying puff volume and breathhold duration.

    Science.gov (United States)

    Azorlosa, J L; Greenwald, M K; Stitzer, M L

    1995-02-01

    Two studies were conducted to quantify biological and behavioral effects resulting from exposure to controlled doses of marijuana smoke. In one study, puff volume (30, 60 and 90 ml) and in a second study, breathhold duration (0, 10 and 20 sec) were systematically varied while holding constant other smoking topography parameters (number of puffs = 10, interpuff interval = 60 sec and inhalation volume = 25% of vital capacity). Each study also varied levels of delta 9-tetrahydro-cannabinol marijuana cigarette content (1.75% and 3.55%). Regular marijuana users served as subjects (n = 7 in each experiment). Subjects smoked 10 puffs in each of six sessions; a seventh, nonsmoking session (all measures recorded at the same times as in active smoking sessions) served as a control. Variations in puff volume produced significant dose-related changes in postsmoking plasma delta 9-tetrahydro-cannabinol levels, carbon monoxide boost and subjective effects (e.g., "high"). In contrast, breathholding for 10 or 20 sec versus 0 sec increased plasma delta 9-tetrahydro-cannabinol levels but not CO boost or subjective effects. Task performance measures were not reliably influenced by marijuana smoke exposure within the dosing ranges examined. These findings confirm the utility of the controlled smoking technology, support the notion that cumulative puff volume systematically influences biological exposure and subjective effects, but cast doubt on the common belief that prolonged breathholding of marijuana smoke enhances classical subjective effects associated with its reinforcing value in humans.

  2. Howard Hughes Medical Institute dose assessment survey

    International Nuclear Information System (INIS)

    O'Brien, S.L.; McDougall, M.M.; Barkley, W.E.

    1996-01-01

    Biomedical science researchers often express frustration that health physics practices vary widely between individual institutions. A survey examining both internal and external dose assessment practices was devised and mailed to fifty institutions supporting biomedical science research. The results indicate that health physics dose assessment practices and policies are highly variable. Factors which may contribute to the degree of variation are discussed. 2 tabs

  3. Influência de variáveis do treinamento contra-resistência sobre a força muscular de idosos: uma revisão sistemática com ênfase nas relações dose-resposta Influencia de las variables de entrenamiento contra-resistencia sobre la fuerza muscular de ancianos: una revisión sistemática con énfasis en las relaciones dosis-respuesta Influence of counter-resistance training variables on elderly muscular strength: a systematic review with emphasis on dose/response relationships

    Directory of Open Access Journals (Sweden)

    Nádia Lima da Silva

    2007-02-01

    Full Text Available A força muscular é considerada componente importante de programas de exercícios físicos. Os benefícios desse tipo de treinamento dependem da combinação do número de repetições, séries, sobrecarga, seqüência e intervalos entre as séries e exercícios. No entanto, não se tem ainda muito clara qual a melhor combinação dessas variáveis para uma ótima relação dose-resposta em pessoas idosas. O objetivo do estudo foi analisar as pesquisas sobre treinamento de força para idosos, por meio de revisão sistemática, com o propósito de identificar tendências comuns em termos de efeitos do treinamento provocados pela manipulação dessas variáveis. Após definição de critérios de inclusão, foram selecionados 22 estudos, agrupados por similaridade de tratamento (número de séries, freqüência semanal, intensidade, intervalos e ordem dos exercícios. Técnicas de estatística descritiva auxiliaram na determinação de possíveis tendências nas relações dose-resposta. Uma vez identificadas, essas tendências foram analisadas qualitativamente. De todas as variáveis revisadas, somente para a intensidade da sobrecarga foram encontradas evidências permitindo afirmar que cargas maiores seriam mais eficazes para induzir aumento de força nessa faixa etária. Quanto às demais variáveis, os resultados disponíveis na literatura não dão respaldo para inferências seguras quanto ao melhor delineamento de programas de treinamento que aliem, ao mesmo tempo, efetividade e segurança. Recomenda-se, então, que estudos sejam realizados para comparar experimentalmente os efeitos da manipulação dessas variáveis sobre a força muscular de idosos.La fuerza muscular es considerada componente importante de programas de ejercicios físicos. Los beneficios de ese tipo de entrenamiento dependen de la combinación del número de repeticiones, series, sobrecarga, secuencia e intervalos entre las series y ejercicios. A pesar de esto, no se

  4. Validation of a rapid micellar electrokinetic capillary chromatographic method for the simultaneous determination of isoniazid and pyridoxine hydrochloride in pharmaceutical formulation.

    Science.gov (United States)

    Nemutlu, E; Celebier, M; Uyar, B; Altinöz, S

    2007-07-01

    An efficient and reliable micellar electrokinetic capillary chromatography (MEKC) method has been developed for the simultaneous determination of isoniazid (ISO) and pyridoxine hydrochloride (PYR) in pharmaceutical formulations. A chemometric two level full factorial design approach was used to search for the optimum conditions of separation. Three parameters were selected for this study: the buffer pH, the buffer concentration and sodium dodecyl sulphate (SDS) concentrations. Resolution, peak symmetry and analysis time were established as response. The two analytes were separated within 6 min with the optimized conditions: 50 mM borate buffer, 25 mM SDS pH 7.8, 35 degrees C, at 50 mbar 4s injection and 30 kV by using a fused silica capillary (72 cm effective length, 50 microm i.d.). The detection wavelength was set to 205 nm. Meloxicam was used as internal standard. The method was validated with respect to stability, linearity range, limit of quantitation and detection, precision, accuracy, specificity and robustness. The detection limits of the method were 1.0 microg mL(-1) for ISO and 0.40 microg mL(-1) for PYR and the method was linear at least in the range of 3.0-100 microg mL(-1) for ISO and 1.0-100 microg mL(-1) for PYR with excellent correlation coefficients (0.9995 for ISO and 0.9998 for PYR). Relative standard deviations (R.S.D.s) of the described method ranged between 0.54 and 2.27% for intra-day precision and between 0.65 and 2.69% for inter-day precision. The developed method was applied to the tablet form of ISO and PYR-containing the pharmaceutical preparations and the data were compared with obtained from the standard addition method. No statistically significant difference was found.

  5. Simultaneous Voltammetric Determination of Acetaminophen and Isoniazid (Hepatotoxicity-Related Drugs) Utilizing Bismuth Oxide Nanorod Modified Screen-Printed Electrochemical Sensing Platforms.

    Science.gov (United States)

    Mahmoud, Bahaa G; Khairy, Mohamed; Rashwan, Farouk A; Banks, Craig E

    2017-02-07

    To overcome the recent outbreaks of hepatotoxicity-related drugs, a new analytical tool for the continuously determination of these drugs in human fluids is required. Electrochemical-based analytical methods offer an effective, rapid, and simple tool for on-site determination of various organic and inorganic species. However, the design of a sensitive, selective, stable, and reproducible sensor is still a major challenge. In the present manuscript, a facile, one-pot hydrothermal synthesis of bismuth oxide (Bi 2 O 2.33 ) nanostructures (nanorods) was developed. These BiO nanorods were cast onto mass disposable graphite screen-printed electrodes (BiO-SPEs), allowing the ultrasensitive determination of acetaminophen (APAP) in the presence of its common interference isoniazid (INH), which are both found in drug samples. The simultaneous electroanalytical sensing using BiO-SPEs exhibited strong electrocatalytic activity toward the sensing of APAP and INH with an enhanced analytical signal (voltammetric peak) over that achievable at unmodified (bare) SPEs. The electroanalytical sensing of APAP and INH are possible with accessible linear ranges from 0.5 to 1250 μM and 5 to 1760 μM with limits of detection (3σ) of 30 nM and 1.85 μM, respectively. The stability, reproducibility, and repeatability of BiO-SPE were also investigated. The BiO-SPEs were evaluated toward the sensing of APAP and INH in human serum, urine, saliva, and tablet samples. The results presented in this paper demonstrate that BiO-SPEs sensing platforms provide a potential candidate for the accurate determination of APAP and INH within human fluids and pharmaceutical formulations.

  6. The role of agency in the implementation of Isoniazid Preventive Therapy (IPT): Lessons from oMakoti in uMgungundlovu District, South Africa.

    Science.gov (United States)

    Boffa, Jody; Mayan, Maria; Ndlovu, Sithembile; Mhlaba, Tsholofelo; Williamson, Tyler; Sauve, Reginald; Fisher, Dina

    2018-01-01

    In response to revisions in global and national policy in 2011, six-month isoniazid preventive therapy (IPT) became freely available as a preventive measure for people living with HIV in the uMgungundlovu District of KwaZulu-Natal province, South Africa. Given a difference in uptake and completion by sex, we sought to explore the reasons why Zulu women were more likely to accept and complete IPT compared to men in an effort to inform future implementation. Utilising a community-based participatory research approach and ethnographic methods, we undertook 17 individual and group interviews, and met regularly with grassroots community advisory teams in three Zulu communities located in uMgungundlovu District between March 2012-December 2016. Three categories described women's willingness to initiate IPT: women are caregivers, women are obedient, and appearance is important. The findings suggest that the success of IPT implementation amongst clinic-utilising women of uMgungundlovu is related to the cultural gender norms of uMakoti, isiZulu for "the bride" or "the wife." We invoke the cultural concept of inhlonipho, meaning "to show respect," to discuss how the cultural values of uMakoti may conflict with biomedical expectations of adherence. Such conflict can result in misinterpretations by healthcare providers or patients, and lead some patients to fear the repercussions of asking questions or contemplating discontinuation with the provider, preferring instead to appear obedient. We propose a shift in emphasis from adherence-focussed strategies, characteristic of the current biomedical approach, to practices that promote patient agency in an effort to offer IPT more appropriately. Building on existing tools, namely the harm reduction model and the use of mini-ethnography, we provide guidance on how to support women to participate as agents in the decision to initiate or continue IPT, decisions which may also impact the health and choices of the family.

  7. Symptom-based screening tool in ruling out active tuberculosis among HIV-infected patients eligible for isoniazid preventive therapy in Tanzania.

    Science.gov (United States)

    Shayo, Grace A; Minja, Lilian T; Egwaga, Said; Bakari, Muhammad; Mugusi, Ferdinand M

    2014-06-01

    We assessed the usefulness of the National TB and Leprosy Control Program (NTLP) symptom-based tuberculosis (TB) screening tool in identifying HIV-infected patients eligible for isoniazid preventive therapy in Muhimbili National Hospital, Dar es Salaam Tanzania. Descriptive cross-sectional study. Data collected included socio-demographic and clinical data. Chest X-ray, sputum for acid-fast bacilli (AFB) microscopy, mycobacterial culture, CD4 + count and complete blood count were performed. Patients were considered not having active TB if they presented with no symptom in the screening tool, which comprised these symptoms: cough, fever and excessive night sweats for ≥2 weeks; weight loss of ≥3 kg in 4 weeks and haemoptysis of any duration. The reference standard was a negative culture for Mycobacterium tuberculosis. We enroled 373 patients, of whom 72.1% were females. Active pulmonary TB was found in 4.1% (14/338) of the participants as defined by a positive culture. The sensitivity and specificity of the NTLP screening tool were 71.4% (10/14) and 75.9% (246/324), respectively. False-negative rate was 28.6% (4/10). Cough, fever for ≥2 weeks and weight loss were independent predictors of NTLP-defined TB. Cough ≥2 weeks predicted TB when a positive culture was used to define TB. The screening tool had fairly good sensitivity and specificity for TB screening; however, there is a possibility that about 29% of the screened population will be given IPT while they are supposed to receive a full course of TB treatment. © 2014 John Wiley & Sons Ltd.

  8. The role of agency in the implementation of Isoniazid Preventive Therapy (IPT: Lessons from oMakoti in uMgungundlovu District, South Africa.

    Directory of Open Access Journals (Sweden)

    Jody Boffa

    Full Text Available In response to revisions in global and national policy in 2011, six-month isoniazid preventive therapy (IPT became freely available as a preventive measure for people living with HIV in the uMgungundlovu District of KwaZulu-Natal province, South Africa. Given a difference in uptake and completion by sex, we sought to explore the reasons why Zulu women were more likely to accept and complete IPT compared to men in an effort to inform future implementation.Utilising a community-based participatory research approach and ethnographic methods, we undertook 17 individual and group interviews, and met regularly with grassroots community advisory teams in three Zulu communities located in uMgungundlovu District between March 2012-December 2016.Three categories described women's willingness to initiate IPT: women are caregivers, women are obedient, and appearance is important. The findings suggest that the success of IPT implementation amongst clinic-utilising women of uMgungundlovu is related to the cultural gender norms of uMakoti, isiZulu for "the bride" or "the wife." We invoke the cultural concept of inhlonipho, meaning "to show respect," to discuss how the cultural values of uMakoti may conflict with biomedical expectations of adherence. Such conflict can result in misinterpretations by healthcare providers or patients, and lead some patients to fear the repercussions of asking questions or contemplating discontinuation with the provider, preferring instead to appear obedient. We propose a shift in emphasis from adherence-focussed strategies, characteristic of the current biomedical approach, to practices that promote patient agency in an effort to offer IPT more appropriately.Building on existing tools, namely the harm reduction model and the use of mini-ethnography, we provide guidance on how to support women to participate as agents in the decision to initiate or continue IPT, decisions which may also impact the health and choices of the family.

  9. Self-reported adherence and associated factors to isoniazid preventive therapy for latent tuberculosis among people living with HIV/AIDS at health centers in Gondar town, North West Ethiopia

    Directory of Open Access Journals (Sweden)

    Ayele AA

    2017-04-01

    Full Text Available Asnakew Achaw Ayele,1 Seyfe Asrade Atnafie,2 Demis Driba Balcha,1 Asegedech Tsegaw Weredekal,2 Birhanu Alemayehu Woldegiorgis,1 Mulgeta Melaku Wotte,1 Begashaw Melaku Gebresillasie1 1Department of Clinical Pharmacy, 2Department of Pharmacology, School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia Purpose: This study aimed to assess self-reported adherence and associated factors to isoniazid preventive therapy (IPT for latent tuberculosis among people living with HIV/AIDS (PLWHA at health centers in Gondar town, North West Ethiopia.Patients and methods: An institution-based prospective cross-sectional study was conducted from March 10 to June 11, 2016. A total of 154 eligible participants were included in the study, using the simple random sampling method, from the available four health centers and one teaching referral hospital that provided antiretroviral therapy (ART for HIV/AIDS patients. Adherence was measured by self-report of isoniazid (INH tablets taken for the preceding 7 days. Participants were recruited through in-depth interviews. The collected data were entered and analyzed using the statistical packages for social sciences (SPSS version 20.Results: The adherence level to IPT was 90.3% for the last 7 days of the study. ART was initiated for 84.4%, and all of them were on a first-line regimen. Isoniazid-related side effects were reported by 48 (31.2% participants, of which the most commonly identified were abdominal pain, vomiting, skin rash, jaundice, and numbness. Only 3 (2% participants discontinued from the study. In the bivariate logistic regression analysis, respondents who had received an explanation about IPT were 83% times more likely to be adherent compared to those who had not received it (95% CI, AOR: 0.266 [0.23–3.127]. Respondents who had taken IPT for ≥5 months were more likely to be adherent than those who had taken it for 1–2 months [95% CI, COR: 1.484]. On the

  10. Spacetime-varying couplings and Lorentz violation

    International Nuclear Information System (INIS)

    Kostelecky, V. Alan; Lehnert, Ralf; Perry, Malcolm J.

    2003-01-01

    Spacetime-varying coupling constants can be associated with violations of local Lorentz invariance and CPT symmetry. An analytical supergravity cosmology with a time-varying fine-structure constant provides an explicit example. Estimates are made for some experimental constraints

  11. Detection of dynamically varying interaural time differences

    DEFF Research Database (Denmark)

    Kohlrausch, Armin; Le Goff, Nicolas; Breebaart, Jeroen

    2010-01-01

    of fringes surrounding the probe is equal to the addition of the effects of the individual fringes. In this contribution, we present behavioral data for the same experimental condition, called dynamically varying ITD detection, but for a wider range of probe and fringe durations. Probe durations varied...

  12. Eesti film võistleb Karlovy Varys

    Index Scriptorium Estoniae

    2008-01-01

    8. juulil esilinastub Karlovy Vary filmifestivalil Rene Vilbre noortefilm "Mina olin siin", mille aluseks on Sass Henno romaan "Mina olin siin. Esimene arest", stsenaariumi kirjutas Ilmar Raag. Film võistleb võistlusprogrammis "East of the West"

  13. Matching Value Propositions with Varied Customer Needs

    DEFF Research Database (Denmark)

    Heikka, Eija-Liisa; Frandsen, Thomas; Hsuan, Juliana

    2018-01-01

    Organizations seek to manage varied customer segments using varied value propositions. The ability of a knowledge-intensive business service (KIBS) provider to formulate value propositions into attractive offerings to varied customers becomes a competitive advantage. In this specific business based...... on often highly abstract service offerings, this requires the provider to have a clear overview of its knowledge and resources and how these can be configured to obtain the desired customization of services. Hence, the purpose of this paper is to investigate how a KIBS provider can match value propositions...... with varied customer needs utilizing service modularity. To accomplish this purpose, a qualitative multiple case study is organized around 5 projects allowing within-case and cross-case comparisons. Our findings describe how through the configuration of knowledge and resources a sustainable competitive...

  14. Compilation of Instantaneous Source Functions for Varying ...

    African Journals Online (AJOL)

    Compilation of Instantaneous Source Functions for Varying Architecture of a Layered Reservoir with Mixed Boundaries and Horizontal Well Completion Part III: B-Shaped Architecture with Vertical Well in the Upper Layer.

  15. Compilation of Instantaneous Source Functions for Varying ...

    African Journals Online (AJOL)

    Compilation of Instantaneous Source Functions for Varying Architecture of a Layered Reservoir with Mixed Boundaries and Horizontal Well Completion Part IV: Normal and Inverted Letter 'h' and 'H' Architecture.

  16. Multiple anatomy optimization of accumulated dose

    International Nuclear Information System (INIS)

    Watkins, W. Tyler; Siebers, Jeffrey V.; Moore, Joseph A.; Gordon, James; Hugo, Geoffrey D.

    2014-01-01

    Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated

  17. Multiple anatomy optimization of accumulated dose

    Energy Technology Data Exchange (ETDEWEB)

    Watkins, W. Tyler, E-mail: watkinswt@virginia.edu; Siebers, Jeffrey V. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia 22908 and Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Moore, Joseph A. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland 21231 and Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Gordon, James [Henry Ford Health System, Detroit, Michigan 48202 and Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States); Hugo, Geoffrey D. [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia 23298 (United States)

    2014-11-01

    Purpose: To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. Methods: MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. Results: By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. Conclusions: MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.

  18. Multiple anatomy optimization of accumulated dose.

    Science.gov (United States)

    Watkins, W Tyler; Moore, Joseph A; Gordon, James; Hugo, Geoffrey D; Siebers, Jeffrey V

    2014-11-01

    To investigate the potential advantages of multiple anatomy optimization (MAO) for lung cancer radiation therapy compared to the internal target volume (ITV) approach. MAO aims to optimize a single fluence to be delivered under free-breathing conditions such that the accumulated dose meets the plan objectives, where accumulated dose is defined as the sum of deformably mapped doses computed on each phase of a single four dimensional computed tomography (4DCT) dataset. Phantom and patient simulation studies were carried out to investigate potential advantages of MAO compared to ITV planning. Through simulated delivery of the ITV- and MAO-plans, target dose variations were also investigated. By optimizing the accumulated dose, MAO shows the potential to ensure dose to the moving target meets plan objectives while simultaneously reducing dose to organs at risk (OARs) compared with ITV planning. While consistently superior to the ITV approach, MAO resulted in equivalent OAR dosimetry at planning objective dose levels to within 2% volume in 14/30 plans and to within 3% volume in 19/30 plans for each lung V20, esophagus V25, and heart V30. Despite large variations in per-fraction respiratory phase weights in simulated deliveries at high dose rates (e.g., treating 4/10 phases during single fraction beams) the cumulative clinical target volume (CTV) dose after 30 fractions and per-fraction dose were constant independent of planning technique. In one case considered, however, per-phase CTV dose varied from 74% to 117% of prescription implying the level of ITV-dose heterogeneity may not be appropriate with conventional, free-breathing delivery. MAO incorporates 4DCT information in an optimized dose distribution and can achieve a superior plan in terms of accumulated dose to the moving target and OAR sparing compared to ITV-plans. An appropriate level of dose heterogeneity in MAO plans must be further investigated.

  19. Isoniazid acetylating phenotype in patients with paracoccidioidomycosis and its relationship with serum sulfadoxin levels, glucose-6-phosphate dehydrogenase and glutathione reductase activities

    Directory of Open Access Journals (Sweden)

    Benedito Barraviera

    1991-06-01

    Full Text Available The authors evaluated the isoniazid acetylating phenotype and measured hematocrit, hemoglobin, glucose-6-phosphate dehydrogenase and glutathione reductase activities plus serum sulfadoxin levels in 39 patients with paracoccidioidomycosis (33 males and 6 females aged 17 to 58 years. Twenty one (53.84% of the patients presented a slow acetylatingphenotype and 18(46.16% a fast acetylating phenotype. Glucose-6-phosphate- dehydrogenase (G6PD acti vity was decreased in 5(23.80% slow acetylators and in 4(22.22% fast acetylators. Glutathione reductase activity was decreased in 14 (66.66% slow acetylators and in 12 (66.66% fast acetylators. Serum levels of free and total sulfadoxin Were higher in slow acetylator (p Os autores avaliaram o fenótipo acetilador da isoniazida, hematócrito, hemoglobina, atividade da glicose-6- fosfato desidrogenase, glutationa redutase e os níveis séricos de sulfadoxina de 39 doentes com paracoccidíoidomicose, senão 33 do sexo masculino e 6 do feminino, com idades compreendidas entre 17 e 58 anos. Vinte e um (53,84% doentes apresentaram fenótipo acetilador lento e 18 (46,16% rápido. A atividade da glicose-6-fosfato desidrogenase (G6PD esteve diminuída em 5 (23,80% acetiladores lentos e 4 (22,22% rápidos. A atividade da glutationa redutase esteve diminuída em 14 (66,66% acetiladores lentos e 12 (66,66% rápidos. Os níveis séricos de sulfadoxina livre e total foram maiores nos acetiladores lentos (p < 0,02. A análise dos resultados permite concluir que os níveis séricos de sulfadoxina relaciona-se com o fenótipo acetilador. Além disso, os níveis estiveram sempre acima de 50 µg/ml, níveis estes considerados terapêuticos. Por outro lado, a deficiência de glutationa redutase pode estar relacionada com a má absorção intestinal de nutrientes, entre eles riboflavina, vitamina precursora de FAD.

  20. The effect of isoniazid preventive therapy on incidence of tuberculosis among HIV-infected clients under pre-ART care, Jimma, Ethiopia: a retrospective cohort study.

    Science.gov (United States)

    Assebe, Lelisa Fekadu; Reda, Hailemariam Lemma; Wubeneh, Alem Desta; Lerebo, Wondwossen Terefe; Lambert, Saba Maria

    2015-04-10

    Tuberculosis (TB) is a major public health problem that accounts for almost half a million human immunodeficiency virus (HIV) associated deaths. Provision of isoniazid preventive therapy (IPT) is one of the public health interventions for the prevention of TB in HIV infected individuals. However, in Ethiopia, the coverage and implementation of IPT is limited. The objective of this study is to compare the incidence rate of TB, TB-free survival time and identify factors associated with development TB among HIV-infected individuals on pre-ART follow up. A retrospective cohort study was conducted from January, 2008 to February 31, 2012 in Jimma hospital. Kaplan-Meier survival plots were used to calculate the crude effect in both groups on TB-free survival probabilities and compared using the log rank test. A Cox proportional hazard model was used to identify predictors of TB. A total of 588 patients on pre-ART care (294 IPT and 294 non-IPT group) were followed retrospectively for a median duration of 24.1 months. The median CD4 (+) cell count was 422 cells/μl (IQR 344-589). During the follow up period, 49 individuals were diagnosed with tuberculosis, giving an overall incidence of 3.78 cases per 100 person year (PY). The incidence rate of TB was 5.06 per 100 PY in non-IPT group and 2.22 per 100 PY in IPT user group. Predictors of higher TB risk were: being on clinical WHO stage III/IV (adjusted hazard ratio (AHR = 3.05, 95% confidence interval (CI): 1.61, 5.81); non-IPT user (AHR = 2.02, 95% CI: 1.04, 3.92); having CD4 (+) cell count less than 350 cells/μl (AHR = 3.16, 95% CI: 1.04, 3.92) and between 350-499 cells/μl, (AHR = 2.87; 95% CI: 1.37-6.03) and having episode of opportunistic infection (OI) in the past (AHR = 2.41, 95% CI: 1.33-4.34). IPT use was associated with fifty percent reduction in new cases of tuberculosis and probability of developing TB was higher in non-IPT group. Implementing the widespread use of IPT has the potential to

  1. Peripheral dose outside applicators in electron beams

    International Nuclear Information System (INIS)

    Chow, James C L; Grigorov, Grigor N

    2006-01-01

    The peripheral dose outside the applicators in electron beams was studied using a Varian 21 EX linear accelerator. To measure the peripheral dose profiles and point doses for the applicator, a solid water phantom was used with calibrated Kodak TL films. Peak dose spot was observed in the 4 MeV beam outside the applicator. The peripheral dose peak was very small in the 6 MeV beam and was ignorable at higher energies. Using the 10 x 10 cm 2 cutout and applicator, the dose peak for the 4 MeV beam was about 12 cm away from the field central beam axis (CAX) and the peripheral dose profiles did not change with depths measured at 0.2, 0.5 and 1 cm. The peripheral doses and profiles were further measured by varying the angle of obliquity, cutout and applicator size for the 4 MeV beam. The local peak dose was increased with about 3% per degree angle of obliquity, and was about 1% of the prescribed dose (angle of obliquity equals zero) at 1 cm depth in the phantom using the 10 x 10 cm 2 cutout and applicator. The peak dose position was also shifted 7 mm towards the CAX when the angle of obliquity was increased from 0 to 15 deg. (note)

  2. Clinical treatment outcomes of tuberculosis treated with the basic regimen recommended by the Brazilian National Ministry of Health using fixed-dose combination tablets in the greater metropolitan area of Goiânia, Brazil.

    Science.gov (United States)

    Ferreira, Anna Carolina Galvão; Silva Júnior, José Laerte Rodrigues da; Conde, Marcus Barreto; Rabahi, Marcelo Fouad

    2013-01-01

    To describe the rates of cure, treatment failure, and treatment abandonment obtained with the basic regimen recommended by the Brazilian National Ministry of Health (rifampin, isoniazid, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for four months) involving the use of fixed-dose combination tablets (self-administered treatment), as well as to describe adverse events and their potential impact on treatment outcomes. This was a descriptive study based on prospective data obtained from the medical records of tuberculosis patients (> 18 years of age) treated with the basic regimen at either of two primary health care facilities in the greater metropolitan area of Goiânia, Brazil. The study sample comprised 40 tuberculosis patients. The rate of cure was 67.5%, the rate of treatment abandonment was 17.5%, and there were no cases of treatment failure. Of the 40 patients in the sample, 19 (47%) reported adverse reactions, which were mild and moderate, respectively, in 87% and 13% of the cases. It was not necessary to alter the regimen or discontinue the treatment in any of the cases evaluated. The rate of cure obtained with the self-administered, fixed-dose combination tablet form of the new basic regimen was similar to the historical rates of cure obtained with the previous regimen. The rate of treatment abandonment in our sample was much higher than that considered appropriate (up to 5%).

  3. Clinical treatment outcomes of tuberculosis treated with the basic regimen recommended by the Brazilian National Ministry of Health using fixed-dose combination tablets in the greater metropolitan area of Goiânia, Brazil *

    Science.gov (United States)

    Ferreira, Anna Carolina Galvão; da Silva, José Laerte Rodrigues; Conde, Marcus Barreto; Rabahi, Marcelo Fouad

    2013-01-01

    OBJECTIVE: To describe the rates of cure, treatment failure, and treatment abandonment obtained with the basic regimen recommended by the Brazilian National Ministry of Health-rifampin, isoniazid, pyrazinamide, and ethambutol for two months, followed by isoniazid and rifampin for four months-involving the use of fixed-dose combination tablets (self-administered treatment), as well as to describe adverse events and their potential impact on treatment outcomes. METHODS: This was a descriptive study based on prospective data obtained from the medical records of tuberculosis patients (≥ 18 years of age) treated with the basic regimen at either of two primary health care facilities in the greater metropolitan area of Goiânia, Brazil. RESULTS: The study sample comprised 40 tuberculosis patients. The rate of cure was 67.5%, the rate of treatment abandonment was 17.5%, and there were no cases of treatment failure. Of the 40 patients in the sample, 19 (47%) reported adverse reactions, which were mild and moderate, respectively, in 87% and 13% of the cases. It was not necessary to alter the regimen or discontinue the treatment in any of the cases evaluated. CONCLUSIONS: The rate of cure obtained with the self-administered, fixed-dose combination tablet form of the new basic regimen was similar to the historical rates of cure obtained with the previous basic regimen. The rate of treatment abandonment in our sample was much higher than that considered appropriate (up to 5%). PMID:23503489

  4. Bioequivalence of fixed-dose combination Myrin®-P Forte and reference drugs in loose combination.

    Science.gov (United States)

    Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Naqvi, A; Jafri, I

    2013-12-01

    Myrin®-P Forte is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg), isoniazid (INH, 75 mg), ethambutol (EMB) hydrochloride (275 mg) and pyrazinamide (PZA, 400 mg) developed for the treatment of tuberculosis (TB). This study was conducted at a single centre--the Pfizer Clinical Research Unit in Singapore. To demonstrate the bioequivalence of each drug component of the Myrin-P Forte FDC and the individual product in loose combination. In a randomized, open-label, single-dose, two-way, crossover study, subjects received single doses of Myrin-P Forte or four individual products under fasting conditions in a crossover fashion with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (C(max)) and the area under plasma concentration-time curve (AUC). Of 36 subjects enrolled, 35 completed the study. The adjusted geometric mean ratios and 90% confidence intervals for C(max) and AUC values were completely contained within bioequivalence limits (80%, 125%) for all four drugs in both formulations. Both treatments were generally well tolerated in the study. The Myrin-P Forte FDC tablet formulation is bioequivalent to the four single-drug references for RMP, INH, EMB hydrochloride and PZA at equivalent doses.

  5. From personnel dose to personal dose

    International Nuclear Information System (INIS)

    Hoefert, M.; Raffnsoe, R.C.; Tuyn, J.W.N.; Wittekind, D.

    1985-01-01

    From following the development of personnel doses at CERN over the past six years it has become evident that work in areas of induced radioactivity is the principal cause of exposure. The results of photon dose measurements free-in-air and around a phantom are presented and discussed in the light of new quantities in individual monitoring. The importance of these results, with respect to the practical situation, is discussed and the problem of phantom size is mentioned. Finally, the results of dose measurements in the phantom are presented, since such information is important in cases where it becomes necessary to transform personnel doses into personal doses. (author)

  6. Varying constants, black holes, and quantum gravity

    International Nuclear Information System (INIS)

    Carlip, S.

    2003-01-01

    Tentative observations and theoretical considerations have recently led to renewed interest in models of fundamental physics in which certain 'constants' vary in time. Assuming fixed black hole mass and the standard form of the Bekenstein-Hawking entropy, Davies, Davis and Lineweaver have argued that the laws of black hole thermodynamics disfavor models in which the fundamental electric charge e changes. I show that with these assumptions, similar considerations severely constrain 'varying speed of light' models, unless we are prepared to abandon cherished assumptions about quantum gravity. Relaxation of these assumptions permits sensible theories of quantum gravity with ''varying constants,'' but also eliminates the thermodynamic constraints, though the black hole mass spectrum may still provide some restrictions on the range of allowable models

  7. Radiation dose from cigarette tobacco

    International Nuclear Information System (INIS)

    Papastefanou, Constantin

    2008-01-01

    The radioactivity in tobacco leaves collected from 15 different regions of Greece before cigarette production was studied in order to estimate the effective dose from cigarette tobacco due to the naturally occurring primordial radionuclides, such as 226 Ra and 210 Pb of the uranium series and 228 Ra of the thorium series and or man-made produced radionuclides, such as 137 Cs of Chernobyl origin. Gamma-ray spectrometry was applied using Ge planar and coaxial type detectors of high resolution and high efficiency. It was concluded that the annual effective dose due to inhalation for adults (smokers) for 226 Ra varied from 42.5 to 178.6 μSv y -1 (average 79.7 μSv y -1 ), while for 228 Ra from 19.3 to 116.0 μSv y -1 (average 67.1 μSv y -1 ) and for 210 Pb from 47.0 to 134.9 μSv y -1 (average 104.7 μSv y -1 ), that is the same order of magnitude for each radionuclide. The sum of the effective dose of the three natural radionuclides varied from 151.9 to 401.3 μSv y -1 (average 251.5 μSv y -1 ). The annual effective dose from 137 Cs of Chernobyl origin was three orders of magnitude lower as it varied from 70.4 to 410.4 μSv y -1 (average 199.3 μSv y -1 ). (author)

  8. Biological influence from low dose and low-dose rate radiation

    International Nuclear Information System (INIS)

    Magae, Junji

    2007-01-01

    Although living organisms have defense mechanisms for radioadaptive response, the influence is considered to vary qualitatively and quantitatively for low dose and high dose, as well as for low-dose rate and high-dose rate. This article describes the bioresponse to low dose and low-dose rate. Among various biomolecules, DNA is the most sensitive to radiation, and accurate replication of DNA is an essential requirement for the survival of living organisms. Also, the influence of active enzymes resulted from the effect of radiation on enzymes in the body is larger than the direct influence of radiation on the body. After this, the article describes the carcinogenic risk by low-dose radiation, and then so-called Hormesis effect to create cancer inhibition effect by stimulating active physiology. (S.K.)

  9. "Mina olin siin" esilinastub Karlovy Varys

    Index Scriptorium Estoniae

    2008-01-01

    Karlovy Vary filmifestivalil esilinastub Rene Vilbre noortefilm "Mina olin siin", mille aluseks on Sass Henno romaan "Mina olin siin. Esimene arest", stsenaariumi kirjutas Ilmar Raag. Film võistleb võistlusprogrammis "East of the West". Esitlema sõidavad R. Vilbre, R. Sildos, R. Kaljujärv, T. Tuisk

  10. Tracking time-varying coefficient-functions

    DEFF Research Database (Denmark)

    Nielsen, Henrik Aalborg; Nielsen, Torben Skov; Joensen, Alfred K.

    2000-01-01

    is a combination of recursive least squares with exponential forgetting and local polynomial regression. It is argued, that it is appropriate to let the forgetting factor vary with the value of the external signal which is the argument of the coefficient functions. Some of the key properties of the modified method...... are studied by simulation...

  11. Filmihullu eluvesi voolab Karlovy Varys / Margit Tõnson

    Index Scriptorium Estoniae

    Tõnson, Margit, 1978-

    2010-01-01

    Karlovy Vary rahvusvahelisest filmifestivalist. Filmidest "Mr. Nobody" (rež. Jaco Van Dormaeli), "Kasside ema Teresa" (rež. Pawel Sala) ja "The Arbor" (rež. Clio Barnardi). Nimekiri võitnud töödest ja viimastel aastatel festivalil näidatud Eesti mängufilmidest

  12. Ellipsometry with randomly varying polarization states

    NARCIS (Netherlands)

    Liu, F.; Lee, C. J.; Chen, J. Q.; E. Louis,; van der Slot, P. J. M.; Boller, K. J.; F. Bijkerk,

    2012-01-01

    We show that, under the right conditions, one can make highly accurate polarization-based measurements without knowing the absolute polarization state of the probing light field. It is shown that light, passed through a randomly varying birefringent material has a well-defined orbit on the Poincar

  13. Õunpuu Karlovy Varys edukas

    Index Scriptorium Estoniae

    2010-01-01

    45. Karlovy Vary filmifestivali võistlusprogrammis "East of the West" märgiti ära Veiko Õunpuu film "Püha Tõnu kiusamine". Peaauhind läks rumeenlase Cristi Puiu filmile "Aurora". Grand prix´sai Augustĺ Vila film "La mosquitera". Teisi preemiasaajaid

  14. Dose sculpting with generalized equivalent uniform dose

    International Nuclear Information System (INIS)

    Wu Qiuwen; Djajaputra, David; Liu, Helen H.; Dong Lei; Mohan, Radhe; Wu, Yan

    2005-01-01

    With intensity-modulated radiotherapy (IMRT), a variety of user-defined dose distribution can be produced using inverse planning. The generalized equivalent uniform dose (gEUD) has been used in IMRT optimization as an alternative objective function to the conventional dose-volume-based criteria. The purpose of this study was to investigate the effectiveness of gEUD optimization to fine tune the dose distributions of IMRT plans. We analyzed the effect of gEUD-based optimization parameters on plan quality. The objective was to determine whether dose distribution to selected structures could be improved using gEUD optimization without adversely altering the doses delivered to other structures, as in sculpting. We hypothesized that by carefully defining gEUD parameters (EUD 0 and n) based on the current dose distributions, the optimization system could be instructed to search for alternative solutions in the neighborhood, and we could maintain the dose distributions for structures already satisfactory and improve dose for structures that need enhancement. We started with an already acceptable IMRT plan optimized with any objective function. The dose distribution was analyzed first. For structures that dose should not be changed, a higher value of n was used and EUD 0 was set slightly higher/lower than the EUD value at the current dose distribution for critical structures/targets. For structures that needed improvement in dose, a higher to medium value of n was used, and EUD 0 was set to the EUD value or slightly lower/higher for the critical structure/target at the current dose distribution. We evaluated this method in one clinical case each of head and neck, lung and prostate cancer. Dose volume histograms, isodose distributions, and relevant tolerance doses for critical structures were used for the assessment. We found that by adjusting gEUD optimization parameters, the dose distribution could be improved with only a few iterations. A larger value of n could lead to

  15. Self-reported adherence and associated factors to isoniazid preventive therapy for latent tuberculosis among people living with HIV/AIDS at health centers in Gondar town, North West Ethiopia.

    Science.gov (United States)

    Ayele, Asnakew Achaw; Asrade Atnafie, Seyfe; Balcha, Demis Driba; Weredekal, Asegedech Tsegaw; Woldegiorgis, Birhanu Alemayehu; Wotte, Mulgeta Melaku; Gebresillasie, Begashaw Melaku

    2017-01-01

    This study aimed to assess self-reported adherence and associated factors to isoniazid preventive therapy (IPT) for latent tuberculosis among people living with HIV/AIDS (PLWHA) at health centers in Gondar town, North West Ethiopia. An institution-based prospective cross-sectional study was conducted from March 10 to June 11, 2016. A total of 154 eligible participants were included in the study, using the simple random sampling method, from the available four health centers and one teaching referral hospital that provided antiretroviral therapy (ART) for HIV/AIDS patients. Adherence was measured by self-report of isoniazid (INH) tablets taken for the preceding 7 days. Participants were recruited through in-depth interviews. The collected data were entered and analyzed using the statistical packages for social sciences (SPSS) version 20. The adherence level to IPT was 90.3% for the last 7 days of the study. ART was initiated for 84.4%, and all of them were on a first-line regimen. Isoniazid-related side effects were reported by 48 (31.2%) participants, of which the most commonly identified were abdominal pain, vomiting, skin rash, jaundice, and numbness. Only 3 (2%) participants discontinued from the study. In the bivariate logistic regression analysis, respondents who had received an explanation about IPT were 83% times more likely to be adherent compared to those who had not received it (95% CI, AOR: 0.266 [0.23-3.127]). Respondents who had taken IPT for ≥5 months were more likely to be adherent than those who had taken it for 1-2 months [95% CI, COR: 1.484]. On the other hand, respondents who experienced side effects were 36% less likely to be adherent compared to those who did not experience any. The level of adherence to IPT among PLWHA was high. Among the predictors reported, carelessness and/or forgetfulness, side effects, and absence from home were the major factors identified for being nonadherent. Health professionals and the Ministry of Health should

  16. Pocket total dose meter

    International Nuclear Information System (INIS)

    Brackenbush, L.W.; Endres, G.W.R.

    1984-10-01

    Laboratory measurements have demonstrated that it is possible to simultaneously measure absorbed dose and dose equivalent using a single tissue equivalent proportional counter. Small, pocket sized instruments are being developed to determine dose equivalent as the worker is exposed to mixed field radiation. This paper describes the electronic circuitry and computer algorithms used to determine dose equivalent in these devices

  17. On dose distribution comparison

    International Nuclear Information System (INIS)

    Jiang, Steve B; Sharp, Greg C; Neicu, Toni; Berbeco, Ross I; Flampouri, Stella; Bortfeld, Thomas

    2006-01-01

    In radiotherapy practice, one often needs to compare two dose distributions. Especially with the wide clinical implementation of intensity-modulated radiation therapy, software tools for quantitative dose (or fluence) distribution comparison are required for patient-specific quality assurance. Dose distribution comparison is not a trivial task since it has to be performed in both dose and spatial domains in order to be clinically relevant. Each of the existing comparison methods has its own strengths and weaknesses and there is room for improvement. In this work, we developed a general framework for comparing dose distributions. Using a new concept called maximum allowed dose difference (MADD), the comparison in both dose and spatial domains can be performed entirely in the dose domain. Formulae for calculating MADD values for various comparison methods, such as composite analysis and gamma index, have been derived. For convenience in clinical practice, a new measure called normalized dose difference (NDD) has also been proposed, which is the dose difference at a point scaled by the ratio of MADD to the predetermined dose acceptance tolerance. Unlike the simple dose difference test, NDD works in both low and high dose gradient regions because it considers both dose and spatial acceptance tolerances through MADD. The new method has been applied to a test case and a clinical example. It was found that the new method combines the merits of the existing methods (accurate, simple, clinically intuitive and insensitive to dose grid size) and can easily be implemented into any dose/intensity comparison tool

  18. Varied line-space gratings and applications

    International Nuclear Information System (INIS)

    McKinney, W.R.

    1991-01-01

    This paper presents a straightforward analytical and numerical method for the design of a specific type of varied line-space grating system. The mathematical development will assume plane or nearly-plane spherical gratings which are illuminated by convergent light, which covers many interesting cases for synchrotron radiation. The gratings discussed will have straight grooves whose spacing varies across the principal plane of the grating. Focal relationships and formulae for the optical grating-pole-to-exist-slit distance and grating radius previously presented by other authors will be derived with a symbolic algebra system. It is intended to provide the optical designer with the tools necessary to design such a system properly. Finally, some possible advantages and disadvantages for application to synchrotron to synchrotron radiation beamlines will be discussed

  19. The Thermal Collector With Varied Glass Covers

    International Nuclear Information System (INIS)

    Luminosu, I.; Pop, N.

    2010-01-01

    The thermal collector with varied glass covers represents an innovation realized in order to build a collector able to reach the desired temperature by collecting the solar radiation from the smallest surface, with the highest efficiency. In the case of the thermal collector with variable cover glasses, the number of the glass plates covering the absorber increases together with the length of the circulation pipe for the working fluid. The thermal collector with varied glass covers compared to the conventional collector better meet user requirements because: for the same temperature increase, has the collecting area smaller; for the same collection area, realizes the highest temperature increase and has the highest efficiency. This works is addressed to researchers in the solar energy and to engineers responsible with air-conditioning systems design or industrial and agricultural products drying.

  20. Spatially varying dispersion to model breakthrough curves.

    Science.gov (United States)

    Li, Guangquan

    2011-01-01

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

  1. New varying speed of light theories

    CERN Document Server

    Magueijo, J

    2003-01-01

    We review recent work on the possibility of a varying speed of light (VSL). We start by discussing the physical meaning of a varying $c$, dispelling the myth that the constancy of $c$ is a matter of logical consistency. We then summarize the main VSL mechanisms proposed so far: hard breaking of Lorentz invariance; bimetric theories (where the speeds of gravity and light are not the same); locally Lorentz invariant VSL theories; theories exhibiting a color dependent speed of light; varying $c$ induced by extra dimensions (e.g. in the brane-world scenario); and field theories where VSL results from vacuum polarization or CPT violation. We show how VSL scenarios may solve the cosmological problems usually tackled by inflation, and also how they may produce a scale-invariant spectrum of Gaussian fluctuations, capable of explaining the WMAP data. We then review the connection between VSL and theories of quantum gravity, showing how ``doubly special'' relativity has emerged as a VSL effective model of quantum space...

  2. Concrete spent fuel storage casks dose rates

    International Nuclear Information System (INIS)

    Bace, M.; Jecmenica, R.; Trontl, K.

    1998-01-01

    Our intention was to model a series of concrete storage casks based on TranStor system storage cask VSC-24, and calculate the dose rates at the surface of the casks as a function of extended burnup and a prolonged cooling time. All of the modeled casks have been filled with the original multi-assembly sealed basket. The thickness of the concrete shield has been varied. A series of dose rate calculations for different burnup and cooling time values have been performed. The results of the calculations show rather conservative original design of the VSC-24 system, considering only the dose rate values, and appropriate design considering heat rejection.(author)

  3. Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications.

    Science.gov (United States)

    Guiastrennec, Benjamin; Ramachandran, Geetha; Karlsson, Mats O; Kumar, A K Hemanth; Bhavani, Perumal Kannabiran; Gangadevi, N Poorana; Swaminathan, Soumya; Gupta, Amita; Dooley, Kelly E; Savic, Radojka M

    2017-12-16

    This work aimed to evaluate the once-daily antituberculosis treatment as recommended by the new Indian pediatric guidelines. Isoniazid, rifampin, and pyrazinamide concentration-time profiles and treatment outcome were obtained from 161 Indian children with drug-sensitive tuberculosis undergoing thrice-weekly dosing as per previous Indian pediatric guidelines. The exposure-response relationships were established using a population pharmacokinetic-pharmacodynamic approach. Rifampin exposure was identified as the unique predictor of treatment outcome. Consequently, children with low body weight (4-7 kg) and/or HIV infection, who displayed the lowest rifampin exposure, were associated with the highest probability of unfavorable treatment (therapy failure, death) outcome (P unfavorable ). Model-based simulation of optimized (P unfavorable ≤ 5%) rifampin once-daily doses were suggested per treatment weight band and HIV coinfection status (33% and 190% dose increase, respectively, from the new Indian guidelines). The established dose-exposure-response relationship could be pivotal in the development of future pediatric tuberculosis treatment guidelines. © 2017, The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  4. Anistropically varying conductivity in irreversible electroporation simulations.

    Science.gov (United States)

    Labarbera, Nicholas; Drapaca, Corina

    2017-11-01

    One recent area of cancer research is irreversible electroporation (IRE). Irreversible electroporation is a minimally invasive procedure where needle electrodes are inserted into the body to ablate tumor cells with electricity. The aim of this paper is to propose a mathematical model that incorporates a tissue's conductivity increasing more in the direction of the electrical field as this has been shown to occur in experiments. It was necessary to mathematically derive a valid form of the conductivity tensor such that it is dependent on the electrical field direction and can be easily implemented into numerical software. The derivation of a conductivity tensor that can take arbitrary functions for the conductivity in the directions tangent and normal to the electrical field is the main contribution of this paper. Numerical simulations were performed for isotropic-varying and anisotropic-varying conductivities to evaluate the importance of including the electrical field's direction in the formulation for conductivity. By starting from previously published experimental results, this paper derived a general formulation for an anistropic-varying tensor for implementation into irreversible electroporation modeling software. The anistropic-varying tensor formulation allows the conductivity to take into consideration both electrical field direction and magnitude, as opposed to previous published works that only took into account electrical field magnitude. The anisotropic formulation predicts roughly a five percent decrease in ablation size for the monopolar simulation and approximately a ten percent decrease in ablation size for the bipolar simulations. This is a positive result as previously reported results found the isotropic formulation to overpredict ablation size for both monopolar and bipolar simulations. Furthermore, it was also reported that the isotropic formulation overpredicts the ablation size more for the bipolar case than the monopolar case. Thus, our

  5. When is a dose not a dose?

    International Nuclear Information System (INIS)

    Green, Patrick

    1992-01-01

    There is confusion over radiation dose limits between the International Commission on Radiological Protection, the National Radiological Protection Board and the Ministry of Agriculture, Fisheries and Food (MAFF), reports a Friends of the Earth's radiation campaigner. MAFF is suggesting the inadequate ICRP public dose limit does not apply to public exposures which arise from environmental contamination from past radioactive discharges. (author)

  6. Dose/dose-rate responses of shrimp larvae to UV-B radiation

    Energy Technology Data Exchange (ETDEWEB)

    Damkaer, D.M.; Dey, D.B.; Heron, G.A.

    1981-01-01

    Previous work indicated dose-rate thresholds in the effects of UV-B on the near-surface larvae of three shrimp species. Additional observations suggest that the total dose response varies with dose-rate. Below 0.002 Wm/sup -2/sub((DNA)) irradiance no significant effect is noted in activity, development, or survival. Beyond that dose-rate threshold, shrimp larvae are significantly affected if the total dose exceeds about 85 Jm/sup -2/sub((DNA)). Predictions cannot be made without both the dose-rate and the dose. These dose/dose-rate thresholds are compared to four-year mean dose/dose-rate solar UV-B irradiances at the experimental site, measured at the surface and calculated for 1 m depth. The probability that the shrimp larvae would receive lethal irradiance is low for the first half of the season of surface occurrence, even with a 44% increase in damaging UV radiation.

  7. Occupational radiation dose in Indonesia 1981-1986

    International Nuclear Information System (INIS)

    Hiswara, E.; Ismono, A.

    1993-01-01

    Occupational radiation dose in Indonesia 1981-1986. This paper presents the occupational radiation dose in Indonesia during the period of 1981-1986. The highest collective dose accurated in 1983 was calculated to be 2.68 man-Sv, with the maximum mean dose per worker, who received dose more than zero, was around 11.07 mSv in the same year. In 1985, a relative collective dose from medical occupations of 1.88 man mSv for 10 6 population was estimated based on its total collective dose of 0.31 man-mSv. The total number of workers who received annual collective dose less than 5 mSv varied from 97.0% in 1981 to 99.5% in 1986. As a group, the industrial occupations has considerably higher risk in receiving a dose than others. (authors). 11 refs., 7 tabs

  8. Progress on MEVVA source VARIS at GSI

    Science.gov (United States)

    Adonin, A.; Hollinger, R.

    2018-05-01

    For the last few years, the development of the VARIS (vacuum arc ion source) was concentrated on several aspects. One of them was the production of high current ion beams of heavy metals such as Au, Pb, and Bi. The requested ion charge state for these ion species is 4+. This is quite challenging to produce in vacuum arc driven sources for reasonable beam pulse length (>120 µs) due to the physical properties of these elements. However, the situation can be dramatically improved by using the composite materials or alloys with enhanced physical properties of the cathodes. Another aspect is an increase of the beam brilliance for intense U4+ beams by the optimization of the geometry of the extraction system. A new 7-hole triode extraction system allows an increase of the extraction voltage from 30 kV to 40 kV and also reduces the outer aperture of the extracted ion beam. Thus, a record beam brilliance for the U4+ beam in front of the RFQ (Radio-Frequency Quadrupole) has been achieved, exceeding the RFQ space charge limit for an ion current of 15 mA. Several new projectiles in the middle-heavy region have been successfully developed from VARIS to fulfill the requirements of the future FAIR (Facility for Antiproton and Ion Research) programs. An influence of an auxiliary gas on the production performance of certain ion charge states as well as on operation stability has been investigated. The optimization of the ion source parameters for a maximum production efficiency and highest particle current in front of the RFQ has been performed. The next important aspect of the development will be the increase of the operation repetition rate of VARIS for all elements especially for uranium to 2.7 Hz in order to provide the maximum availability of high current ion beams for future FAIR experiments.

  9. New varying speed of light theories

    International Nuclear Information System (INIS)

    Magueijo, Joao

    2003-01-01

    We review recent work on the possibility of a varying speed of light (VSL). We start by discussing the physical meaning of a varying-c, dispelling the myth that the constancy of c is a matter of logical consistency. We then summarize the main VSL mechanisms proposed so far: hard breaking of Lorentz invariance; bimetric theories (where the speeds of gravity and light are not the same); locally Lorentz invariant VSL theories; theories exhibiting a colour-dependent speed of light; varying-c induced by extra dimensions (e.g. in the brane-world scenario); and field theories where VSL results from vacuum polarization or CPT violation. We show how VSL scenarios may solve the cosmological problems usually tackled by inflation, and also how they may produce a scale-invariant spectrum of Gaussian fluctuations, capable of explaining the WMAP data. We then review the connection between VSL and theories of quantum gravity, showing how 'doubly special' relativity has emerged as a VSL effective model of quantum space-time, with observational implications for ultra-high energy cosmic rays (UHECRs) and gamma ray bursts. Some recent work on the physics of 'black' holes and other compact objects in VSL theories is also described, highlighting phenomena associated with spatial (as opposed to temporal) variations in c. Finally, we describe the observational status of the theory. The evidence is currently slim-redshift dependence in the atomic fine structure, anomalies with UHECRs, and (to a much lesser extent) the acceleration of the universe and the WMAP data. The constraints (e.g. those arising from nucleosynthesis or geological bounds) are tight but not insurmountable. We conclude with the observational predictions of the theory and the prospects for its refutation or vindication

  10. Dose from radiological examinations

    International Nuclear Information System (INIS)

    Imamura, Keiko; Uji, Teruyuki; Sakuyama, Keiko; Fujikawa, Mitsuhiro; Fujii, Masamichi

    1976-01-01

    Relatively high gonad doses, several hundred to one thousand mR, have been observed in case of pelvis, hip-joint, coccyx, lower abdomen and lumber examination. Dose to the ovary is especially high in barium enema and I.V.P. examinations. About 12 per cent of the 4-ray examination are high-dose. The gonad dose is relatively high in examination of abdomen and lower extremities, in infants. The dose to the eyes is especially high, 1.0 to 2.5R per exposure, in temporal bone and nasal sinuses tomography. X-ray doses have been compared with dose limits recommended by ICRP and with the gonad dose from natural radiations. The gonad dose in lumbar examination, barium enema, I.V.P. etc. is as high as the maximum permissible dose per year recommended by ICRP. Several devices have been made for dose reduction in the daily examinations: (1) separating the radiation field from the gonad by one centimeter decreases the gonad dose about one-half. (2) using sensitive screens and films. In pelvimetry and in infant hip-joint examination, the most sensitive screen and film are used. In the I.V.P. examination of adult, use of MS screen in place of FS screen decreases the dose to one-third, in combination with careful setting of radiation field, (3) use of grid increases the dose about 50 percent and the lead rubber protection (0.1mm lead equivalent) decreases the gonad dose to one-thirtieth in the spinal column examination of infant, (4) A lead protector, 1mm thickness and 2.5cm in diameter, on the eyes decreases the dose to about one-eighth in the face and nead examinations. These simple and effective methods for dose reduction. Should be carried out in as many examinations as possible in addition to observing dose limits recommended by ICRP. (Evans, J.)

  11. Conceptual Modeling of Time-Varying Information

    DEFF Research Database (Denmark)

    Gregersen, Heidi; Jensen, Christian S.

    2004-01-01

    A wide range of database applications manage information that varies over time. Many of the underlying database schemas of these were designed using the Entity-Relationship (ER) model. In the research community as well as in industry, it is common knowledge that the temporal aspects of the mini......-world are important, but difficult to capture using the ER model. Several enhancements to the ER model have been proposed in an attempt to support the modeling of temporal aspects of information. Common to the existing temporally extended ER models, few or no specific requirements to the models were given...

  12. A time-varying magnetic flux concentrator

    International Nuclear Information System (INIS)

    Kibret, B; Premaratne, M; Lewis, P M; Thomson, R; Fitzgerald, P B

    2016-01-01

    It is known that diverse technological applications require the use of focused magnetic fields. This has driven the quest for controlling the magnetic field. Recently, the principles in transformation optics and metamaterials have allowed the realization of practical static magnetic flux concentrators. Extending such progress, here, we propose a time-varying magnetic flux concentrator cylindrical shell that uses electric conductors and ferromagnetic materials to guide magnetic flux to its center. Its performance is discussed based on finite-element simulation results. Our proposed design has potential applications in magnetic sensors, medical devices, wireless power transfer, and near-field wireless communications. (paper)

  13. Linear Parameter Varying Control of Induction Motors

    DEFF Research Database (Denmark)

    Trangbæk, Klaus

    The subject of this thesis is the development of linear parameter varying (LPV) controllers and observers for control of induction motors. The induction motor is one of the most common machines in industrial applications. Being a highly nonlinear system, it poses challenging control problems...... for high performance applications. This thesis demonstrates how LPV control theory provides a systematic way to achieve good performance for these problems. The main contributions of this thesis are the application of the LPV control theory to induction motor control as well as various contributions...

  14. Pharmacokinetics of Pyrazinamide and Optimal Dosing Regimens for Drug-Sensitive and -Resistant Tuberculosis.

    Science.gov (United States)

    Chirehwa, Maxwell T; McIlleron, Helen; Rustomjee, Roxana; Mthiyane, Thuli; Onyebujoh, Philip; Smith, Peter; Denti, Paolo

    2017-08-01

    Pyrazinamide is used in the treatment of tuberculosis (TB) because its sterilizing effect against tubercle bacilli allows the shortening of treatment. It is part of standard treatment for drug-susceptible and drug-resistant TB, and it is being considered as a companion drug in novel regimens. The aim of this analysis was to characterize factors contributing to the variability in exposure and to evaluate drug exposures using alternative doses, thus providing evidence to support revised dosing recommendations for drug-susceptible and multidrug-resistant tuberculosis (MDR-TB). Pyrazinamide pharmacokinetic (PK) data from 61 HIV/TB-coinfected patients in South Africa were used in the analysis. The patients were administered weight-adjusted doses of pyrazinamide, rifampin, isoniazid, and ethambutol in fixed-dose combination tablets according to WHO guidelines and underwent intensive PK sampling on days 1, 8, 15, and 29. The data were interpreted using nonlinear mixed-effects modeling. PK profiles were best described using a one-compartment model with first-order elimination. Allometric scaling was applied to disposition parameters using fat-free mass. Clearance increased by 14% from the 1st day to the 29th day of treatment. More than 50% of patients with weight less than 55 kg achieved lower pyrazinamide exposures at steady state than the targeted area under the concentration-time curve from 0 to 24 h of 363 mg · h/liter. Among patients with drug-susceptible TB, adding 400 mg to the dose for those weighing 30 to 54 kg improved exposure. Average pyrazinamide exposure in different weight bands among patients with MDR-TB could be matched by administering 1,500 mg, 1,750 mg, and 2,000 mg to patients in the 33- to 50-kg, 51- to 70-kg, and greater than 70-kg weight bands, respectively. Copyright © 2017 American Society for Microbiology.

  15. Varying prior information in Bayesian inversion

    International Nuclear Information System (INIS)

    Walker, Matthew; Curtis, Andrew

    2014-01-01

    Bayes' rule is used to combine likelihood and prior probability distributions. The former represents knowledge derived from new data, the latter represents pre-existing knowledge; the Bayesian combination is the so-called posterior distribution, representing the resultant new state of knowledge. While varying the likelihood due to differing data observations is common, there are also situations where the prior distribution must be changed or replaced repeatedly. For example, in mixture density neural network (MDN) inversion, using current methods the neural network employed for inversion needs to be retrained every time prior information changes. We develop a method of prior replacement to vary the prior without re-training the network. Thus the efficiency of MDN inversions can be increased, typically by orders of magnitude when applied to geophysical problems. We demonstrate this for the inversion of seismic attributes in a synthetic subsurface geological reservoir model. We also present results which suggest that prior replacement can be used to control the statistical properties (such as variance) of the final estimate of the posterior in more general (e.g., Monte Carlo based) inverse problem solutions. (paper)

  16. Brown Dwarf Variability: What's Varying and Why?

    Science.gov (United States)

    Marley, Mark Scott

    2014-01-01

    Surveys by ground based telescopes, HST, and Spitzer have revealed that brown dwarfs of most spectral classes exhibit variability. The spectral and temporal signatures of the variability are complex and apparently defy simplistic classification which complicates efforts to model the changes. Important questions include understanding if clearings are forming in an otherwise uniform cloud deck or if thermal perturbations, perhaps associated with breaking gravity waves, are responsible. If clouds are responsible how long does it take for the atmospheric thermal profile to relax from a hot cloudy to a cooler cloudless state? If thermal perturbations are responsible then what atmospheric layers are varying? How do the observed variability timescales compare to atmospheric radiative, chemical, and dynamical timescales? I will address such questions by presenting modeling results for time-varying partly cloudy atmospheres and explore the importance of various atmospheric processes over the relevant timescales for brown dwarfs of a range of effective temperatures. Regardless of the origin of the observed variability, the complexity seen in the atmospheres of the field dwarfs hints at the variability that we may encounter in the next few years in directly imaged young Jupiters. Thus understanding the nature of variability in the field dwarfs, including sensitivity to gravity and metallicity, is of particular importance for exoplanet characterization.

  17. The starting dose of levothyroxine in primary hypothyroidism treatment: a prospective, randomized, double-blind trial

    NARCIS (Netherlands)

    Roos, Annemieke; Linn-Rasker, Suzanne P.; van Domburg, Ron T.; Tijssen, Jan P.; Berghout, Arie

    2005-01-01

    BACKGROUND: The treatment of hypothyroidism with levothyroxine is effective and simple; however, recommendations for the starting dose vary considerably. To our knowledge, the levothyroxine starting dose has never been studied prospectively. METHODS: We conducted a prospective, randomized,

  18. Insignificant levels of dose

    International Nuclear Information System (INIS)

    Webb, G.A.M.; McLean, A.S.

    1977-01-01

    The procedures recommended by the International Commission on Radiological Protection (ICRP) for making decisions concerning controllable sources of radiation exposure of the public include 'justification' and 'optimisation'. The tool recommended by the ICRP for reaching these decisions is collective dose or dose commitment supplemented by consideration of doses to individuals. In both these considerations the practical problem arises of whether very small doses to large numbers of people should contribute to the final decision-making process. It may be that at levels of dose which are small increments on natural background, the relationship between dose and effect is linear even though the slope may be close to zero. If so, collective dose is a meaningful concept and the calculation of total detriment for the purpose of justification could legitimately include all doses. In the calculation of collective doses for the purpose of optimisation, which involves decisions on how much money or resource should be allocated to dose reduction, it is necessary to appraise radiation detriment realistically. At low levels of dose to the individual such as those small by comparison with variations in natural background within the UK, the risk to the individual is such that his well-being will not be significantly changed by the presence or absence of the radiation dose. These small doses, which are well below the point at which an individual attaches significance, should not carry a societal significance. Societal acceptance of risk is analysed with a view to assessing a level of possible risk, and hence dose, below which resources should not in general be diverted to secure further reduction. A formulation for collective dose commitment is proposed incorporating a cut-off to exclude insignificant doses. The implications of this formulation in practical situations are discussed

  19. Time-Varying Periodicity in Intraday Volatility

    DEFF Research Database (Denmark)

    Andersen, Torben Gustav; Thyrsgaard, Martin; Todorov, Viktor

    We develop a nonparametric test for deciding whether return volatility exhibits time-varying intraday periodicity using a long time-series of high-frequency data. Our null hypothesis, commonly adopted in work on volatility modeling, is that volatility follows a stationary process combined...... with a constant time-of-day periodic component. We first construct time-of-day volatility estimates and studentize the high-frequency returns with these periodic components. If the intraday volatility periodicity is invariant over time, then the distribution of the studentized returns should be identical across...... with estimating volatility moments through their sample counterparts. Critical values are computed via easy-to-implement simulation. In an empirical application to S&P 500 index returns, we find strong evidence for variation in the intraday volatility pattern driven in part by the current level of volatility...

  20. Flexible time-varying filter banks

    Science.gov (United States)

    Tuncer, Temel E.; Nguyen, Truong Q.

    1993-09-01

    Linear phase maximally flat FIR Butterworth filter approximations are discussed and a new filter design method is introduced. This variable cutoff filter design method uses the cosine modulated versions of a prototype filter. The design procedure is simple and different variants of this procedure can be used to obtain close to optimum linear phase filters. Using this method, flexible time-varying filter banks with good reconstruction error are introduced. These types of oversampled filter banks have small magnitude error which can be easily controlled by the appropriate choice of modulation frequency. This error can be further decreased by magnitude equalization without increasing the computational complexity considerably. Two dimensional design examples are also given.

  1. Behavior of varying-alpha cosmologies

    International Nuclear Information System (INIS)

    Barrow, John D.; Sandvik, Haavard Bunes; Magueijo, Joao

    2002-01-01

    We determine the behavior of a time-varying fine structure 'constant' α(t) during the early and late phases of universes dominated by the kinetic energy of changing α(t), radiation, dust, curvature, and lambda, respectively. We show that after leaving an initial vacuum-dominated phase during which α increases, α remains constant in universes such as our own during the radiation era, and then increases slowly, proportional to a logarithm of cosmic time, during the dust era. If the universe becomes dominated by a negative curvature or a positive cosmological constant then α tends rapidly to a constant value. The effect of an early period of de Sitter or power-law inflation is to drive α to a constant value. Various cosmological consequences of these results are discussed with reference to recent observational studies of the value of α from quasar absorption spectra and to the existence of life in expanding universes

  2. Emergence of epidemics in rapidly varying networks

    International Nuclear Information System (INIS)

    Kohar, Vivek; Sinha, Sudeshna

    2013-01-01

    We describe a simple model mimicking disease spreading on a network with dynamically varying connections, and investigate the dynamical consequences of switching links in the network. Our central observation is that the disease cycles get more synchronized, indicating the onset of epidemics, as the underlying network changes more rapidly. This behavior is found for periodically switched links, as well as links that switch randomly in time. We find that the influence of changing links is more pronounced in networks where the nodes have lower degree, and the disease cycle has a longer infective stage. Further, when the switching of links is periodic we observe finer dynamical features, such as beating patterns in the emergent oscillations and resonant enhancement of synchronization, arising from the interplay between the time-scales of the connectivity changes and that of the epidemic outbreaks

  3. Time varying, multivariate volume data reduction

    Energy Technology Data Exchange (ETDEWEB)

    Ahrens, James P [Los Alamos National Laboratory; Fout, Nathaniel [UC DAVIS; Ma, Kwan - Liu [UC DAVIS

    2010-01-01

    Large-scale supercomputing is revolutionizing the way science is conducted. A growing challenge, however, is understanding the massive quantities of data produced by large-scale simulations. The data, typically time-varying, multivariate, and volumetric, can occupy from hundreds of gigabytes to several terabytes of storage space. Transferring and processing volume data of such sizes is prohibitively expensive and resource intensive. Although it may not be possible to entirely alleviate these problems, data compression should be considered as part of a viable solution, especially when the primary means of data analysis is volume rendering. In this paper we present our study of multivariate compression, which exploits correlations among related variables, for volume rendering. Two configurations for multidimensional compression based on vector quantization are examined. We emphasize quality reconstruction and interactive rendering, which leads us to a solution using graphics hardware to perform on-the-fly decompression during rendering. In this paper we present a solution which addresses the need for data reduction in large supercomputing environments where data resulting from simulations occupies tremendous amounts of storage. Our solution employs a lossy encoding scheme to acrueve data reduction with several options in terms of rate-distortion behavior. We focus on encoding of multiple variables together, with optional compression in space and time. The compressed volumes can be rendered directly with commodity graphics cards at interactive frame rates and rendering quality similar to that of static volume renderers. Compression results using a multivariate time-varying data set indicate that encoding multiple variables results in acceptable performance in the case of spatial and temporal encoding as compared to independent compression of variables. The relative performance of spatial vs. temporal compression is data dependent, although temporal compression has the

  4. Image quality and dose in computed tomography

    International Nuclear Information System (INIS)

    Jurik, A.G.; Jessen, K.A.; Hansen, J.

    1997-01-01

    Radiation exposure to the patient during CT is relatively high, and it is therefore important to optimize the dose so that it is as low as possible but still consistent with required diagnostic image quality. There is no established method for measuring diagnostic image quality; therefore, a set of image quality criteria which must be fulfilled for optimal image quality was defined for the retroperitoneal space and the mediastinum. The use of these criteria for assessment of image quality was tested based on 113 retroperitoneal and 68 mediastinal examinations performed in seven different CT units. All the criteria, except one, were found to be usable for measuring diagnostic image quality. The fulfilment of criteria was related to the radiation dose given in the different departments. By examination of the retroperitoneal space the effective dose varied between 5.1 and 20.0 mSv (milli Sievert), and there was a slight correlation between dose and high percent of ''yes'' score for the image quality criteria. For examination of the mediastinum the dose range was 4.4-26.5 mSv, and there was no significant increment of image quality at high doses. The great variation of dose at different CT units was due partly to differences regarding the examination procedure, especially the number of slices and the mAs (milli ampere second), but inherent dose variation between different scanners also played a part. (orig.). With 6 figs., 6 tabs

  5. Vancomycin Dosing in Obese Patients: Special Considerations and Novel Dosing Strategies.

    Science.gov (United States)

    Durand, Cheryl; Bylo, Mary; Howard, Brian; Belliveau, Paul

    2018-06-01

    To review the literature regarding vancomycin pharmacokinetics in obese patients and strategies used to improve dosing in this population. PubMed, EMBASE (1974 to November 2017), and Google Scholar searches were conducted using the search terms vancomycin, obese, obesity, pharmacokinetics, strategy, and dosing. Additional articles were selected from reference lists of selected studies. Included articles were those published in English with a primary focus on vancomycin pharmacokinetic parameters in obese patients and practical vancomycin dosing strategies, clinical experiences, or challenges of dosing vancomycin in this population. Volume of distribution and clearance are the pharmacokinetic parameters that most often affect vancomycin dosing in obese patients; both are increased in this population. Challenges with dosing in obese patients include inconsistent and inadequate dosing, observations that the obese population may not be homogeneous, and reports of an increased likelihood of supratherapeutic trough concentrations. Investigators have revised and developed dosing and monitoring protocols to address these challenges. These approaches improved target trough attainment to varying degrees. Some of the vancomycin dosing approaches provided promising results in obese patients, but there were notable differences in methods used to develop these approaches, and sample sizes were small. Although some approaches can be considered for validation in individual institutions, further research is warranted. This may include validating approaches in larger populations with narrower obesity severity ranges, investigating target attainment in indication-specific target ranges, and evaluating the impact of different dosing weights and methods of creatinine clearance calculation.

  6. Total dose meter development

    International Nuclear Information System (INIS)

    Brackenbush, L.W.

    1986-09-01

    This report describes an alarming ''pocket'' monitor/dosimeter, based on a tissue-equivalent proportional counter, that measure both neutron and gamma dose and determines dose equivalent for the mixed radiation field. This report details the operation of the device and provides information on: the necessity for a device to measure dose equivalent in mixed radiation fields; the mathematical theory required to determine dose equivalent from tissue equivalent proportional; the detailed electronic circuits required; the algorithms required in the microprocessor used to calculate dose equivalent; the features of the instrument; program accomplishments and future plans

  7. Dose reader CD-02

    International Nuclear Information System (INIS)

    Jakowiuk, A.; Kaluska, I.; Machaj, B.

    2005-01-01

    Dose Reader CD-02 is designed for measurement of dose from a long narrow band of dosimetric foil used for check up and control of electron beam dose during sterilization of materials and products on conveyor belt. Irradiated foil after processing (heating) is inserted into foil driving (moving) system and when the foil is moved across focused light beam the absorbed dose is measured and displayed at the same time at computer monitor (in form of a diagram). The absorbed dose is measured on the principle of light attenuation at selected light wavelength (foil absorbance is measured). (author)

  8. Dose conversion factors

    International Nuclear Information System (INIS)

    Kocher, D.C.; Eckerman, K.F.

    1992-01-01

    The following is discussed in this report: concepts and quantities used in calculating radiation dose from internal and external exposure. Tabulations of dose conversion factor for internal and external exposure to radionuclides. Dose conversion factors give dose per unit intake (internal) or dose per unit concentration in environment (external). Intakes of radionuclides for internal exposure and concentrations of radionuclides in environment for external exposure are assumed to be known. Intakes and concentrations are obtained, e.g., from analyses of environmental transport and exposure pathways. differences between dosimetry methods for radionuclides and hazardous chemicals are highlighted

  9. Ilio inguinal block: do we know the correct dose?

    African Journals Online (AJOL)

    Adele

    TRAVEL FELLOWSHIP. Introduction. Although Ilio-inguinal nerve blocks are commonly used, the dose advocated varies between 0.3-0.5ml/kg. Despite these doses a failure rate of up to 20-30% has been described using the standard technique. These failures may be due to inadequate understanding of the anatomy, faulty ...

  10. High dose potassium-nitrate chemical dosimeter

    International Nuclear Information System (INIS)

    Dorda de Cancio, E.M.; Munoz, S.S.

    1982-01-01

    This dosimeter is used to control 10 kGY-order doses (1 Mrad). Nitrate suffers a radiolitic reduction phenomena, which is related to the given dose. The method to use potassium nitrate as dosimeter is described, as well as effects of the temperature of irradiation, pH, nitrate concentration and post-irradiation stability. Nitrate powder was irradiated at a Semi-Industrial Plant, at Centro Atomico Ezeiza, and also in a Gammacell-220 irradiator. The dose rates used were 2,60 and 1,80 KGY/hour, and the given doses varied between 1,0 and 150 KGY. The uncertainty was +-3% in all the range. (author) [es

  11. Modelling tourists arrival using time varying parameter

    Science.gov (United States)

    Suciptawati, P.; Sukarsa, K. G.; Kencana, Eka N.

    2017-06-01

    The importance of tourism and its related sectors to support economic development and poverty reduction in many countries increase researchers’ attentions to study and model tourists’ arrival. This work is aimed to demonstrate time varying parameter (TVP) technique to model the arrival of Korean’s tourists to Bali. The number of Korean tourists whom visiting Bali for period January 2010 to December 2015 were used to model the number of Korean’s tourists to Bali (KOR) as dependent variable. The predictors are the exchange rate of Won to IDR (WON), the inflation rate in Korea (INFKR), and the inflation rate in Indonesia (INFID). Observing tourists visit to Bali tend to fluctuate by their nationality, then the model was built by applying TVP and its parameters were approximated using Kalman Filter algorithm. The results showed all of predictor variables (WON, INFKR, INFID) significantly affect KOR. For in-sample and out-of-sample forecast with ARIMA’s forecasted values for the predictors, TVP model gave mean absolute percentage error (MAPE) as much as 11.24 percent and 12.86 percent, respectively.

  12. Microsatellites in varied arenas of research

    Directory of Open Access Journals (Sweden)

    K S Remya

    2010-01-01

    Full Text Available Microsatellites known as simple-sequence repeats (SSRs or short-tandem repeats (STRs, represent specific sequences of DNA consisting of tandemly repeated units of one to six nucleotides. The repetitive nature of microsatellites makes them particularly prone to grow or shrink in length and these changes can have both good and bad consequences for the organisms that possess them. They are responsible for various neurological diseases and hence the same cause is now utilized for the early detection of various diseases, such as, Schizophrenia and Bipolar Disorder, Congenital generalized Hypertrichosis, Asthma, and Bronchial Hyperresponsiveness. These agents are widely used for forensic identification and relatedness testing, and are predominant genetic markers in this area of application. The application of microsatellites is an extending web and covers the varied scenarios of science, such as, conservation biology, plant genetics, and population studies. At present, researches are progressing round the globe to extend the use of these genetic repeaters to unmask the hidden genetic secrets behind the creation of the world.

  13. Varying coefficients model with measurement error.

    Science.gov (United States)

    Li, Liang; Greene, Tom

    2008-06-01

    We propose a semiparametric partially varying coefficient model to study the relationship between serum creatinine concentration and the glomerular filtration rate (GFR) among kidney donors and patients with chronic kidney disease. A regression model is used to relate serum creatinine to GFR and demographic factors in which coefficient of GFR is expressed as a function of age to allow its effect to be age dependent. GFR measurements obtained from the clearance of a radioactively labeled isotope are assumed to be a surrogate for the true GFR, with the relationship between measured and true GFR expressed using an additive error model. We use locally corrected score equations to estimate parameters and coefficient functions, and propose an expected generalized cross-validation (EGCV) method to select the kernel bandwidth. The performance of the proposed methods, which avoid distributional assumptions on the true GFR and residuals, is investigated by simulation. Accounting for measurement error using the proposed model reduced apparent inconsistencies in the relationship between serum creatinine and GFR among different clinical data sets derived from kidney donor and chronic kidney disease source populations.

  14. Stratospheric Impact of Varying Sea Surface Temperatures

    Science.gov (United States)

    Newman, Paul A.; Nash, Eric R.; Nielsen, Jon E.; Waugh, Darryn; Pawson, Steven

    2004-01-01

    The Finite-Volume General Circulation Model (FVGCM) has been run in 50 year simulations with the: 1) 1949-1999 Hadley Centre sea surface temperatures (SST), and 2) a fixed annual cycle of SSTs. In this presentation we first show that the 1949-1999 FVGCM simulation produces a very credible stratosphere in comparison to an NCEP/NCAR reanalysis climatology. In particular, the northern hemisphere has numerous major and minor stratospheric warming, while the southern hemisphere has only a few over the 50-year simulation. During the northern hemisphere winter, temperatures are both warmer in the lower stratosphere and the polar vortex is weaker than is found in the mid-winter southern hemisphere. Mean temperature differences in the lower stratosphere are shown to be small (less than 2 K), and planetary wave forcing is found to be very consistent with the climatology. We then will show the differences between our varying SST simulation and the fixed SST simulation in both the dynamics and in two parameterized trace gases (ozone and methane). In general, differences are found to be small, with subtle changes in planetary wave forcing that lead to reduced temperatures in the SH and increased temperatures in the NH.

  15. TIME-VARYING DYNAMICAL STAR FORMATION RATE

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eve J.; Chang, Philip; Murray, Norman, E-mail: evelee@berkeley.edu [Canadian Institute for Theoretical Astrophysics, 60 St. George Street, University of Toronto, Toronto, ON M5S 3H8 (Canada)

    2015-02-10

    We present numerical evidence of dynamic star formation in which the accreted stellar mass grows superlinearly with time, roughly as t {sup 2}. We perform simulations of star formation in self-gravitating hydrodynamic and magnetohydrodynamic turbulence that is continuously driven. By turning the self-gravity of the gas in the simulations on or off, we demonstrate that self-gravity is the dominant physical effect setting the mass accretion rate at early times before feedback effects take over, contrary to theories of turbulence-regulated star formation. We find that gravitational collapse steepens the density profile around stars, generating the power-law tail on what is otherwise a lognormal density probability distribution function. Furthermore, we find turbulent velocity profiles to flatten inside collapsing regions, altering the size-line width relation. This local flattening reflects enhancements of turbulent velocity on small scales, as verified by changes to the velocity power spectra. Our results indicate that gas self-gravity dynamically alters both density and velocity structures in clouds, giving rise to a time-varying star formation rate. We find that a substantial fraction of the gas that forms stars arrives via low-density flows, as opposed to accreting through high-density filaments.

  16. Antiorthostatic immobilization with varied sodium intake

    Science.gov (United States)

    Hinghofer-Szalkay, H.; Haditsch, B.; Pilz, K.; Rössler, A.; Laszlo, Z.

    The study investigated, in 10 normotensive male persons, heart rate responses to graded lower body suction (LBNP) with adaptation to various oral sodium clamping during both ambulatory (AMB) conditions for 4 days, and thereafter to additional antiorthostatic (6° head down) positioning. A ,low' (LS: 143+/-10 mM Na +/ d excreted) and a ,high' (HS: 434+/-17 mM Na +/d excreted) sodium treatment - in randomized order and separated =1 mo - followed a ,conditioning' run with moderate sodium (237+/-9 mM Na +/d excreted). Urinary volume and sodium output were monitored, hormone levels (PRA, aldosterone, AVP) determined, and extracellular volume (ECV) estimated by whole body electrical impedance spectroscopy. ECV was not differently reduced (p>0.1) in LS (-5.8+/-2.3%, p=0.018) and HS (-4.0+/-1.0%. p=0.002). Morning AVP was lower (5.5+/-0.1 pg/ml) in HS than in LS (7.2+/-0.3 pg/ml; N=7 days), as well as aldosterone (69+/-7 pg/ml in HS vs. 180+/-24 pg/ml in LS). LBNP dose responses of PRA and aldosterone were higher in LS than HS after 8 days AOB, whereas microvascular fluid filtration was unchanged by any experimental condition. Heart rate responses to LBNP were unchanged by sodium supply, whereas mean arterial and pulse pressure was lower in LS than HS during all LBNP intensities. Thus, HS was able to increase arterial blood and pulse pressure and reduced PRA and aldosterone levels during graded simulated orthostatic challenge, but did neither ameliorate AOB-induced ECV decrease nor alter LBNP-induced filtration and heart rate responses. These results are relevant for planning of future countermeasures in astronauts. Supported by the Austrian Research Fund (P13451-MED)

  17. Enjebi Island dose assessment

    International Nuclear Information System (INIS)

    Robison, W.L.; Conrado, C.L.; Phillips, W.A.

    1987-07-01

    We have updeated the radiological dose assessment for Enjebi Island at Enewetak Atoll using data derived from analysis of food crops grown on Enjebi. This is a much more precise assessment of potential doses to people resettling Enjebi Island than the 1980 assessment in which there were no data available from food crops on Enjebi. Details of the methods and data used to evaluate each exposure pathway are presented. The terrestrial food chain is the most significant potential exposure pathway and 137 Cs is the radionuclide responsible for most of the estimated dose over the next 50 y. The doses are calculated assuming a resettlement date of 1990. The average wholebody maximum annual estimated dose equivalent derived using our diet model is 166 mremy;the effective dose equivalent is 169 mremy. The estimated 30-, 50-, and 70-y integral whole-body dose equivalents are 3.5 rem, 5.1 rem, and 6.2 rem, respectively. Bone-marrow dose equivalents are only slightly higher than the whole-body estimates in each case. The bone-surface cells (endosteal cells) receive the highest dose, but they are a less sensitive cell population and are less sensitive to fatal cancer induction than whole body and bone marrow. The effective dose equivalents for 30, 50, and 70 y are 3.6 rem, 5.3 rem, and 6.6 rem, respectively. 79 refs., 17 figs., 24 tabs

  18. Urban contamination and dose model

    International Nuclear Information System (INIS)

    Robertson, E.; Barry, P.J.

    1995-10-01

    Nuclear power reactors and other nuclear facilities are being built near or even within urban centres. Accidental releases of radionuclides to the atmosphere in built-up areas result in radiological exposure pathways that differ from those caused by releases in rural environments. Other than inhalation, exposure pathways involve external radiation from the plume while it passes and from radioactivity deposited onto the many and varied surfaces after it has passed. Radiation fields inside buildings are attenuated but many people are potentially exposed so while individual doses may be relatively low, population integrated doses may be high enough to cause concern. It is important, therefore, to assess the potential exposures and to estimate the cost-effectiveness of dose reduction measures in urban environments. This report describes a model developed to carry out such assessments. The model draws heavily on experience gained in European cities after their contamination fallout from the Chernobyl accident. Input is time integrated concentrations of specific radionuclides in urban air, obtained either by direct measurement or by prediction using an atmospheric dispersion model. The code includes default values for site specific variables and transfer parameters but the user is invited if desired to enter other values from the keyboard. Output is the time integrated dose rates for individuals selected because of the characteristic living, working and recreational habits. An accompanying manual documents the technical background on which the model is based and leads a first-time suer through various steps and operations encountered while the model is running. (author). 60 refs., 10 tabs., 1 fig

  19. Registration of radiation doses

    International Nuclear Information System (INIS)

    2000-02-01

    In Finland the Radiation and Nuclear Safety Authority (STUK) is maintaining the register (called Dose Register) of the radiation exposure of occupationally exposed workers in order to ensure compliance with the principles of optimisation and individual protection. The guide contains a description of the Dose Register and specifies the responsibilities of the party running a radiation practice to report the relevant information to the Dose Register

  20. Optimizing Radiation Doses for Computed Tomography Across Institutions: Dose Auditing and Best Practices.

    Science.gov (United States)

    Demb, Joshua; Chu, Philip; Nelson, Thomas; Hall, David; Seibert, Anthony; Lamba, Ramit; Boone, John; Krishnam, Mayil; Cagnon, Christopher; Bostani, Maryam; Gould, Robert; Miglioretti, Diana; Smith-Bindman, Rebecca

    2017-06-01

    Radiation doses for computed tomography (CT) vary substantially across institutions. To assess the impact of institutional-level audit and collaborative efforts to share best practices on CT radiation doses across 5 University of California (UC) medical centers. In this before/after interventional study, we prospectively collected radiation dose metrics on all diagnostic CT examinations performed between October 1, 2013, and December 31, 2014, at 5 medical centers. Using data from January to March (baseline), we created audit reports detailing the distribution of radiation dose metrics for chest, abdomen, and head CT scans. In April, we shared reports with the medical centers and invited radiology professionals from the centers to a 1.5-day in-person meeting to review reports and share best practices. We calculated changes in mean effective dose 12 weeks before and after the audits and meeting, excluding a 12-week implementation period when medical centers could make changes. We compared proportions of examinations exceeding previously published benchmarks at baseline and following the audit and meeting, and calculated changes in proportion of examinations exceeding benchmarks. Of 158 274 diagnostic CT scans performed in the study period, 29 594 CT scans were performed in the 3 months before and 32 839 CT scans were performed 12 to 24 weeks after the audit and meeting. Reductions in mean effective dose were considerable for chest and abdomen. Mean effective dose for chest CT decreased from 13.2 to 10.7 mSv (18.9% reduction; 95% CI, 18.0%-19.8%). Reductions at individual medical centers ranged from 3.8% to 23.5%. The mean effective dose for abdominal CT decreased from 20.0 to 15.0 mSv (25.0% reduction; 95% CI, 24.3%-25.8%). Reductions at individual medical centers ranged from 10.8% to 34.7%. The number of CT scans that had an effective dose measurement that exceeded benchmarks was reduced considerably by 48% and 54% for chest and abdomen, respectively. After

  1. Dose reconstruction in deforming lung anatomy: Dose grid size effects and clinical implications

    International Nuclear Information System (INIS)

    Rosu, Mihaela; Chetty, Indrin J.; Balter, James M.; Kessler, Marc L.; McShan, Daniel L.; Ten Haken, Randall K.

    2005-01-01

    In this study we investigated the accumulation of dose to a deforming anatomy (such as lung) based on voxel tracking and by using time weighting factors derived from a breathing probability distribution function (p.d.f.). A mutual information registration scheme (using thin-plate spline warping) provided a transformation that allows the tracking of points between exhale and inhale treatment planning datasets (and/or intermediate state scans). The dose distributions were computed at the same resolution on each dataset using the Dose Planning Method (DPM) Monte Carlo code. Two accumulation/interpolation approaches were assessed. The first maps exhale dose grid points onto the inhale scan, estimates the doses at the 'tracked' locations by trilinear interpolation and scores the accumulated doses (via the p.d.f.) on the original exhale data set. In the second approach, the 'volume' associated with each exhale dose grid point (exhale dose voxel) is first subdivided into octants, the center of each octant is mapped to locations on the inhale dose grid and doses are estimated by trilinear interpolation. The octant doses are then averaged to form the inhale voxel dose and scored at the original exhale dose grid point location. Differences between the interpolation schemes are voxel size and tissue density dependent, but in general appear primarily only in regions with steep dose gradients (e.g., penumbra). Their magnitude (small regions of few percent differences) is less than the alterations in dose due to positional and shape changes from breathing in the first place. Thus, for sufficiently small dose grid point spacing, and relative to organ motion and deformation, differences due solely to the interpolation are unlikely to result in clinically significant differences to volume-based evaluation metrics such as mean lung dose (MLD) and tumor equivalent uniform dose (gEUD). The overall effects of deformation vary among patients. They depend on the tumor location, field

  2. Paediatric dose display

    International Nuclear Information System (INIS)

    Griffin, D.W.; Derges, S.; Hesslewood, S.

    1984-01-01

    A compact, inexpensive unit, based on an 8085 microprocessor, has been designed for calculating doses of intravenous radioactive injections for children. It has been used successfully for over a year. The dose is calculated from the body surface area and the result displayed in MBq. The operator can obtain the required dose on a twelve character alphanumeric display by entering the age of the patient and the adult dose using a hexadecimal keyboard. Circuit description, memory map and input/output, and firmware are dealt with. (U.K.)

  3. An environmental dose experiment

    Science.gov (United States)

    Peralta, Luis

    2017-11-01

    Several radiation sources worldwide contribute to the delivered dose to the human population. This radiation also acts as a natural background when detecting radiation, for instance from radioactive sources. In this work a medium-sized plastic scintillation detector is used to evaluate the dose delivered by natural radiation sources. Calibration of the detector involved the use of radioactive sources and Monte Carlo simulation of the energy deposition per disintegration. A measurement of the annual dose due to background radiation to the body was then estimated. A dose value compatible with the value reported by the United Nations Scientific Committee on the Effects of Atomic Radiation was obtained.

  4. An environmental dose experiment

    International Nuclear Information System (INIS)

    Peralta, Luis

    2017-01-01

    Several radiation sources worldwide contribute to the delivered dose to the human population. This radiation also acts as a natural background when detecting radiation, for instance from radioactive sources. In this work a medium-sized plastic scintillation detector is used to evaluate the dose delivered by natural radiation sources. Calibration of the detector involved the use of radioactive sources and Monte Carlo simulation of the energy deposition per disintegration. A measurement of the annual dose due to background radiation to the body was then estimated. A dose value compatible with the value reported by the United Nations Scientific Committee on the Effects of Atomic Radiation was obtained. (paper)

  5. Doses from portable gauges

    International Nuclear Information System (INIS)

    Linauskas, S.H.

    1988-08-01

    Field studies to measure actual radiation exposures of operators of commercial moisture-density gauges were undertaken in several regions of Canada. Newly developed bubble detector dosimeter technology and conventional dosimetry such as thermoluminescent dosimeters (TLDs), integrating electronic dosimeters (DRDs), and CR-39 neutron track-etch detectors were used to estimate the doses received by 23 moisture-density gauge operators and maintenance staff. These radiation dose estimates were supported by mapping radiation fields and accounting for the time an operator was near a gauge. Major findings indicate that gauge maintenance and servicing workers were more likely than gauge operators to receive exposures above the level of 5 mSv, and that neutron doses were roughly the same as gamma doses. Gauge operators receive approximately 75% of their dose when transporting and carrying the gauge. Dose to their hands is similar to the dose to their trunks, but the dose to their feet area is 6 to 30 times higher. Gamma radiation is the primary source of radiation contributing to operator dose

  6. Radiation dose in vertebroplasty

    International Nuclear Information System (INIS)

    Mehdizade, A.; Lovblad, K.O.; Wilhelm, K.E.; Somon, T.; Wetzel, S.G.; Kelekis, A.D.; Yilmaz, H.; Abdo, G.; Martin, J.B.; Viera, J.M.; Ruefenacht, D.A.

    2004-01-01

    We wished to measure the absorbed radiation dose during fluoroscopically controlled vertebroplasty and to assess the possibility of deterministic radiation effects to the operator. The dose was measured in 11 consecutive procedures using thermoluminescent ring dosimeters on the hand of the operator and electronic dosimeters inside and outside of the operator's lead apron. We found doses of 0.022-3.256 mGy outside and 0.01-0.47 mGy inside the lead apron. Doses on the hand were higher, 0.5-8.5 mGy. This preliminary study indicates greater exposure to the operator's hands than expected from traditional apron measurements. (orig.)

  7. Radiation doses to children with shunt-treated hydrocephalus

    Energy Technology Data Exchange (ETDEWEB)

    Holmedal, Lise J. [Helse Fonna, Department of Radiology, Stord Hospital, Stord (Norway); Friberg, Eva G.; Boerretzen, Ingelin; Olerud, Hilde [The Norwegian Radiation Protection Authority, Oesteraas (Norway); Laegreid, Liv [Haukeland University Hospital, Department of Paediatrics, Bergen (Norway); Rosendahl, Karen [University of Bergen, Department of Surgical Sciences, Radiology Section, Bergen (Norway); Great Ormond Street Hospital for Children, Department of Diagnostic Radiology, London (United Kingdom)

    2007-12-15

    Children with shunt-treated hydrocephalus are still followed routinely with frequent head CT scans. To estimate the effective dose, brain and lens doses from these examinations during childhood, and to assess dose variation per examination. All children born between 1983 and 1995 and treated for hydrocephalus between 1983 and 2002 were included. We retrospectively registered the number of examinations and the applied scan parameters. The effective dose was calculated using mean conversion factors from the CT dose index measured free in air, while doses to the lens and brain were estimated using tabulated CT dose index values measured in a head phantom. A total of 687 CT examinations were performed in 67 children. The mean effective dose, lens dose and brain dose to children over 6 months of age were 1.2 mSv, 52 mGy and 33 mGy, respectively, and the corresponding doses to younger children were 3.2 mSv, 60 mGy and 48 mGy. The effective dose per CT examination varied by a factor of 64. None of the children was exposed to doses known to cause deterministic effects. However, since the threshold for radiation-induced damage is not known with certainty, alternative modalities such as US and MRI should be used whenever possible. (orig.)

  8. Determination of the radiation dose to the body due to external radiation

    International Nuclear Information System (INIS)

    Drexler, G.; Eckerl, H.

    1985-01-01

    Section 63 of the Radiation Protection Ordinance defines the basic requirement, determination of radiation dose to the body. The determination of dose equivalents for the body is the basic step in practical monitoring of dose equivalents or dose limits with regard to individuals or population groups, both for constant or varying conditions of exposure. The main field of monitoring activities is the protection of persons occupationally exposed to ionizing radiation. Conversion factors between body doses and radiation quantities are explained. (DG) [de

  9. Low dose stimulation in foeniculum vulgare

    International Nuclear Information System (INIS)

    Jahagirdar, H.A.; Khalatkar, A.W.; Dnyansagar, V.R.

    1974-01-01

    Genetically pure seeds with a moisture content of 12.5% were irradiated in a 60 Co γ-source at a dose rate of 1.1 KR/min, the radiation dose varying between 2 and 14 KR. Four days after irradiation the seeds were sown into the open field. Stimulation was determined on the basis of a lot of parameters e.g. height. The results indicated a significant stimulation after 10 KR as far as seed yield is concerned. (MG) [de

  10. Monte Carlo dose calibration in CT scanner

    International Nuclear Information System (INIS)

    Yadav, Poonam; Ramasubramanian, V.; Subbaiah, K.V.; Thayalan, K.

    2008-01-01

    Computed Tomography (CT) scanner is a high radiation imaging modality compared to radiography. The dose from a CT examination can vary greatly depending on the particular CT scanner used, the area of the body examined, and the operating parameters of the scan. CT is a major contributor to collective effective dose in diagnostic radiology. Apart from the clinical benefits, the widespread use of multislice scanner is increasing radiation level to patient in comparison with conventional CT scanner. So, it becomes necessary to increase awareness about the CT scanner. (author)

  11. In vitro antimicrobial efficacy of a fixed-dose combination of RHZE against M. tuberculosis

    Directory of Open Access Journals (Sweden)

    Vanessa Albertina Agertt

    Full Text Available ABSTRACT The use of drugs in fixed-dose combination (FDC is now recommended by the World Health Organization (WHO due to the emergence of multidrug-resistant strains of Mycobacterium tuberculosis. FDC uses different drugs against tuberculosis (TB in a single tablet for phase-intensive therapeutic intervention. This therapy aims to optimize treatment, to prevent inappropriate use of drugs, and to prevent the emergence of new resistant strains. This study aims to evaluate the susceptibility of clinical isolates of M. tuberculosis against rifampicin, isoniazid, ethambutol, and pyrazinamide. The antimicrobials were tested separately and in associations according to FDC. This was used for broth microdilution method, which was compared to the proportions method previously considered as the gold standard. In antimicrobials testing alone, several strains were resistant to one, two, or three drugs. However, when applied to association of drugs in FDC, there was no antimicrobial resistance. The results strengthen the FDC's concept, which aims to unite the four anti-TB drugs to combat bacterial resistance.

  12. Effective dose equivalent

    International Nuclear Information System (INIS)

    Huyskens, C.J.; Passchier, W.F.

    1988-01-01

    The effective dose equivalent is a quantity which is used in the daily practice of radiation protection as well as in the radiation hygienic rules as measure for the health risks. In this contribution it is worked out upon which assumptions this quantity is based and in which cases the effective dose equivalent can be used more or less well. (H.W.)

  13. Doses from radiation exposure

    International Nuclear Information System (INIS)

    Menzel, H-G.; Harrison, J.D.

    2012-01-01

    Practical implementation of the International Commission on Radiological Protection’s (ICRP) system of protection requires the availability of appropriate methods and data. The work of Committee 2 is concerned with the development of reference data and methods for the assessment of internal and external radiation exposure of workers and members of the public. This involves the development of reference biokinetic and dosimetric models, reference anatomical models of the human body, and reference anatomical and physiological data. Following ICRP’s 2007 Recommendations, Committee 2 has focused on the provision of new reference dose coefficients for external and internal exposure. As well as specifying changes to the radiation and tissue weighting factors used in the calculation of protection quantities, the 2007 Recommendations introduced the use of reference anatomical phantoms based on medical imaging data, requiring explicit sex averaging of male and female organ-equivalent doses in the calculation of effective dose. In preparation for the calculation of new dose coefficients, Committee 2 and its task groups have provided updated nuclear decay data (ICRP Publication 107) and adult reference computational phantoms (ICRP Publication 110). New dose coefficients for external exposures of workers are complete (ICRP Publication 116), and work is in progress on a series of reports on internal dose coefficients to workers from inhaled and ingested radionuclides. Reference phantoms for children will also be provided and used in the calculation of dose coefficients for public exposures. Committee 2 also has task groups on exposures to radiation in space and on the use of effective dose.

  14. Gonad dose in cineurethrocystography

    International Nuclear Information System (INIS)

    Ardran, G.M.; Dixon-Brown, A.; Fursdon, P.S.

    1978-01-01

    The technical factors used for cineurethrocystography for the true lateral projection in females are given. The mid-line radiation dose has been measured with LiF TLD inserted into the vagina in 19 examinations. The average dose recorded was 148 mrad, the range being 50 to 306 mrad, the average number of cine frames exposed was 96. Data obtained using a Rando phantom indicated that the average ovary dose would be 30% greater than the mid-line dose since the near ovary receives a higher dose than the more distant one. The technique used for men is also given, the average gonad dose in six men being 123 mrad, range 56 to 243 mrad when simple lead foil gonad protection was used; the average number of cine frames was 107. The dose in one man without gonad protection was 1575 mrad for 112 cine frames. The results for both sexes compare favourably with those of others reported in the literature and with gonad doses recorded in typical IVP examinations. (author)

  15. Internal dose estimates

    International Nuclear Information System (INIS)

    Wrenn, M.E.

    1977-01-01

    Internal doses, the procedures for making them and their significance has been reviewed. Effects of uranium, radium, lead-210, polonium-210, thorium in man are analysed based on data from tables and plots. Dosimetry of some ingested nuclides and inhalation dose due to radon-222, radon-220 and their daugther products are discussed [pt

  16. Occupational dose constraint

    International Nuclear Information System (INIS)

    Heilbron Filho, Paulo Fernando Lavalle; Xavier, Ana Maria

    2005-01-01

    The revision process of the international radiological protection regulations has resulted in the adoption of new concepts, such as practice, intervention, avoidable and restriction of dose (dose constraint). The latter deserving of special mention since it may involve reducing a priori of the dose limits established both for the public and to individuals occupationally exposed, values that can be further reduced, depending on the application of the principle of optimization. This article aims to present, with clarity, from the criteria adopted to define dose constraint values to the public, a methodology to establish the dose constraint values for occupationally exposed individuals, as well as an example of the application of this methodology to the practice of industrial radiography

  17. Ionization chamber for high dose measurements

    International Nuclear Information System (INIS)

    Rodrigues Junior, Ary de Araujo

    2005-01-01

    Industrial gamma irradiators facilities are designed for processing large amounts of products, which are exposed to large doses of gamma radiation. The irradiation, in industrial scale, is usually carried out in a dynamic form, where the products go through a 60 Co gamma source with activity of TBq to P Bq (k Ci to MCi). The dose is estimated as being directly proportional to the time that the products spend to go through the source. However, in some situations, mainly for research purposes or for validation of customer process following the ISO 11137 requirements, it is required to irradiate small samples in a static position with fractional deliver doses. The samples are put inside the irradiation room at a fixed distance from the source and the dose is usually determined using dosimeters. The dose is only known after the irradiation, by reading the dosimeter. Nevertheless, in the industrial irradiators, usually different kinds of products with different densities go through between the source and the static position samples. So, the dose rate varies in function of the product density. A suitable methodology would be to monitor the samples dose in real time, measuring the dose on line with a radiation detector, which would improve the dose accuracy and avoid the overdose. A cylindrical ionization chamber of 0.9 cm 3 has been developed for high-doses real-time monitoring, during the sample irradiation at a static position in a 60 Co gamma industrial plant. Nitrogen and argon gas at pressure of 10 exp 5 Pa (1 bar) was utilized to fill the ionization chamber, for which an appropriate configuration was determined to be used as a detector for high-dose measurements. To transmit the signal generated in the ionization chamber to the associated electronic and processing unit, a 20 m mineral insulated cable was welded to the ionization chamber. The signal to noise ratio produced by the detector was about 100. The dosimeter system was tested at a category I gamma

  18. Dose response relationship at low doses

    International Nuclear Information System (INIS)

    Schull, W.J.

    1992-01-01

    The data that have accrued in Hiroshima and Nagasaki on the effects of ionizing radiation on the developing human brain are reviewed. Effects considered are severe mental retardation, lowered IQ scores, decline in school performance, seizures, other neuropsychological effects, and small head size. All these factors may be related to radiation doses received by the mother during pregnancy. (L.L.) 3 figs., tab., 7 refs

  19. The combined fixed-dose antituberculous drugs alter some reproductive functions with oxidative stress involvement in wistar rats

    Directory of Open Access Journals (Sweden)

    O. Awodele, B.Pharm M.Sc MPH PhD D.Sc FPCPharm FASI

    Full Text Available The reproductive toxicity of combined fixed-dose first-line antituberculosis (CFDAT regimen was assessed in rats. Thirty-two (32 Wistar rats weighing 168.1 ± 8.0 g were divided into four groups of eight rats per group. Two groups of male and female rats were administered oral distilled water (1.6 ml and CFDAT drugs containing rifampicin, isoniazid, pyrazinamide and ethambutol (RIPE, 92.5 mg/m2 per body surface area respectively for forty-five days. Serum follicle stimulating hormone, luteinizing and testosterone were reduced significantly (p  0.05 levels in the treated females. In addition, RIPE reduced (p < 0.05 total proteins levels and increased (p < 0.05, 53% catalase levels in male but not female animals. Superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, reduced glutathione levels as well as lipid peroxidation were unaltered in all rats respectively. Histopathological studies revealed congested peritesticular vessels and no changes in the ovary when compared with control. Overall, our results demonstrate reproductive toxicity potentials of RIPE in the rat, thus, suggesting that these reproductive parameters be monitored during antituberculous chemotherapy. Keywords: Fixed dose combined antituberculous drugs, Sub-chronic study, Reproductive toxicity, Rats

  20. Ingestion of Nevada Test Site Fallout: Internal dose estimates

    International Nuclear Information System (INIS)

    Whicker, F.W.; Kirchner, T.B.; Anspaugh, L.R.

    1996-01-01

    This paper summarizes individual and collective dose estimates for the internal organs of hypothetical yet representative residents of selected communities that received measurable fallout from nuclear detonations at the Nevada Test Site. The doses, which resulted from ingestion of local and regional food products contaminated with over 20 radionuclides, were estimated with use of the PATHWAY food-chain-transport model to provide estimates of central tendency and uncertainty. The thyroid gland received much higher doses than other internal organs and tissues. In a avery few cases, infants might have received thyroid doses in excess of 1 Gy, depending on location, diet, and timing of fallout. 131 I was the primary thyroid dose contributor, and fresh milk was the main exposure pathway. With the exception of the thyroid, organ doses from the ingestion pathway were much smaller (<3%) than those from external gamma exposure to deposited fallout. Doses to residents living closest to the Nevada Test Site were contributed mainly by a few fallout events; doses to more distantly located people were generally smaller, but a greater number of events provided measurable contributions. The effectiveness of different fallout events in producing internal organ doses through ingestion varied dramatically with seasonal timing of the test, with maximum dose per unit fallout occurring for early summer depositions when milk cows were on pasture and fresh, local vegetables were used. Within specific communities, internal doses differed by age, sex, and lifestyle. Collective internal dose estimates for specific geographic areas are provided

  1. True dose from incorporated activities. Models for internal dosimetry

    International Nuclear Information System (INIS)

    Breustedt, B.; Eschner, W.; Nosske, D.

    2012-01-01

    The assessment of doses after incorporation of radionuclides cannot use direct measurements of the doses, as for example dosimetry in external radiation fields. The only observables are activities in the body or in excretions. Models are used to calculate the doses based on the measured activities. The incorporated activities and the resulting doses can vary by more than seven orders of magnitude between occupational and medical exposures. Nevertheless the models and calculations applied in both cases are similar. Since the models for the different applications have been developed independently by ICRP and MIRD different terminologies have been used. A unified terminology is being developed. (orig.)

  2. Radiographic film: surface dose extrapolation techniques

    International Nuclear Information System (INIS)

    Cheung, T.; Yu, P.K.N.; Butson, M.J.; Cancer Services, Wollongong, NSW; Currie, M.

    2004-01-01

    Full text: Assessment of surface dose delivered from radiotherapy x-ray beams for optimal results should be performed both inside and outside the prescribed treatment fields An extrapolation technique can be used with radiographic film to perform surface dose assessment for open field high energy x-ray beams. This can produce an accurate 2 dimensional map of surface dose if required. Results have shown that surface % dose can be estimated within ±3% of parallel plate ionisation chamber results with radiographic film using a series of film layers to produce an extrapolated result. Extrapolated percentage dose assessment for 10cm, 20cmand 30cm square fields was estimated to be 15% ± 2%, 29% ± 3% and 38% ± 3% at the central axis and relatively uniform across the treatment field. Corresponding parallel plate ionisation chamber measurement are 16%, 27% and 37% respectively. Surface doses are also measured outside the treatment field which are mainly due to scattered electron contamination. To achieve this result, film calibration curves must be irradiated to similar x-ray field sizes as the experimental film to minimize quantitative variations in film optical density caused by varying x-ray spectrum with field size. Copyright (2004) Australasian College of Physical Scientists and Engineers in Medicine

  3. Patient surface doses in computerized tomography examinations

    International Nuclear Information System (INIS)

    Vekic, B; Kovacevic, S.; Ranogajec-Komor, M.; Duvnjak, N.; Marusic, P.; Anic, P.; Dolencic, P.

    1996-01-01

    The diagnostic value of computerized tomography has increased due to very rapid technical advances in both equipment and techniques. When the CT scanners were introduced, a significant problem for the specification of the radiation dose imparted to the patient undergoing CT examination has been created. In CT, the conditions of exposure are quite different from those in conventional X-ray imaging. CT procedure involves the continuous tomography of thin layers. Some of these layers touch each other while others overlap. The radiation doses received by patients can vary considerably. In addition to the radiation from the collimated primary beam, patients are exposed to significant scattered doses in unpredictable amounts. Every effort should be made to keep these doses to a reasonable minimum, without sacrificing the image quality. The aims of this work were to determine the surface doses delivered to various organs of patients during various computerized tomography examinations (head, thorax, kidney, abdomen and pelvis). Particular attention was directed to the precise determination of doses received by the eyes (during CT of head) and gonads (during CT of pelvis and lower abdomen) since these organs can be near or even in the primary X-ray beam

  4. Converting dose distributions into tumour control probability

    International Nuclear Information System (INIS)

    Nahum, A.E.

    1996-01-01

    The endpoints in radiotherapy that are truly of relevance are not dose distributions but the probability of local control, sometimes known as the Tumour Control Probability (TCP) and the Probability of Normal Tissue Complications (NTCP). A model for the estimation of TCP based on simple radiobiological considerations is described. It is shown that incorporation of inter-patient heterogeneity into the radiosensitivity parameter a through s a can result in a clinically realistic slope for the dose-response curve. The model is applied to inhomogeneous target dose distributions in order to demonstrate the relationship between dose uniformity and s a . The consequences of varying clonogenic density are also explored. Finally the model is applied to the target-volume DVHs for patients in a clinical trial of conformal pelvic radiotherapy; the effect of dose inhomogeneities on distributions of TCP are shown as well as the potential benefits of customizing the target dose according to normal-tissue DVHs. (author). 37 refs, 9 figs

  5. Converting dose distributions into tumour control probability

    Energy Technology Data Exchange (ETDEWEB)

    Nahum, A E [The Royal Marsden Hospital, London (United Kingdom). Joint Dept. of Physics

    1996-08-01

    The endpoints in radiotherapy that are truly of relevance are not dose distributions but the probability of local control, sometimes known as the Tumour Control Probability (TCP) and the Probability of Normal Tissue Complications (NTCP). A model for the estimation of TCP based on simple radiobiological considerations is described. It is shown that incorporation of inter-patient heterogeneity into the radiosensitivity parameter a through s{sub a} can result in a clinically realistic slope for the dose-response curve. The model is applied to inhomogeneous target dose distributions in order to demonstrate the relationship between dose uniformity and s{sub a}. The consequences of varying clonogenic density are also explored. Finally the model is applied to the target-volume DVHs for patients in a clinical trial of conformal pelvic radiotherapy; the effect of dose inhomogeneities on distributions of TCP are shown as well as the potential benefits of customizing the target dose according to normal-tissue DVHs. (author). 37 refs, 9 figs.

  6. Surface dose extrapolation measurements with radiographic film

    International Nuclear Information System (INIS)

    Butson, Martin J; Cheung Tsang; Yu, Peter K N; Currie, Michael

    2004-01-01

    Assessment of surface dose delivered from radiotherapy x-ray beams for optimal results should be performed both inside and outside the prescribed treatment fields. An extrapolation technique can be used with radiographic film to perform surface dose assessment for open field high energy x-ray beams. This can produce an accurate two-dimensional map of surface dose if required. Results have shown that the surface percentage dose can be estimated within ±3% of parallel plate ionization chamber results with radiographic film using a series of film layers to produce an extrapolated result. Extrapolated percentage dose assessment for 10 cm, 20 cm and 30 cm square fields was estimated to be 15% ± 2%, 29% ± 3% and 38% ± 3% at the central axis and relatively uniform across the treatment field. The corresponding parallel plate ionization chamber measurements are 16%, 27% and 37%, respectively. Surface doses are also measured outside the treatment field which are mainly due to scattered electron contamination. To achieve this result, film calibration curves must be irradiated to similar x-ray field sizes as the experimental film to minimize quantitative variations in film optical density caused by varying x-ray spectrum with field size. (note)

  7. Dose and dose rate effects of whole-body gamma-irradiation: I. Lymphocytes and lymphoid organs

    Science.gov (United States)

    Pecaut, M. J.; Nelson, G. A.; Gridley, D. S.

    2001-01-01

    The major goal of part I of this study was to compare varying doses and dose rates of whole-body gamma-radiation on lymphoid cells and organs. C57BL/6 mice (n = 75) were exposed to 0, 0.5, 1.5, and 3.0 Gy gamma-rays (60Co) at 1 cGy/min (low-dose rate, LDR) and 80 cGy/min (high-dose rate, HDR) and euthanized 4 days later. A significant dose-dependent loss of spleen mass was observed with both LDR and HDR irradiation; for the thymus this was true only with HDR. Decreasing leukocyte and lymphocyte numbers occurred with increasing dose in blood and spleen at both dose rates. The numbers (not percentages) of CD3+ T lymphocytes decreased in the blood in a dose-dependent manner at both HDR and LDR. Splenic T cell counts decreased with dose only in HDR groups; percentages increased with dose at both dose rates. Dose-dependent decreases occurred in CD4+ T helper and CD8+ T cytotoxic cell counts at HDR and LDR. In the blood the percentages of CD4+ cells increased with increasing dose at both dose rates, whereas in the spleen the counts decreased only in the HDR groups. The percentages of the CD8+ population remained stable in both blood and spleen. CD19+ B cell counts and percentages in both compartments declined markedly with increasing HDR and LDR radiation. NK1.1+ natural killer cell numbers and proportions remained relatively stable. Overall, these data indicate that the observed changes were highly dependent on the dose, but not dose rate, and that cells in the spleen are more affected by dose rate than those in blood. The results also suggest that the response of lymphocytes in different body compartments may be variable.

  8. 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

  9. Synchronized dynamic dose reconstruction

    International Nuclear Information System (INIS)

    Litzenberg, Dale W.; Hadley, Scott W.; Tyagi, Neelam; Balter, James M.; Ten Haken, Randall K.; Chetty, Indrin J.

    2007-01-01

    Variations in target volume position between and during treatment fractions can lead to measurable differences in the dose distribution delivered to each patient. Current methods to estimate the ongoing cumulative delivered dose distribution make idealized assumptions about individual patient motion based on average motions observed in a population of patients. In the delivery of intensity modulated radiation therapy (IMRT) with a multi-leaf collimator (MLC), errors are introduced in both the implementation and delivery processes. In addition, target motion and MLC motion can lead to dosimetric errors from interplay effects. All of these effects may be of clinical importance. Here we present a method to compute delivered dose distributions for each treatment beam and fraction, which explicitly incorporates synchronized real-time patient motion data and real-time fluence and machine configuration data. This synchronized dynamic dose reconstruction method properly accounts for the two primary classes of errors that arise from delivering IMRT with an MLC: (a) Interplay errors between target volume motion and MLC motion, and (b) Implementation errors, such as dropped segments, dose over/under shoot, faulty leaf motors, tongue-and-groove effect, rounded leaf ends, and communications delays. These reconstructed dose fractions can then be combined to produce high-quality determinations of the dose distribution actually received to date, from which individualized adaptive treatment strategies can be determined

  10. Low doses effects

    International Nuclear Information System (INIS)

    Tubiana, M.

    1997-01-01

    In this article is asked the question about a possible carcinogens effect of low dose irradiation. With epidemiological data, knowledge about the carcinogenesis, the professor Tubiana explains that in spite of experiments made on thousand or hundred of thousands animals it has not been possible to bring to the fore a carcinogens effect for low doses and then it is not reasonable to believe and let the population believe that low dose irradiation could lead to an increase of neoplasms and from this point of view any hardening of radiation protection standards could in fact, increase anguish about ionizing radiations. (N.C.)

  11. Studying and measuring the gamma radiation doses in Homs city

    International Nuclear Information System (INIS)

    Sofaan, A. H.

    2001-01-01

    The gamma radiation dose was measured in Homs city by using many portable dosimeters (electronic dosimeter and Geiger-Muller). The measurements were carried out in the indoor and outdoor buildings, for different time period, through one year (1999-2000). High purity germanium detector with low back ground radiation (HpGe) was used to determine radiation element contained in some building and the surrounding soil. The statistical analysis laws were applied to make sure that the measured dose distribution around average value is normal distribution. The measurement indicates that the gamma indoor dose varies from 312μSv/y to 511μSv/y, with the average annual dose of 385μSv/y. However the gamma outdoor dose rate varies from 307μSv/y to 366μSv/y with an average annual dose 385μSv/y. The annual outdoor gamma radiation dose is about %16 lower than the outdoor dose in Homs City. These measurements have indicated that environmental gamma doses in Homs City are relatively low. This is because that most of the soils and rocks in the area are limestone. (author)

  12. The Use Of Optical Properties Of Cr-39 In Alpha Particle Equivalent Dose Measurements

    International Nuclear Information System (INIS)

    Shnishin, K.A.

    2007-01-01

    In this work, optical properties of alpha irradiated Cr-39 were measured as a function of optical photon wavelength from 200-1100 nm. Optical energy gap and optical absorption at finite wavelength was also calculated and correlated to alpha fluence and dose equivalent. Alpha doses were calculated from the corresponding irradiation fluence and specific energy loss using TRIM computer program. It was found that, the optical absorption of unattached Cr-39 was varied with alpha fluence and corresponding equivalent doses. Also the optical energy gab was varied with fluence and dose equivalent of alpha particles. This work introduces a reasonably simple method for the Rn dose equivalent calculation by Cr-39 track

  13. Uncertainties on lung doses from inhaled plutonium.

    Science.gov (United States)

    Puncher, Matthew; Birchall, Alan; Bull, Richard K

    2011-10-01

    In a recent epidemiological study, Bayesian uncertainties on lung doses have been calculated to determine lung cancer risk from occupational exposures to plutonium. These calculations used a revised version of the Human Respiratory Tract Model (HRTM) published by the ICRP. In addition to the Bayesian analyses, which give probability distributions of doses, point estimates of doses (single estimates without uncertainty) were also provided for that study using the existing HRTM as it is described in ICRP Publication 66; these are to be used in a preliminary analysis of risk. To infer the differences between the point estimates and Bayesian uncertainty analyses, this paper applies the methodology to former workers of the United Kingdom Atomic Energy Authority (UKAEA), who constituted a subset of the study cohort. The resulting probability distributions of lung doses are compared with the point estimates obtained for each worker. It is shown that mean posterior lung doses are around two- to fourfold higher than point estimates and that uncertainties on doses vary over a wide range, greater than two orders of magnitude for some lung tissues. In addition, we demonstrate that uncertainties on the parameter values, rather than the model structure, are largely responsible for these effects. Of these it appears to be the parameters describing absorption from the lungs to blood that have the greatest impact on estimates of lung doses from urine bioassay. Therefore, accurate determination of the chemical form of inhaled plutonium and the absorption parameter values for these materials is important for obtaining reliable estimates of lung doses and hence risk from occupational exposures to plutonium.

  14. Doses from radioactive methane

    International Nuclear Information System (INIS)

    Phipps, A.W.; Kendall, G.M.; Fell, T.P.; Harrison, J.D.

    1990-01-01

    A possible radiation hazard arises from exposure to methane labelled with either a 3 H or a 14 C nuclide. This radioactive methane could be released from a variety of sources, e.g. land burial sites containing radioactive waste. Standard assumptions adopted for vapours would not apply to an inert alkane like methane. This paper discusses mechanisms by which radioactive methane would irradiate tissues and provides estimates of doses. Data on skin thickness and metabolism of methane are discussed with reference to these mechanisms. It is found that doses are dominated by dose from the small fraction of methane which is inhaled and metabolised. This component of dose has been calculated under rather conservative assumptions. (author)

  15. Controllable dose; Dosis controlable

    Energy Technology Data Exchange (ETDEWEB)

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

    2004-07-01

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

  16. Acetaminophen dosing for children

    Science.gov (United States)

    ... your child, call your provider. Proper Dosing of Suppositories If your child is vomiting or will not take oral medicine, you can use suppositories. Suppositories are placed in the anus to deliver ...

  17. Radiation dose electrophysiology procedures

    International Nuclear Information System (INIS)

    Hernandez-Armas, J.; Rodriguez, A.; Catalan, A.; Hernandez Armas, O.; Luque Japon, L.; Moral, S.; Barroso, L.; Rfuez-Hdez, R.

    2006-01-01

    The aim of this paper has been to measure and analyse some of the parameters which are directly related with the doses given to patients in two electrophysiology procedures: diagnosis and ablation with radiofrequency. 16 patients were considered in this study. 13 them had an ablation with radiofrequency at the Unit of Electrophysiology at the University Hospital of the Canaries, La Laguna., Tenerife. The results of skin doses, in the ablation cases, were higher than 2 Gy (threshold of some deterministic effects). The average value was 1.1 Gy. The personal doses, measured under the lead apron, for physician and nurses were 4 and 3 micro Sievert. These results emphasised the necessity of radiation protection measures in order to reduce, ad much as possible, the doses to patients. (Author)

  18. Dose in conventional radiography

    International Nuclear Information System (INIS)

    Acuna D, E.; Padilla R, Z. P.; Escareno J, E.; Vega C, H. R.

    2011-10-01

    It has been pointed out that medical exposures are the most significant sources of exposure to ionizing radiation for the general population. Inside the medical exposures the most important is the X-ray use for diagnosis, which is by far the largest contribution to the average dose received by the population. From all studies performed in radiology the chest radiography is the most abundant. In an X-ray machine, voltage and current are combined to obtain a good image and a reduce dose, however due to the workload in a radiology service individual dose is not monitored. In order to evaluate the dose due to chest radiography in this work a plate phantom was built according to the ISO recommendations using methylmethacrylate walls and water. The phantom was used in the Imaging department of the Zacatecas General Hospital as a radiology patient asking for a chest study; using thermoluminescent dosimeters, TLD 100 the kerma at the surface entrance was determined. (Author)

  19. Maximum permissible dose

    International Nuclear Information System (INIS)

    Anon.

    1979-01-01

    This chapter presents a historic overview of the establishment of radiation guidelines by various national and international agencies. The use of maximum permissible dose and maximum permissible body burden limits to derive working standards is discussed

  20. Irradiation dose of cosmonauts

    International Nuclear Information System (INIS)

    Makra, Zs.

    1978-01-01

    The results obtained by determining the irradiation dose during the spaceflights of Apollo as well as the Sojouz-3 and Sojouz-9 spacecrafts have been compared in the form of tables. In case of Apollo astronauts the irradiation dose was determined by two methods and its sources were also pointed out, in tables. During Sojouz spacetravels the cosmonauts were exposed to a negligible dose. In spite of this fact the radiation danger is considerable. The small irradiation doses noticed so far are due to the fact that during the spaceflights there was no big proturberance. However, during the future long-range spacetravels a better radiation shielding than the one used up to now will be necessary. (P.J.)

  1. Ibuprofen dosing for children

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000772.htm Ibuprofen dosing for children To use the sharing features ... much of this medicine can be harmful. How Ibuprofen can Help Your Child Ibuprofen is a type ...

  2. Partially linear varying coefficient models stratified by a functional covariate

    KAUST Repository

    Maity, Arnab; Huang, Jianhua Z.

    2012-01-01

    We consider the problem of estimation in semiparametric varying coefficient models where the covariate modifying the varying coefficients is functional and is modeled nonparametrically. We develop a kernel-based estimator of the nonparametric

  3. Effects of low doses

    International Nuclear Information System (INIS)

    Le Guen, B.

    2001-01-01

    Actually, even though it is comfortable for the risk management, the hypothesis of the dose-effect relationship linearity is not confirmed for any model. In particular, in the area of low dose rate delivered by low let emitters. this hypothesis is debated at the light of recent observations, notably these ones relative to the mechanisms leading to genetic instability and induction eventuality of DNA repair. The problem of strong let emitters is still to solve. (N.C.)

  4. Gonadal doses from radiotherapy

    International Nuclear Information System (INIS)

    Solomon, S.B.; Morris, N.D.

    1980-06-01

    The method of calculation of gonadal doses arising from different radiotherapeutic procedures is described. The measurement of scatter factors to the gonads from superficial and deep therapy is detailed and the analytic fits to the experimental data, as a function of field position, field size and beam energy are given. The data used to calculate the gonadal doses from treatments using linear accelerators, teletherapy and sealed sources are described and the analytic fits to the data given

  5. Comparison of Linear Microinstability Calculations of Varying Input Realism

    International Nuclear Information System (INIS)

    Rewoldt, G.

    2003-01-01

    The effect of varying ''input realism'' or varying completeness of the input data for linear microinstability calculations, in particular on the critical value of the ion temperature gradient for the ion temperature gradient mode, is investigated using gyrokinetic and gyrofluid approaches. The calculations show that varying input realism can have a substantial quantitative effect on the results

  6. Comparison of linear microinstability calculations of varying input realism

    International Nuclear Information System (INIS)

    Rewoldt, G.; Kinsey, J.E.

    2004-01-01

    The effect of varying 'input realism' or varying completeness of the input data for linear microinstability calculations, in particular on the critical value of the ion temperature gradient for the ion temperature gradient mode, is investigated using gyrokinetic and gyrofluid approaches. The calculations show that varying input realism can have a substantial quantitative effect on the results

  7. Receptor dose and patient dose in radiographic exposures: a 15 year review

    International Nuclear Information System (INIS)

    Peet, D.J.; Tyler, N.; Pryor, M.; Hollaway, P.; Strudley, C.; Leavesley, L.

    2008-01-01

    A patient dose programme has been established locally for the last 15 years across 109 hospitals and 250 X-ray rooms in line with the National Protocol, in conjunction with a programme to look at routine performance of these rooms. Routine performance checks initially looked primarily at film density and AEC performance but with the introduction of Computerised Radiography (CR) across UK hospitals and a revision of recommended procedures in the UK, the emphasis has shifted to assessing receptor dose under AEC control. Results show a wide variation in film density in the early years indicating sub optimal performance and dose. The spread was reduced over later years. The introduction of CR has led to a variety of approaches by the CR companies, X-ray companies and local sites. Receptor doses vary widely as a result. Large variations within hospitals were also observed. The doses over the last 15 years are reviewed and compared against diagnostic reference levels and with the performance of the imaging chain. Results show that patient dose programmes and optimisation strategies were having an impact, but the introduction of CR requires renewed efforts to ensure images and doses are optimised. (author)

  8. Absorbed dose from traversing spherically symmetric, Gaussian radioactive clouds

    International Nuclear Information System (INIS)

    Thompson, J.M.; Poston, J.W.

    1999-01-01

    If a large radioactive cloud is produced, sampling may require that an airplane traverse the cloud. A method to predict the absorbed dose to the aircrew from penetrating the radioactive cloud is needed. Dose rates throughout spherically symmetric Gaussian clouds of various sizes, and the absorbed doses from traversing the clouds, were calculated. Cloud size is a dominant parameter causing dose to vary by orders of magnitude for a given dose rate measured at some distance. A method to determine cloud size, based on dose rate readings at two or more distances from the cloud center, was developed. This method, however, failed to resolve the smallest cloud sizes from measurements made at 1,000 m to 2,000 m from the cloud center

  9. Patterns of dose variability in radiation prescription of breast cancer

    International Nuclear Information System (INIS)

    Das, Indra J.; Chee-Wai, Cheng; Fein, Douglas A.; Fowble, Barbara

    1995-01-01

    Objective: Radiation dose distribution varies with breast size, beam energy, beam modifiers (wedge, bolus), and beam weights. A dose variation as low as ± 5% has been observed to change outcome of the radiation treatment. Various reports suggest that radiation dose >50 Gy and dose inhomogeneity >10% have unfavorable cosmesis. It is difficult to estimate treatment outcome and compare data in various protocols due to the variability of dose prescriptions. A retrospective analysis of the pattern of dose prescription and intercomparison of various protocols is presented for the treatment of breast cancer. Materials and Methods: In this study, five prescription points were chosen to represent the commonly used protocols for breast irradiation. All these points lie on a line of height, h, of the breast apex from the posterior non-divergent beam edge at half the chest-wall separation,s . The points are located at a distance 1.5 cm, chest wall-lung interface (2-3 cm), (h(3)), (h(2)), and at isocenter. One hundred consecutive patients treated with intact breast irradiation following excisional biopsy were selected. For analysis, treatment planning was carried out without lung correction with a 6 MV beam for all patients, even though some of the patients were treated with high energy beams. Dose distributions were optimized with proper wedges and beam weights to provide a symmetrical dose distribution on the central axis plane. A multivariate analysis of the different parameters, s,h , dose at the hot spot, and doses at various prescription points were carried out. The patients were divided into three groups based on the chest-wall separations: small ( 22.0 cm). The dose distributions related to various prescription points used in different protocols were analyzed for three groups of the patients. Results: The magnitudes of the hot spots varied from +5% to +27% among the patient population, were directly related to s, and appeared to be independent of h. The hot spots

  10. A patient dose survey for femoral arteriogram diagnostic radiographic examinations using a dose-area product meter

    International Nuclear Information System (INIS)

    Thwaites, J.H.; Rafferty, M.W.; Gray, N.; Black, J.; Stock, B.

    1996-01-01

    A patient dose survey was carried out for femoral arteriogram procedures at the Sir Charles Gairdner Hospital. The procedure involves fluoroscopy to the pelvic region to locate a guide wire and catheter, followed by a series of radiographs extending from the pelvic area to the feet to form a collage image of the entire arterial system. Radiographs are taken whilst a bolus of contrast media is injected into the arterial system. A dose-area product meter was used to determine the dose-area product delivered to patients. Radiographic and patient details were logged with dose-area product for each part of each procedure. Mean energy imparted, mean effective dose and effective dose equivalent are calculated for the examinations. Calculated effective doses are shown to produce results consistent with those of other authors. We present a method for dealing with a complex radiographic procedure including multiple radiographs and fluoroscopy in an attempt to provide a simple way of calculating effective dose from which a general risk factor can be determined. The effective dose varies considerably from examination to examination due to the large range in the number of radiographs taken in any one procedure. A useful index can be obtained by logging the number of radiographs in each region, and fluoroscopy time, from which the effective dose may be easily calculated. These measurements extend a continuing survey of doses for common diagnostic radiographic examinations which previously included the simple examinations: lumbar spine, abdoment and pelvis. (author)

  11. Holographic cinematography of time-varying reflecting and time-varying phase objects using a Nd:YAG laser

    Science.gov (United States)

    Decker, A. J.

    1982-01-01

    The use of a Nd:YAG laser to record holographic motion pictures of time-varying reflecting objects and time-varying phase objects is discussed. Sample frames from both types of holographic motion pictures are presented. The holographic system discussed is intended for three-dimensional flow visualization of the time-varying flows that occur in jet-engine components.

  12. Internal 40K radiation dose to Indians

    International Nuclear Information System (INIS)

    Ranganathan, S.; Someswara Rao, M.; Nagaratnam, A.; Mishra, U.C.

    2002-01-01

    A group of 350 Indians from both sexes (7-65 years) representing different regions of India was studied for internal 40 K radiation dose from the naturally occurring body 40 K, which was measured in the National Institute of Nutrition (NIN) whole-body counter. Although the 40 K radioactivity reached a peak value by 18 years in female (2,412 Bq) and by 20 years in male (3,058 Bq) and then varied inversely with age in both sexes, the radiation dose did not show such a trend. Boys and girls of 11 years had annual effective dose of nearly 185 mSv, which decreased during adolescence (165 mSv), increased to 175 mSv by 18-20 years in adults and decreased progressively on further ageing to 99 mSv in males and 69 mSv in females at 65 years. The observed annual effective dose (175 mSv) of the young adults was close to that of the ICRP Reference Man (176 mSv) and Indian Reference Man (175 mSv). With a mean specific activity of 55 Bq/kg for the subjects and a conversion coefficient close to 3 mSv per annum per Bq/kg, the average annual effective dose from the internal 40 K turned out to be 165 mSv for Indians. (author)

  13. A modified thrombolytic scheme for the treatment of thrombosis in anatomically varied cerebral venous sinus

    International Nuclear Information System (INIS)

    Zhao Lin; Li Linfang; Liu Zengpin; Qin Huimin; Wang Tiegang; Zhou Cunhe

    2010-01-01

    Objective: To discuss the curative effect of unremitting pump infusion of microdose urokinase (100000 u / 24 h) into the cerebral venous sinus in treating thrombosis in cerebral venous sinus which had anatomical variation. Methods: Mechanical disruption of the thrombus and unremitting pump infusion of microdose urokinase (100000 u / 24 h) into the cerebral venous sinus for 48-96 hours were employed in 9 patients with thrombosis in anatomically varied cerebral venous sinus. After the procedure the original disorder was actively treated and the anticoagulant therapy was continued for 6 months. A follow-up of 6-12 months (mean 10 months) was conducted. Results: Recanalization of the previously occluded cerebral venous sinus was obtained in all 9 patients. The dose of urokinase was 100 000 u / 24 h in 8 patients. For the remaining one patient the dose of urokinase was 100000 u / 24 h in the first 48 hours, then the dose was increased to 250000 u / 24 h. Excellent result was obtained in all patients. Conclusion: Unremitting pump infusion of microdose urokinase into the cerebral venous sinus can effectively treat the thrombosis in anatomically varied cerebral venous sinus. (authors)

  14. Mutaciones asociadas con resistencia a rifampicina o isoniazida en aislamientos clínicos de M. tuberculosis de Sonora, México DNA mutations associated to rifampicin or isoniazid resistance in M. tuberculosis clinical isolates from Sonora, Mexico

    Directory of Open Access Journals (Sweden)

    Enrique Bolado-Martínez

    2012-04-01

    Full Text Available OBJETIVO: Realizar el análisis de regiones específicas de genes asociados con resistencia a isoniazida o rifampicina. MATERIAL Y MÉTODOS: Se estudiaron 22 cepas de M. tuberculosis, aisladas en Sonora, México. Se utilizaron iniciadores para regiones específicas de los genes rpoB, katG e inhA y la región ahpC-oxyR. Los productos de PCR se secuenciaron y analizaron. RESULTADOS: Se identificaron mutaciones en la región promotora del gen inhA, región ahpC-oxyR, codón 315 del gen katG y codones 451 ó 456 del gen rpoB. CONCLUSIONES: La identificación de mutaciones no descritas previamente obliga a continuar el análisis genotípico de cepas aisladas en Sonora.OBJECTIVE: To perform the analysis of specific regions of the major genes associated with resistance to isoniazid or rifampin. MATERIALS AND METHODS: Twenty two M. tuberculosis strains, isolated from human samples obtained in Sonora, Mexico. Specific primers for hotspots of the rpoB, katG, inhA genes and the ahpC-oxyR intergenic region were used. The purified PCR products were sequenced. RESULTS: Mutations in the promoter of inhA, the ahpC-oxyR region, and codon 315 of katG and in 451 or 456 codons of rpoB, were identified. CONCLUSIONS: Detection of mutations not previously reported requires further genotypic analysis of Mycobacterium tuberculosis isolates in Sonora.

  15. Analysis of T101 outage radiation dose

    International Nuclear Information System (INIS)

    Li, Zhonghua

    2008-01-01

    Full text: Collective radiation dose during outage is about 80% of annual collective radiation dose at nuclear power plants (NPPs). T 101 Outage is the first four-year outage of Unit 1 at Tianwan Nuclear Power Station (TNPS) and thorough overhaul was undergone for the 105-day's duration. Therefore, T 101 Outage has significant reference meaning to reducing collective radiation dose at TNPS. This paper collects the radiation dose statistics during T 101 Outage and analyses the radiation dose distribution according to tasks, work kinds and varying trend of the collective radiation dose etc., comparing with other similar PWRs in the world. Based on the analysis this paper attempts to find out the major factors in collective radiation dose during T 101 Outage. The major positive factor is low radiation level at workplace, which profits from low content of Co in reactor construction materials, optimised high-temperature p H value of the primary circuit coolant within the tight range and reactor operation without trips within the first fuel cycle. One of the most negative factors is long outage duration and many person-hours spent in the radiological controlled zone, caused by too many tasks and inefficient work. So besides keeping good performance of reducing radioactive sources, it should be focused on how to improve implementation of work management including work selection, planning and scheduling, work preparation, work implementation, work assessment and feedback, which can lead to reduced numbers of workers needed to perform a task, of person-hours spent in the radiological controlled zone. Moreover, this leads to reduce occupational exposures in an ALARA fashion. (author)

  16. Optimized Dose Distribution of Gammamed Plus Vaginal Cylinders

    International Nuclear Information System (INIS)

    Supe, Sanjay S.; Bijina, T.K.; Varatharaj, C.; Shwetha, B.; Arunkumar, T.; Sathiyan, S.; Ganesh, K.M.; Ravikumar, M.

    2009-01-01

    Endometrial carcinoma is the most common malignancy arising in the female genital tract. Intracavitary vaginal cuff irradiation may be given alone or with external beam irradiation in patients determined to be at risk for locoregional recurrence. Vaginal cylinders are often used to deliver a brachytherapy dose to the vaginal apex and upper vagina or the entire vaginal surface in the management of postoperative endometrial cancer or cervical cancer. The dose distributions of HDR vaginal cylinders must be evaluated carefully, so that clinical experiences with LDR techniques can be used in guiding optimal use of HDR techniques. The aim of this study was to optimize dose distribution for Gammamed plus vaginal cylinders. Placement of dose optimization points was evaluated for its effect on optimized dose distributions. Two different dose optimization point models were used in this study, namely non-apex (dose optimization points only on periphery of cylinder) and apex (dose optimization points on periphery and along the curvature including the apex points). Thirteen dwell positions were used for the HDR dosimetry to obtain a 6-cm active length. Thus 13 optimization points were available at the periphery of the cylinder. The coordinates of the points along the curvature depended on the cylinder diameters and were chosen for each cylinder so that four points were distributed evenly in the curvature portion of the cylinder. Diameter of vaginal cylinders varied from 2.0 to 4.0 cm. Iterative optimization routine was utilized for all optimizations. The effects of various optimization routines (iterative, geometric, equal times) was studied for the 3.0-cm diameter vaginal cylinder. The effect of source travel step size on the optimized dose distributions for vaginal cylinders was also evaluated. All optimizations in this study were carried for dose of 6 Gy at dose optimization points. For both non-apex and apex models of vaginal cylinders, doses for apex point and three dome

  17. Dose Recalculation and the Dose-Guided Radiation Therapy (DGRT) Process Using Megavoltage Cone-Beam CT

    International Nuclear Information System (INIS)

    Cheung, Joey; Aubry, Jean-Francois; Yom, Sue S.; Gottschalk, Alexander R.; Celi, Juan Carlos; Pouliot, Jean

    2009-01-01

    Purpose: At University of California San Francisco, daily or weekly three-dimensional images of patients in treatment position are acquired for image-guided radiation therapy. These images can be used for calculating the actual dose delivered to the patient during treatment. In this article, we present the process of performing dose recalculation on megavoltage cone-beam computed tomography images and discuss possible strategies for dose-guided radiation therapy (DGRT). Materials and Methods: A dedicated workstation has been developed to incorporate the necessary elements of DGRT. Patient image correction (cupping, missing data artifacts), calibration, completion, recontouring, and dose recalculation are all implemented in the workstation. Tools for dose comparison are also included. Examples of image correction and dose analysis using 6 head-and-neck and 2 prostate patient datasets are presented to show possible tracking of interfraction dosimetric endpoint variation over the course of treatment. Results: Analysis of the head-and-neck datasets shows that interfraction treatment doses vary compared with the planning dose for the organs at risk, with the mean parotid dose and spinal cord D 1 increasing by as much as 52% and 10%, respectively. Variation of the coverage to the target volumes was small, with an average D 5 dose difference of 1%. The prostate patient datasets revealed accurate dose coverage to the targeted prostate and varying interfraction dose distributions to the organs at risk. Conclusions: An effective workflow for the clinical implementation of DGRT has been established. With these techniques in place, future clinical developments in adaptive radiation therapy through daily or weekly dosimetric measurements of treatment day images are possible.

  18. Assessment of internal doses

    CERN Document Server

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

    2002-01-01

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

  19. Mean inactivation dose (D)

    International Nuclear Information System (INIS)

    Vijayakumar, S.; Ng, T.C.; Raudkivi, U.; Meaney, T.J.

    1990-01-01

    By predicting treatment outcome to radiotherapy from in vitro radiobiological parameters, not only individual patient treatments can be tailored, but also new promising treatment protocols can be tried in patients in whom unfavorable outcome is predicted. In this respect, choosing the right parameter can be very important. Unlike D 0 and N which provide information of the distal part of the survival curve, mean inactivation dose (D) estimates overall radiosensitivity. However, the parameters reflecting the response at the clinically relevant low-dose region are neglected in the literature. In a literature survey of 98 papers in which survival curves or D 0 /N were used, only in 2 D was used. In 21 papers the D 0 /n values were important in drawing conclusions. By calculating D in 3 of these 21 papers, we show that the conclusion drawn may be altered with the use of D. The importance of ''low-dose-region-parameters'' is reviewed. (orig.)

  20. Committed effective dose from thoron daughters inhalation

    International Nuclear Information System (INIS)

    Campos, M.P.; Pecequilo, B.R.S.

    2000-01-01

    Mankind's interest in natural radiation exposure levels has increased over the past fifty years and it is now recognized that the most significant contributors to human irradiation by natural sources are the short-lived decay products of radon ( 222 Rn) and thoron ( 220 Rn). Despite the thoron short half-life of 55 s, effective dose from inhalation of thoron an its progeny ( 212 Pb and 212 Bi) must be considered, owing to the high thorium background in countries like Brazil, China and India, for example. The indoor committed effective dose was assessed by air sampling at the thorium purification plant and the nuclear materials storage site of the Instituto de Pesquisas Energeticas e Nucleares; Sao Paulo, Brazil. A total of 21 glass fiber filter samples was analyzed by high resolution gamma ray spectrometry in order to obtain the 212 Pb and 212 Bi activities. The equilibrium equivalent concentration (EEC) varied from 0.3 Bq/m 3 to 6.8 Bq/m 3 for the storage site air samples and from 9.9 Bq/m 3 to 249.8 Bq/m 3 for the thorium purification plant air samples. As retention studies indicate a biological half-life of a few hours inhaled thoron progeny in the human lungs, the main fraction of the potential alpha energy (PAEC) deposited is absorbed in the lungs, meaning negligible to the effective dose the contribution of the dose in other times. The committed effective dose due thoron progeny was performed by compartimental analysis following the ICRP 66 lung compartimental model and ICRP 67 lead compartimental model. The values obtained varied from 0.03 mSv/a to 0.67 mSv/a for the storage site air samples and from 0.12 mSv/a to 6.00 mSv/a for the thorium purification plant air samples. (author)

  1. Dose Reduction Techniques

    International Nuclear Information System (INIS)

    WAGGONER, L.O.

    2000-01-01

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

  2. CT dose management

    International Nuclear Information System (INIS)

    Zasheva, Ts.; Georgiev, E.; Kirova, G.

    2013-01-01

    Full text: Introduction: In recent decades Computed Tomography established itself as one of the most common study with a very wide range of applications and techniques of scanning. Best diagnostic value of the method resist to the risks of ionizing radiation, as statistics show that CT is one of the main sources of continuously increasing dose to the population. What you will learn: The physical parameters of the X-ray tube and the principles of image reconstruction; The relationship between variables parameters and the received dose; The ratio between the force and voltage of the current to the image quality, Influence of the used contrast medium to the physical properties of the image, The ratio of patient BMI to image processing, Effective use of knowledge for the optimal CT protocol. Discussions: The goal to reduce the dose received by the patient during a CT scan while keeping the diagnostic quality of the image puts to the test as handset X-ray producers and technicians who need to master the technique of study protocol forming as well as to balance the harm - benefit ratio. Among the most popular techniques are these of dose modulation, low-dose computed tomography at the expense of a reduction of the current or voltage intensity, and control of the number of post-processing algorithms for the image reconstruction. Conclusion: The training of radiologists and X-ray technicians plays a major role in optimizing of technical parameters in view of the reduction of the dose for the patient, while maintaining the diagnostic quality of the image

  3. Dose Reduction Techniques

    Energy Technology Data Exchange (ETDEWEB)

    WAGGONER, L.O.

    2000-05-16

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

  4. In vitro and in vivo effects of low dose HTO contamination modulated by dose rate

    International Nuclear Information System (INIS)

    Petcu, I.; Savu, D.; Moisoi, N.; Koeteles, G.J.

    1997-01-01

    The experiment performed in vitro intended to examine whether an adaptive response could be elicited on lymphocytes by low-level contamination of whole blood with tritiated water and if the modification of the dose rate has any influence on it. Lymphocytes pre-exposed to 3 HOH (0.2 - 6.6 MBq/ml) and subsequently irradiated with I Gy γ-rays showed micronuclei frequency significantly lower (40% - 45%) than the expected member (sum of the yields induced by 3 HOH and γ-rays separately). The degree of the radioresistance induced by HTO pre-treatments became higher with decreasing dose-rate for a rather similar total adapting dose. In vivo, the aim of the study was to investigate if different dose rates are inducing modulation of the lipid peroxidation level and of the thymidine uptake in different tissues of animals contaminated by HTO ingestion. The total doses varied between 5 and 20 cGy and were delivered as chronic (100 days) or acute contamination (5 days). It was observed that only doses about 20 cGy caused a dose-rate dependent increase of the lipid peroxidation level in the tissues of small intestine, kidney and spleen. Both chronic and acute contamination did produce reduced incorporation of thymidine in the cells of bone marrow. The most effective decrease of thymidine uptake was induced by the acute contamination in the lower dose domain (approx. 5 cGy). Our hypothesis is that in this dose domain the modification of thymidine uptake could be due to changes at the level of membrane transport. (author)

  5. Radioactive cloud dose calculations

    International Nuclear Information System (INIS)

    Healy, J.W.

    1984-01-01

    Radiological dosage principles, as well as methods for calculating external and internal dose rates, following dispersion and deposition of radioactive materials in the atmosphere are described. Emphasis has been placed on analytical solutions that are appropriate for hand calculations. In addition, the methods for calculating dose rates from ingestion are discussed. A brief description of several computer programs are included for information on radionuclides. There has been no attempt to be comprehensive, and only a sampling of programs has been selected to illustrate the variety available

  6. Simulation experiment on total ionization dose effects of linear CCD

    International Nuclear Information System (INIS)

    Tang Benqi; Zhang Yong; Xiao Zhigang; Wang Zujun; Huang Shaoyan

    2004-01-01

    We carry out the ionization radiation experiment of linear CCDs operated in unbiased, biased, biased and driven mode respectively by Co-60 γ source with our self-designed test system, and offline test the Dark signal and Saturation voltage and SNR varied with total dose for TCD132D, and get some valuable results. On the basis of above work, we set forth a primary experiment approaches to simulate the total dose radiation effects of charge coupled devices. (authors)

  7. Biological effective dose studies in carcinoma of uterine cervix

    International Nuclear Information System (INIS)

    Yadav, Poonam; Ramasubramanian, V.

    2008-01-01

    Cancer of cervix is the second most common cancer worldwide among women. Several treatments related protocols of radiotherapy have been followed over few decades in its treatment for evaluating the response. These physical doses varying on the basics of fractionation size, dose rate and total dose needed to be indicated as biological effective dose (BED) to rationalize these treatments. The curative potential of radiation therapy in the management of carcinoma of the cervix is greatly enhanced by the use of intracavitary brachytherapy. Successful brachytherapy requires the high radiation dose to be delivered to the tumor where as minimum radiation dose reach to surrounding normal tissue. Present study is aimed to evaluate biologically effective dose in patients receiving high dose-rate brachytherapy plus external beam radiotherapy based on tumor cell proliferation values in cancer of the cervix patients. The study includes 30 patients' data as a retrospective analysis. In addition determine extent of a dose-response relationship existing between the biological effective dose at Point A and the bladder and rectum and the clinical outcomes

  8. Effect of low gamma ray doses on sugar beet

    International Nuclear Information System (INIS)

    Al-Oudat, M.

    1993-01-01

    We studied the effect of presowing irradiation simulation on sugar beet seeds in two regions (Deir Elzour and Damascus) and for three successive cropping seasons (1986-1989). Those seeds were irradiated with gamma radiation doses varying from 0.005 to 0.050 kGy in the first region, and from 0.005 to 0.025 kGy in the second region. Results showed that doses varying from 0.005 to 0.05 kGy in Deir Elzour gave a mean yield increase varying from 17.4% to 22.6%. However, doses varying from 0.005 to 0.025 in Damascus gave an increase of the same parameter between 19.5% and 23.8%. The best results for pure sugar yield increase obtained for a dose of 0.015 kGy (27.1% in Deir Elzour and 31.9% in Damascus). Yields on the farm level obtained from presowing irradiated seeds showed an increase in sugar beets when using 0.015 kGy gamma radiation dose. (author)

  9. Lead in teeth from lead-dosed goats: Microdistribution and relationship to the cumulative lead dose

    International Nuclear Information System (INIS)

    Bellis, David J.; Hetter, Katherine M.; Jones, Joseph; Amarasiriwardena, Dula; Parsons, Patrick J.

    2008-01-01

    Teeth are commonly used as a biomarker of long-term lead exposure. There appear to be few data, however, on the content or distribution of lead in teeth where data on specific lead intake (dose) are also available. This study describes the analysis of a convenience sample of teeth from animals that were dosed with lead for other purposes, i.e., a proficiency testing program for blood lead. Lead concentration of whole teeth obtained from 23 animals, as determined by atomic absorption spectrometry, varied from 0.6 to 80 μg g -1 . Linear regression of whole tooth lead (μg g -1 ) on the cumulative lead dose received by the animal (g) yielded a slope of 1.2, with r 2 =0.647 (p -1 , were found in circumpulpal dentine. Linear regression of circumpulpal lead (μg g -1 ) on cumulative lead dose (g) yielded a slope of 23 with r 2 =0.961 (p=0.0001). The data indicated that whole tooth lead, and especially circumpulpal lead, of dosed goats increased linearly with cumulative lead exposure. These data suggest that circumpulpal dentine is a better biomarker of cumulative lead exposure than is whole tooth lead, at least for lead-dosed goats

  10. Estimating varying coefficients for partial differential equation models.

    Science.gov (United States)

    Zhang, Xinyu; Cao, Jiguo; Carroll, Raymond J

    2017-09-01

    Partial differential equations (PDEs) are used to model complex dynamical systems in multiple dimensions, and their parameters often have important scientific interpretations. In some applications, PDE parameters are not constant but can change depending on the values of covariates, a feature that we call varying coefficients. We propose a parameter cascading method to estimate varying coefficients in PDE models from noisy data. Our estimates of the varying coefficients are shown to be consistent and asymptotically normally distributed. The performance of our method is evaluated by a simulation study and by an empirical study estimating three varying coefficients in a PDE model arising from LIDAR data. © 2017, The International Biometric Society.

  11. Fertilizer micro-dosing

    International Development Research Centre (IDRC) Digital Library (Canada)

    Localized application of small quantities of fertilizer (micro-dosing), combined with improved planting pits for rainwater harvesting, has generated greater profits and food security for women farmers in the Sahel. • Women are 25% more likely to use combined applications, and have expanded areas of food crops (cowpea,.

  12. Weldon Spring dose calculations

    International Nuclear Information System (INIS)

    Dickson, H.W.; Hill, G.S.; Perdue, P.T.

    1978-09-01

    In response to a request by the Oak Ridge Operations (ORO) Office of the Department of Energy (DOE) for assistance to the Department of the Army (DA) on the decommissioning of the Weldon Spring Chemical Plant, the Health and Safety Research Division of the Oak Ridge National Laboratory (ORNL) performed limited dose assessment calculations for that site. Based upon radiological measurements from a number of soil samples analyzed by ORNL and from previously acquired radiological data for the Weldon Spring site, source terms were derived to calculate radiation doses for three specific site scenarios. These three hypothetical scenarios are: a wildlife refuge for hunting, fishing, and general outdoor recreation; a school with 40 hr per week occupancy by students and a custodian; and a truck farm producing fruits, vegetables, meat, and dairy products which may be consumed on site. Radiation doses are reported for each of these scenarios both for measured uranium daughter equilibrium ratios and for assumed secular equilibrium. Doses are lower for the nonequilibrium case

  13. Low dose epidemiologic studies

    International Nuclear Information System (INIS)

    Anon.

    1990-01-01

    In this chapter the BEIR committee has reviewed low-dose irradiation studies since the BEIR III report. They have considered the carcinogenic effectiveness of low-LET in populations exposed to radiation from a number of different sources: diagnostic radiography; fallout from nuclear weapons testing; nuclear installations; radiation in the workplace and high levels of natural background radiation

  14. Radiation doses to Finns

    International Nuclear Information System (INIS)

    Rantalainen, L.

    1996-01-01

    The estimated annual radiation doses to Finns have been reduced in the recent years without any change in the actual radiation environment. This is because the radiation types have been changed. The risk factors will probably be changed again in the future, because recent studies show discrepancies in the neutron dosimetry concerning the city of Hiroshima. Neutron dosimetry discrepancy has been found between the predicted and estimated neutron radiation. The prediction of neutron radiation is calculated by Monte Carlo simulations, which have also been used when designing recommendations for the limits of radiation doses (ICRP60). Estimation of the neutron radiation is made on the basis of measured neutron activation of materials in the city. The estimated neutron dose beyond 1 km is two to ten, or more, times as high as the predicted dose. This discrepancy is important, because the most relevant distances with respect to radiation risk evaluation are between 1 and 2 km. Because of this discrepancy, the present radiation risk factors for gamma and neutron radiation, which rely on the Monte Carlo calculations, are false, too. The recommendations of ICRP60 have been adopted in a few countries, including Finland, and they affect the planned common limits of the EU. It is questionable whether happiness is increased by adopting false limits, even if they are common. (orig.) (2 figs., 1 tab.)

  15. Dose Reduction Techniques

    CERN Document Server

    Waggoner, L O

    2000-01-01

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

  16. Dose tracking and dose auditing in a comprehensive computed tomography dose-reduction program.

    Science.gov (United States)

    Duong, Phuong-Anh; Little, Brent P

    2014-08-01

    Implementation of a comprehensive computed tomography (CT) radiation dose-reduction program is a complex undertaking, requiring an assessment of baseline doses, an understanding of dose-saving techniques, and an ongoing appraisal of results. We describe the role of dose tracking in planning and executing a dose-reduction program and discuss the use of the American College of Radiology CT Dose Index Registry at our institution. We review the basics of dose-related CT scan parameters, the components of the dose report, and the dose-reduction techniques, showing how an understanding of each technique is important in effective auditing of "outlier" doses identified by dose tracking. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. When is a dose not a dose?

    International Nuclear Information System (INIS)

    Bond, V.P.

    1991-01-01

    Although an enormous amount of progress has been made in the fields of radiation protection and risk assessment, a number of significant problems remain. The one problem which transcends all the rest, and which has been subject to considerable misunderstanding, involves what has come to be known as the 'linear non-threshold hypothesis', or 'linear hypothesis'. Particularly troublesome has been the interpretation that any amount of radiation can cause an increase in the excess incidence of cancer. The linear hypothesis has dominated radiation protection philosophy for more than three decades, with enormous financial, societal and political impacts and has engendered an almost morbid fear of low-level exposure to ionizing radiation in large segments of the population. This document presents a different interpretation of the linear hypothesis. The basis for this view lies in the evolution of dose-response functions, particularly with respect to their use initially in the context of early acute effects, and then for the late effects, carcinogenesis and mutagenesis. 11 refs., 4 figs

  18. Dose specification for radiation therapy: dose to water or dose to medium?

    International Nuclear Information System (INIS)

    Ma, C-M; Li Jinsheng

    2011-01-01

    The Monte Carlo method enables accurate dose calculation for radiation therapy treatment planning and has been implemented in some commercial treatment planning systems. Unlike conventional dose calculation algorithms that provide patient dose information in terms of dose to water with variable electron density, the Monte Carlo method calculates the energy deposition in different media and expresses dose to a medium. This paper discusses the differences in dose calculated using water with different electron densities and that calculated for different biological media and the clinical issues on dose specification including dose prescription and plan evaluation using dose to water and dose to medium. We will demonstrate that conventional photon dose calculation algorithms compute doses similar to those simulated by Monte Carlo using water with different electron densities, which are close (<4% differences) to doses to media but significantly different (up to 11%) from doses to water converted from doses to media following American Association of Physicists in Medicine (AAPM) Task Group 105 recommendations. Our results suggest that for consistency with previous radiation therapy experience Monte Carlo photon algorithms report dose to medium for radiotherapy dose prescription, treatment plan evaluation and treatment outcome analysis.

  19. The background and rationale for a new fixed-dose combination for first-line treatment of tuberculosis in children.

    Science.gov (United States)

    Graham, S M; Grzemska, M; Gie, R P

    2015-12-01

    In 2010, the World Health Organization revised the recommendations for the treatment of tuberculosis (TB) in children. The major revision was to increase isoniazid, rifampicin and pyrazinamide dosages according to body weight in children. The recommendations for higher dosages are based on consistent evidence from 1) pharmacokinetic studies suggesting that young children require higher dosages than adolescents and adults to achieve desired serum concentrations; and 2) observational studies reporting that the higher dosages would not be associated with increased risk of toxicity in children. However, national tuberculosis programmes faced unforeseen challenges in implementing the revised recommendations. The main difficulty was to adapt the revised dosages for the treatment of children with drug-susceptible TB using available fixed-dose combinations (FDCs). A more suitable FDC for the intensive and continuation phases of treatment has now been developed for planned implementation in 2015. This paper explains the background and rationale for the development of a new FDC tablet for children with drug-susceptible TB.

  20. Dose prescription in boron neutron capture therapy

    International Nuclear Information System (INIS)

    Gupta, N.M.S.; Gahbauer, R.A.; Blue, T.E.; Wambersie, A.

    1994-01-01

    The purpose of this paper is to address some aspects of the many considerations that need to go into a dose prescription in boron neutron capture therapy (BNCT) for brain tumors; and to describe some methods to incorporate knowledge from animal studies and other experiments into the process of dose prescription. Previously, an algorithm to estimate the normal tissue tolerance to mixed high and low linear energy transfer radiations in BNCT was proposed. The authors have developed mathematical formulations and computational methods to represent this algorithm. Generalized models to fit the central axis dose rate components for an epithermal neutron field were also developed. These formulations and beam fitting models were programmed into spreadsheets to simulate two treatment techniques which are expected to be used in BNCT: a two-field bilateral scheme and a single-field treatment scheme. Parameters in these spreadsheets can be varied to represent the fractionation scheme used, the 10 B microdistribution in normal tissue, and the ratio of 10 B in tumor to normal tissue. Most of these factors have to be determined for a given neutron field and 10 B compound combination from large animal studies. The spreadsheets have been programmed to integrate all of the treatment-related information and calculate the location along the central axis where the normal tissue tolerance is exceeded first. This information is then used to compute the maximum treatment time allowable and the maximum tumor dose that may be delivered for a given BNCT treatment. The effect of different treatment variables on the treatment time and tumor dose has been shown to be very significant. It has also been shown that the location of D max shifts significantly, depending on some of the treatment variables-mainly the fractionation scheme used. These results further emphasize the fact that dose prescription in BNCT is very complicated and nonintuitive. 11 refs., 6 figs., 3 tabs

  1. How Do Parenting Concepts Vary within and between the Families?

    Science.gov (United States)

    Roskam, Isabelle; Meunier, Jean Christophe

    2009-01-01

    How do parenting concepts vary within and between the families? The present study regards parenting as a complex family process by considering three concepts of parenting: styles, differential treatment and coparenting consistency. A main question was addressed: whether and how these parenting concepts vary within the families towards siblings or…

  2. Specimen loading list for the varying temperature experiment

    International Nuclear Information System (INIS)

    Qualls, A.L.; Sitterson, R.G.

    1998-01-01

    The varying temperature experiment HFIR-RB-13J has been assembled and inserted in the reactor. Approximately 5300 specimens were cleaned, inspected, matched, and loaded into four specimen holders. A listing of each specimen loaded into the steady temperature holder, its position in the capsule, and the identification of the corresponding specimen loaded into the varying temperature holder is presented in this report

  3. Response of rabbits to varying levels of cassava and Leucaena ...

    African Journals Online (AJOL)

    Response of rabbits to varying levels of cassava and Leucaena leucocephala leaf meal diets. ... Bulletin of Animal Health and Production in Africa ... An experiment was carried out to determine the performance, haematology, carcass characteristics and sensory evaluation of meat from rabbits (n = 30) fed varying levels of ...

  4. Analysis of time-varying psoriasis lesion image patterns

    DEFF Research Database (Denmark)

    Maletti, Gabriela Mariel; Ersbøll, Bjarne Kjær; Nielsen, Allan Aasbjerg

    2004-01-01

    The multivariate alteration detection transform is applied to pairs of within and between time varying registered psoriasis image patterns. Color band contribution to the variates explaining maximal change is analyzed.......The multivariate alteration detection transform is applied to pairs of within and between time varying registered psoriasis image patterns. Color band contribution to the variates explaining maximal change is analyzed....

  5. Multivariate time-varying volatility modeling using probabilistic fuzzy systems

    NARCIS (Netherlands)

    Basturk, N.; Almeida, R.J.; Golan, R.; Kaymak, U.

    2016-01-01

    Methods to accurately analyze financial risk have drawn considerable attention in financial institutions. One difficulty in financial risk analysis is the fact that banks and other financial institutions invest in several assets which show time-varying volatilities and hence time-varying financial

  6. Radiation dose to technologists per nuclear medicine examination and estimation of annual dose.

    Science.gov (United States)

    Bayram, Tuncay; Yilmaz, A Hakan; Demir, Mustafa; Sonmez, Bircan

    2011-03-01

    markedly reduced the external dose to technologists. The doses to technologists varied significantly for different diagnostic applications. Consequently, the estimated annual dose to a technologist performing only a particular scintigraphic procedure is very different from one type of procedure to another. The results of this study should help in determining the rotation time of technologists in different procedures and differences in their individual techniques.

  7. [Evaluation of Organ Dose Estimation from Indices of CT Dose Using Dose Index Registry].

    Science.gov (United States)

    Iriuchijima, Akiko; Fukushima, Yasuhiro; Ogura, Akio

    Direct measurement of each patient organ dose from computed tomography (CT) is not possible. Most methods to estimate patient organ dose is using Monte Carlo simulation with dedicated software. However, dedicated software is too expensive for small scale hospitals. Not every hospital can estimate organ dose with dedicated software. The purpose of this study was to evaluate the simple method of organ dose estimation using some common indices of CT dose. The Monte Carlo simulation software Radimetrics (Bayer) was used for calculating organ dose and analysis relationship between indices of CT dose and organ dose. Multidetector CT scanners were compared with those from two manufactures (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare). Using stored patient data from Radimetrics, the relationships between indices of CT dose and organ dose were indicated as each formula for estimating organ dose. The accuracy of estimation method of organ dose was compared with the results of Monte Carlo simulation using the Bland-Altman plots. In the results, SSDE was the feasible index for estimation organ dose in almost organs because it reflected each patient size. The differences of organ dose between estimation and simulation were within 23%. In conclusion, our estimation method of organ dose using indices of CT dose is convenient for clinical with accuracy.

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2010-09-01

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

  10. Response of cellulose nitrate track detectors to electron doses

    CERN Document Server

    Segovia, N; Moreno, A; Vazquez-Polo, G; Santamaría, T; Aranda, P; Hernández, A

    1999-01-01

    In order to study alternative dose determination methods, the bulk etching velocity and the latent track annealing of LR 115 track detectors was studied during electron irradiation runs from a Pelletron accelerator. For this purpose alpha irradiated and blank detectors were exposed to increasing electron doses from 10.5 to 317.5 kGy. After the irradiation with electrons the detectors were etched under routine conditions, except for the etching time, that was varied for each electron dose in order to reach a fixed residual thickness. The variation of the bulk etching velocity as a function of each one of the electron doses supplied, was interpolated in order to obtain dosimetric response curves. The observed annealing effect on the latent tracks is discussed as a function of the total electron doses supplied and the temperature.

  11. Effects of dose, species, and dosing vehicle on the disposition of methacrylonitrile (MAN) in male rats

    International Nuclear Information System (INIS)

    Sanchez, I.M.; Ghanayem, B.I.

    1991-01-01

    MAN is structurally similar to known carcinogen acrylontrile (AN), with nitriles having similar industrial uses. Current studies were designed to investigate the biological fate of 2- 14 C-MAN in rats. After gavage administration of 115, 11.5 or 1.15 mg MAN/kg in water, F344 male rats were placed in glass metabolism cages and urine, expired air and feces were collected. Rats were sacrificed at various times and concentration of MAN-derived radioactivity in tissues was determined. MAN was rapidly absorbed from the GI tract and distributed to all major tissues. Sixty-70% of the low and medium doses were exhaled as 14 CO 2 in 72 hr compared to 25% of the highest dose. While 40% of the highest dose was expired as organic volatiles in 72 hr, only 9-12% of the low and accounted for 20-30% of all doses within 72 hr after dosing. Comparison of MAN disposition in Sprague-Dawley (SD) and F344 rats at 115 mg/kg revealed that SD rats excreted a greater % of the dose as 14 CO 2 and in the urine than did F344 rats. Administration of 115 mg MAN/kg to SD male rats in safflower oil resulted in increased elimination of MAN-derived radioactivity as CO 2 , volatiles, and in the urine over that observed when administered in water. These results suggest that: (1) saturation of MAN metabolism occurs at high doses: (2) MAN metabolism and disposition differ with the strain of rats studied; (3) MAN disposition may vary with the dosing vehicle used; and (4) MAN metabolism and disposition is apparently different from that reported on AN

  12. Time varying voltage combustion control and diagnostics sensor

    Science.gov (United States)

    Chorpening, Benjamin T [Morgantown, WV; Thornton, Jimmy D [Morgantown, WV; Huckaby, E David [Morgantown, WV; Fincham, William [Fairmont, WV

    2011-04-19

    A time-varying voltage is applied to an electrode, or a pair of electrodes, of a sensor installed in a fuel nozzle disposed adjacent the combustion zone of a continuous combustion system, such as of the gas turbine engine type. The time-varying voltage induces a time-varying current in the flame which is measured and used to determine flame capacitance using AC electrical circuit analysis. Flame capacitance is used to accurately determine the position of the flame from the sensor and the fuel/air ratio. The fuel and/or air flow rate (s) is/are then adjusted to provide reduced flame instability problems such as flashback, combustion dynamics and lean blowout, as well as reduced emissions. The time-varying voltage may be an alternating voltage and the time-varying current may be an alternating current.

  13. Occupational dose assessment and national dose registry system in Iran

    International Nuclear Information System (INIS)

    Jafari-Zadeh, M.; Nazeri, F.; Hosseini-Pooya, S. M.; Taheri, M.; Gheshlaghi, F.; Kardan, M. R.; Babakhani, A.; Rastkhah, N.; Yousefi-Nejad, F.; Darabi, M.; Oruji, T.; Gholamali-Zadeh, Z.; Karimi-Diba, J.; Kazemi-Movahed, A. A.; Dashti-Pour, M. R.; Enferadi, A.; Jahanbakhshian, M. H.; Sadegh-Khani, M. R.

    2011-01-01

    This report presents status of external and internal dose assessment of workers and introducing the structure of National Dose Registry System of Iran (NDRSI). As well as types of individual dosemeters in use, techniques for internal dose assessment are presented. Results obtained from the International Atomic Energy Agency intercomparison programme on measurement of personal dose equivalent H p (10) and consistency of the measured doses with the delivered doses are shown. Also, implementation of dosimetry standards, establishment of quality management system, authorisation and approval procedure of dosimetry service providers are discussed. (authors)

  14. Thermoluminescence dosemeter for personal dose equivalent assessment

    International Nuclear Information System (INIS)

    Silva, T.A. da; Rosa, L.A.R. da; Campos, L.L.

    1995-01-01

    The possibility was investigated of utilising a Brazilian thermoluminescence individual dosemeter, usually calibrated in terms of photon dose equivalent, for the assessment of the personal dose equivalent, H p (d), at depths of 0.07 and 10 mm. The dosemeter uses four CaSO 4 :Dy thermoluminescent detectors, between different filters, as the sensitive materials. It was calibrated in gamma and X radiation fields in the energy range from 17 to 1250 keV. Linear combinations of the responses of three detectors, in this energy range, allow the evaluation of H p (0.07) and H p (10), for radiation incidence angles varying from 0 to 60 degrees, with an accuracy better than 35%. The method is not applicable to mixed photon-beta fields. (author)

  15. Breast dose variability in a bi-racial population undergoing screening mammography

    International Nuclear Information System (INIS)

    Schubauer-Berigan, M.K.; Baron, L.; Frey, G.D.; Hoel, D.G.

    2002-01-01

    This study evaluated individual and population dose variability during screening mammography among 570 white and black women in South Carolina, USA. Aspects of dosimetry that were considered include compressed breast thickness (CBT), number of films per screening session, and dose in previous or subsequent sessions. Breast dose was log-normally distributed in the population, with a geometric mean of 6.6 mGy per session. Doses were significantly higher for black women, for women with high CBT or who receive more than two views per breast, and for the mediolateral oblique, compared to the craniocaudal view. No relationship was observed between age and dose. Total dose per breast varied by a factor of 20 across the study population, but the individual's dose varied little among repeat screening sessions, especially after adjusting for the number of films received per session. These results may inform assessments of the projected risks of inducing breast cancer from screening mammography. (author)

  16. Dose monitoring in radiology departments. Status quo and future perspectives

    International Nuclear Information System (INIS)

    Boos, J.; Bethge, O.T.; Antoch, G.; Kroepil, P.

    2016-01-01

    The number of computed tomography examinations has continuously increased over the last decades and accounts for a major part of the collective radiation dose from medical investigations. For purposes of quality assurance in modern radiology a systematic monitoring and analysis of dose related data from radiological examinations is mandatory. Various ways of collecting dose data are available today, for example the Digital Imaging and Communication in Medicine - Structured Report (DICOM-SR), optical character recognition and DICOM-modality performed procedure steps (MPPS). The DICOM-SR is part of the DICOM-standard and provides the DICOM-Radiation Dose Structured Report, which is an easily applicable and comprehensive solution to collect radiation dose parameters. This standard simplifies the process of data collection and enables comprehensive dose monitoring. Various commercial dose monitoring software devices with varying characteristics are available today. In this article, we discuss legal obligations, various ways to monitor dose data, current dose monitoring software solutions and future perspectives in regard to the EU Council Directive 2013/59/EURATOM.

  17. A paired wedge filter system for compensation in dose differences

    International Nuclear Information System (INIS)

    Kobayashi, H.; Sakurai, Y.; Kondo, S.; Abe, S.; Hayakawa, N.; Aoyama, Y.; Obata, Y.; Ishigaki, T.

    1998-01-01

    Objective: In radiotherapy, it is important to conform the high dose volume to the planned target volume. A variable thickness paired wedge filter system was developed to compensate for dose inhomogeneity arising from field width segment variation in conformal irradiation. Materials and methods: The present study used a 6 MV linear accelerator equipped with multileaf collimator leaves and a paired wedge compensating filter system. The dose variation due to field width was measured in each field segment width. The variation in attenuation of the compensators was measured as a function of filter position. As the field width increases, the relative absorbed dose also increases; this is the point of requiring compensation, so it can be in reverse proportion. Results: As the field width increases, the relative absorbed dose also increases; this is why compensation is required and thus it must be in reverse proportion. Attenuation of the absorbed dose by the paired filters was in proportion to the filter position. The filter position to compensate for the difference of absorbed doses was defined by the square root of the field width. For a field varying in width from 4 to 16 cm, the variation in the absorbed dose across the field was reduced from 12% to 2.7%. Conclusion: This paired wedge filter system reduced absorbed dose variations across multileaf collimator shaped fields and can facilitate treatment planning in conformal therapy. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  18. Doses from radiation exposure

    CERN Document Server

    Menzel, H G

    2012-01-01

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

  19. Radiation dose rate meter

    International Nuclear Information System (INIS)

    Kronenberg, S.; Siebentritt, C.R.

    1981-01-01

    A combined dose rate meter and charger unit therefor which does not require the use of batteries but on the other hand produces a charging potential by means of a piezoelectric cylinder which is struck by a manually triggered hammer mechanism. A tubular type electrometer is mounted in a portable housing which additionally includes a geiger-muller (Gm) counter tube and electronic circuitry coupled to the electrometer for providing multi-mode operation. In one mode of operation, an rc circuit of predetermined time constant is connected to a storage capacitor which serves as a timed power source for the gm tube, providing a measurement in terms of dose rate which is indicated by the electrometer. In another mode, the electrometer indicates individual counts

  20. Small dose... big poison.

    Science.gov (United States)

    Braitberg, George; Oakley, Ed

    2010-11-01

    It is not possible to identify all toxic substances in a single journal article. However, there are some exposures that in small doses are potentially fatal. Many of these exposures are particularly toxic to children. Using data from poison control centres, it is possible to recognise this group of exposures. This article provides information to assist the general practitioner to identify potential toxic substance exposures in children. In this article the authors report the signs and symptoms of toxic exposures and identify the time of onset. Where clear recommendations on the period of observation and known fatal dose are available, these are provided. We do not discuss management or disposition, and advise readers to contact the Poison Information Service or a toxicologist for this advice.

  1. Patient dose simulation in X-ray CT using a radiation treatment-planning system

    International Nuclear Information System (INIS)

    Nakae, Yasuo; Oda, Masahiko; Minamoto, Takahiro

    2003-01-01

    Medical irradiation dosage has been increasing with the development of new radiological equipment and new techniques like interventional radiology. It is fair to say that patient dose has been increased as a result of the development of multi-slice CT. A number of studies on the irradiation dose of CT have been reported, and the computed tomography dose index (CTDI) is now used as a general means of determining CT dose. However, patient dose distribution in the body varies with the patient's constitution, bowel gas in the body, and conditions of exposure. In this study, patient dose was analyzed from the viewpoint of dose distribution, using a radiation treatment-planning computer. Percent depth dose (PDD) and the off-center ratio (OCR) of the CT beam are needed to calculate dose distribution by the planning computer. Therefore, X-ray CT data were measured with various apparatuses, and beam data were sent to the planning computer. Measurement and simulation doses in the elliptical phantom (Mix-Dp: water equivalent material) were collated, and the CT irradiation dose was determined for patient dose simulation. The rotational radiation treatment technique was used to obtain the patient dose distribution of CT, and patient dose was evaluated through simulation of the dose distribution. CT images of the thorax were sent to the planning computer and simulated. The result was that the patient dose distribution of the thorax was obtained for CT examination. (author)

  2. Dose evaluation in special fluoroscopy procedures: Hysterosalpingography and Dacryocystography

    International Nuclear Information System (INIS)

    Lopes, Cintya Carolina Barbosa

    2006-04-01

    The hysterosalpingography (HSG) and dacryocystography (DCG) are among the special fluoroscopy procedures. The HSG is a radiodiagnostic technique used to detect uterine and tubal pathologies and it is fundamental for the investigation of infertility. The DCG is a form of lacrimal system imaging, being important to show the level of obstruction, the presence of dilatation of the lacrimal sac, as well as alterations in nearby structures. At this research, the study of skin entrance dose was evaluated for these two special fluoroscopy procedures, besides the analyses of staff doses whose performs the exams. The exams of 22 HSG patients and 8 DCG patients were evaluated using TL-100 dosimeters attached on patient' skin at anatomical landmarks evolved on each exam. In the case of HSG, the results showed that skin entrance doses varied from 0.5 mGy to 73.4 mGy, with an average value of 22.1 mGy. The estimated uterus dose was 5.5 mGy, and 6.6 mGy was the average dose estimated to the ovaries. The patient' skin entrance dose undergoing to DCG examinations varied from 2.1 mGy to 10.6 mGy, and the average eye's dose was 6.1 mGy. The results of staff dose showed that, on HSG, the average dose on doctor's right hand was 4.3 mGy per examination. This value had to the fact that the physician introduces the contrast manually while all contrast exposures. In relation of DCG, the staff's dose values were nearby background radiation, evidencing that, inside of permitted limits, there is no risk for the physicians at this procedure. (author)

  3. Radiation dose measurements

    International Nuclear Information System (INIS)

    1960-01-01

    About 200 scientists from 28 countries and 5 international organizations met at a symposium on radiation dosimetry held by the International Atomic Energy Agency in June 1960. The aim of the symposium was not so much the description of a large number of measuring instruments as a discussion of the methods used, with special emphasis on those problems which had become important in the context of recent developments, such as the measurement of mixed or very large doses

  4. Low dose epidemiology

    International Nuclear Information System (INIS)

    Tirmarche, M.; Hubert, P.

    1992-01-01

    Actually, epidemiological studies have to establish if the assessment of cancer risk can be verified at low chronic radiation doses. The population surveillance must be very long, the side effects and cancers of such radiation appearing much later. In France, this epidemiological study on nuclear workers have been decided recently. Before describing the experiment and french projects in epidemiology of nuclear workers, the authors present the main english and american studies

  5. Chromosome aberration studies and microdosimetry with radiations of varying quality

    International Nuclear Information System (INIS)

    Grillmaier, R.E.; Bihy, L.; Menzel, H.G.; Schuhmacher, H.

    1978-01-01

    To investigate the biological effectivity of complex irradiation fields encountered in radiation protection and high LET radiation therapy and to find meaningful specification of radiation quality closely related to the biological effectivity, correlated chromosome aberration studies and microdosimetric investigations have been carried out using cyclotron produced collimated fast neutrons. Human lymphocytes have been irradiated at different dose levels in the direct beam and in different positions in the penumbra and the rates of acentric fragments and dicentrics have been determined. In identical positions microdosimetric measurements have been performed. The dose relationship of aberration rates after irradiation in the direct beam, the aberration rates observed in the penumbra and the microdosimetric quantities ysub(D), ysub(F) and y* are presented and their relations are discussed. Furthermore the dose relationship of chromosome aberrations induced by 60 Co-γ-rays has been investigated and used to establish the RBE dose relationship of cyclotron neutrons

  6. Time-dose modifications

    International Nuclear Information System (INIS)

    Kian Ang, K.

    1987-01-01

    Changes in fractionation schedule can be made by various approaches. However, from the first principle, it is anticipated that strategies of hyperfractionation and/or accelerated fractionation offer the most promised in improving the therapeutic ratio. Hyperfractionation is defined as a treatment schedule in which a large number of significantly reduced dose fractions (--1.2 Gy/fraction) is used to give a greater total dose in a conventional overall time period. The results of the pilot studies testing the efficacy of hyperfractionation have been encouraging. The most valid clinical trial of pure hyperfractionation, however, is that conducted by the EORTC. This study compared 70 Gy in 35 fractions or 80.5 Gy in 70 fractions over 7 weeks in the treatment of patients with oropharyngeal carcinomas. The local tumor control was significantly improved in the hyperfractionated arm without increasing the morbidity. Accelerated fractionation is defined as a schedule in which the overall time of treatment is reduced without significant changes in the total dose and fraction size. The strategy has been used to treat patients with malignant gliomas, melanomas and Head and Neck cancers. The data in Head and Neck Cancers seem to be promising

  7. Dose calculation for electrons

    International Nuclear Information System (INIS)

    Hirayama, Hideo

    1995-01-01

    The joint working group of ICRP/ICRU is advancing the works of reviewing the ICRP publication 51 by investigating the data related to radiation protection. In order to introduce the 1990 recommendation, it has been demanded to carry out calculation for neutrons, photons and electrons. As for electrons, EURADOS WG4 (Numerical Dosimetry) rearranged the data to be calculated at the meeting held in PTB Braunschweig in June, 1992, and the question and request were presented by Dr. J.L. Chartier, the responsible person, to the researchers who are likely to undertake electron transport Monte Carlo calculation. The author also has carried out the requested calculation as it was the good chance to do the mutual comparison among various computation codes regarding electron transport calculation. The content that the WG requested to calculate was the absorbed dose at depth d mm when parallel electron beam enters at angle α into flat plate phantoms of PMMA, water and ICRU4-element tissue, which were placed in vacuum. The calculation was carried out by the versatile electron-photon shower computation Monte Carlo code, EGS4. As the results, depth dose curves and the dependence of absorbed dose on electron energy, incident angle and material are reported. The subjects to be investigated are pointed out. (K.I.)

  8. Dose reduction in evacuation proctography

    International Nuclear Information System (INIS)

    Hare, C.; Halligan, S.; Bartram, C.I.; Gupta, R.; Walker, A.E.; Renfrew, I.

    2001-01-01

    The goal of this study was to reduce the patient radiation dose from evacuation proctography. Ninety-eight consecutive adult patients referred for proctography to investigate difficult rectal evacuation were studied using a digital imaging system with either a standard digital program for barium examinations, a reduced dose digital program (both with and without additional copper filtration), or Video fluoroscopy. Dose-area products were recorded for each examination and the groups were compared. All four protocols produced technically acceptable examinations. The low-dose program with copper filtration (median dose 382 cGy cm 2 ) and Video fluoroscopy (median dose 705 cGy cm 2 ) were associated with significantly less dose than other groups (p < 0.0001). Patient dose during evacuation proctography can be reduced significantly without compromising the diagnostic quality of the examination. A digital program with added copper filtration conveyed the lowest dose. (orig.)

  9. Optimized dose distribution of a high dose rate vaginal cylinder

    International Nuclear Information System (INIS)

    Li Zuofeng; Liu, Chihray; Palta, Jatinder R.

    1998-01-01

    Purpose: To present a comparison of optimized dose distributions for a set of high-dose-rate (HDR) vaginal cylinders calculated by a commercial treatment-planning system with benchmark calculations using Monte-Carlo-calculated dosimetry data. Methods and Materials: Optimized dose distributions using both an isotropic and an anisotropic dose calculation model were obtained for a set of HDR vaginal cylinders. Mathematical optimization techniques available in the computer treatment-planning system were used to calculate dwell times and positions. These dose distributions were compared with benchmark calculations with TG43 formalism and using Monte-Carlo-calculated data. The same dwell times and positions were used for a quantitative comparison of dose calculated with three dose models. Results: The isotropic dose calculation model can result in discrepancies as high as 50%. The anisotropic dose calculation model compared better with benchmark calculations. The differences were more significant at the apex of the vaginal cylinder, which is typically used as the prescription point. Conclusion: Dose calculation models available in a computer treatment-planning system must be evaluated carefully to ensure their correct application. It should also be noted that when optimized dose distribution at a distance from the cylinder surface is calculated using an accurate dose calculation model, the vaginal mucosa dose becomes significantly higher, and therefore should be carefully monitored

  10. Molecular Mechanisms That Underlie the Dynamic Adaptation of Innate Monocyte Memory to Varying Stimulant Strength of TLR Ligands.

    Science.gov (United States)

    Yuan, Ruoxi; Geng, Shuo; Li, Liwu

    2016-01-01

    In adaptation to rising stimulant strength, innate monocytes can be dynamically programed to preferentially express either pro- or anti-inflammatory mediators. Such dynamic innate adaptation or programing may bear profound relevance in host health and disease. However, molecular mechanisms that govern innate adaptation to varying strength of stimulants are not well understood. Using lipopolysaccharide (LPS), the model stimulant of toll-like-receptor 4 (TLR4), we reported that the expressions of pro-inflammatory mediators are preferentially sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in monocytes adapted by higher doses of LPS. Mechanistically, monocytes adapted by super-low dose LPS exhibited higher levels of transcription factor, interferon regulatory factor 5 (IRF5), and reduced levels of transcriptional modulator B lymphocyte-induced maturation protein-1 (Blimp-1). Intriguingly, the inflammatory monocyte adaptation by super-low dose LPS is dependent upon TRAM/TRIF but not MyD88. Similar to LPS, we also observed biphasic inflammatory adaptation and tolerance in monocytes challenged with varying dosages of TLR7 agonist. In sharp contrast, rising doses of TLR3 agonist preferentially caused inflammatory adaptation without inducing tolerance. At the molecular level, the differential regulation of IRF5 and Blimp-1 coincides with unique monocyte adaptation dynamics by TLR4/7 and TLR3 agonists. Our study provides novel clue toward the understanding of monocyte adaptation and memory toward distinct TLR ligands.

  11. Molecular mechanisms that underlie the dynamic adaptation of innate monocyte memory to varying stimulant strength of TLR ligands

    Directory of Open Access Journals (Sweden)

    Ruoxi Yuan

    2016-11-01

    Full Text Available In adaptation to rising stimulant strength, innate monocytes can be dynamically programmed to preferentially express either pro- or anti-inflammatory mediators. Such dynamic innate adaptation or programming may bear profound relevance in host health and disease. However, molecular mechanisms that govern innate adaptation to varying strength of stimulants are not well understood. Using lipopolysaccharide (LPS, the model stimulant of Toll-Like-Receptor 4 (TLR4, we reported that the expressions of pro-inflammatory mediators are preferentially sustained in monocytes adapted by lower doses of LPS, and suppressed/tolerized in monocytes adapted by higher doses of LPS. Mechanistically, monocytes adapted by super-low dose LPS exhibited higher levels of transcription factor IRF5 and reduced levels of transcriptional modulator BLIMP-1. Intriguingly, the inflammatory monocyte adaptation by super-low dose LPS is dependent upon TRAM/TRIF but not MyD88. Similar to LPS, we also observed biphasic inflammatory adaptation and tolerance in monocytes challenged with varying dosages of TLR7 agonist. In sharp contrast, rising doses of TLR3 agonist preferentially caused inflammatory adaptation without inducing tolerance. At the molecular level, the differential regulation of IRF5 and Blimp-1 coincides with unique monocyte adaptation dynamics by TLR4/7 and TLR3 agonists. Our study provides novel clue toward the understanding of monocyte adaptation and memory toward distinct TLR ligands.

  12. Vitamin concentrations in human milk vary with time within feed, circadian rhythm, and single-dose supplementation

    Science.gov (United States)

    Importance: Human milk is the subject of many nutrition studies but methods for representative sample collection are not established. Our recently improved, validated methods for analyzing micronutrients in human milk now enable systematic study of factors affecting their concentration. Objective...

  13. Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

    Science.gov (United States)

    Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

    2001-01-01

    The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

  14. Dose evaluation in special fluoroscopy procedures: Hysterosalpingography and Dacryocystography; Avaliacao de dose em procedimentos especiais de fluoroscopia: histerossalpingografia e dacriocistografia

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, Cintya Carolina Barbosa

    2006-04-15

    The hysterosalpingography (HSG) and dacryocystography (DCG) are among the special fluoroscopy procedures. The HSG is a radiodiagnostic technique used to detect uterine and tubal pathologies and it is fundamental for the investigation of infertility. The DCG is a form of lacrimal system imaging, being important to show the level of obstruction, the presence of dilatation of the lacrimal sac, as well as alterations in nearby structures. At this research, the study of skin entrance dose was evaluated for these two special fluoroscopy procedures, besides the analyses of staff doses whose performs the exams. The exams of 22 HSG patients and 8 DCG patients were evaluated using TL-100 dosimeters attached on patient' skin at anatomical landmarks evolved on each exam. In the case of HSG, the results showed that skin entrance doses varied from 0.5 mGy to 73.4 mGy, with an average value of 22.1 mGy. The estimated uterus dose was 5.5 mGy, and 6.6 mGy was the average dose estimated to the ovaries. The patient' skin entrance dose undergoing to DCG examinations varied from 2.1 mGy to 10.6 mGy, and the average eye's dose was 6.1 mGy. The results of staff dose showed that, on HSG, the average dose on doctor's right hand was 4.3 mGy per examination. This value had to the fact that the physician introduces the contrast manually while all contrast exposures. In relation of DCG, the staff's dose values were nearby background radiation, evidencing that, inside of permitted limits, there is no risk for the physicians at this procedure. (author)

  15. Dose evaluation in special fluoroscopy procedures: Hysterosalpingography and Dacryocystography; Avaliacao de dose em procedimentos especiais de fluoroscopia: histerossalpingografia e dacriocistografia

    Energy Technology Data Exchange (ETDEWEB)

    Lopes, Cintya Carolina Barbosa

    2006-04-15

    The hysterosalpingography (HSG) and dacryocystography (DCG) are among the special fluoroscopy procedures. The HSG is a radiodiagnostic technique used to detect uterine and tubal pathologies and it is fundamental for the investigation of infertility. The DCG is a form of lacrimal system imaging, being important to show the level of obstruction, the presence of dilatation of the lacrimal sac, as well as alterations in nearby structures. At this research, the study of skin entrance dose was evaluated for these two special fluoroscopy procedures, besides the analyses of staff doses whose performs the exams. The exams of 22 HSG patients and 8 DCG patients were evaluated using TL-100 dosimeters attached on patient' skin at anatomical landmarks evolved on each exam. In the case of HSG, the results showed that skin entrance doses varied from 0.5 mGy to 73.4 mGy, with an average value of 22.1 mGy. The estimated uterus dose was 5.5 mGy, and 6.6 mGy was the average dose estimated to the ovaries. The patient' skin entrance dose undergoing to DCG examinations varied from 2.1 mGy to 10.6 mGy, and the average eye's dose was 6.1 mGy. The results of staff dose showed that, on HSG, the average dose on doctor's right hand was 4.3 mGy per examination. This value had to the fact that the physician introduces the contrast manually while all contrast exposures. In relation of DCG, the staff's dose values were nearby background radiation, evidencing that, inside of permitted limits, there is no risk for the physicians at this procedure. (author)

  16. Robust Stabilization of Nonlinear Systems with Uncertain Varying Control Coefficient

    Directory of Open Access Journals (Sweden)

    Zaiyue Yang

    2014-01-01

    Full Text Available This paper investigates the stabilization problem for a class of nonlinear systems, whose control coefficient is uncertain and varies continuously in value and sign. The study emphasizes the development of a robust control that consists of a modified Nussbaum function to tackle the uncertain varying control coefficient. By such a method, the finite-time escape phenomenon has been prevented when the control coefficient is crossing zero and varying its sign. The proposed control guarantees the asymptotic stabilization of the system and boundedness of all closed-loop signals. The control performance is illustrated by a numerical simulation.

  17. Dose gradient curve: A new tool for evaluating dose gradient.

    Science.gov (United States)

    Sung, KiHoon; Choi, Young Eun

    2018-01-01

    Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice.

  18. Determination of organ doses and effective doses in radiooncology

    International Nuclear Information System (INIS)

    Roth, J.; Martinez, A.E.

    2007-01-01

    Background and Purpose: With an increasing chance of success in radiooncology, it is necessary to estimate the risk from radiation scatter to areas outside the target volume. The cancer risk from a radiation treatment can be estimated from the organ doses, allowing a somewhat limited effective dose to be estimated and compared. Material and Methods: The doses of the radiation-sensitive organs outside the target volume can be estimated with the aid of the PC program PERIDOSE developed by van der Giessen. The effective doses are determined according to the concept of ICRP, whereby the target volume and the associated organs related to it are not taken into consideration. Results: Organ doses outside the target volume are generally < 1% of the dose in the target volume. In some cases, however, they can be as high as 3%. The effective doses during radiotherapy are between 60 and 900 mSv, depending upon the specific target volume, the applied treatment technique, and the given dose in the ICRU point. Conclusion: For the estimation of the radiation risk, organ doses in radiooncology can be calculated with the aid of the PC program PERIDOSE. While evaluating the radiation risk after ICRP, for the calculation of the effective dose, the advanced age of many patients has to be considered to prevent that, e.g., the high gonad doses do not overestimate the effective dose. (orig.)

  19. Dose specification for 192Ir high dose rate brachytherapy in terms of dose-to-water-in-medium and dose-to-medium-in-medium

    International Nuclear Information System (INIS)

    Fonseca, Gabriel Paiva; Yoriyaz, Hélio; Tedgren, Åsa Carlsson; Nilsson, Josef; Persson, Maria; Reniers, Brigitte; Verhaegen, Frank

    2015-01-01

    Dose calculation in high dose rate brachytherapy with 192 Ir is usually based on the TG-43U1 protocol where all media are considered to be water. Several dose calculation algorithms have been developed that are capable of handling heterogeneities with two possibilities to report dose: dose-to-medium-in-medium (D m,m ) and dose-to-water-in-medium (D w,m ). The relation between D m,m and D w,m for 192 Ir is the main goal of this study, in particular the dependence of D w,m on the dose calculation approach using either large cavity theory (LCT) or small cavity theory (SCT). A head and neck case was selected due to the presence of media with a large range of atomic numbers relevant to tissues and mass densities such as air, soft tissues and bone interfaces. This case was simulated using a Monte Carlo (MC) code to score: D m,m, D w,m (LCT), mean photon energy and photon fluence. D w,m (SCT) was derived from MC simulations using the ratio between the unrestricted collisional stopping power of the actual medium and water. Differences between D m,m and D w,m (SCT or LCT) can be negligible (<1%) for some tissues e.g. muscle and significant for other tissues with differences of up to 14% for bone. Using SCT or LCT approaches leads to differences between D w,m (SCT) and D w,m (LCT) up to 29% for bone and 36% for teeth. The mean photon energy distribution ranges from 222 keV up to 356 keV. However, results obtained using mean photon energies are not equivalent to the ones obtained using the full, local photon spectrum. This work concludes that it is essential that brachytherapy studies clearly report the dose quantity. It further shows that while differences between D m,m and D w,m (SCT) mainly depend on tissue type, differences between D m,m and D w,m (LCT) are, in addition, significantly dependent on the local photon energy fluence spectrum which varies with distance to implanted sources. (paper)

  20. Uus Eesti film pandi eile Karlovy Varys projektorisse / Kristiina Davidjants

    Index Scriptorium Estoniae

    Davidjants, Kristiina, 1974-

    2008-01-01

    8. juulil esilinastus Karlovy Vary filmifestivalil Rene Vilbre noortefilm "Mina olin siin", mille aluseks on Sass Henno romaan "Mina olin siin. Esimene arest". Film võistleb võistlusprogrammis "East of the West"

  1. Enhancement of heat transfer using varying width twisted tape inserts

    African Journals Online (AJOL)

    International Journal of Engineering, Science and Technology ... experimental investigations of the augmentation of turbulent flow heat transfer in a horizontal tube by means of varying width twisted tape inserts with air as the working fluid.

  2. Influence of feeding varying crude protein and digestible energy ...

    African Journals Online (AJOL)

    Influence of feeding varying crude protein and digestible energy levels on the development of individual muscles, rate of lean and fat deposition in pigs reared from 9 to 60kg liveweight in a humid tropical environment.

  3. Design of 2D Time-Varying Vector Fields

    KAUST Repository

    Chen, Guoning; Kwatra, Vivek; Wei, Li-Yi; Hansen, Charles D.; Zhang, Eugene

    2012-01-01

    Design of time-varying vector fields, i.e., vector fields that can change over time, has a wide variety of important applications in computer graphics. Existing vector field design techniques do not address time-varying vector fields. In this paper, we present a framework for the design of time-varying vector fields, both for planar domains as well as manifold surfaces. Our system supports the creation and modification of various time-varying vector fields with desired spatial and temporal characteristics through several design metaphors, including streamlines, pathlines, singularity paths, and bifurcations. These design metaphors are integrated into an element-based design to generate the time-varying vector fields via a sequence of basis field summations or spatial constrained optimizations at the sampled times. The key-frame design and field deformation are also introduced to support other user design scenarios. Accordingly, a spatial-temporal constrained optimization and the time-varying transformation are employed to generate the desired fields for these two design scenarios, respectively. We apply the time-varying vector fields generated using our design system to a number of important computer graphics applications that require controllable dynamic effects, such as evolving surface appearance, dynamic scene design, steerable crowd movement, and painterly animation. Many of these are difficult or impossible to achieve via prior simulation-based methods. In these applications, the time-varying vector fields have been applied as either orientation fields or advection fields to control the instantaneous appearance or evolving trajectories of the dynamic effects. © 1995-2012 IEEE.

  4. Design of 2D time-varying vector fields.

    Science.gov (United States)

    Chen, Guoning; Kwatra, Vivek; Wei, Li-Yi; Hansen, Charles D; Zhang, Eugene

    2012-10-01

    Design of time-varying vector fields, i.e., vector fields that can change over time, has a wide variety of important applications in computer graphics. Existing vector field design techniques do not address time-varying vector fields. In this paper, we present a framework for the design of time-varying vector fields, both for planar domains as well as manifold surfaces. Our system supports the creation and modification of various time-varying vector fields with desired spatial and temporal characteristics through several design metaphors, including streamlines, pathlines, singularity paths, and bifurcations. These design metaphors are integrated into an element-based design to generate the time-varying vector fields via a sequence of basis field summations or spatial constrained optimizations at the sampled times. The key-frame design and field deformation are also introduced to support other user design scenarios. Accordingly, a spatial-temporal constrained optimization and the time-varying transformation are employed to generate the desired fields for these two design scenarios, respectively. We apply the time-varying vector fields generated using our design system to a number of important computer graphics applications that require controllable dynamic effects, such as evolving surface appearance, dynamic scene design, steerable crowd movement, and painterly animation. Many of these are difficult or impossible to achieve via prior simulation-based methods. In these applications, the time-varying vector fields have been applied as either orientation fields or advection fields to control the instantaneous appearance or evolving trajectories of the dynamic effects.

  5. Design of 2D Time-Varying Vector Fields

    KAUST Repository

    Chen, Guoning

    2012-10-01

    Design of time-varying vector fields, i.e., vector fields that can change over time, has a wide variety of important applications in computer graphics. Existing vector field design techniques do not address time-varying vector fields. In this paper, we present a framework for the design of time-varying vector fields, both for planar domains as well as manifold surfaces. Our system supports the creation and modification of various time-varying vector fields with desired spatial and temporal characteristics through several design metaphors, including streamlines, pathlines, singularity paths, and bifurcations. These design metaphors are integrated into an element-based design to generate the time-varying vector fields via a sequence of basis field summations or spatial constrained optimizations at the sampled times. The key-frame design and field deformation are also introduced to support other user design scenarios. Accordingly, a spatial-temporal constrained optimization and the time-varying transformation are employed to generate the desired fields for these two design scenarios, respectively. We apply the time-varying vector fields generated using our design system to a number of important computer graphics applications that require controllable dynamic effects, such as evolving surface appearance, dynamic scene design, steerable crowd movement, and painterly animation. Many of these are difficult or impossible to achieve via prior simulation-based methods. In these applications, the time-varying vector fields have been applied as either orientation fields or advection fields to control the instantaneous appearance or evolving trajectories of the dynamic effects. © 1995-2012 IEEE.

  6. Do Time-Varying Covariances, Volatility Comovement and Spillover Matter?

    OpenAIRE

    Lakshmi Balasubramanyan

    2005-01-01

    Financial markets and their respective assets are so intertwined; analyzing any single market in isolation ignores important information. We investigate whether time varying volatility comovement and spillover impact the true variance-covariance matrix under a time-varying correlation set up. Statistically significant volatility spillover and comovement between US, UK and Japan is found. To demonstrate the importance of modelling volatility comovement and spillover, we look at a simple portfo...

  7. Performance of a solar chimney by varying design parameters

    CSIR Research Space (South Africa)

    Kumirai, T

    2015-08-01

    Full Text Available the design of solar chimneys to ensure optimal performance. The purpose of this chapter is to discuss the performance of an example solar chimney by varying the design parameters and examining their effects on the interior ventilation performance... chimney by varying design parameters Tichaona Kumirai, Researcher, Built Environment CSIR Jan-Hendrik Grobler, DPSS CSIR Dr D.C.U. Conradie, Senior researcher, Built Environment CSIR 1 Introduction Trombe walls and solar chimneys are not widely...

  8. Perturbation methods and the Melnikov functions for slowly varying oscillators

    International Nuclear Information System (INIS)

    Lakrad, Faouzi; Charafi, Moulay Mustapha

    2005-01-01

    A new approach to obtaining the Melnikov function for homoclinic orbits in slowly varying oscillators is proposed. The present method applies the Lindstedt-Poincare method to determine an approximation of homoclinic solutions. It is shown that the resultant Melnikov condition is the same as that obtained in the usual way involving distance functions in three dimensions by Wiggins and Holmes [Homoclinic orbits in slowly varying oscillators. SIAM J Math Anal 1987;18(3):612

  9. Marketingový mix HC Enegie Karlovy Vary

    OpenAIRE

    Štrobl, Adam

    2016-01-01

    Title: Marketing mix of HC Energie Karlovy Vary Objectives: This thesis is based on a questionnaire responses obtained from HC Energie Karlovy Vary fans. Its objective is focused on evaluation of their opinions on the marketing mix, their subsequent interpretation, and finally even development of recommendations for improvement based on previous analysis. Methods: Two methods are used to analyse the marketing mix. The first method is qualitative participant observation. The second method is a...

  10. Testing for time-varying loadings in dynamic factor models

    DEFF Research Database (Denmark)

    Mikkelsen, Jakob Guldbæk

    Abstract: In this paper we develop a test for time-varying factor loadings in factor models. The test is simple to compute and is constructed from estimated factors and residuals using the principal components estimator. The hypothesis is tested by regressing the squared residuals on the squared...... there is evidence of time-varying loadings on the risk factors underlying portfolio returns for around 80% of the portfolios....

  11. Bounds and asymptotics for orthogonal polynomials for varying weights

    CERN Document Server

    Levin, Eli

    2018-01-01

    This book establishes bounds and asymptotics under almost minimal conditions on the varying weights, and applies them to universality limits and entropy integrals.  Orthogonal polynomials associated with varying weights play a key role in analyzing random matrices and other topics.  This book will be of use to a wide community of mathematicians, physicists, and statisticians dealing with techniques of potential theory, orthogonal polynomials, approximation theory, as well as random matrices. .

  12. Pemodelan Markov Switching Dengan Time-varying Transition Probability

    OpenAIRE

    Savitri, Anggita Puri; Warsito, Budi; Rahmawati, Rita

    2016-01-01

    Exchange rate or currency is an economic variable which reflects country's state of economy. It fluctuates over time because of its ability to switch the condition or regime caused by economic and political factors. The changes in the exchange rate are depreciation and appreciation. Therefore, it could be modeled using Markov Switching with Time-Varying Transition Probability which observe the conditional changes and use information variable. From this model, time-varying transition probabili...

  13. Quantum capacity under adversarial quantum noise: arbitrarily varying quantum channels

    OpenAIRE

    Ahlswede, Rudolf; Bjelakovic, Igor; Boche, Holger; Noetzel, Janis

    2010-01-01

    We investigate entanglement transmission over an unknown channel in the presence of a third party (called the adversary), which is enabled to choose the channel from a given set of memoryless but non-stationary channels without informing the legitimate sender and receiver about the particular choice that he made. This channel model is called arbitrarily varying quantum channel (AVQC). We derive a quantum version of Ahlswede's dichotomy for classical arbitrarily varying channels. This includes...

  14. Effect of IX dosing on polypropylene and PVDF membrane fouling control

    KAUST Repository

    Myat, Darli Theint; Mergen, Max R D; Zhao, Oliver; Stewart, Matthew B.; Orbell, John D.; Merle, Tony; Croue, Jean-Philippe; Gray, Stephen R.

    2013-01-01

    The performance of ion exchange (IX) resin for organics removal from wastewater was assessed using advanced characterisation techniques for varying doses of IX. Organic characterisation using liquid chromatography with a photodiode array (PDA

  15. Ozonation for source treatment of pharmaceuticals in hospital wastewater - ozone lifetime and required ozone dose

    DEFF Research Database (Denmark)

    Hansen, Kamilla Marie Speht; Spiliotopoulou, Aikaterini; Chhetri, Ravi Kumar

    2016-01-01

    Ozonation aimed at removing pharmaceuticals was studied in an effluent from an experimental pilot system using staged moving bed biofilm reactor (MBBR) tanks for the optimal biological treatment of wastewater from a medical care unit of Aarhus University Hospital. Dissolved organic carbon (DOC......) and pH in samples varied considerably, and the effect of these two parameters on ozone lifetime and the efficiency of ozone in removing pharmaceuticals were determined. The pH in the effluent varied from 5.0 to 9.0 resulting in approximately a doubling of the required ozone dose at the highest p......H for each pharmaceutical. DOC varied from 6 to 20 mg-DOC/L. The ozone required for removing each pharmaceutical, varied linearly with DOC and thus, ozone doses normalized to DOC (specific ozone dose) agreed between water samples (typically within 15%). At neutral pH the specific ozone dose required...

  16. Induction of oral tolerance with micro-doses of ovomucoid depends on the length of the feeding period

    DEFF Research Database (Denmark)

    Kjær, Tanja; Frøkiær, Hanne

    2002-01-01

    Oral administration of antigen induces antigen-specific immunologic tolerance, which is known to be dose-dependent. We studied the influence of continuous oral administration of nanogram and microgram doses of antigen on oral tolerance induction. Mice were continuously exposed to varying doses (1...

  17. Intercomparison On Depth Dose Measurement

    International Nuclear Information System (INIS)

    Rohmah, N; Akhadi, M

    1996-01-01

    Intercomparation on personal dose evaluation system has been carried out between CSRSR-NAEA of Indonesia toward Standard Laboratory of JAERI (Japan) and ARL (Australia). The intercomparison was in 10 amm depth dose measurement , Hp (10), from the intercomparison result could be stated that personal depth dose measurement conducted by CSRSR was sufficiently good. Deviation of dose measurement result using personal dosemeter of TLD BG-1 type which were used by CSRSR in the intercomparison and routine photon personal dose monitoring was still in internationally agreed limit. Maximum deviation of reported doses by CSRSR compared to delivered doses for dosemeter irradiation by JAERI was -10.0 percent and by ARL was +29 percent. Maximum deviation permitted in personal dose monitoring is ± 50 percent

  18. Dose-to-man studies

    International Nuclear Information System (INIS)

    Anon.

    1976-01-01

    Dose-to-Man Studies focused on developing computer data handling and computer modules which permit easy, rapid assessment of the dose to southeastern United States populations from routine or accidental releases of radionuclides to atmospheric and stream systems

  19. Dose monitoring in nuclear emergency

    International Nuclear Information System (INIS)

    Nan Hongjie; Yang Zhongping; Lei Xin

    2012-01-01

    In order to protect people from irradiation sickness and rebuild the radiation filed in nuclear emergency, personal and environmental dose need to be monitored. The application of TLD in dose monitoring is discussed in this paper. (authors)

  20. A review of radiology staff doses and dose monitoring requirements

    International Nuclear Information System (INIS)

    Martin, C. J.

    2009-01-01

    Studies of radiation doses received during X-ray procedures by radiology, cardiology and other clinical staff have been reviewed. Data for effective dose (E), and doses to the eyes, thyroid, hands and legs have been analysed. These data have been supplemented with local measurements to determine the most exposed part of the hand for monitoring purposes. There are ranges of 60-100 in doses to individual tissues reported in the literature for similar procedures at different centres. While ranges in the doses per unit dose-area product (DAP) are between 10 and 25, large variations in dose result from differences in the sensitivity of the X-ray equipment, the type of procedure and the operator technique, but protection factors are important in maintaining dose levels as low as possible. The influence of shielding devices is significant for determining the dose to the eyes and thyroid, and the position of the operator, which depends on the procedure, is the most significant factor determining doses to the hands. A second body dosemeter worn at the level of the collar is recommended for operators with high workloads for use in assessment of effective dose and the dose to the eye. It is proposed that the third quartile values from the distributions of dose per unit DAP identified in the review might be employed in predicting the orders of magnitude of doses to the eye, thyroid and hands, based on interventional operator workloads. Such dose estimates could be employed in risk assessments when reviewing protection and monitoring requirements. A dosemeter worn on the little finger of the hand nearest to the X-ray tube is recommended for monitoring the hand. (authors)

  1. Dose. Detriment. Limit assessment

    International Nuclear Information System (INIS)

    Breckow, J.

    2015-01-01

    One goal of radiation protection is the limitation of stochastic effects due to radiation exposure. The probability of occurrence of a radiation induced stochastic effect, however, is only one of several other parameters which determine the radiation detriment. Though the ICRP-concept of detriment is a quantitative definition, the kind of detriment weighting includes somewhat subjective elements. In this sense, the detriment-concept of ICRP represents already at the stage of effective dose a kind of assessment. Thus, by comparing radiation protection standards and concepts interconvertible or with those of environment or occupational protection one should be aware of the possibly different principles of detriment assessment.

  2. Radon dose and aerosols

    International Nuclear Information System (INIS)

    Planinic, J.; Radolic, V.; Faj, Z.; Vukovic, B.

    2000-01-01

    The equilibrium factor value (F) was measured in the NRPB radon chamber and the corresponding track density ratio (r = D/D 0 ) of bare (D) and diffusion (D 0 ) LR-115 nuclear track detectors was determined, as well as the regression equation F(r). Experiments with LR-115 nuclear track detectors and aerosol sources (burning candle and cigarette) were carried out in the Osijek University radon chamber and afterwards an empirical relationship between the equilibrium factor and aerosol concentration was derived. For the purpose of radon dose equivalent assessment, procedures for determining the unattached fraction of radon progeny were introduced using two nuclear track detectors. (author)

  3. Hanford Environmental Dose Reconstruction Project

    International Nuclear Information System (INIS)

    Cannon, S.D.; Finch, S.M.

    1992-10-01

    The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates):Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates

  4. Effective dose and dose to crystalline lens during angiographic procedures

    International Nuclear Information System (INIS)

    Pages, J.

    1998-01-01

    The highest radiation doses levels received by radiologists are observed during interventional procedures. Doses to forehead and neck received by a radiologist executing angiographic examinations at the department of radiology at the academic hospital (AZ-VUB) have been measured for a group of 34 examinations. The doses to crystalline lens and the effective doses for a period of one year have been estimated. For the crystalline lens the maximum dose approaches the ICRP limit, that indicates the necessity for the radiologist to use leaded glasses. (N.C.)

  5. Dosimetric study of varying aperture-surface distance at the Finnish BNCT facility

    International Nuclear Information System (INIS)

    Uusi-Simola, Jouni; Seppaelae, Tiina; Nieminen, Katja; Kotiluoto, Petri; Seren, Tom; Auterinen, Iiro; Kortesniemi, Mika; Savolainen, Sauli

    2006-01-01

    Comparison of experimental and calculated dosimetric values in a water phantom was performed at the Finnish BNCT facility at the FiR 1 research reactor. The purpose was to study the effect of changing aperture to surface distance (ASD) to radiation dose and to verify the accuracy of the treatment planning and to provide data for comparison of the methods. A magnesium ionisation chamber flushed with argon gas was used to measure absorbed photon dose rate. Diluted manganese (Mn) and gold (Au) foils and Mn wires were used to determine Mn and Au activation reaction rates. Computer simulations with both SERA and MCNP programs were used to independently calculate the corresponding values. Photon dose and activation reaction rate depth profiles at beam central axis an axial profiles at 2.5 and 6 cm depths were measured and calculated for 11 and 14 and 17 cm diameter apertures. Depth profiles for activation reaction rates were determined for the clinically used 11 and 14 cm diameter apertures for 0, 5, and 10 cm ASD. In addition, the optional 17 cm beam was characterised at 0 and 5 cm ASD. The beam intensity decreases by approximately 20% and 40% when ASD is increased to 5 cm or 10 cm, respectively. The shape of the 55 Mn activation reaction rate depth profile and photon depth radial profile did not vary more than 5% for the 14 cm beam when the ASD was increased from 0 cm to 10 cm. (author)

  6. Dose planning and dose delivery in radiation therapy

    International Nuclear Information System (INIS)

    Knoeoes, T.

    1991-01-01

    A method has been developed for calibration of CT-numbers to volumetric electron density distributions using tissue substitutes of known elemental composition and experimentally determined electron density. This information have been used in a dose calculation method based on photon and electron interaction processes. The method utilizes a convolution integral between the photon fluence matrix and dose distribution kernels. Inhomogeneous media are accounted for using the theorems of Fano and O'Connor for scaling dose distribution kernels in proportion to electron density. For clinical application of a calculated dose plan, a method for prediction of accelerator output have been developed. The methods gives the number of monitor units that has to be given to obtain a certain absorbed dose to a point inside an irregular, inhomogeneous object. The method for verification of dose distributions outlined in this study makes it possible to exclude the treatment related variance contributions, making an objective evaluation of dose calculations with experiments feasible. The methods for electron density determination, dose calculation and prediction of accelerator output discussed in this study will all contribute to an increased accuracy in the mean absorbed dose to the target volume. However, a substantial gain in the accuracy for the spatial absorbed dose distribution will also follow, especially using CT for mapping of electron density together with the dose calculation algorithm. (au)

  7. Normal tissue dose-effect models in biological dose optimisation

    International Nuclear Information System (INIS)

    Alber, M.

    2008-01-01

    Sophisticated radiotherapy techniques like intensity modulated radiotherapy with photons and protons rely on numerical dose optimisation. The evaluation of normal tissue dose distributions that deviate significantly from the common clinical routine and also the mathematical expression of desirable properties of a dose distribution is difficult. In essence, a dose evaluation model for normal tissues has to express the tissue specific volume effect. A formalism of local dose effect measures is presented, which can be applied to serial and parallel responding tissues as well as target volumes and physical dose penalties. These models allow a transparent description of the volume effect and an efficient control over the optimum dose distribution. They can be linked to normal tissue complication probability models and the equivalent uniform dose concept. In clinical applications, they provide a means to standardize normal tissue doses in the face of inevitable anatomical differences between patients and a vastly increased freedom to shape the dose, without being overly limiting like sets of dose-volume constraints. (orig.)

  8. Radiation dose in paediatric cardiac catheterisation: A systematic literature review

    International Nuclear Information System (INIS)

    Gould, R.; McFadden, S.L.; Hughes, C.M.

    2017-01-01

    Objectives: It is believed that children are more sensitive to ionising radiation than adults. This work reviewed the reported radiation dose estimates for paediatric cardiac catheterisation. A systematic literature review was performed by searching healthcare databases for studies reporting radiation dose using predetermined key words relating to children having cardiac catheterisation. The quality of publications was assessed using relevant Critical Appraisal Skills Programme questions and their reported radiation exposures were evaluated. Key findings: It is only in recent years that larger cohort observations have been undertaken. Although radiation dose from paediatric cardiac catheterisation has decreased in recent years, the literature indicated that it remains varied and potentially substantial. Conclusion: Standardisation of weight categories and procedure types such as those recommended by the PiDRL project could help compare current and future radiation dose estimates. - Highlights: • 31 articles reporting radiation dose from paediatric cardiac catheterisation were reviewed. • In recent years, larger cohorts (>1000) have been reported. • Radiation dose to children has been lowered in the last decade but remains varied. • Future dosimetry should be consistent for weight categories and procedure types.

  9. Comparison between linear quadratic and early time dose models

    International Nuclear Information System (INIS)

    Chougule, A.A.; Supe, S.J.

    1993-01-01

    During the 70s, much interest was focused on fractionation in radiotherapy with the aim of improving tumor control rate without producing unacceptable normal tissue damage. To compare the radiobiological effectiveness of various fractionation schedules, empirical formulae such as Nominal Standard Dose, Time Dose Factor, Cumulative Radiation Effect and Tumour Significant Dose, were introduced and were used despite many shortcomings. It has been claimed that a recent linear quadratic model is able to predict the radiobiological responses of tumours as well as normal tissues more accurately. We compared Time Dose Factor and Tumour Significant Dose models with the linear quadratic model for tumour regression in patients with carcinomas of the cervix. It was observed that the prediction of tumour regression estimated by the Tumour Significant Dose and Time Dose factor concepts varied by 1.6% from that of the linear quadratic model prediction. In view of the lack of knowledge of the precise values of the parameters of the linear quadratic model, it should be applied with caution. One can continue to use the Time Dose Factor concept which has been in use for more than a decade as its results are within ±2% as compared to that predicted by the linear quadratic model. (author). 11 refs., 3 figs., 4 tabs

  10. Absorbed dose in CT. Comparison by CT dose index

    International Nuclear Information System (INIS)

    Yamamoto, Kenji; Akazawa, Hiroshi; Andou, Takashi

    2002-01-01

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

  11. Towards a new dose and dose-rate effectiveness factor (DDREF)? Some comments.

    Science.gov (United States)

    Chadwick, K H

    2017-06-26

    The aim of this article is to offer a broader, mechanism-based, analytical tool than that used by (Rühm et al 2016 Ann. ICRP 45 262-79) for the interpretation of cancer induction relationships. The article explains the limitations of this broader analytical tool and the implications of its use in view of the publications by Leuraud et al 2015 (Lancet Haematol. 2 e276-81) and Richardson et al 2015 (Br. Med. J. 351 h5359). The publication by Rühm et al 2016 (Ann. ICRP 45 262-79), which is clearly work in progress, reviews the current status of the dose and dose-rate effectiveness factor (DDREF) as recommended by the ICRP. It also considers the issues which might influence a reassessment of both the value of the DDREF as well as its application in radiological protection. In this article, the problem is approached from a different perspective and starts by commenting on the limited scientific data used by Rühm et al 2016 (Ann. ICRP 45 262-79) to develop their analysis which ultimately leads them to use a linear-quadratic dose effect relationship to fit solid cancer mortality data from the Japanese life span study of atomic bomb survivors. The approach taken here includes more data on the induction of DNA double strand breaks and, using experimental data taken from the literature, directly relates the breaks to cell killing, chromosomal aberrations and somatic mutations. The relationships are expanded to describe the induction of cancer as arising from radiation induced cytological damage coupled to cell killing since the cancer mutated cell has to survive to express its malignant nature. Equations are derived for the induction of cancer after both acute and chronic exposure to sparsely ionising radiation. The equations are fitted to the induction of cancer in mice to illustrate a dose effect relationship over the total dose range. The 'DDREF' derived from the two equations varies with dose and the DDREF concept is called into question. Although the equation for

  12. Dose Calculation Accuracy of the Monte Carlo Algorithm for CyberKnife Compared with Other Commercially Available Dose Calculation Algorithms

    International Nuclear Information System (INIS)

    Sharma, Subhash; Ott, Joseph; Williams, Jamone; Dickow, Danny

    2011-01-01

    Monte Carlo dose calculation algorithms have the potential for greater accuracy than traditional model-based algorithms. This enhanced accuracy is particularly evident in regions of lateral scatter disequilibrium, which can develop during treatments incorporating small field sizes and low-density tissue. A heterogeneous slab phantom was used to evaluate the accuracy of several commercially available dose calculation algorithms, including Monte Carlo dose calculation for CyberKnife, Analytical Anisotropic Algorithm and Pencil Beam convolution for the Eclipse planning system, and convolution-superposition for the Xio planning system. The phantom accommodated slabs of varying density; comparisons between planned and measured dose distributions were accomplished with radiochromic film. The Monte Carlo algorithm provided the most accurate comparison between planned and measured dose distributions. In each phantom irradiation, the Monte Carlo predictions resulted in gamma analysis comparisons >97%, using acceptance criteria of 3% dose and 3-mm distance to agreement. In general, the gamma analysis comparisons for the other algorithms were <95%. The Monte Carlo dose calculation algorithm for CyberKnife provides more accurate dose distribution calculations in regions of lateral electron disequilibrium than commercially available model-based algorithms. This is primarily because of the ability of Monte Carlo algorithms to implicitly account for tissue heterogeneities, density scaling functions; and/or effective depth correction factors are not required.

  13. Measurement of multi-slice computed tomography dose profile with the Dose Magnifying Glass and the MOSkin radiation dosimeter

    International Nuclear Information System (INIS)

    Lian, C.P.L.; Wong, J.H.D.; Young, A.; Cutajar, D.; Petasecca, M.; Lerch, M.L.F.; Rosenfeld, A.B.

    2013-01-01

    This study describes the application of two in-house developed dosimeters, the Dose Magnifying Glass (DMG) and the MOSkin dosimeter at the Centre for Medical Radiation Physics, University of Wollongong, Australia, for the measurement of CT dose profiles for a clinical diagnostic 16-slice MSCT scanner. Two scanner modes were used; axial mode and helical mode, and the effect of varying beam collimation and pitch was studied. With an increase in beam collimation in axial mode and an increase of CT pitch in helical mode, cumulative point dose at scanner isocentre decreased while FWHM increased. There was generally good agreement to within 3% between the acquired dose profiles obtained by the DMG and the film except at dose profile tails, where film over-responded by up to 30% due to its intrinsic depth dose dependence at low doses. -- Highlights: ► This study shows the CT beam profiles acquired with our institution's detectors. ► The DMG is a relative dosimeter calibrated to absolute MOSkin readings. ► There was good agreement between dose profiles acquired by the DMG and the film

  14. New recommendations for dose equivalent

    International Nuclear Information System (INIS)

    Bengtsson, G.

    1985-01-01

    In its report 39, the International Commission on Radiation Units and Measurements (ICRU), has defined four new quantities for the determination of dose equivalents from external sources: the ambient dose equivalent, the directional dose equivalent, the individual dose equivalent, penetrating and the individual dose equivalent, superficial. The rationale behind these concepts and their practical application are discussed. Reference is made to numerical values of these quantities which will be the subject of a coming publication from the International Commission on Radiological Protection, ICRP. (Author)

  15. Evaluation of the Occupational Doses of Interventional Radiologists

    International Nuclear Information System (INIS)

    Kuipers, Gerritjan; Velders, Xandra L.; Winter, Robbert J. de; Reekers, Jim A.; Piek, Jan J.

    2008-01-01

    The aim of the present study was to determine whether there is a linear relation between the doses measured above and those measured under the lead apron of the radiologists performing interventional procedures. To monitor radiation exposure the International Commission of Radiological Protection (ICRP) recommends the use of a single dosimeter under the protective apron. To determine the exposure more accurately an additional dosimeter is recommended above the protective apron. The exposure of eight radiologists was monitored with two personal dosimeters during 3 consecutive years. To measure the doses uniformly the two dosimeters were worn in a special holder attached to the lead apron. The two personal dosimeters were replaced every 4 weeks on the same day. The doses above and under the protective aprons of seven radiologists did not differ significantly. A significant lower dose above and under the protective apron was measured for one of the radiologists. During a 4-week period the average dose measured above the lead apron was 3.44 mSv (median, 3.05 mSv), while that under the 0.25-mm lead apron was 0.12 mSv (median, 0.1 mSv). The coefficients of the regression line result in the equation Y = 0.036X - 0.004, with Y as the dose under the lead apron and X as the dose above the lead apron. The statistical analysis of the data established a linear relation between the doses above and those under the lead apron (R 2 = 0.59). Before the special holder was introduced it was not possible to derive a relation between the doses above and those under the lead apron, as the doses were measured at varying places above and under the lead apron. There is no evidence that the effective dose can be estimated more accurately when an additional dosimeter is used. The present study revealed a threshold before doses under the lead apron were measured. Due to the threshold it can be concluded that the doses under the lead apron will not be underestimated easily when doses above the

  16. Mediation analysis with time varying exposures and mediators.

    Science.gov (United States)

    VanderWeele, Tyler J; Tchetgen Tchetgen, Eric J

    2017-06-01

    In this paper we consider causal mediation analysis when exposures and mediators vary over time. We give non-parametric identification results, discuss parametric implementation, and also provide a weighting approach to direct and indirect effects based on combining the results of two marginal structural models. We also discuss how our results give rise to a causal interpretation of the effect estimates produced from longitudinal structural equation models. When there are time-varying confounders affected by prior exposure and mediator, natural direct and indirect effects are not identified. However, we define a randomized interventional analogue of natural direct and indirect effects that are identified in this setting. The formula that identifies these effects we refer to as the "mediational g-formula." When there is no mediation, the mediational g-formula reduces to Robins' regular g-formula for longitudinal data. When there are no time-varying confounders affected by prior exposure and mediator values, then the mediational g-formula reduces to a longitudinal version of Pearl's mediation formula. However, the mediational g-formula itself can accommodate both mediation and time-varying confounders and constitutes a general approach to mediation analysis with time-varying exposures and mediators.

  17. Varying ultrasound power level to distinguish surgical instruments and tissue.

    Science.gov (United States)

    Ren, Hongliang; Anuraj, Banani; Dupont, Pierre E

    2018-03-01

    We investigate a new framework of surgical instrument detection based on power-varying ultrasound images with simple and efficient pixel-wise intensity processing. Without using complicated feature extraction methods, we identified the instrument with an estimated optimal power level and by comparing pixel values of varying transducer power level images. The proposed framework exploits the physics of ultrasound imaging system by varying the transducer power level to effectively distinguish metallic surgical instruments from tissue. This power-varying image-guidance is motivated from our observations that ultrasound imaging at different power levels exhibit different contrast enhancement capabilities between tissue and instruments in ultrasound-guided robotic beating-heart surgery. Using lower transducer power levels (ranging from 40 to 75% of the rated lowest ultrasound power levels of the two tested ultrasound scanners) can effectively suppress the strong imaging artifacts from metallic instruments and thus, can be utilized together with the images from normal transducer power levels to enhance the separability between instrument and tissue, improving intraoperative instrument tracking accuracy from the acquired noisy ultrasound volumetric images. We performed experiments in phantoms and ex vivo hearts in water tank environments. The proposed multi-level power-varying ultrasound imaging approach can identify robotic instruments of high acoustic impedance from low-signal-to-noise-ratio ultrasound images by power adjustments.

  18. A summary of data on accumulated occupational radiation doses among Canadian workers

    International Nuclear Information System (INIS)

    Sont, W.N.

    1994-01-01

    This paper is based on work done on accumulated career doses. The data are taken from the National Dose Registry and consist of accumulated doses to the monitored workforce from the years 1970, 1975, 1980, 1985, and 1990. Four broad occupational categories are analyzed: medicine, nuclear power, uranium processing (including mining, milling, refining, and fuel fabrication), and industry. Two- and three-dimensional bar charts are used to display workforce sizes, collective accumulated doses, and average accumulated doses over time, broken down by career start. Lognormal plots are used to show the distribution of accumulated doses. Many trends are as could be expected, and some of those may be used for construction of statistical models for career-dose accumulation. The size and accumulated career doses in the workforces of the uranium processing category do not vary regularly with time, and in this case modeling is likely to be difficult. 5 refs., 16 figs., 1 tab

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Effective dose to radon considering people's activities

    International Nuclear Information System (INIS)

    Shimo, M.; Seki, K.; Kikuchi, I.

    1992-01-01

    The tidal volume was estimated for evaluating the effective dose due to radon concentration in the atmosphere. In this study regional population was separated to vocation and non-vocation. The occupancy time and the breathing rate for both vocation and non-vocation groups were estimated, and the annual tidal volume for both groups were calculated. Human actions were separated to 18 activities in the process for estimating the breathing rate. It was clear that the breathing rate depended on human activity and that the human activity changed with its age, so the breathing rate varied with age. Finally the effective doses due to radon and radon progeny indoors and outdoors were evaluated. The maximum annual effective dose was estimated to be 1.2 mSv, minimum 0.2 mSv, and mean 0.51 mSv for vocation. For non-vocation, the male maximum value 0.43 mSv was obtained at the 16 age and the minimum 0.12 mSv at the 70 age, whereas female maximum 0.26 mSv was obtained at the 12 age and the minimum 0.11 mSv at the 70 age. In addition in this study objective areas are Aichi, Gifu, and Mie prefectures for vocation and only Aichi prefecture for non-vocation. (author)

  1. Uncertainty on faecal analysis on dose assessment

    Energy Technology Data Exchange (ETDEWEB)

    Juliao, Ligia M.Q.C.; Melo, Dunstana R.; Sousa, Wanderson de O.; Santos, Maristela S.; Fernandes, Paulo Cesar P. [Instituto de Radioprotecao e Dosimetria, Comissao Nacional de Energia Nuclear, Av. Salvador Allende s/n. Via 9, Recreio, CEP 22780-160, Rio de Janeiro, RJ (Brazil)

    2007-07-01

    Monitoring programmes for internal dose assessment may need to have a combination of bioassay techniques, e.g. urine and faecal analysis, especially in workplaces where compounds of different solubilities are handled and also in cases of accidental intakes. Faecal analysis may be an important data for assessment of committed effective dose due to exposure to insoluble compounds, since the activity excreted by urine may not be detectable, unless a very sensitive measurement system is available. This paper discusses the variability of the daily faecal excretion based on data from just one daily collection; collection during three consecutive days: samples analysed individually and samples analysed as a pool. The results suggest that just 1 d collection is not appropriate for dose assessment, since the 24 h uranium excretion may vary by a factor of 40. On the basis of this analysis, the recommendation should be faecal collection during three consecutive days, and samples analysed as a pool, it is more economic and faster. (authors)

  2. Comments on 'Reconsidering the definition of a dose-volume histogram'-dose-mass histogram (DMH) versus dose-volume histogram (DVH) for predicting radiation-induced pneumonitis

    International Nuclear Information System (INIS)

    Mavroidis, Panayiotis; Plataniotis, Georgios A; Gorka, Magdalena Adamus; Lind, Bengt K

    2006-01-01

    In a recently published paper (Nioutsikou et al 2005 Phys. Med. Biol. 50 L17) the authors showed that the use of the dose-mass histogram (DMH) concept is a more accurate descriptor of the dose delivered to lung than the traditionally used dose-volume histogram (DVH) concept. Furthermore, they state that if a functional imaging modality could also be registered to the anatomical imaging modality providing a functional weighting across the organ (functional mass) then the more general and realistic concept of the dose-functioning mass histogram (D[F]MH) could be an even more appropriate descriptor. The comments of the present letter to the editor are in line with the basic arguments of that work since their general conclusions appear to be supported by the comparison of the DMH and DVH concepts using radiobiological measures. In this study, it is examined whether the dose-mass histogram (DMH) concept deviated significantly from the widely used dose-volume histogram (DVH) concept regarding the expected lung complications and if there are clinical indications supporting these results. The problem was investigated theoretically by applying two hypothetical dose distributions (Gaussian and semi-Gaussian shaped) on two lungs of uniform and varying densities. The influence of the deviation between DVHs and DMHs on the treatment outcome was estimated by using the relative seriality and LKB models using the Gagliardi et al (2000 Int. J. Radiat. Oncol. Biol. Phys. 46 373) and Seppenwoolde et al (2003 Int. J. Radiat. Oncol. Biol. Phys. 55 724) parameter sets for radiation pneumonitis, respectively. Furthermore, the biological equivalent of their difference was estimated by the biologically effective uniform dose (D-bar) and equivalent uniform dose (EUD) concepts, respectively. It is shown that the relation between the DVHs and DMHs varies depending on the underlying cell density distribution and the applied dose distribution. However, the range of their deviation in terms of

  3. Integral dose conservation in radiotherapy

    International Nuclear Information System (INIS)

    Reese, Adam S.; Das, Shiva K.; Curle, Charles; Marks, Lawrence B.

    2009-01-01

    Treatment planners frequently modify beam arrangements and use IMRT to improve target dose coverage while satisfying dose constraints on normal tissues. The authors herein analyze the limitations of these strategies and quantitatively assess the extent to which dose can be redistributed within the patient volume. Specifically, the authors hypothesize that (1) the normalized integral dose is constant across concentric shells of normal tissue surrounding the target (normalized to the average integral shell dose), (2) the normalized integral shell dose is constant across plans with different numbers and orientations of beams, and (3) the normalized integral shell dose is constant across plans when reducing the dose to a critical structure. Using the images of seven patients previously irradiated for cancer of brain or prostate cancer and one idealized scenario, competing three-dimensional conformal and IMRT plans were generated using different beam configurations. Within a given plan and for competing plans with a constant mean target dose, the normalized integral doses within concentric ''shells'' of surrounding normal tissue were quantitatively compared. Within each patient, the normalized integral dose to shells of normal tissue surrounding the target was relatively constant (1). Similarly, for each clinical scenario, the normalized integral dose for a given shell was also relatively constant regardless of the number and orientation of beams (2) or degree of sparing of a critical structure (3). 3D and IMRT planning tools can redistribute, rather than eliminate dose to the surrounding normal tissues (intuitively known by planners). More specifically, dose cannot be moved between shells surrounding the target but only within a shell. This implies that there are limitations in the extent to which a critical structure can be spared based on the location and geometry of the critical structure relative to the target.

  4. Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

    Science.gov (United States)

    Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

    2001-01-01

    The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p < 0.05). Basal proliferation of leukocytes in the blood and spleen increased significantly with increasing dose (p < 0.05). Significant dose rate effects were observed only in thrombocyte counts. Plasma levels of transforming growth factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

  5. Required ozone doses for removing pharmaceuticals from wastewater effluents

    DEFF Research Database (Denmark)

    Antoniou, Maria; Hey, Gerly; Rodríguez Vega, Sergio

    2013-01-01

    of each investigated API (DDO3) was determined for each effluent by fitting a first order equation to the remaining concentration of API at each applied ozone dose. Ozone dose requirements were found to vary significantly between effluents depending on their matrix characteristics.The specific ozone dose...... was then normalized to the dissolved organic carbon (DOC) of each effluent. The DDO3/DOC ratios were comparable for each API between the effluents.15 of the 42 investigated APIs could be classified as easily degradable (DDO3/DOC≤0.7), while 19 were moderately degradable (0.71.4). Furthermore, we predict...... that a reasonable estimate of the ozone dose required to remove any of the investigated APIs may be attained by multiplying the experimental average DDO3/DOC obtained with the actual DOC of any effluent....

  6. Newtonian cosmology with a time-varying constant of gravitation

    International Nuclear Information System (INIS)

    McVittie, G.C.

    1978-01-01

    Newtonian cosmology is based on the Eulerian equations of fluid mechanics combined with Poisson's equation modified by the introduction of a time-varying G. Spherically symmetric model universes are worked out with instantaneously uniform densities. They are indeterminate unless instantaneous uniformity of the pressure is imposed. When G varies as an inverse power of the time, the models can in some cases be shown to depend on the solution of a second-order differential equation which also occurs in the Friedmann models of general relativity. In Section 3, a method for 'passing through' a singularity of this equation is proposed which entails making four arbitrary mathematical assumptions. When G varies as (time) -1 , models with initially cycloidal motion are possible, each cycle becoming longer as time progresses. Finally, gravitation becomes so weak that the model expands to infinity. Kinetic and potential energies for the whole model are derived from the basic equations; their sum is not constant. (author)

  7. Brane world cosmologies with varying speed of light

    International Nuclear Information System (INIS)

    Youm, Donam

    2001-02-01

    We study cosmologies in the Randall-Sundrum models, incorporating the possibility of time-varying speed of light and Newton's constant. The cosmologies with varying speed of light (VSL) were proposed by Moffat and by Albrecht and Magueijo as an alternative to inflation for solving the cosmological problems. We consider the case in which the speed of light varies with time after the radion or the scale of the extra dimension has been stabilized. We elaborate on the conditions under which the flatness problem and the cosmological constant problem can be resolved. Particularly, the VSL cosmologies may provide a possible mechanism for bringing the quantum corrections to the fine-tuned brane tensions after the SUSY breaking under control. (author)

  8. Hematological toxicity in radioimmunotherapy is predicted both by the computed absorbed whole body dose (cGy) and by the administered dose (mCi)

    International Nuclear Information System (INIS)

    Marquez, Sheri D.; Knox, Susan J.; Trisler, Kirk D.; Goris, Michael L.

    1997-01-01

    Purpose/Objective: Radioimmunotherapy (RIT) has yielded encouraging response rates in patients with recurrent non-Hodgkin's lymphoma, but myelotoxicity remains the dose limiting factor. Dose optimization is theoretically possible, since a pretreatment biodistribution study with tracer doses allows for a fairly accurate estimate of the whole body (and by implication the bone marrow) dose in patients. It has been shown that the radiation dose as a function of the administered dose varies widely from patient to patient. The pretreatment study could therefore be used to determine the maximum tolerable dose for each individual patient. The purpose of this study was to examine whether the administered dose or the estimated whole body absorbed radiation dose were indeed predictors of bone marrow toxicity. Materials and Methods: We studied two cohorts of patients to determine if the computed integral whole body or marrow dose is predictive of myelotoxicity. The first cohort consisted of 13 patients treated with Yttrium-90 labeled anti-CD20 (2B8) monoclonal antibody. Those patients were treated in a dose escalation protocol, based on the administered dose, without correction for weight or body surface. The computed whole body dose varied from 41 to 129 cGy. The second cohort (6 patients) were treated with Iodine-131 labeled anti-CD20 (B1) antibody. In this group the administered dose was tailored to deliver an estimated 75 cGy whole body dose. The administered dose varied from 54 to 84 mCi of Iodine-131. For each patient, white blood cell count with differential, hemoglobin, hematocrit, and platelet levels were measured before and at regular intervals after RIT was administered. Using linear regression analysis, a relationship between administered dose, absorbed dose and myelotoxicity was determined for each patient cohort. Results: Marrow toxicity was measured by the absolute decrease in white blood cell (DWBC), platelet (DPLAT), and neutrophil (DN) values. In the Yttrium

  9. Partially linear varying coefficient models stratified by a functional covariate

    KAUST Repository

    Maity, Arnab

    2012-10-01

    We consider the problem of estimation in semiparametric varying coefficient models where the covariate modifying the varying coefficients is functional and is modeled nonparametrically. We develop a kernel-based estimator of the nonparametric component and a profiling estimator of the parametric component of the model and derive their asymptotic properties. Specifically, we show the consistency of the nonparametric functional estimates and derive the asymptotic expansion of the estimates of the parametric component. We illustrate the performance of our methodology using a simulation study and a real data application.

  10. Varied appearance of lymphoma in patients with AIDS

    International Nuclear Information System (INIS)

    Sider, L.; Weiss, A.

    1988-01-01

    Lymphoma is frequently present in patients with acquired immunodeficiency (AIDS). But unlike in the general population, the appearance of lymphoma in patients with AIDS is extremely varied. The computed tomographic scans, chest radiographs, and subsequent hospital courses of 15 patients with AIDS-related lymphoma are presented. The patients presented with isolated pleural effusion (six patients), pleural and pericardial effusion (one patient), pulmonary infiltrates (five patients), and mediastinal adenopathy (three patients). This varied manner of presentation of lymphoma in AIDS patients should be recognized if diagnosis is to be made in the earlier stages of presentation

  11. Entropy Rate of Time-Varying Wireless Networks

    DEFF Research Database (Denmark)

    Cika, Arta; Badiu, Mihai Alin; Coon, Justin P.

    2018-01-01

    In this paper, we present a detailed framework to analyze the evolution of the random topology of a time-varying wireless network via the information theoretic notion of entropy rate. We consider a propagation channel varying over time with random node positions in a closed space and Rayleigh...... fading affecting the connections between nodes. The existence of an edge between two nodes at given locations is modeled by a Markov chain, enabling memory effects in network dynamics. We then derive a lower and an upper bound on the entropy rate of the spatiotemporal network. The entropy rate measures...

  12. Investigating Time-Varying Drivers of Grid Project Emissions Impacts

    Energy Technology Data Exchange (ETDEWEB)

    Barrett, Emily L.; Thayer, Brandon L.; Pal, Seemita; Studarus, Karen E.

    2017-11-15

    The emissions consequences of smart grid technologies depend heavily on their context and vary not only by geographical location, but by time of year. The same technology operated to meet the same objective may increase the emissions associated with energy generation for part of the year and decrease emissions during other times. The Grid Project Impact Quantification (GridPIQ) tool provides the ability to estimate these seasonal variations and garner insight into the time-varying drivers of grid project emissions impacts. This work leverages GridPIQ to examine the emissions implications across years and seasons of adding energy storage technology to reduce daily peak demand in California and New York.

  13. Patient dose measurement and dose reduction in East Anglia (UK)

    International Nuclear Information System (INIS)

    Wade, J.P.; Goldstone, K.E.; Dendy, P.P.

    1995-01-01

    At the end of 1990 a programme of patient dose measurements was introduced as part of the quality assurance service already provided for X ray departments throughout the East Anglian Health Region (UK). Thermoluminescence dosemeters (TLDs) were used to measure over 1200 skin entrance surface doses for four common radiographic views in 33 hospitals in both the NHS and private sector. The four views were chosen to cover a wide range of equipment and techniques. The data collected have enabled Regional reference doses to be set which, for all views considered, fall below the National Radiological Protection Board (NRPB) Reference levels. In departments which exceeded reference levels, techniques were reviewed, improvements suggested and doses re-measured, in accordance with the recommended procedure for patient dose audit. A significant finding was that, given appropriate controls, X ray departments in the private sector could achieve the same acceptably low doses as NHS departments. (Author)

  14. Efficacy of secondary isoniazid preventive therapy among ...

    African Journals Online (AJOL)

    Objective. To determine the efficacy of secondary preventive therapy against tuberculosis (TB) among goldminers working in South Africa. Design. An observational study. Methods. The incidence of recurrent TB was compared between two cohorts of HIV-infected miners: one cohort had received secondary preventive ...

  15. Niosomal Delivery of Isoniazid - Development and Characterization

    African Journals Online (AJOL)

    Erah

    high as 61.8 %, a level that is capable of achieving effective treatment of tuberculosis. Conclusion: The ... inactivation of the drug, targets the ... bath for 1 h and at room temperature over- .... culture medium, RPMI 1640 supplemented with 5% ...

  16. Radiation dose from food to man after Chernobyl

    International Nuclear Information System (INIS)

    1988-01-01

    The geographical distribution in Norway of radioactive fallout from the Chernobyl accident varied considerably. In order to estimate radioactivity dose levels, two main categories of people were selected for study. The first category covered people who were assumed to have been exposed to much higher doses of radioactivity than the average, i.e. people consuming large amounts of food containing high levels of radioactivity. The other category covered people who were assumed to have received doses of radioactivity close to average. Two procedures were utilized for exposure measurements: Body levels of radioactivity were measured directly, and dietary studies were carried out to estimate the total intake of radioactivity through food as well as the proportion of the total intake which derived from the various foodstuffs. Furthermore, dietary changes and other precautions taken in consequence of the Chernobyl fallout were registered, and assessments were made of the degree to which radioactive cesium intake had been reduced as a result of these changes. The average effective dose equivalent due to the consumption of contaminated food during the first year after the Chernobyl accident was estimated to be in the range 0.12 to 0.25 mSv. A quarter of this dose was due to the consumption of milk. Apart from the Sami reindeer herdsmen in central and southern Norway, the dose which the especially exposed groups had received during the first year was estimated to 0.5 to 1.0 mSv. Almost 90% of the dose derived from the consumption of ''wild'' freshwater fish, reindeer meat and milk. Most of the Sami people received doses varying from 1 to 3 mSv in the first year. By far the greatest contribution (90%) arised from the consumption of reindeer meat

  17. Radiation exposure during paediatric CT in Sudan: CT dose, organ and effective doses

    International Nuclear Information System (INIS)

    Suliman, I.I.; Khamis, H.M.; Ombada, T.H.; Alzimami, K.; Alkhorayef, M.; Sulieman, A.

    2015-01-01

    The purpose of this study was to assess the magnitude of radiation exposure during paediatric CT in Sudanese hospitals. Doses were determined from CT acquisition parameters using CT-Expo 2.1 dosimetry software. Doses were evaluated for three patient ages (0-1, 1-5 and 5-10 y) and two common procedures (head and abdomen). For children aged 0-1 y, volume CT air kerma index (C vol ), air Kerma-length product and effective dose (E) values were 19.1 mGy, 265 mGy.cm and 3.1 mSv, respectively, at head CT and those at abdominal CT were 8.8 mGy, 242 mGy.cm and 7.7 mSv, respectively. Those for children aged 1-5 y were 22.5 mGy, 305 mGy.cm and 1.1 mSv, respectively, at head CT and 12.6 mGy, 317 mGy.cm, and 5.1 mSv, respectively, at abdominal CT. Dose values and variations were comparable with those reported in the literature. Organ equivalent doses vary from 7.5 to 11.6 mSv for testes, from 9.0 to 10.0 mSv for ovaries and from 11.1 to 14.3 mSv for uterus in abdominal CT. The results are useful for dose optimisation and derivation of national diagnostic reference levels. (authors)

  18. Dose-response relationship for breast cancer induction at radiotherapy dose

    Directory of Open Access Journals (Sweden)

    Gruber Günther

    2011-06-01

    Full Text Available Abstract Purpose Cancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer. Materials and methods In this work a dose-response relationship for breast cancer is derived based on (i the analysis of breast cancer induction after Hodgkin's disease, (ii a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy, (iv the breast cancer induction of the A-bomb survivor data. Results The fitted model parameters for an α/β = 3 Gy were α = 0.067Gy-1 and R = 0.62. The risk for breast cancer is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 20 Gy and drops off only slightly at larger doses. The predicted EAR for breast cancer after radiotherapy of Hodgkin's disease is 11.7/10000PY which can be compared to the findings of several epidemiological studies where EAR for breast cancer varies between 10.5 and 29.4/10000PY. The model was used to predict the impact of the reduction of radiation volume on breast cancer risk. It was estimated that mantle field irradiation is associated with a 3.2-fold increased risk compared with mediastinal irradiation alone, which is in agreement with a published value of 2.7. It was also shown that the modelled age dependency of breast cancer risk is in satisfying agreement with published data. Conclusions The dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients.

  19. A study on seasonal variations of indoor gamma dose in Bangladesh

    International Nuclear Information System (INIS)

    Miah, M. Idrish

    2005-01-01

    Monthly variation of gamma dose rate measured in indoor air of buildings of Bangladesh was found to vary cosinusoidally through a period of 1 year. Significant seasonal variations were observed. Maximum dose rate, however, was observed in January and a minimum in July. Dose rate in January was 32% higher than the annual average, whereas dose rate in July was 50% lower. Seasonally varied ventilation and air exchange rates of the houses might play an important role in the observed variation. The average reduction with respect to winter dose was 59% in summer. Because of lower ventilation and air exchange rates between indoor and outdoor atmosphere, it is expected that the indoor dose rate would be higher in basements than that of upper floors. Monthly dose rate was also found to be influenced by the meteorological conditions. Correlations between dose rate and temperature (r 2 =0.85), rainfall (r=-0.83) and atmospheric pressure (r=0.92) were obtained, but no significant correlation (r=-0.45) was seen between dose rate and humidity. The results show that the seasonal variations of indoor dose rates should be taken into account to estimate annual effective dose equivalent. (author)

  20. Investigation of tilted dose kernels for portal dose prediction in a-Si electronic portal imagers

    International Nuclear Information System (INIS)

    Chytyk, K.; McCurdy, B. M. C.

    2006-01-01

    The effect of beam divergence on dose calculation via Monte Carlo generated dose kernels was investigated in an amorphous silicon electronic portal imaging device (EPID). The flat-panel detector was simulated in EGSnrc with an additional 3.0 cm water buildup. The model included details of the detector's imaging cassette and the front cover upstream of it. To approximate the effect of the EPID's rear housing, a 2.1 cm air gap and 1.0 cm water slab were introduced into the simulation as equivalent backscatter material. Dose kernels were generated with an incident pencil beam of monoenergetic photons of energy 0.1, 2, 6, and 18 MeV. The orientation of the incident pencil beam was varied from 0 deg. to 14 deg. in 2 deg. increments. Dose was scored in the phosphor layer of the detector in both cylindrical (at 0 deg. ) and Cartesian (at 0 deg. -14 deg.) geometries. To reduce statistical fluctuations in the Cartesian geometry simulations at large radial distances from the incident pencil beam, the voxels were first averaged bilaterally about the pencil beam and then combined into concentric square rings of voxels. Profiles of the EPID dose kernels displayed increasing asymmetry with increasing angle and energy. A comparison of the superposition (tilted kernels) and convolution (parallel kernels) dose calculation methods via the χ-comparison test (a derivative of the γ-evaluation) in worst-case-scenario geometries demonstrated an agreement between the two methods within 0.0784 cm (one pixel width) distance-to-agreement and up to a 1.8% dose difference. More clinically typical field sizes and source-to-detector distances were also tested, yielding at most a 1.0% dose difference and the same distance-to-agreement. Therefore, the assumption of parallel dose kernels has less than a 1.8% dosimetric effect in extreme cases and less than a 1.0% dosimetric effect in most clinically relevant situations and should be suitable for most clinical dosimetric applications. The