Acute Psychosis after Recent Isoniazid Initiation

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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

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

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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.

Isoniazid release from suppositories compounded with selected bases.

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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.

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

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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.

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....

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

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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.

Development and Evaluation of Isoniazid Loaded Silk Fibroin Microsphere

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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.

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

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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.

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...

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...

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.

[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.

Fast BIA-amperometric determination of isoniazid in tablets.

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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.

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

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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.

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

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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.

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

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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.

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.

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

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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.

Spirulina maxima Protects Liver From Isoniazid and Rifampicin Drug Toxicity.

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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.

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

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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.

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....

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.

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.

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

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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.

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.

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.

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

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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

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

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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

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.

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.

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

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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.

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

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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.

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...

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.

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.

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.

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

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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.

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

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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.

Synthesis and antitubercular activity of isoniazid condensed with carbohydrate derivatives

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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.

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

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

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

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,.

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...

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

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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.

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...

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.

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.

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.

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.

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

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

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

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

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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

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

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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.

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.

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. ...

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

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 ...

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.

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 ...

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.

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 ...

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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 ...

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.

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.

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

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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.

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

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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.

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

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

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...

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

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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.

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.

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

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

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.

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.

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.

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.

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.

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...

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

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.

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

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...

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,

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.

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

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

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.

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.

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.

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

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.

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.

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.

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.)

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]).

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

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

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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.

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...

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

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.

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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.

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

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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

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

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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.

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

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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.

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

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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.

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....

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

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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.

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

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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.

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)

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

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

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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.

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.

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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.

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.

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)

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.

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

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

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

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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.

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 ...

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

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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.

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.)

Oral matrix tablet formulations for concomitant controlled release of anti-tubercular drugs: design and in vitro evaluations.

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Hiremath, Praveen S; Saha, Ranendra N

2008-10-01

The aim of the present investigation was to develop controlled release (C.R.) matrix tablet formulations of rifampicin and isoniazid combination, to study the design parameters and to evaluate in vitro release characteristics. In the present study, a series of formulations were developed with different release rates and duration using hydrophilic polymers hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC). The duration of rifampicin and isoniazid release could be tailored by varying the polymer type, polymer ratio and processing techniques. Further, Eudragit L100-55 was incorporated in the matrix tablets to compensate for the pH-dependent release of rifampicin. Rifampicin was found to follow linear release profile with time from HPMC formulations. In case of formulations with HPC, there was an initial higher release in simulated gastric fluid (SGF) followed by zero order release profiles in simulated intestinal fluid (SIFsp) for rifampicin. The release of isoniazid was found to be predominantly by diffusion mechanism in case of HPMC formulations, and with HPC formulations release was due to combination of diffusion and erosion. The initial release was sufficiently higher for rifampicin from HPC thus ruling out the need to incorporate a separate loading dose. The initial release was sufficiently higher for isoniazid in all formulations. Thus, with the use of suitable polymer or polymer combinations and with the proper optimization of the processing techniques it was possible to design the C.R. formulations of rifampicin and isoniazid combination that could provide the sufficient initial release and release extension up to 24h for both the drugs despite of the wide variations in their physicochemical properties.

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

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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.

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.

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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.

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

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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.

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

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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.

[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.

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

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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.

[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.

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.

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

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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

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

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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.

Morphine potentiates seizures induced by GABA antagonists and attenuates seizures induced by electroshock in the rat.

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Foote, F; Gale, K

1983-11-25

In a naloxone-reversible, dose-dependent manner, morphine (10-50 mg/kg i.p.) protected against seizures induced by maximal electroshock and increased the incidence and severity of seizures induced by bicuculline, in rats. Morphine also potentiated seizures induced by isoniazid and by picrotoxin. Thus, opiate activity influences the expression of seizures in contrasting ways depending upon the mode of seizure induction. Since morphine consistently potentiated seizures induced by interference with GABA transmission, it appears that GABAergic systems may be of particular significance for the elucidation of the varied effects of morphine on seizure susceptibility.

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

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

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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.

Eligibility for isoniazid preventive therapy in South African gold mines.

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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.

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.

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

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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.

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

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

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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

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

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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.

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

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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.

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

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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.

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

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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

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

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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

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

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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.

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.

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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%).

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 *

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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

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

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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.

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.)

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

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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

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.)

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

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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.

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)

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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.

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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.

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

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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.

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.

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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

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

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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.

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

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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

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.

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

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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

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

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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.

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

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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.

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

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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.

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

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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.

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

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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.

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)

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

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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.

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

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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

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

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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

Meta-analysis of clinical studies supports the pharmacokinetic variability hypothesis for acquired drug resistance and failure of antituberculosis therapy.

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Pasipanodya, Jotam G; Srivastava, Shashikant; Gumbo, Tawanda

2012-07-01

Using hollow-fiber tuberculosis studies, we recently demonstrated that nonadherence is not a significant factor for ADR and that therapy failure only occurs after a large proportion of doses are missed. Computer-aided clinical trial simulations have suggested that isoniazid and rifampin pharmacokinetic variability best explained poor outcomes. We were interested in determining whether isoniazid pharmacokinetic variability was associated with either microbiological failure or ADR in the clinic. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Prospective, randomized, controlled clinical trials that reported isoniazid acetylation status and microbiological outcomes were selected. The main effects examined were microbiological sputum conversion, ADR, and relapse. Effect size was expressed as pooled risk ratios (RRs) comparing rapid with slow acetylators. Thirteen randomized studies with 1631 rapid acetylators and 1751 slow acetylators met inclusion and exclusion criteria. Rapid acetylators were more likely than slow acetylators to have microbiological failure (RR, 2.0; 95% confidence interval [CI], 1.5-2.7), ADR (RR, 2.0; CI, 1.1-3.4), and relapse (RR, 1.3; CI, .9-2.0). Higher failure rates were encountered even in drug regimens comprising >3 antibiotics. No publication bias or small-study effects were observed for the outcomes evaluated. Pharmacokinetic variability to a single drug in the regimen is significantly associated with failure of therapy and ADR in patients. This suggests that individualized dosing for tuberculosis may be more effective than standardized dosing, which is prescribed in directly observed therapy programs.

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

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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.

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

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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.

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

The background and rationale for a new fixed-dose combination for first-line treatment of tuberculosis in children.

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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.

Improvement of classification of real estate of railway transport

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Людмила Володимирівна Гайова

2015-09-01

Full Text Available It was proposed a method of determining the optimum ratio of doses of the most pronounced therapeutic effect and minimal side effects.The aim of the study was to conduct morphological evaluation of lesions of internal organs (lungs, liver, kidneys, spleen after treatment of experimental tuberculosis of guinea pigs different ratios of doses of isoniazid and pyridoxine hydro- chloride.Methods: 50 guinea pigs infection dose of 1 mg Mycobacterium death porpoises from generalized tuberculosis occurs after an average of 45 days, at infection doses of 0.1–0.01 mg – after 60–70 days. Smaller doses of 0.0001 and 0.000001 mg cause chronic disease that ends in death.Results: The optimal therapeutic effect is obtained by treating animals with experimental tuberculosis isoniazid at a dose of 32 mg/kg of vitamin B6 and5 mg/kg body weight of the animal, thus completely disappeared phenomenon specific inflammation in the lungs, liver, kidneys and spleen. This phenomenon also disappeared perifocal nonspecific inflammation. Disappeared dystrophic and necrotic changes in the studied organs.Conclusions: In the experiment Shuttle "INH – pyridoxine hydrochloride" 32 and 5 mg/kg respectively leads to a lack of specific and non-specific manifestations of inflammation in the lungs, liver, kidneys and spleen

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/

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.

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)

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.

Acarbose

Science.gov (United States)

Acarbose comes as a tablet to take by mouth. It is usually taken three times a day. It is very important to take each dose ... for diabetes, digoxin (Lanoxin), diuretics ('water pills'), estrogens, isoniazid, medications for high blood pressure or colds, oral ...

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

The safety of antituberculosis medications during breastfeeding.

Science.gov (United States)

Tran, J H; Montakantikul, P

1998-12-01

Most antituberculosis drugs appear to be safe for use with breastfeeding. These agents are excreted in breast milk at relatively small concentrations. No adverse effects have been reported to date. The percentages of the therapeutic dose of antituberculosis agents that potentially may be delivered to the nursing infants range from 0.05% to 28%. Currently isoniazid, rifampin, ethambutol, streptomycin (first-line agents), kanamycin and cycloserine (second-line agents) are the only agents considered by the AAP to be compatible with breastfeeding. Unfortunately, there are still no clear data on the safety of pyrazinamide, ethionamide, and capreomycin during breastfeeding. If the mother chooses to breastfeed, it may be prudent to examine the infant for signs and symptoms of toxicity. In infants requiring treatment with antituberculosis agents, it is important to use therapeutic doses since drug concentrations in breast milk are not adequate as effective therapy for treatment or prevention. However, dosing at the lower end of the therapeutic range should be prescribed (i.e., 10 mg/kg/day of isoniazid) to decrease the risk of toxicity.

SILVER NANOPARTICLES IN THE SOLUTION OF THE PROBLEM OF DRUG RESISTANCE IN MYCOBACTERIUM TUBERCULOSIS

Directory of Open Access Journals (Sweden)

A. V. Zaharov

2017-01-01

Full Text Available The goal — a scientific evaluation of the effectiveness and safety of NHS in the treatment of experimental drug-resistant tuberculosis. Materials and methods. Used silver nanoparticles obtained by an electrochemical method. With a size of 5-60 nm, 120-270 kontsentratsiey- 1 mcm² and the size of the stabilizer shell — 2-5 nm. 750 crops studied Inhibitory activity of the silver nanoparticles in an isolated form and as part of a nanocomposite with chemotherapy in concentrations of 5; 25 and 50 mcg/ml. Defines the minimum inhibitory concentration of bactericidal nanoparticles composed of a nanocomposite with isoniazid. To evaluate the morphometry M.tuberculosis used atomic force microscopy. Toxicology nanopreparations studied 83 non-linear white mice and 146 white rats. Chemotherapeutic Activity nanopreparations determined on an experimental model of tuberculosis in 65 white male mice imbrednoy line BALB/c. Infectivity dose amount 5х106 colony forming units injected into the sinus venosus animal eyes. Isoniazid, nanoparticles and nanocomposite began administered 14 days after infection by intramuscular injection daily. Treatment efficacy was determined by comparing the evaluation criteria in the experimental and control groups of animals. Evaluated the following indicators: survival index, body mass index and weight of target organ, lesions index, index smear and inoculation of affected organs. Conducted pathological examination. Results. When using isoniazid, which had resistant pathogens, with silver nanoparticles full and significant inhibition of the growth of the M.tuberculosis observed in 49,2% of cases. When the concentration of the nanoparticles 5 mcg/ml in the composite bactericidal activity reached 91,3%. The minimum inhibitory concentration of silver nanoperticles in combination with isoniazid was 2,5 mcg/ml, the minimum bactericidal — 5 mcg /ml. There have been changes in the M.tuberculosis morphometry under the influence of the

The role of the time-kill kinetics assay as part of a preclinical modeling framework for assessing the activity of anti-tuberculosis drugs.

Science.gov (United States)

Bax, Hannelore I; Bakker-Woudenberg, Irma A J M; de Vogel, Corné P; van der Meijden, Aart; Verbon, Annelies; de Steenwinkel, Jurriaan E M

2017-07-01

Novel treatment strategies for tuberculosis are urgently needed. Many different preclinical models assessing anti-tuberculosis drug activity are available, but it is yet unclear which combination of models is most predictive of clinical treatment efficacy. The aim of this study was to determine the role of our in vitro time kill-kinetics assay as an asset to a predictive preclinical modeling framework assessing anti-tuberculosis drug activity. The concentration- and time-dependent mycobacterial killing capacities of six anti-tuberculosis drugs were determined during exposure as single drugs or in dual, triple and quadruple combinations towards a Mycobacterium tuberculosis Beijing genotype strain and drug resistance was assessed. Streptomycin, rifampicin and isoniazid were most active against fast-growing M. tuberculosis. Isoniazid with rifampicin or high dose ethambutol were the only synergistic drug combinations. The addition of rifampicin or streptomycin to isoniazid prevented isoniazid resistance. In vitro ranking showed agreement with early bactericidal activity in tuberculosis patients for some but not all anti-tuberculosis drugs. The time-kill kinetics assay provides important information on the mycobacterial killing dynamics of anti-tuberculosis drugs during the early phase of drug exposure. As such, this assay is a valuable component of the preclinical modeling framework. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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)

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

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

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)

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)

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.

Estimation dose in organs of hyperthyroidism patients treated with I-131

International Nuclear Information System (INIS)

Farias de Lima, F.; Khoury, H.C.; Bertelli Neto, L.; Hazin, C.

1997-01-01

Full text: The absorbed dose in organs of hyperthyroidism patients, which received 370 MBq and 555 MBq of I-131 were estimated, using the MIRDOSE computational program and data of the ICRP-53 publication. The calculus were done considering an equal uptake to 45% and an effective half life of 5 days, these values are closed to the average values found in 17 studied patients. The thyroidal masses were previously determined by the physicians and varied between 40 g and 80 g The results showed that the dose in the thyroid, for an activity of 370 MBq, varied between 99 Gy and 49,5 Gy for the masses of 40 g and 80 g respectively. In the case of the administration of 555 MBq the patients had thyroidal masses between 60 g and 80 g and the doses varied between 99 Gy and 74,2 Gy, respectively. These values showed that the absorbed doses in thyroid are within limits expected for the hyperthyroidism therapy, which are of 506 Gy to 100 Gy. The 100 Gy dose would be exceeded, if the patients with thyroidal mass of 40 g had received a therapeutic dose of 555 MBq. The estimated media doses in others organs were relatively low, with inferior values of 0,1 Gy in kidneys, bone marrow and ovaries and of 0,19 Gy in stomach

Mutations in rpoB and katG genes of multidrug resistant ...

African Journals Online (AJOL)

Introduction: Tuberculosis remains the leading causes of death worldwide with frequencies of mutations in rifampicin and isoniazid resistant Mycobacterium tuberculosis isolates varying according to geographical location. There is limited information in Zimbabwe on specific antibiotic resistance gene mutation patterns in ...

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.

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)

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

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.

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.

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.

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...

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.

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.

Bone-and-muscle-equivalent solid chemical dose meters for photon and electron doses above one kilorad

International Nuclear Information System (INIS)

McLaughlin, W.L.; Rosenstein, M.; Levine, H.

1975-01-01

Conventional solid dose meters, such as plastic films, powders, emulsions, glasses, ceramics and gels, have a response to ionizing photons and electrons that varies markedly over a broad spectrum when compared with the absorption characteristics of biological tissues. New radiochromic dyed plastic dose meters have been developed with X- and gamma ray and electron energy absorption cross-sections (calculated) and radiation energy responses (experimental) corresponding approximately to those for human muscle and bone, for a spectrum from a few keV to at least 10 MeV. Three-dimensional solid dose meters useful over the absorbed dose range of 10 3 to 10 6 rad are formed by thermosetting a selected combination of monomers containing the radiochromic dye in solution. Thin-film dose meters for the dose range 10 5 to 10 7 rad are formed by casting on optically flat surfaces strippable layers of special combinations of polymers and dyes in solution. The response of these systems to X- and gamma rays and electrons has been studied over various radiation spectra, dose-rates and temperatures during irradiation. (author)

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

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)

Mecanismos de acción y de resistencia a rifampicina e isoniacida en Mycobacterium tuberculosis: nueva información sobre viejos conocidos Mechanisms of action of and resistance to rifampicin and isoniazid in Mycobacterium tuberculosis: new information on old friends

Directory of Open Access Journals (Sweden)

A. I. De la Iglesia

2006-04-01

Full Text Available La tuberculosis constituye todavía una de la causas más frecuentes de mortalidad en el mundo. A pesar de la implementación de tratamientos con cuatro drogas antituberculosas, la aparición de cepas resistentes y multirresistentes ha comprometido la eficacia de los mismos. Dos de las drogas en uso, la rifampicina y la isoniacida, recibieron gran atención por su importancia terapéutica, incluso se han identificado los genes involucrados en los mecanismos de resistencia y los que codifican para sus blancos moleculares. La rifampicina es un inhibidor de la subunidad beta de la ARN polimerasa de procariotas, incluido Mycobacterium tuberculosis. La resistencia a esta droga está principalmente mediada por mutaciones agrupadas en una región del gen rpoB. Una pequeña fracción de cepas resistentes no mostró mutaciones en rpoB, lo que sugiere la existencia de otros mecanismos de resistencia, posiblemente eflujo de la droga. La isoniacida es una prodroga que se activa por la catalasa-peroxidasa KatG. Mutaciones en katG son las más comúnmente identificadas en cepas clínicas de M. tuberculosis resistentes a isoniacida, confiriendo altos niveles de resistencia. Sin embargo, el blanco molecular de acción para la isoniacida es la InhA, una enoil-ACP reductasa involucrada en la vía de síntesis de los ácidos micólicos. Otras mutaciones involucradas en la resistencia a la isoniacida afectan al gen ndh, que codifica para la NADH deshidrogenasa.Human tuberculosis is still one of the most frequent causes of death worldwide. Despite the implementation of therapeutic regimes combining four drugs, the rise of resistant and multidrug-resistant Mycobacterium tuberculosis strains has compromised their efficacy. Two of the most effective anti-tubercular drugs in use, rifampicin and isoniazid, have been closely studied due to their therapeutic importance. These studies have led to the identification of the genes involved in resistance mechanisms and of those

Optimizing CT technique to reduce radiation dose: effect of changes in kVp, iterative reconstruction, and noise index on dose and noise in a human cadaver.

Science.gov (United States)

Chang, Kevin J; Collins, Scott; Li, Baojun; Mayo-Smith, William W

2017-06-01

For assessment of the effect of varying the peak kilovoltage (kVp), the adaptive statistical iterative reconstruction technique (ASiR), and automatic dose modulation on radiation dose and image noise in a human cadaver, a cadaver torso underwent CT scanning at 80, 100, 120 and 140 kVp, each at ASiR settings of 0, 30 and 50 %, and noise indices (NIs) of 5.5, 11 and 22. The volume CT dose index (CTDI vol ), image noise, and attenuation values of liver and fat were analyzed for 20 data sets. Size-specific dose estimates (SSDEs) and liver-to-fat contrast-to-noise ratios (CNRs) were calculated. Values for different combinations of kVp, ASiR, and NI were compared. The CTDI vol varied by a power of 2 with kVp values between 80 and 140 without ASiR. Increasing ASiR levels allowed a larger decrease in CTDI vol and SSDE at higher kVp than at lower kVp while image noise was held constant. In addition, CTDI vol and SSDE decreased with increasing NI at each kVp, but the decrease was greater at higher kVp than at lower kVp. Image noise increased with decreasing kVp despite a fixed NI; however, this noise could be offset with the use of ASiR. The CT number of the liver remained unchanged whereas that of fat decreased as the kVp decreased. Image noise and dose vary in a complicated manner when the kVp, ASiR, and NI are varied in a human cadaver. Optimization of CT protocols will require balancing of the effects of each of these parameters to maximize image quality while minimizing dose.

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

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

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.

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.

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

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

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 ...

Optimal dose-response relationships in voice therapy.

Science.gov (United States)

Roy, Nelson

2012-10-01

Like other areas of speech-language pathology, the behavioural management of voice disorders lacks precision regarding optimal dose-response relationships. In voice therapy, dosing can presumably vary from no measurable effect (i.e., no observable benefit or adverse effect), to ideal dose (maximum benefit with no adverse effects), to doses that produce toxic or harmful effects on voice production. Practicing specific vocal exercises will inevitably increase vocal load. At ideal doses, these exercises may be non-toxic and beneficial, while at intermediate or high doses, the same exercises may actually be toxic or damaging to vocal fold tissues. In pharmacology, toxicity is a critical concept, yet it is rarely considered in voice therapy, with little known regarding "effective" concentrations of specific voice therapies vs "toxic" concentrations. The potential for vocal fold tissue damage related to overdosing on specific vocal exercises has been under-studied. In this commentary, the issue of dosing will be explored within the context of voice therapy, with particular emphasis placed on possible "overdosing".

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.

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)

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.

The possibility of the dose limitation system application non-ionizing radiation protection

International Nuclear Information System (INIS)

Ranisavljevic, M., Markovic, S.

1997-01-01

Modern conception of the ionizing radiation protection is based on Dose Limitation System. In the base of every human decision lies compromise. Balance between positive and negative factors, benefit and detriment, profit and expense includes the decision about possibilities for realization any defined radiation practice. The optimal option for the given value of the varying parameter gives the maximum benefit and the minimum detriment. In radiation protection field, detriment is related with human health or expenses, and varying parameter is level of radiation protection (for example dimensions of the installed shielding). The problem lies in fact that for the given value of the varying shielding parameter the maximum benefit and the minimum detriment are not achievable simultaneously because the greater benefit includes the greater expense. The problems which have to be solved because of introducing Dose Limitation System, in regard to create Modified Dose Limitation System, are presented. (author)

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

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.

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)

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)

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

Thermoluminescence kinetics in materials exposed to the low doses applicable to dating and dosimetry

International Nuclear Information System (INIS)

Levy, P.W.

1984-11-01

Thermoluminescence (TL) kinetics have been investigated for low dose situations applicable to dating, dosimetry, and recent geological deposits. Studied were the general one-trap kinetic equation, which reduces to the well known 1st and 2nd order kinetic equations when various assumptions apply, and the interactive kinetic equations, which describes TL in materials exhibiting more than one glow peak. In materials with one glow peak area varies linearly with dose; however, peak height is not linear with dose unless the TL obeys 1st order kinetics at all doses. In materials with two or more glow peaks neither peak height nor peak area varies linearly with dose, except in special situations. In fact, many peak height vs dose curves will be supralinear with the initial low-slope region occurring at relatively low doses. These considerations indicate: (1) Dating and dosimetry technique based on assumed linear peak height vs dose curves will usually underestimate the accumulated dose. (2) Dating techniques can be improved and/or made more reliable by determining the TL kinetics of the glow peaks measured

Patterns of dose variability in radiation prescription of breast cancer

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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

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

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.

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

Thoron in the air: assessment of the occupational dose

International Nuclear Information System (INIS)

Campos, Marcia Pires de

1999-01-01

The occupational dose due to inhalation of thoron was assessed through the committed effective dose and the committed equivalent dose received by workers exposed to the radionuclide at the nuclear materials storage site and the thorium purification plant of the Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP). The radiation doses were performed by compartmental analysis following the compartmental model of the lung and biokinetic model of the lead, through the thoron equilibrium equivalent concentrations. These values were obtained by gamma ray spectrometry, total alpha count and alpha particle spectrometry of air samples glass fiber filters. The results of the thoron equilibrium equivalent concentration varied from 0.3 to 0,67 Bq/m 3 at the nuclear materials storage site and from 0.9 to 249.8 Bq/m 3 at the thorium purification plant. The committed effective dose due to thoron inhalation varied from 0.03 mSv/a to 0.67 mSv/a at the nuclear materials storage site and from 0.12 mSv/a to 6.0 mSv/a at the thorium purification plant. The risk assessment of lung cancer and fatal cancers for the workers exposed to thoron at the nuclear materials storage site and the thorium purification plant showed an increment for both risk cancer. (author)

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)

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

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

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)

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

UV-radiation and skin cancer dose effect curves

International Nuclear Information System (INIS)

Henriksen, T.; Dahlback, A.; Larsen, S.H.

1988-08-01

Norwegian skin cancer data were used in an attempt to arrive at the dose effect relationship for UV-carcinogenesis. The Norwegian population is relatively homogenous with regard to skin type and live in a country where the annual effective UV-dose varies by approximately 40 percent. Four different regions of the country, each with a broadness of 1 o in latitude (approximately 111 km), were selected . The annual effective UV-doses for these regions were calculated assuming normal ozone conditions throughout the year. The incidence of malignant melanoma and non-melanoma skin cancer (mainly basal cell carcinoma) in these regions were considered and compared to the annual UV-doses. For both these types of cancer a quadratic dose effect curve seems to be valid. Depletions of the ozone layer results in larger UV-doses which in turn may yield more skin cancer. The dose effect curves suggest that the incidence rate will increase by an ''amplification factor'' of approximately 2

Dose-response relationship for breast cancer induction at radiotherapy dose

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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.

Measuring the absorbed dose in critical organs during low rate dose brachytherapy with 137 Cs using thermoluminescent dosemeters

International Nuclear Information System (INIS)

Torres, A.; Gonzalez, P.R.; Furetta, C.; Azorin, J.; Andres, U.; Mendez, G.

2003-01-01

Intracavitary Brachytherapy is one of the most used methods for the treatment of the cervical-uterine cancer. This treatment consists in the insertion of low rate dose 137 Cs sources into the patient. The most used system for the treatment dose planning is that of Manchester. This planning is based on sources, which are considered fixed during the treatment. However, the experience has shown that, during the treatment, the sources could be displaced from its initial position, changing the dose from that previously prescribed. For this reason, it is necessary to make measurements of the absorbed dose to the surrounding organs (mainly bladder and rectum). This paper presents the results of measuring the absorbed dose using home-made LiF: Mg, Cu, P + Ptfe thermoluminescent dosimeters (TLD). Measurements were carried out in-vivo during 20 minutes at the beginning and at the end of the treatments. Results showed that the absorbed dose to the critical organs vary significantly due to the movement of the patient during the treatment. (Author)

The use of linear programming in optimization of HDR implant dose distributions

International Nuclear Information System (INIS)

Jozsef, Gabor; Streeter, Oscar E.; Astrahan, Melvin A.

2003-01-01

The introduction of high dose rate brachytherapy enabled optimization of dose distributions to be used on a routine basis. The objective of optimization is to homogenize the dose distribution within the implant while simultaneously satisfying dose constraints on certain points. This is accomplished by varying the time the source dwells at different locations. As the dose at any point is a linear function of the dwell times, a linear programming approach seems to be a natural choice. The dose constraints are inherently linear inequalities. Homogeneity requirements are linearized by minimizing the maximum deviation of the doses at points inside the implant from a prescribed dose. The revised simplex method was applied for the solution of this linear programming problem. In the homogenization process the possible source locations were chosen as optimization points. To avoid the problem of the singular value of the dose at a source location from the source itself we define the 'self-contribution' as the dose at a small distance from the source. The effect of varying this distance is discussed. Test cases were optimized for planar, biplanar and cylindrical implants. A semi-irregular, fan-like implant with diverging needles was also investigated. Mean central dose calculation based on 3D Delaunay-triangulation of the source locations was used to evaluate the dose distributions. The optimization method resulted in homogeneous distributions (for brachytherapy). Additional dose constraints--when applied--were satisfied. The method is flexible enough to include other linear constraints such as the inclusion of the centroids of the Delaunay-triangulation for homogenization, or limiting the maximum allowable dwell time

4D cone beam CT-based dose assessment for SBRT lung cancer treatment

International Nuclear Information System (INIS)

Cai, Weixing; Dhou, Salam; Cifter, Fulya; Myronakis, Marios; Hurwitz, Martina H; Williams, Christopher L; Berbeco, Ross I; Seco, Joao; Lewis, John H

2016-01-01

The purpose of this research is to develop a 4DCBCT-based dose assessment method for calculating actual delivered dose for patients with significant respiratory motion or anatomical changes during the course of SBRT. To address the limitation of 4DCT-based dose assessment, we propose to calculate the delivered dose using time-varying (‘fluoroscopic’) 3D patient images generated from a 4DCBCT-based motion model. The method includes four steps: (1) before each treatment, 4DCBCT data is acquired with the patient in treatment position, based on which a patient-specific motion model is created using a principal components analysis algorithm. (2) During treatment, 2D time-varying kV projection images are continuously acquired, from which time-varying ‘fluoroscopic’ 3D images of the patient are reconstructed using the motion model. (3) Lateral truncation artifacts are corrected using planning 4DCT images. (4) The 3D dose distribution is computed for each timepoint in the set of 3D fluoroscopic images, from which the total effective 3D delivered dose is calculated by accumulating deformed dose distributions. This approach is validated using six modified XCAT phantoms with lung tumors and different respiratory motions derived from patient data. The estimated doses are compared to that calculated using ground-truth XCAT phantoms. For each XCAT phantom, the calculated delivered tumor dose values generally follow the same trend as that of the ground truth and at most timepoints the difference is less than 5%. For the overall delivered dose, the normalized error of calculated 3D dose distribution is generally less than 3% and the tumor D95 error is less than 1.5%. XCAT phantom studies indicate the potential of the proposed method to accurately estimate 3D tumor dose distributions for SBRT lung treatment based on 4DCBCT imaging and motion modeling. Further research is necessary to investigate its performance for clinical patient data. (paper)

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.

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)

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.)

Preliminary estimation of minimum target dose in intracavitary radiotherapy for cervical cancer

Energy Technology Data Exchange (ETDEWEB)

Ohara, Kiyoshi; Oishi-Tanaka, Yumiko; Sugahara, Shinji; Itai, Yuji [Tsukuba Univ., Ibaraki (Japan). Inst. of Clinical Medicine

2001-08-01

In intracavitary radiotherapy (ICRT) for cervical cancer, minimum target dose (D{sub min}) will pertain to local disease control more directly than will reference point A dose (D{sub A}). However, ICRT has been performed traditionally without specifying D{sub min} since the target volume was not identified. We have estimated D{sub min} retrospectively by identifying tumors using magnetic resonance (MR) images. Pre- and posttreatment MR images of 31 patients treated with high-dose-rate ICRT were used. ICRT was performed once weekly at 6.0 Gy D{sub A}, and involved 2-5 insertions for each patient, 119 insertions in total. D{sub min} was calculated arbitrarily simply at the point A level using the tumor width (W{sub A}) to compare with D{sub A}. W{sub A} at each insertion was estimated by regression analysis with pre- and posttreatment W{sub A}. D{sub min} for each insertion varied from 3.0 to 46.0 Gy, a 16-fold difference. The ratio of total D{sub min} to total D{sub A} for each patient varied from 0.5 to 6.5. Intrapatient D{sub min} difference between the initial insertion and final insertion varied from 1.1 to 3.4. Preliminary estimation revealed that D{sub min} varies widely under generic dose prescription. Thorough D{sub min} specification will be realized when ICRT-applicator insertion is performed under MR imaging. (author)

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.)

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)

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

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.

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.

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)

Distribution and characteristics of gamma and cosmic ray dose rate in living environment

International Nuclear Information System (INIS)

Nagaoka, Toshi; Moriuchi, Shigeru

1991-01-01

A series of environmental radiation surveys was carried out from the viewpoint of characterizing the natural radiation dose rate distribution in the living environment, including natural and artificial ones. Through the analysis of the data obtained at numbers of places, several aspects of the radiation field in living environments were clarified. That is the gamma ray dose rate varies due to the following three dominant causes: 1) the radionuclide concentration of surrounding materials acting as gamma ray sources, 2) the spatial distribution of surrounding materials, and 3) the geometrical and shielding conditions between the natural gamma ray sources and the measured point; whereas, the cosmic ray dose rate varies due to the thickness of upper shielding materials. It was also suggested that the gamma ray dose rate generally shows an upward tendency, and the cosmic ray dose rate a downward one in artificial environment. This kind of knowledge is expected to serve as fundamental information for accurate and realistic evaluation of the collective dose in the living environment. (author)

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

Enhanced low dose rate radiation effect test on typical bipolar devices

International Nuclear Information System (INIS)

Liu Minbo; Chen Wei; Yao Zhibin; He Baoping; Huang Shaoyan; Sheng Jiangkun; Xiao Zhigang; Wang Zujun

2014-01-01

Two types of bipolar transistors and nine types bipolar integrated circuit were selected in the irradiation experiment at different "6"0Co γ dose rate. The base current of bipolar transistor and input bias current of amplifier and comparator was measured, low dose enhance factor of test device was obtained. The results show that bipolar device have enhanced low dose rate sensitivity, enhancement factor of bipolar integrated circuit was bigger than that of transistor, and enhanced low dose rate sensitivity greatly varied with different structure and process of bipolar device. (authors)

Outdoor γ-ray dose rate in Shariki Village and environmental factors affecting outdoor γ-ray dose rate in IES

International Nuclear Information System (INIS)

Iyogi, Takashi; Hisamatsu, Shun'ichi; Inaba, Jiro

2000-01-01

Previously, we surveyed the outdoor γ-ray dose rate throughout Aomori Prefecture from 1992 to 1995, and found an annual mean dose rate of 51 nGy h -1 . Relatively high dose rates were also observed in several areas (municipalities) of the survey locations. In this study, we examined the detailed distribution of the γ-ray dose rate in one such high dose rate area, Shariki Village. Glass dosemeters were used for the monitoring of cumulative γ-ray dose rate at 10 locations in the village. The dose rate from each radioactive nuclide in the ground at the monitoring locations was measured by using an in situ γ-ray spectrometer with a Ge detector. The results obtained with the glass dosemeters showed that the γ-ray dose rates in Shariki Village varied from 49 to 55 nGy h -1 . Although the dose rates were generally higher than the mean dose in Aomori Prefecture (1992-1995), the rates were lower than other high dose rate areas which had already been measured. The in situ γ-ray spectrometry revealed that these relatively high dose rates were mainly caused by 40 K and Th series radionuclides in the village. The effect of meteorological conditions on the γ-ray dose rate was studied at a monitoring station in the IES site. The dose rate was continuously recorded by a DBM NaI(Tl) scintillation detector system. The mean dose rate obtained when precipitation was sensed was 27 nGy h -1 and higher than when no precipitation was sensed (25 nGy h -1 ). (author)

Outdoor γ-ray dose rate in Mutsu city and environmental factors affecting outdoor γ-ray dose rate in IES

International Nuclear Information System (INIS)

Iyogi, Takashi; Hisamatsu, Shun'ichi; Inaba, Jiro

2001-01-01

Previously, we surveyed outdoor γ-ray dose rates throughout Aomori Prefecture from 1992 to 1995, and found a mean annual dose rate of 28 nGy h -1 . Relatively high dose rates were also observed in several areas (municipalities) of the survey locations. In this study, we examined the detailed distribution of the γ-ray dose rate in one such high dose rate area, Mutsu City. Glass dosemeters were used for the monitoring of cumulative γ-ray dose rate at 10 locations in the city. The dose rate from each radioactive nuclide in the ground at the monitoring locations was measured by using an in situ γ-ray spectrometer with a Ge detector. The results obtained with the glass dosemeters showed that the γ-ray dose rates in Mutsu City varied from 17 to 32 nGy h -1 . Although the dose rates were almost the same as the mean dose in Aomori Prefecture (1992-1995), the rates were lower than other high dose rate areas which had already been measured. The in situ γ-ray spectrometry revealed that these relatively high dose rates were mainly caused by 40 K and Th series radionuclides in the local ground. The effect of meteorological conditions on the γ-ray dose rate was studied at a monitoring station in the IES site. The dose rate was continuously recorded by a DBM NaI(Tl) scintillation detector system. The mean dose rate obtained when precipitation was sensed was 26 nGy h -1 and higher than when no precipitation was sensed (24 nGy h -1 ). (author)

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)

Computation of the glandular radiation dose in digital tomosynthesis of the breast

International Nuclear Information System (INIS)

Sechopoulos, Ioannis; Suryanarayanan, Sankararaman; Vedantham, Srinivasan; D'Orsi, Carl; Karellas, Andrew

2007-01-01

Tomosynthesis of the breast is currently a topic of intense interest as a logical next step in the evolution of digital mammography. This study reports on the computation of glandular radiation dose in digital tomosynthesis of the breast. Previously, glandular dose estimations in tomosynthesis have been performed using data from studies of radiation dose in conventional planar mammography. This study evaluates, using Monte Carlo methods, the normalized glandular dose (D g N) to the breast during a tomosynthesis study, and characterizes its dependence on breast size, tissue composition, and x-ray spectrum. The conditions during digital tomosynthesis imaging of the breast were simulated using a computer program based on the Geant4 toolkit. With the use of simulated breasts of varying size, thickness and tissue composition, the D g N to the breast tissue was computed for varying x-ray spectra and tomosynthesis projection angle. Tomosynthesis projections centered about both the cranio-caudal (CC) and medio-lateral oblique (MLO) views were simulated. For each projection angle, the ratio of the glandular dose for that projection to the glandular dose for the zero degree projection was computed. This ratio was denoted the relative glandular dose (RGD) coefficient, and its variation under different imaging parameters was analyzed. Within mammographic energies, the RGD was found to have a weak dependence on glandular fraction and x-ray spectrum for both views. A substantial dependence on breast size and thickness was found for the MLO view, and to a lesser extent for the CC view. Although RGD values deviate substantially from unity as a function of projection angle, the RGD averaged over all projections in a complete tomosynthesis study varies from 0.91 to 1.01. The RGD results were fit to mathematical functions and the resulting equations are provided

Radiation doses to patients receiving computed tomography examinations in British Columbia

International Nuclear Information System (INIS)

Aldrich, J.E.; Bilawich, A.-M.; Mayo, J.R.

2006-01-01

To estimate the diagnostic reference levels and effective radiation dose to patients from routine computed tomography (CT) examinations in the province of British Columbia, Canada. The patient weight, height and computed tomography dose index or dose linear product (DLP) were recorded on study sheets for 1070 patients who were referred for clinically indicated routine CT examinations at 18 radiology departments in British Columbia. Sixteen of the scanners were multidetector row scanners. The average patient dose varied from hospital to hospital. The largest range was found for CT of the abdomen, for which the dose varied from 3.6 to 26.5 (average 10.1) mSv. For head CT, the range was 1.7 to 4.9 (average 2.8) mSv; for chest CT, it was 3.8 to 26 (average 9.3) mSv; for pelvis CT, it was 3.5 to 15.5 (average 9.0) mSv; and for abdomen/pelvis CT, it was 7.3 to 31.5 (average 16.3) mSv. Reference dose values were calculated for each exam. These DLP values are as follows: head, 1300 mGy cm; chest, 600 mGy cm; abdomen, 920 mGy cm; pelvis, 650 mGy cm; and abdomen/pelvis, 1100 mGy cm. Among hospitals, there was considerable variation in the DLP and patient radiation dose for a specific exam. Reference doses and patient doses were higher than those found in similar recent surveys carried out in the United Kingdom and the European Union. Patient doses were similar to those found in a recent survey in Germany. (author)

SU-E-T-514: Investigating the Dose Distributions of Equiangular Spaced Noncoplanar Beams

International Nuclear Information System (INIS)

Mitchell, T; Maxim, P; Hadsell, M; Loo, B

2015-01-01

Purpose It has been demonstrated that the use of noncoplanar beams in radiation therapy may Result in dose distributions that are comparable or better than standard coplanar beams [Pugachev, 2001]. A radiation therapy system designed with a noncoplanar beam geometry could allow for a full ring diagnostic quality imaging system to be placed around the patient. Additionally, if the noncoplanar beams were fixed in number and in their angle with respect to the patient’s axial plane, then both treatment and imaging could be achieved concurrently without the need for moving parts, which could greatly reduce treatment times. For such a system to be designed, it is necessary to determine the appropriate number of beams and the beam angles to achieve optimal dose distributions. For simplicity, the beam angles are assumed to be equiangular in the patient’s axial plane, and only the beam angle with respect to the axial plane are varied. This study aims to investigate the dose distributions produced by equiangular noncoplanar beams for multiple beam numbers and beam angles, and to compare these dose distributions with distributions achieved in coplanar volumetric arc therapy (VMAT). Methods Dose distributions produced by noncoplanar beams were calculated using the Varian Eclipse treatment planning system by varying the gantry, collimator, and couch angles to simulate the noncoplanar delivery method. Noncoplanar intensity-modulated (NC-IMRT) beams using 8, 12, and 16 beams with angles varying from 45 degrees to 54 with respect to the patient’s axial plane were studied. Results The NC-IMRT beams produced dose distributions comparable to VMAT plans for a number of treatment sites, and were capable of meeting similar dose-volume histogram constraints. Conclusion This study has demonstrated that a noncoplanar beam delivery method with fixed beam numbers and beam angles is capable of delivering dose distributions comparable to VMAT plans currently in use

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.

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.

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.

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.

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.

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

Patient dose reduction by changing the amount of {sup 18}F-FDG radiopharmaceutical injected

Energy Technology Data Exchange (ETDEWEB)

Paiva, Fernanda G. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Engenharia Nuclear. Programa de Pós Graduação em Ciências e Técnicas Nucleares; Santana, Priscila C. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Anatomia e Imagem; Mourão Filho, Arnaldo P., E-mail: fgpaiva92@gmail.com, E-mail: pridili@gmail.com, E-mail: apratabhz@gmail.com [Centro Federal de Educação Tecnológica de Minas Gerais (CEFET-MG), Belo Horizonte, MG (Brazil). Centro de Engenharia Biomédica

2017-07-01

Images of Positron Emission Tomography (PET) associated with Computed Tomography (CT) have important diagnostic applications, mainly for oncology. These compound tomographic devices allow the overlapping of functional images obtained from the administration of radiopharmaceuticals and anatomical images generated by X-ray beam attenuation. This work evaluated the impact of reducing the effective dose by reducing the activity injected into the patient using the ICRP 106 biokinetic model. The activity to be injected may vary according to the patient mass and the detector sensitivity. In this work was used the fixed mass of Alderson phantoms, as a standard adult, this mass is 73.5 kg for the male, and 50 kg for the female. Different values of activity to be injected were simulated, from 0.07 mCi to 0.15 mCi, and with 10 mCi, protocol used in some services. Thus, for the acquisition of PET scans, any reduction of the administered activity implies a proportional reduction of the effective dose in patient. The effective dose may vary up to 114% altering the injected activity between 0.07 and 0.15 mCi. Comparing the results found for the effective dose range using 10 mCi the effective dose may vary by up to approximately 14000%. It is expected that the PET/CT scans protocols are changed at the end of the study, so that the absorbed and effective dose received by the patient decreases. (author)

The use of polymer gel dosimetry to measure dose distribution around metallic implants

International Nuclear Information System (INIS)

Nagahata, Tomomasa; Yamaguchi, Hajime; Monzen, Hajime; Nishimura, Yasumasa

2014-01-01

A semi-solid polymer dosimetry system using agar was developed to measure the dose distribution close to metallic implants. Dosimetry of heterogeneous fields where electron density markedly varies is often problematic. This prompted us to develop a polymer gel dosimetry technique using agar to measure the dose distribution near substance boundaries. Varying the concentration of an oxygen scavenger (tetra-hydroxymethyl phosphonium chloride) showed the absorbed dose and transverse relaxation rate of the magnetic resonance signal to be linear between 3 and 12 Gy. Although a change in the dosimeter due to oxidization was observed in room air after 24 hours, no such effects were observed in the first 4 hours. The dose distribution around the metal implants was measured using agar dosimetry. The metals tested were a lead rod, a titanium hip joint, and a metallic stent. A maximum 30% dose increase was observed near the lead rod, but only a 3% increase in the absorbed dose was noted near the surface of the titanium hip joint and metallic stent. Semi-solid polymer dosimetry using agar thus appears to be a useful method for dosimetry around metallic substances. (author)

[The use of polymer gel dosimetry to measure dose distribution around metallic implants].

Science.gov (United States)

Nagahata, Tomomasa; Yamaguchi, Hajime; Monzen, Hajime; Nishimura, Yasumasa

2014-10-01

A semi-solid polymer dosimetry system using agar was developed to measure the dose distribution close to metallic implants. Dosimetry of heterogeneous fields where electron density markedly varies is often problematic. This prompted us to develop a polymer gel dosimetry technique using agar to measure the dose distribution near substance boundaries. Varying the concentration of an oxygen scavenger (tetra-hydroxymethyl phosphonium chloride) showed the absorbed dose and transverse relaxation rate of the magnetic resonance signal to be linear between 3 and 12 Gy. Although a change in the dosimeter due to oxidization was observed in room air after 24 hours, no such effects were observed in the first 4 hours. The dose distribution around the metal implants was measured using agar dosimetry. The metals tested were a lead rod, a titanium hip joint, and a metallic stent. A maximum 30% dose increase was observed near the lead rod, but only a 3% increase in the absorbed dose was noted near the surface of the titanium hip joint and metallic stent. Semi-solid polymer dosimetry using agar thus appears to be a useful method for dosimetry around metallic substances.

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

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)

Conventional-Dose versus High-Dose Chemotherapy for Relapsed Germ Cell Tumors

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Deaglan J. McHugh

2018-01-01

Full Text Available The majority of metastatic germ cell tumors (GCTs are cured with cisplatin-based chemotherapy, but 20–30% of patients will relapse after first-line chemotherapy and require additional salvage strategies. The two major salvage approaches in this scenario are high-dose chemotherapy (HDCT with autologous stem cell transplant (ASCT or conventional-dose chemotherapy (CDCT. Both CDCT and HDCT have curative potential in the management of relapsed/refractory GCT. However, due to a lack of conclusive randomized trials, it remains unknown whether sequential HDCT or CDCT represents the optimal initial salvage approach, with practice varying between tertiary institutions. This represents the most pressing question remaining for defining GCT treatment standards and optimizing outcomes. The authors review prognostic factors in the initial salvage setting as well as the major studies assessing the efficacy of CDCT, HDCT, or both, describing the strengths and weaknesses that formed the rationale behind the ongoing international phase III “TIGER” trial.

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.

Antitubercular drugs for an old target: GSK693 as a promising InhA direct inhibitor

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María Martínez-Hoyos

2016-06-01

Full Text Available Despite being one of the first antitubercular agents identified, isoniazid (INH is still the most prescribed drug for prophylaxis and tuberculosis (TB treatment and, together with rifampicin, the pillars of current chemotherapy. A high percentage of isoniazid resistance is linked to mutations in the pro-drug activating enzyme KatG, so the discovery of direct inhibitors (DI of the enoyl-ACP reductase (InhA has been pursued by many groups leading to the identification of different enzyme inhibitors, active against Mycobacterium tuberculosis (Mtb, but with poor physicochemical properties to be considered as preclinical candidates. Here, we present a series of InhA DI active against multidrug (MDR and extensively (XDR drug-resistant clinical isolates as well as in TB murine models when orally dosed that can be a promising foundation for a future treatment.

Some hybrid models applicable to dose-response relationships

International Nuclear Information System (INIS)

Kumazawa, Shigeru

1992-01-01

A new type of models of dose-response relationships has been studied as an initial stage to explore a reliable extrapolation of the relationships decided by high dose data to the range of low dose covered by radiation protection. The approach is to use a 'hybrid scale' of linear and logarithmic scales; the first model is that the normalized surviving fraction (ρ S > 0) in a hybrid scale decreases linearly with dose in a linear scale, and the second is that the induction in a log scale increases linearly with the normalized dose (τ D > 0) in a hybrid scale. The hybrid scale may reflect an overall effectiveness of a complex system against adverse events caused by various agents. Some data of leukemia in the atomic bomb survivors and of rodent experiments were used to show the applicability of hybrid scale models. The results proved that proposed models fit these data not less than the popular linear-quadratic models, providing the possible interpretation of shapes of dose-response curves, e.g. shouldered survival curves varied by recovery time. (author)

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.

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

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...

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.

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,

Thyrotoxicosis and radioiodine therapy: Does the dose matter?

Directory of Open Access Journals (Sweden)

Andrew Collier

2012-01-01

Full Text Available There are 3 treatment options for thyrotoxicosis: Antithyroid drugs, Surgery and radioiodine. The choice of treatment varies geographically. Radioiodine therapy is preferred in the United States. The aim of radioiodine is to destroy sufficient thyroid tissue to cure the hyperthyroidism. There is a lack of consensus towards what dose of radioiodine should be used. Several methods are used to determine the dose. In our practice we administer 400 MBq to patients with Graves and in patients with large multinodular goiter, we would administer 800 MBq.

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

Iron Oxide Nanoparticle Agglomeration Influences Dose-Rates and Modulates Oxidative Stress Mediated Dose-Response Profiles In Vitro

Energy Technology Data Exchange (ETDEWEB)

Sharma, Gaurav; Kodali, Vamsi K.; Gaffrey, Matthew J.; Wang, Wei; Minard, Kevin R.; Karin, Norman J.; Teeguarden, Justin G.; Thrall, Brian D.

2013-07-31

Spontaneous agglomeration of engineered nanoparticles (ENPs) is a common problem in cell culture media which can confound interpretation of in vitro nanotoxicity studies. The authors created stable agglomerates of iron oxide nanoparticles (IONPs) in conventional culture medium, which varied in hydrodynamic size (276 nm-1.5 μm) but were composed of identical primary particles with similar surface potentials and protein coatings. Studies using C10 lung epithelial cells show that the dose rate effects of agglomeration can be substantial, varying by over an order of magnitude difference in cellular dose in some cases. Quantification by magnetic particle detection showed that small agglomerates of carboxylated IONPs induced greater cytotoxicity and redox-regulated gene expression when compared with large agglomerates on an equivalent total cellular IONP mass dose basis, whereas agglomerates of amine-modified IONPs failed to induce cytotoxicity or redox-regulated gene expression despite delivery of similar cellular doses. Dosimetry modelling and experimental measurements reveal that on a delivered surface area basis, large and small agglomerates of carboxylated IONPs have similar inherent potency for the generation of ROS, induction of stress-related genes and eventual cytotoxicity. The results suggest that reactive moieties on the agglomerate surface are more efficient in catalysing cellular ROS production than molecules buried within the agglomerate core. Because of the dynamic, size and density-dependent nature of ENP delivery to cells in vitro, the biological consequences of agglomeration are not discernible from static measures of exposure concentration (μg/ml) alone, highlighting the central importance of integrated physical characterisation and quantitative dosimetry for in vitro studies. The combined experimental and computational approach provides a quantitative framework for evaluating relationships between the biocompatibility of nanoparticles and their

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

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....

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

A novel time dependent gamma evaluation function for dynamic 2D and 3D dose distributions

International Nuclear Information System (INIS)

Podesta, Mark; Persoon, Lucas CGG; Verhaegen, Frank

2014-01-01

Modern external beam radiotherapy requires detailed verification and quality assurance so that confidence can be placed on both the delivery of a single treatment fraction and on the consistency of delivery throughout the treatment course. To verify dose distributions, a comparison between prediction and measurement must be made. Comparisons between two dose distributions are commonly performed using a Gamma evaluation which is a calculation of two quantities on a pixel by pixel basis; the dose difference, and the distance to agreement. By providing acceptance criteria (e.g. 3%, 3 mm), the function will find the most appropriate match within its two degrees of freedom. For complex dynamic treatments such as IMRT or VMAT it is important to verify the dose delivery in a time dependent manner and so a gamma evaluation that includes a degree of freedom in the time domain via a third parameter, time to agreement, is presented here. A C++ (mex) based gamma function was created that could be run on either CPU and GPU computing platforms that would allow a degree of freedom in the time domain. Simple test cases were created in both 2D and 3D comprising of simple geometrical shapes with well-defined boundaries varying over time. Changes of varying magnitude in either space or time were introduced and repeated gamma analyses were performed varying the criteria. A clinical VMAT case was also included, artificial air bubbles of varying size were introduced to a patient geometry, along with shifts of varying magnitude in treatment time. For all test cases where errors in distance, dose or time were introduced, the time dependent gamma evaluation could accurately highlight the errors. The time dependent gamma function presented here allows time to be included as a degree of freedom in gamma evaluations. The function allows for 2D and 3D data sets which are varying over time to be compared using appropriate criteria without penalising minor offsets of subsequent radiation

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)

Effects of prescription depth, cylinder size, treatment length, tip space, and curved end on doses in high-dose-rate vaginal brachytherapy

International Nuclear Information System (INIS)

Li Shidong; Aref, Ibrahim; Walker, Eleanor; Movsas, Benjamin

2007-01-01

Purpose: To determine the effects of the prescription depth, cylinder size, treatment length, tip space, and curved end on high-dose-rate vaginal brachytherapy (HDR-VBT) of endometrial cancer. Methods and Materials: Treatment plans were prescribed and optimized based on points at the cylinder surface or at 0.5-cm depth. Cylinder sizes ranging from 2 to 4 cm in diameter, and treatment lengths ranging from 3 to 8 cm were used. Dose points in various depths were precisely defined along the cylinder dome. The given dose and dose uniformity to a depth of interest were measured by the mean dose (MD) and standard deviation (SD), respectively, among the dose points belonging to the depth. Dose fall-off beyond the 0.5 cm treatment depth was determined by the ratio of MD at 0.75-cm depth to MD at 0.5-cm depth. Results: Dose distribution varies significantly with different prescriptions. The surface prescription provides more uniform doses at all depths in the target volume, whereas the 0.5-cm depth prescription creates larger dose variations at the cylinder surface. Dosimetric uncertainty increases significantly (>30%) with shorter tip space. Extreme hot (>150%) and cold spots (<60%) occur if no optimization points were placed at the curved end. Conclusions: Instead of prescribing to a depth of 0.5 cm, increasing the dose per fraction and prescribing to the surface with the exact surface points around the cylinder dome appears to be the optimal approach

Communicating doses of pediatric liquid medicines to parents/caregivers: a comparison of written dosing directions on prescriptions with labels applied by dispensed pharmacy.

Science.gov (United States)

Shah, Rita; Blustein, Leona; Kuffner, Ed; Davis, Lisa

2014-03-01

To identify and compare volumetric measures used by healthcare providers in communicating dosing instructions for pediatric liquid prescriptions to parents/caregivers. Dosing instructions were retrospectively reviewed for the 10 most frequently prescribed liquid medications dispensed from 4 community pharmacies for patients aged ≤ 12 years during a 3-month period. Volumetric measures on original prescriptions (ie, milliliters, teaspoons) were compared with those utilized by the pharmacist on the pharmacy label dispensed to the parent/caregiver. Of 649 prescriptions and corresponding pharmacy labels evaluated, 68% of prescriptions and 62% of pharmacy labels communicated dosing in milliliters, 24% of prescriptions and 29% of pharmacy labels communicated dosing in teaspoonfuls, 7% of prescriptions and 0% of pharmacy labels communicated dosing in other measures (ie, milligrams, cubic centimeters, "dose"), and 25% of dispensed pharmacy labels did not reflect units as written in the prescription. Volumetric measures utilized by healthcare professionals in dosing instructions for prescription pediatric oral liquid medications are not consistent. Healthcare professionals and parents/caregivers should be educated on safe dosing practices for liquid pediatric medications. Generalizability to the larger pediatric population may vary depending on pharmacy chain, location, and medications evaluated. Copyright © 2014 Mosby, Inc. All rights reserved.

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

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

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

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)

3D delivered dose assessment using a 4DCT-based motion model

Energy Technology Data Exchange (ETDEWEB)

Cai, Weixing; Hurwitz, Martina H.; Williams, Christopher L.; Dhou, Salam; Berbeco, Ross I.; Mishra, Pankaj, E-mail: wcai@lroc.harvard.edu, E-mail: jhlewis@lroc.harvard.edu; Lewis, John H., E-mail: wcai@lroc.harvard.edu, E-mail: jhlewis@lroc.harvard.edu [Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States); Seco, Joao [Francis H. Burr Proton Therapy Center, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115 (United States)

2015-06-15

Purpose: The purpose of this work is to develop a clinically feasible method of calculating actual delivered dose distributions for patients who have significant respiratory motion during the course of stereotactic body radiation therapy (SBRT). Methods: A novel approach was proposed to calculate the actual delivered dose distribution for SBRT lung treatment. This approach can be specified in three steps. (1) At the treatment planning stage, a patient-specific motion model is created from planning 4DCT data. This model assumes that the displacement vector field (DVF) of any respiratory motion deformation can be described as a linear combination of some basis DVFs. (2) During the treatment procedure, 2D time-varying projection images (either kV or MV projections) are acquired, from which time-varying “fluoroscopic” 3D images of the patient are reconstructed using the motion model. The DVF of each timepoint in the time-varying reconstruction is an optimized linear combination of basis DVFs such that the 2D projection of the 3D volume at this timepoint matches the projection image. (3) 3D dose distribution is computed for each timepoint in the set of 3D reconstructed fluoroscopic images, from which the total effective 3D delivered dose is calculated by accumulating deformed dose distributions. This approach was first validated using two modified digital extended cardio-torso (XCAT) phantoms with lung tumors and different respiratory motions. The estimated doses were compared to the dose that would be calculated for routine 4DCT-based planning and to the actual delivered dose that was calculated using “ground truth” XCAT phantoms at all timepoints. The approach was also tested using one set of patient data, which demonstrated the application of our method in a clinical scenario. Results: For the first XCAT phantom that has a mostly regular breathing pattern, the errors in 95% volume dose (D95) are 0.11% and 0.83%, respectively for 3D fluoroscopic images

3D delivered dose assessment using a 4DCT-based motion model

International Nuclear Information System (INIS)

Cai, Weixing; Hurwitz, Martina H.; Williams, Christopher L.; Dhou, Salam; Berbeco, Ross I.; Mishra, Pankaj; Lewis, John H.; Seco, Joao

2015-01-01

Purpose: The purpose of this work is to develop a clinically feasible method of calculating actual delivered dose distributions for patients who have significant respiratory motion during the course of stereotactic body radiation therapy (SBRT). Methods: A novel approach was proposed to calculate the actual delivered dose distribution for SBRT lung treatment. This approach can be specified in three steps. (1) At the treatment planning stage, a patient-specific motion model is created from planning 4DCT data. This model assumes that the displacement vector field (DVF) of any respiratory motion deformation can be described as a linear combination of some basis DVFs. (2) During the treatment procedure, 2D time-varying projection images (either kV or MV projections) are acquired, from which time-varying “fluoroscopic” 3D images of the patient are reconstructed using the motion model. The DVF of each timepoint in the time-varying reconstruction is an optimized linear combination of basis DVFs such that the 2D projection of the 3D volume at this timepoint matches the projection image. (3) 3D dose distribution is computed for each timepoint in the set of 3D reconstructed fluoroscopic images, from which the total effective 3D delivered dose is calculated by accumulating deformed dose distributions. This approach was first validated using two modified digital extended cardio-torso (XCAT) phantoms with lung tumors and different respiratory motions. The estimated doses were compared to the dose that would be calculated for routine 4DCT-based planning and to the actual delivered dose that was calculated using “ground truth” XCAT phantoms at all timepoints. The approach was also tested using one set of patient data, which demonstrated the application of our method in a clinical scenario. Results: For the first XCAT phantom that has a mostly regular breathing pattern, the errors in 95% volume dose (D95) are 0.11% and 0.83%, respectively for 3D fluoroscopic images

Estimating effective dose to pediatric patients undergoing interventional radiology procedures using anthropomorphic phantoms and MOSFET dosimeters.

Science.gov (United States)

Miksys, Nelson; Gordon, Christopher L; Thomas, Karen; Connolly, Bairbre L

2010-05-01

The purpose of this study was to estimate the effective doses received by pediatric patients during interventional radiology procedures and to present those doses in "look-up tables" standardized according to minute of fluoroscopy and frame of digital subtraction angiography (DSA). Organ doses were measured with metal oxide semiconductor field effect transistor (MOSFET) dosimeters inserted within three anthropomorphic phantoms, representing children at ages 1, 5, and 10 years, at locations corresponding to radiosensitive organs. The phantoms were exposed to mock interventional radiology procedures of the head, chest, and abdomen using posteroanterior and lateral geometries, varying magnification, and fluoroscopy or DSA exposures. Effective doses were calculated from organ doses recorded by the MOSFET dosimeters and are presented in look-up tables according to the different age groups. The largest effective dose burden for fluoroscopy was recorded for posteroanterior and lateral abdominal procedures (0.2-1.1 mSv/min of fluoroscopy), whereas procedures of the head resulted in the lowest effective doses (0.02-0.08 mSv/min of fluoroscopy). DSA exposures of the abdomen imparted higher doses (0.02-0.07 mSv/DSA frame) than did those involving the head and chest. Patient doses during interventional procedures vary significantly depending on the type of procedure. User-friendly look-up tables may provide a helpful tool for health care providers in estimating effective doses for an individual procedure.

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.

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

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

Assessment of CT dose to the fetus and pregnant female patient using patient-specific computational models

Energy Technology Data Exchange (ETDEWEB)

Xie, Tianwu; Poletti, Pierre-Alexandre; Platon, Alexandra; Becker, Christoph D. [Geneva University Hospital, Department of Medical Imaging and Information Sciences, Geneva (Switzerland); Zaidi, Habib [Geneva University Hospital, Department of Medical Imaging and Information Sciences, Geneva (Switzerland); Geneva University, Geneva Neuroscience Center, Geneva (Switzerland); University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, Groningen (Netherlands); University of Southern Denmark, Department of Nuclear Medicine, Odense (Denmark); Geneva University Hospital, Division of Nuclear Medicine and Molecular Imaging, Geneva (Switzerland)

2018-03-15

This work provides detailed estimates of the foetal dose from diagnostic CT imaging of pregnant patients to enable the assessment of the diagnostic benefits considering the associated radiation risks. To produce realistic biological and physical representations of pregnant patients and the embedded foetus, we developed a methodology for construction of patient-specific voxel-based computational phantoms based on existing standardised hybrid computational pregnant female phantoms. We estimated the maternal absorbed dose and foetal organ dose for 30 pregnant patients referred to the emergency unit of Geneva University Hospital for abdominal CT scans. The effective dose to the mother varied from 1.1 mSv to 2.0 mSv with an average of 1.6 mSv, while commercial dose-tracking software reported an average effective dose of 1.9 mSv (range 1.7-2.3 mSv). The foetal dose normalised to CTDI{sub vol} varies between 0.85 and 1.63 with an average of 1.17. The methodology for construction of personalised computational models can be exploited to estimate the patient-specific radiation dose from CT imaging procedures. Likewise, the dosimetric data can be used for assessment of the radiation risks to pregnant patients and the foetus from various CT scanning protocols, thus guiding the decision-making process. (orig.)

Work practices and occupational radiation dose among radiologic technologists in Korea

International Nuclear Information System (INIS)

Cha, Eun Shil; Lee, Won Jin; Ha, Mina; Hwang, Seung Sik; Lee, Kyoung Mu; Jeong, Mee Seon

2013-01-01

Radiologic technologists are one of the occupational groups exposed to the highest dose of radiation worldwide. In Korea, radiologic technologists occupy the largest group (about 33%) among medical radiation workers and they are exposed to the highest dose of occupational dose of radiation as well (1). Although work experience with diagnostic radiation procedure of U.S. radiologic technologists was reported roughly (2), few studies have been conducted for description of overall work practices and the change by calendar year and evaluation of related factors on occupational radiation dose. The aims of the study are to describe work practices and to assess risk factors for occupational radiation dose among radiologic technologists in Korea. This study showed the work practices and occupational radiation dose among representative sample of radiologic technologists in Korea. The annual effective dose among radiologic technologists in Korea remains higher compared with those of worldwide average and varied according to demographic factors, year began working, and duration of working

Commissioning of a MOSFET in-vivo patient dose verification system

International Nuclear Information System (INIS)

Jenetsky, G.O.; Brown, R.L.

2004-01-01

Full text: TLD dosimetry has long been used for in-vivo measurements in estimating absorbed dose to critical structures on patients. Preparing TLDs for measurement, and then obtaining the results is a time consuming process taking many hours. The Thomson-Neilson 'MOSFET 20' (Metal Oxide Semiconducting Field Effect Transistor) dose assessment system, allows for in-vivo measurements (preparation and results) within minutes. Before being used clinically for dose verification, the MOSFETs were tested against the manufacturer's technical specifications, and compared with results from TLDs measured under controlled experiments and patient measurements. Standard sensitivity MOSFETs (TN-502RD) were used with the bias supply set to High sensitivity range. MOSFETs were tested for linearity (5-100cGy) and their calibration factors obtained for all energies (6MV, 18MV, 6MeV, 12MeV, 16MeV, 20MeV) using the method described by Ramani. MOSFETs and TLDs were exposed to a 6MV beam for 50MU at various depths (RW3 solid water phantom) and field sizes and compared to results taken with an ion chamber. Measurements using both systems were also taken at beam edge and 5mm and 10mm out of the field. Eleven patients, who had lens dose assessment requests were measured with both TLDs and MOSFETs and a paired t-test was performed on the results. On two patients, multiple (nine and four) MOSFET measurements were taken and the range of results compared to the range obtained from the TLDs. MOSFET linearity obtained co-efficients of R 2 ≥ 0.996 for all energies, this compared to R 2 ≥ 0.996 recorded by both Ramani and Chaung. The y-intercept values varied from 0 to -2.0mV. Greatest variation between calibration factors, measured for each energy, was 7.5%, this is substantially greater than 3.8% quoted by the manufacturer. For the measurements taken at varying depths and field sizes both TLDs and MOSFETs agreed with the ion chamber results ±IcGy. Measurements taken at beam edge varied ±6c

Dose-effect curves for electron-beam irradiation of some collection microbial strains

International Nuclear Information System (INIS)

Ferdes, O.; Dumitru, E.; Catargiu, L.; Ferdes, M.; Minea, R.; Oproiu, C.; Niculescu, A.

1994-01-01

There were electron-beam irradiated some microbial strains of B.subtilis ICA I-60 both in germination and in sporulated forms. The irradiation were performed at the IPTRD's electron accelerator at 6 MeV, and in the dose range between 0.1-5.0 kGy, at different dose-rate varying from 50 Gy/minute to 100 Gy/minute. The dosimetry was carried out by a PTW medical dosemeter. There were established the dose-effect relationships and curves, the inactivation dose (factor) and the optimum domain for electron-beam mutagenesis. There were obtained some mutant strains with 2-3.5 higher biosynthesis potential, which are in the IFC's collection. (Author)

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.

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

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.

Cone beam computed tomography radiation dose and image quality assessments.

Science.gov (United States)

Lofthag-Hansen, Sara

2010-01-01

examinations of impacted lower third molars and retained upper cuspids. It varied between 11-77 microSv. Radiation dose should be evaluated together with image quality. Images of a skull phantom were obtained with both units varying tube voltage, tube current, degree of rotation and FOVs. Seven observers assessed subjective image quality using a six-point rating scale for two diagnostic tasks: periapical diagnosis and implant planning in the posterior part of the jaws. Intra-observer agreement was good and inter-observer agreement moderate. Periapical diagnosis was found to, regardless of jaw, require higher exposure parameters compared to implant planning. Implant planning in the lower jaw required higher exposure parameters compared to upper jaw. Substantial dose reduction could be made without loss of diagnostic information by using a rotation of 180 degrees, in particular implant planning in upper jaw. CBCT with small FOVs was found to be well-suited for periapical diagnosis and implant planning. The CTDI method is not applicable estimating effective dose for these units. Based on DAP values effective dose varied between 11-77 microSv (ICRP 60, 1991) in a retrospectively selected patient material. Adaptation of exposure parameters to diagnostic task can give substantial dose reduction.

Investigation of lung nodule detectability in low-dose 320-slice computed tomography

Energy Technology Data Exchange (ETDEWEB)

Silverman, J. D.; Paul, N. S.; Siewerdsen, J. H. [Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Department of Medical Imaging, Toronto General Hospital, Toronto, Ontario M5G 2C6 (Canada); Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5G 2M9 (Canada); Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Ontario M5G 2M9 (Canada) and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9 (Canada)

2009-05-15

Low-dose imaging protocols in chest CT are important in the screening and surveillance of suspicious and indeterminate lung nodules. Techniques that maintain nodule detectability yet permit dose reduction, particularly for large body habitus, were investigated. The objective of this study was to determine the extent to which radiation dose can be minimized while maintaining diagnostic performance through knowledgeable selection of reconstruction techniques. A 320-slice volumetric CT scanner (Aquilion ONE, Toshiba Medical Systems) was used to scan an anthropomorphic phantom at doses ranging from {approx}0.1 mGy up to that typical of low-dose CT (LDCT, {approx}5 mGy) and diagnostic CT ({approx}10 mGy). Radiation dose was measured via Farmer chamber and MOSFET dosimetry. The phantom presented simulated nodules of varying size and contrast within a heterogeneous background, and chest thickness was varied through addition of tissue-equivalent bolus about the chest. Detectability of a small solid lung nodule (3.2 mm diameter, -37 HU, typically the smallest nodule of clinical significance in screening and surveillance) was evaluated as a function of dose, patient size, reconstruction filter, and slice thickness by means of nine-alternative forced-choice (9AFC) observer tests to quantify nodule detectability. For a given reconstruction filter, nodule detectability decreased sharply below a threshold dose level due to increased image noise, especially for large body size. However, nodule detectability could be maintained at lower doses through knowledgeable selection of (smoother) reconstruction filters. For large body habitus, optimal filter selection reduced the dose required for nodule detection by up to a factor of {approx}3 (from {approx}3.3 mGy for sharp filters to {approx}1.0 mGy for the optimal filter). The results indicate that radiation dose can be reduced below the current low-dose (5 mGy) and ultralow-dose (1 mGy) levels with knowledgeable selection of

Estimation of the total effective dose from low-dose CT scans and radiopharmaceutical administrations delivered to patients undergoing SPECT/CT explorations

International Nuclear Information System (INIS)

Montes, C.; Hernandez, J.; Gomez-Caminero, F.; Garcia, S.; Martin, C.; Rosero, A.; Tamayo, P.

2013-01-01

Hybrid imaging, such as single photon emission computed tomography (SPECT)/CT, is used in routine clinical practice, allowing coregistered images of the functional and structural information provided by the two imaging modalities. However, this multimodality imaging may mean that patients are exposed to a higher radiation dose than those receiving SPECT alone. The study aimed to determine the radiation exposure of patients who had undergone SPECT/CT examinations and to relate this to the Background Equivalent Radiation Time (BERT). 145 SPECT/CT studies were used to estimate the total effective dose to patients due to both radiopharmaceutical administrations and low-dose CT scans. The CT contribution was estimated by the Dose-Length Product method. Specific conversion coefficients were calculated for SPECT explorations. The radiation dose from low-dose CTs ranged between 0.6 mSv for head and neck CT and 2.6 mSv for whole body CT scan, representing a maximum of 1 year of background radiation exposure. These values represent a decrease of 80-85% with respect to the radiation dose from diagnostic CT. The radiation exposure from radiopharmaceutical administration varied from 2.1 mSv for stress myocardial perfusion SPECT to 26 mSv for gallium SPECT in patients with lymphoma. The BERT ranged from 1 to 11 years. The contribution of low-dose CT scans to the total radiation dose to patients undergoing SPECT/CT examinations is relatively low compared with the effective dose from radiopharmaceutical administration. When a CT scan is only acquired for anatomical localization and attenuation correction, low-dose CT scan is justified on the basis of its lower dose. (author)

IMPACT OF THE FORM OF MEDICATION ON TREATMENT ADHERENCE IN RESPIRATORY TUBERCULOSIS PATIENTS

Directory of Open Access Journals (Sweden)

T. E. Tyulkova

2017-01-01

Full Text Available The goal of the study: to investigate treatment adherence in respiratory tuberculosis patients depending on the choice of therapy.Subjects and methods: retrospective full-design study. The case histories of adult new tuberculosis cases who were treated in TB Dispensary in 2015 were analyzed. The groups were formed based on the intake of combined drugs with fixed doses (1 tablet contained 60 mg of isoniazid, 120 mg of rifampicin, 300 mg of pyrazinamide, 225 mg of ethambutol, and 20 mg of pyridoxine – Group 1 (n = 38; or separate tablets in the doses as per drug use instructions (isoniazid, rifampicin, pyrazinamide, ethambutol – Group 2 (n = 78. The groups were compatible as per sex, age, and clinical manifestations of tuberculosis. Patients from Group 1 with the weight of 60 kg received 5 tablets and patients from Group 2 received more than 12 tablets. Patients' adherence to treatment was assessed as per regularity of intake and number of doses during the intensive phase of treatment.Results. Patients from Group 1 were regularly taking anti-tuberculosis drugs, while in Group 2 there were interruptions of treatment (7-21 days in 12 (15.4% patients. In Group, the intensive phase increased up to 90.2 ± 30.6 doses and in Group 2 this increase made 131.6 ± 65.4 doses due to late sputum conversion. In Group 1, sputum conversion was achieved during the first month of treatment in 60% of patients; and in Group 2 – in 10% of cases (p = 0.044. The frequency of transaminase elevation as a side effect was higher in Group 1, but it did not result in discontinuation of drugs. Thus, the intake of combined medication with fixed doses improved tuberculosis patients' adherence to treatment.

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

[Case reports of drug-induced liver injury in a reference hospital of Zulia state, Venezuela].

Science.gov (United States)

Mengual-Moreno, Edgardo; Lizarzábal-García, Maribel; Ruiz-Soler, María; Silva-Suarez, Niniveth; Andrade-Bellido, Raúl; Lucena-González, Maribel; Bessone, Fernando; Hernández, Nelia; Sánchez, Adriana; Medina-Cáliz, Inmaculada

2015-03-01

Drug-induced liver injury (DILI) is an important cause of morbidity and mortality worldwide, with varied geographical differences. The aim of this prospective, descriptive, cross-sectional study was to identify and characterize cases of DILI in a hospital of Zulia state, Venezuela. Thirteen patients with a presumptive diagnosis of DILI attended by the Department of Gastroenterology, Hospital Universitario, Zulia state, Venezuela, from December-2012 to December-2013 were studied. Ibuprofen (n = 3; 23.1%), acetaminophen (n = 3; 23.1), isoniazid (n = 2; 15.4%) and Herbalife products (n = 2; 15.4%) were the main drugs involved with DILI. Acetaminophen and ibuprofen showed a mixed pattern of liver injury (n = 3; 23.1%) and isoniazid presented a hepatocellular pattern (n = 2; 15.4%). The CIOMS/RUCAMS allowed the identification of possible (n = 7; 53.9%), probable (n = 4; 30.8%) and highly-probable cases (n = 2; 15.4%) of DILI. Amoxicillin/clavulanate, isoniazid, isotretinoin, methotrexate and Herbalife nutritional products were implicated as highly-probable and probable agents. The highest percentage of DILI corresponded to mild cases that recovered after the discontinuation of the agent involved (n = 9; 69.3%). The consumption of Herbalife botanical products is associated with probable causality and fatality (n = 1; 7.7%). In conclusion, the frequency of DILI cases controlled by the Department of Gastroenterology of the Hospital Universitario of Maracaibo was low, being ibuprofen, acetaminophen, isoniazid and products Herbalife the products most commonly involved. It is recommended to continue with the prospective registration of cases, with an extended follow up monitoring period and to facilitate the incorporation of other hospitals in the Zulia State and Venezuela.

Patient dose surveys for radiological examinations in Dutch hospitals between 1993 and 2000

International Nuclear Information System (INIS)

Spoelstra, F.M.; Geleijns, J.; Broerse, J.J.; Teeuwisse, W.M.; Zweers, D.

2001-01-01

Our inventory studies on radiation dose to patients in Dutch hospitals are reviewed and compared with current European guidelines on patient dose and reference dose values of the NRPB. Between the years 1993 and 2000 doses were measured and effective dose was assessed at 14 hospitals for paediatric radiography, at 18 hospitals for PA chest radiography, at 10 respectively 9 hospitals for barium meal and barium enema examinations and at 18 hospitals for CT scans of the brain, chest (including high resolution CT of the chest), abdomen and lumbar spine in The Netherlands. Effective doses varied from 1 μSv (AP chest radiograph premature) to 26 mSv (CT abdomen scan). Doses were in general well below the reference dose values, with the exception of CT where the dose length product often exceeded reference levels. Interhospital variations were considerable, the largest range was observed for PA chest examinations, i.e.a ratio of 27 between maximum and minimum effective dose. (author)

[Comparison of dose calculation algorithms in stereotactic radiation therapy in lung].

Science.gov (United States)

Tomiyama, Yuki; Araki, Fujio; Kanetake, Nagisa; Shimohigashi, Yoshinobu; Tominaga, Hirofumi; Sakata, Jyunichi; Oono, Takeshi; Kouno, Tomohiro; Hioki, Kazunari

2013-06-01

Dose calculation algorithms in radiation treatment planning systems (RTPSs) play a crucial role in stereotactic body radiation therapy (SBRT) in the lung with heterogeneous media. This study investigated the performance and accuracy of dose calculation for three algorithms: analytical anisotropic algorithm (AAA), pencil beam convolution (PBC) and Acuros XB (AXB) in Eclipse (Varian Medical Systems), by comparison against the Voxel Monte Carlo algorithm (VMC) in iPlan (BrainLab). The dose calculations were performed with clinical lung treatments under identical planning conditions, and the dose distributions and the dose volume histogram (DVH) were compared among algorithms. AAA underestimated the dose in the planning target volume (PTV) compared to VMC and AXB in most clinical plans. In contrast, PBC overestimated the PTV dose. AXB tended to slightly overestimate the PTV dose compared to VMC but the discrepancy was within 3%. The discrepancy in the PTV dose between VMC and AXB appears to be due to differences in physical material assignments, material voxelization methods, and an energy cut-off for electron interactions. The dose distributions in lung treatments varied significantly according to the calculation accuracy of the algorithms. VMC and AXB are better algorithms than AAA for SBRT.

Desfechos clínicos do tratamento de tuberculose utilizando o esquema básico recomendado pelo Ministério da Saúde do Brasil com comprimidos em dose fixa combinada na região metropolitana de Goiânia 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

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Anna Carolina Galvão Ferreira

2013-02-01

Full Text Available OBJETIVO: Descrever as taxas de cura, falência e abandono do tratamento da tuberculose com o esquema básico preconizado pelo Ministério da Saúde (tratamento com rifampicina, isoniazida, pirazinamida e etambutol por dois meses seguido de isoniazida e rifampicina por quatro meses utilizando comprimidos em dose fixa combinada em regime autoadministrado e descrever os eventos adversos e seus possíveis impactos nos desfechos do tratamento. MÉTODOS: Estudo descritivo utilizando dados coletados prospectivamente dos prontuários médicos de pacientes com tuberculose (idade > 18 anos tratados com o esquema básico em duas unidades básicas de saúde da região metropolitana de Goiânia, GO. RESULTADOS: A amostra foi composta por 40 pacientes com tuberculose. A taxa de cura foi de 67,5%, a taxa de abandono foi de 17,5%, e não ocorreram casos de falência. Nessa amostra, 19 pacientes (47% relataram reações adversas aos medicamentos. Essas foram leves e moderadas, respectivamente, em 87% e 13% dos casos. Em nenhum caso houve necessidade de mudança do esquema ou suspensão do tratamento. CONCLUSÕES: A taxa de cura do esquema básico com o uso de comprimidos em dose fixa combinada sob regime autoadministrado foi semelhante às taxas históricas do esquema anterior. A taxa de abandono, na amostra estudada, foi muito acima da taxa preconizada como adequada (até 5%.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

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

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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.

Assessment of ambient gamma dose rate around a prospective uranium mining area of South India - A comparative study of dose by direct methods and soil radioactivity measurements

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Karunakara, N.; Yashodhara, I.; Sudeep Kumara, K.; Tripathi, R. M.; Menon, S. N.; Kadam, S.; Chougaonkar, M. P.

Indoor and outdoor gamma dose rates were evaluated around a prospective uranium mining region - Gogi, South India through (i) direct measurements using a GM based gamma dose survey meter, (ii) integrated measurement days using CaSO4:Dy based thermo luminescent dosimeters (TLDs), and (iii) analyses of 273 soil samples for 226Ra, 232Th, and 40K activity concentration using HPGe gamma spectrometry. The geometric mean values of indoor and outdoor gamma dose rates were 104 nGy h-1 and 97 nGy h-1, respectively with an indoor to outdoor dose ratio of 1.09. The gamma dose rates and activity concentrations of 226Ra, 232Th, and 40K varied significantly within a small area due to the highly localized mineralization of the elements. Correlation study showed that the dose estimated from the soil radioactivity is better correlated with that measured directly using the portable survey meter, when compared to that obtained from TLDs. This study showed that in a region having localized mineralization in situ measurements using dose survey meter provide better representative values of gamma dose rates.

Indication-related dosing for magnetic resonance contrast media

International Nuclear Information System (INIS)

Yuh, W.T.C.; Parker, J.R.; Carvlin, M.J.

1997-01-01

This presentation reviews the issue of contrast media dosing and imaging protocols for the optimal MR imaging detection and characterization of pathology. The cumulative clinical experience gained in performing contrast-enhanced MR examinations with gadolinium chelates indicates that a dose of 0.1 mmol/kg body weight provides safe and effective enhancement of most CNS pathology. Doses lower than 0.1 mmol/kg have been shown to be inadequate for delineating all but selected types of CNS pathology, such as masses with a high lesion to background ratio on post-contrast images (acoustic neuromas) or lesions located in areas in which the normal tissue very rapidly takes up contrast agent (e. g. microadenomas in the pituitary gland). Recent clinical studies have suggested a role for high dose gadolinium administration (up to 0.3 mmol/kg) for the optimal detection and delineation of cerebral metastases or other small or poorly enhancing lesions. Differences in the histopathologic characteristics (capillary permeability, vascularity, location, size) of specific diseased tissues may require varying doses or even a different contrast agent to be used for optimal imaging results. As new MR contrast agents and new scanning techniques are introduced, the specific diagnostic question posed will likely determine the choice of pulse sequence, contrast agent and dose used. (orig.)

Age-dependent radiation dose due to intake of uranium through drinking water in India

International Nuclear Information System (INIS)

Sahoo, S.K.; Mohapatra, S.; Chakrabarty, A.; Sumesh, C.G.; Tripathi, R.M.; Puranik, V.D.

2009-01-01

In the present study, an attempt has been made to estimate the content of uranium in drinking water in various states of India by laser fluorimetry. Depending upon the rate of water intake for the different age groups, the associated radiation dose was calculated. The concentration of uranium varied between 0.1 ± 0.01 and 19.6 ± 1.8 ppb which is much lower than the drinking water guideline value of 60 ppb. The total radiation dose due to ingestion of uranium through drinking water for various age groups is found to vary from 0.14 μSv/y to 48 μSv/y. (author)

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

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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

Radiation dose exposure in patients affected by lymphoma undergoing repeat CT examinations: how to manage the radiation dose variability.

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Paolicchi, Fabio; Bastiani, Luca; Guido, Davide; Dore, Antonio; Aringhieri, Giacomo; Caramella, Davide

2018-03-01

To assess the variability of radiation dose exposure in patients affected by lymphoma undergoing repeat CT (computed tomography) examinations and to evaluate the influence of different scan parameters on the overall radiation dose. A series of 34 patients (12 men and 22 women with a median age of 34.4 years) with lymphoma, after the initial staging CT underwent repeat follow-up CT examinations. For each patient and each repeat examination, age, sex, use of AEC system (Automated Exposure Control, i.e. current modulation), scan length, kV value, number of acquired scans (i.e. number of phases), abdominal size diameter and dose length product (DLP) were recorded. The radiation dose of just one venous phase was singled out from the DLP of the entire examination. All scan data were retrieved by our PACS (Picture Archiving and Communication System) by means of a dose monitoring software. Among the variables we considered, no significant difference of radiation dose was observed among patients of different ages nor concerning tube voltage. On the contrary the dose delivered to the patients varied depending on sex, scan length and usage of AEC. No significant difference was observed depending on the behaviour of technologists, while radiologists' choices had indirectly an impact on the radiation dose due to the different number of scans requested by each of them. Our results demonstrate that patients affected by lymphoma who undergo repeat whole body CT scanning may receive unnecessary overexposure. We quantified and analyzed the most relevant variables in order to provide a useful tool to manage properly CT dose variability, estimating the amount of additional radiation dose for every single significant variable. Additional scans, incorrect scan length and incorrect usage of AEC system are the most relevant cause of patient radiation exposure.

Investigation of the Entrance Surface Dose and Dose to Different Organs in Lumbar Spine Imaging

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Sina, S; Zeinali, B; Karimipoorfard, M; Lotfalizadeh, F; Sadeghi, M; Zamani, E; Faghihi, R

2014-01-01

Background: Dose assessment using proper dosimeters is especially important in radiation protection optimization and imaging justification in diagnostic radiology. Objective: The aim of this study is to obtain the Entrance Skin Dose (ESD) of patients undergoing lumbar spine imaging using two thermoluminescence dosimeters TLD-100 (LiF: Mg, Ti) and GR-200 (LiF: Mg, Cu, P) and also to obtain the absorbed dose to different organs in lumbar spine imaging with several views. Methods: To measure the ESD values of the patients undergoing lumbar spine imaging, the two TLD types were put on their skin surface. The ESD values for different views of lumbar spine imaging were also measured by putting the TLDs at the surface of the Rando phantom. Several TLD chips were inserted inside different organs of Rando phantom to measure the absorbed dose to different organs in lumbar spine imaging. Results: The results indicate that there is a close agreement between the results of the two dosimeters. Based on the results of this experiment, the ESD dose of the 16 patients included in this study varied between 2.71 mGy and 26.29 mGy with the average of 11.89 mGy for TLD-100, and between 2.55 mGy and 27.41 mGy with the average of 12.32 mGy for GR-200 measurements. The ESDs obtained by putting the two types of TLDs at the surface of Rando phantom are in close agreement. Conclusion: According to the results, the GR200 has greater sensitivity than the TLD-100. PMID:25599058

Investigation of the Entrance Surface Dose and Dose to Different Organs in Lumbar Spine Imaging

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Sina S

2014-12-01

Full Text Available Background: Dose assessment using proper dosimeters is especially important in radiation protection optimization and imaging justification in diagnostic radiology. Objective: The aim of this study is to obtain the Entrance Skin Dose (ESD of patients undergoing lumbar spine imaging using two thermoluminescence dosimeters TLD-100 (LiF: Mg, Ti and GR-200 (LiF: Mg, Cu, P and also to obtain the absorbed dose to different organs in lumbar spine imaging with several views. Methods: To measure the ESD values of the patients undergoing lumbar spine imaging, the two TLD types were put on their skin surface. The ESD values for different views of lumbar spine imaging were also measured by putting the TLDs at the surface of the Rando phantom. Several TLD chips were inserted inside different organs of Rando phantom to measure the absorbed dose to different organs in lumbar spine imaging. Results: The results indicate that there is a close agreement between the results of the two dosimeters. Based on the results of this experiment, the ESD dose of the 16 patients included in this study varied between 2.71 mGy and 26.29 mGy with the average of 11.89 mGy for TLD-100, and between 2.55 mGy and 27.41 mGy with the average of 12.32 mGy for GR-200 measurements. The ESDs obtained by putting the two types of TLDs at the surface of Rando phantom are in close agreement. Conclusion: According to the results, the GR200 has greater sensitivity than the TLD-100.

Measurement of californium-252 gamma photons depth dose distribution in tissue equivalent material. Vol. 4

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Fadel, M A; El-Fiki, M A; Eissa, H M; Abdel-Hafez, A; Naguib, S H [National Institute of Standards, Cairo (Egypt)

1996-03-01

Phantom of tissue equivalent material with and without bone was used measuring depth dose distribution of gamma-rays from californium-252 source. The source was positioned at center of perspex walled phantom. Depth dose measurements were recorded for X, Y and Z planes at different distances from source. TLD 700 was used for measuring the dose distribution. Results indicate that implantation of bone in tissue equivalent medium cause changes in the gamma depth dose distribution which varies according to variation in bone geometry. 9 figs.

Uncertainty on faecal analysis on dose assessment

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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)

Thermoluminescent dose measurements on board Salyut type orbital stations

International Nuclear Information System (INIS)

Akatov, Yu.A.; Arkhangelskij, V.V.; Aleksandrov, A.P.

1984-06-01

A small, vibration- and shock-resistant thermoluminescent dosemeter (TLD) system - named PILLE - was developed for orbital stations at the Central Research Institute for Physics, Hungary, to measure the cosmic radiation dose on-board. The first on-board measurements with this system were performed by B. Farkas, the Hungarian astronaut, on the Salyut-6 space station in 1980. The same instrument was used by other crews in the following years. Doses measured at different sites in Salyut-6 are presented. The dose rates varied from 0.7 to 0.11 mGy.day -1 . After the first cosmic measurements, the system was further developed. The minimum detectable dose of the new TLD system is 1 μGy, i.e. less by one order of magnitude than that of the former system. The self-irradiation dose rate of the TLD bulbs is also reduced by more than an order of magnitude to 10 nGy.h -1 , by use of potassium-free glass for the bulb envelope. This new type of PILLE TLD system is currently on-board Salyut-7. The dose rates (0.12-0.23 mGy.day -1 ) measured in 1983 are presented in detail. (author)

Evaluation of concave dose distributions created using an inverse planning system

International Nuclear Information System (INIS)

Hunt, Margie A.; Hsiung, C.-Y.; Spirou, Spirodon V.; Chui, C.-S.; Amols, Howard I.; Ling, Clifton C.

2002-01-01

Purpose: To evaluate and develop optimum inverse treatment planning strategies for the treatment of concave targets adjacent to normal tissue structures. Methods and Materials: Optimized dose distributions were designed using an idealized geometry consisting of a cylindrical phantom with a concave kidney-shaped target (PTV) and cylindrical normal tissues (NT) placed 5-13 mm from the target. Targets with radii of curvature from 1 to 2.75 cm were paired with normal tissues with radii between 0.5 and 2.25 cm. The target was constrained to a prescription dose of 100% and minimum and maximum doses of 95% and 105% with relative penalties of 25. Maximum dose constraint parameters for the NT varied from 10% to 70% with penalties from 10 to 1000. Plans were evaluated using the PTV uniformity index (PTV D max /PTV D 95 ) and maximum normal tissue doses (NT D max /PTV D 95 ). Results: In nearly all situations, the achievable PTV uniformity index and the maximum NT dose exceeded the corresponding constraints. This was particularly true for small PTV-NT separations (5-8 mm) or strict NT dose constraints (10%-30%), where the achievable doses differed from the requested by 30% or more. The same constraint parameters applied to different PTV-NT separations yielded different dose distributions. For most geometries, a range of constraints could be identified that would lead to acceptable plans. The optimization results were fairly independent of beam energy and radius of curvature, but improved as the number of beams increased, particularly for small PTV-NT separations or strict dose constraints. Conclusion: Optimized dose distributions are strongly affected by both the constraint parameters and target-normal tissue geometry. Standard site-specific constraint templates can serve as a starting point for optimization, but the final constraints must be determined iteratively for individual patients. A strategy whereby NT constraints and penalties are modified until the highest

SU-F-18C-12: On the Relationship of the Weighted Dose to the Surface Dose In Abdominal CT - Patient Size Dependency

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Zhou, Y; Scott, A; Allahverdian, J [Cedars-Sinai Medical Center, Los Angeles, CA (United States)

2014-06-15

Purpose: It is possible to measure the patient surface dose non-invasively using radiolucent dosimeters. However, the patient size specific weighted dose remains unknown. We attempted to study the weighted dose to surface dose relationship as the patient size varies in abdominal CT. Methods: Seven abdomen phantoms (CIRS TE series) simulating patients from an infant to a large adult were used. Size specific doses were measured with a 100 mm CT chamber under axial scans using a Siemens Sensation 64 (mCT) and a GE 750 HD. The scanner settings were 120 kVp, 200 mAs with fully opened collimations. Additional kVps (80, 100, 140) were added depending on the phantom sizes. The ratios (r) of the weighted CT dose (Dw) to the surface dose (Ds) were related to the phantom size (L) defined as the diameter resulting the equivalent cross-sectional area. Results: The Dw versus Ds ratio (r) was fitted to a linear relationship: r = 1.083 − 0.007L (R square = 0.995), and r = 1.064 − 0.007L (R square = 0.953), for Siemens Sensation 64 and GE 750 HD, respectively. The relationship appears to be independent of the scanner specifics. Conclusion: The surface dose to the weighted dose ratio decreases linearly as the patient size increases. The result is independent of the scanner specifics. The result can be used to obtain in vivo CT dosimetry in abdominal CT.

SU-F-18C-12: On the Relationship of the Weighted Dose to the Surface Dose In Abdominal CT - Patient Size Dependency

International Nuclear Information System (INIS)

Zhou, Y; Scott, A; Allahverdian, J

2014-01-01

Purpose: It is possible to measure the patient surface dose non-invasively using radiolucent dosimeters. However, the patient size specific weighted dose remains unknown. We attempted to study the weighted dose to surface dose relationship as the patient size varies in abdominal CT. Methods: Seven abdomen phantoms (CIRS TE series) simulating patients from an infant to a large adult were used. Size specific doses were measured with a 100 mm CT chamber under axial scans using a Siemens Sensation 64 (mCT) and a GE 750 HD. The scanner settings were 120 kVp, 200 mAs with fully opened collimations. Additional kVps (80, 100, 140) were added depending on the phantom sizes. The ratios (r) of the weighted CT dose (Dw) to the surface dose (Ds) were related to the phantom size (L) defined as the diameter resulting the equivalent cross-sectional area. Results: The Dw versus Ds ratio (r) was fitted to a linear relationship: r = 1.083 − 0.007L (R square = 0.995), and r = 1.064 − 0.007L (R square = 0.953), for Siemens Sensation 64 and GE 750 HD, respectively. The relationship appears to be independent of the scanner specifics. Conclusion: The surface dose to the weighted dose ratio decreases linearly as the patient size increases. The result is independent of the scanner specifics. The result can be used to obtain in vivo CT dosimetry in abdominal CT

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.

Effects of low dose radiation and epigenetic regulation

International Nuclear Information System (INIS)

Jiao Benzheng; Ma Shumei; Yi Heqing; Kong Dejuan; Zhao Guangtong; Gao Lin; Liu Xiaodong

2010-01-01

Purpose: To conclude the relationship between epigenetics regulation and radiation responses, especially in low-dose area. Methods: The literature was examined for papers related to the topics of DNA methylation, histone modifications, chromatin remodeling and non-coding RNA modulation in low-dose radiation responses. Results: DNA methylation and radiation can regulate reciprocally, especially in low-dose radiation responses. The relationship between histone methylation and radiation mainly exists in the high-dose radiation area; histone deacetylase (HDAC) inhibitors show a promising application to enhance radiation sensitivity, no matter whether in low-dose or high-dose areas; the connection between γ-H2AX and LDR has been remained unknown, although γ-H2AX has been shown no radiation sensitivities with 1-15 Gy irradiation; histone ubiquitination play an important role in DNA damage repair mechanism. Moreover, chromatin remodeling has an integral role in DSB repair and the chromatin response, in general, may be precede DNA end resection. Finally, the effect of radiation on miRNA expression seems to vary according to cell type, radiation dose, and post-irradiation time point. Conclusion: Although the advance of epigenetic regulation on radiation responses, which we are managing to elucidate in this review, has been concluded, there are many questions and blind blots deserved to investigated, especially in low-dose radiation area. However, as progress on epigenetics, we believe that many new elements will be identified in the low-dose radiation responses which may put new sights into the mechanisms of radiation responses and radiotherapy. (authors)

Radiation dose response of N channel MOSFET submitted to filtered X-ray photon beam

Science.gov (United States)

Gonçalves Filho, Luiz C.; Monte, David S.; Barros, Fabio R.; Santos, Luiz A. P.

2018-01-01

MOSFET can operate as a radiation detector mainly in high-energy photon beams, which are normally used in cancer treatments. In general, such an electronic device can work as a dosimeter from threshold voltage shift measurements. The purpose of this article is to show a new way for measuring the dose-response of MOSFETs when they are under X-ray beams generated from 100kV potential range, which is normally used in diagnostic radiology. Basically, the method consists of measuring the MOSFET drain current as a function of the radiation dose. For this the type of device, it has to be biased with a high value resistor aiming to see a substantial change in the drain current after it has been irradiated with an amount of radiation dose. Two types of N channel device were used in the experiment: a signal transistor and a power transistor. The delivered dose to the device was varied and the electrical curves were plotted. Also, a sensitivity analysis of the power MOSFET response was made, by varying the tube potential of about 20%. The results show that both types of devices have responses very similar, the shift in the electrical curve is proportional to the radiation dose. Unlike the power MOSFET, the signal transistor does not provide a linear function between the dose rate and its drain current. We also have observed that the variation in the tube potential of the X-ray equipment produces a very similar dose-response.

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

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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.

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

Evaluation of Anticonvulsant, Sedative, Anxiolytic, and Phytochemical Profile of the Methanol Extract from the Aerial Parts of Swertia corymbosa (Griseb. Wight ex C.B. Clarke

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G. Mahendran

2014-01-01

Full Text Available The objective of the present study was to evaluate the anxiolytic, antidepressant, and anticonvulsant activity of the methanolic extract of Swertia corymbosa (SCMeOH. After acute toxicity test, oral treatment with SCMeOH at doses of 125, 250, and 500 mg/kg behavioral models of open field, elevated-plus-maze, actophotometer, rotarod, pentylenetetrazole, isoniazid, and maximal electroshock induced seizure models were utilized. In open field test, SCMeOH (125, 250, and 500 mg/kg (P<0.01, P<0.001 increased the number of rearings. However, the number of central motor and ambulation (P<0.01, P<0.001 were reduced. Likewise, the number of entries and the time spent in open arm were increased while the number of locomotion was decreased (P<0.001 in elevated-plus-maze and actophotometer test, respectively. SCMeOH (125–500 mg/kg protected the mice against the pentylenetetrazole and isoniazid induced convulsions; it causes significant (P<0.01 and P<0.001 dose dependent increase in latency of convulsion. Treatment with SCMeOH reduced the duration of the tonic hind limb extension induced by electroshock. Two major compounds such as gentiopicroside and swertianin were analyzed by HPLC system.

Cumulative effective and individual organ dose levels in paediatric patients undergoing multiple catheterizations for congenital heart disease

International Nuclear Information System (INIS)

Jones, T.P.; Brennan, P.C.; Ryan, E.

2017-01-01

This study examines the cumulative radiation dose levels received by a group of children who underwent multiple cardiac catheterisation procedures during the investigation and management of congenital heart disease (CHD). The purpose is to calculate cumulative doses, identify higher dose individuals, outline the inconsistencies with risk assessment and encourage the establishment of dose databases in order to facilitate the longitudinal research necessary to better understand health risks. A retrospective review of patient records for 117 paediatric patients who have undergone two or more cardiac catheterizations for the investigation of CHD was undertaken. This cohort consisted of patients who were catheterised over a period from September 2002 to August 2014. The age distribution was from newborn to 17 y. Archived kerma-area product (P KA ) and fluoroscopy time (T) readings were retrieved and analysed. Cumulative effective and individual organ doses were determined. The cumulative P KA levels ranged from 1.8 to 651.2 Gycm 2 , whilst cumulative effective dose levels varied from 2 to 259 mSv. The cumulative fluoroscopy time was shown to vary from 8.1 to 193.5 min. Median cumulative organ doses ranged from 3 to 94 mGy. Cumulative effective dose levels are highly variable but may exceed 250 mSv. Individual organ and effective dose measurements remain useful for comparison purposes between institutions although current methodologies used for determining lifetime risks are inadequate. (authors)

TB control programmes: the challenges for Africa.

Science.gov (United States)

Harries, T

1996-11-01

Governmental neglect of tuberculosis (TB), inadequately managed and inaccurately designed TB control programs, population growth, and the HIV epidemic account for the resurgence of TB in sub-Saharan Africa. The World Health Organization and the International Union against TB and Lung Disease have developed a TB control strategy that aims to reduce mortality, morbidity, and transmission of TB. It aims for an 85% cure rate among detected new cases of smear-positive TB and a 70% rate of detecting existing smear-positive TB cases. The strategy involves the provision of short-course chemotherapy (SCC) to all identified smear-positive TB cases through directly observed treatment (DOTS). SCC treatment regimens for smear-positive pulmonary TB recommended for sub-Saharan African countries are: initial phase = daily administration over 2 months of streptomycin, rifampicin, isoniazid, and pyrazinamide; continuation phase = 3 doses over 4 months of isoniazid and rifampicin or daily administration of thiacetazone and isoniazid or of ethambutol and isoniazid. A TB control policy must be implemented to bring about effective TB control. The essential elements of this policy include political commitment, case detection through passive case-finding, SCC, a regular supply of essential drugs, and a monitoring and evaluation system. Political commitment involves establishing a National TB Control Program to be integrated into the existing health structure. Increased awareness of TB in the community and among health workers and a reference laboratory are needed to make case finding successful. A distribution and logistics system is needed to ensure uninterrupted intake of drugs throughout treatment. These regimens have been very successful and cost-effective but pose several disadvantages (e.g., heavy workload of recommended 3 sputum smear tests). A simplified approach involves 1 initial sputum smear for 6 months; 6-months, intermittent rifampicin-based therapy, 100% DOTS throughout

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.

Monte Carlo simulation for radiation dose in children radiology

International Nuclear Information System (INIS)

Mendes, Hitalo R.; Tomal, Alessandra

2016-01-01

The dosimetry in pediatric radiology is essential due to the higher risk that children have in comparison to adults. The focus of this study is to present how the dose varies depending on the depth in a 10 year old and a newborn, for this purpose simulations are made using the Monte Carlo method. Potential differences were considered 70 and 90 kVp for the 10 year old and 70 and 80 kVp for the newborn. The results show that in both cases, the dose at the skin surface is larger for smaller potential value, however, it decreases faster for larger potential values. Another observation made is that because the newborn is less thick the ratio between the initial dose and the final is lower compared to the case of a 10 year old, showing that it is possible to make an image using a smaller entrance dose in the skin, keeping the same level of exposure at the detector. (author)

Genitourinary and pulmonary multidrug resistant Mycobacterium tuberculosis infection in an Asian elephant (Elephas maximus).

Science.gov (United States)

Dumonceaux, Genevieve A; St Leger, Judy; Olsen, John H; Burton, Michael S; Ashkin, David; Maslow, Joel N

2011-12-01

A female Asian elephant (Elephas maximus) developed vaginal and trunk discharge. Cultures were positive for pan-susceptible Mycobacterium tuberculosis. Isoniazid and pyrazinamide were given rectally and monitored by serum levels. After being trained at 10 mo to accept oral dosing, treatment was changed and rifampin was added. Oral medications were administered for another 10 mo. A year after completion of therapy, the vaginal discharge increased and cultures yielded M. tuberculosis, resistant to isoniazid and rifampin. Treatment with oral ethambutol, pyrazinamide, and enrofloxacin and intramuscular amikacin was initiated. Although followup cultures became negative, adverse reactions to medications precluded treatment completion. Due to public health concerns related to multidrug resistant M. tuberculosis (MDR-TB), the elephant was euthanized. Postmortem smears from the lung, peribronchial, and abdominal lymph nodes yielded acid-fast bacteria, although cultures were negative. This case highlights important considerations in the treatment of M. tuberculosis in animals and the need for a consistent approach to diagnosis, treatment, and follow-up.

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

Calculations of the photon dose behind concrete shielding of high energy proton accelerators

International Nuclear Information System (INIS)

Dworak, D.; Tesch, K.; Zazula, J.M.

1992-02-01

The photon dose per primary beam proton behind lateral concrete shieldings was calculated by using an extension of the Monte Carlo particle shower code FLUKA. The following photon-producing processes were taken into account: capture of thermal neutrons, deexcitation of nuclei after nuclear evaporation, inelastic neutron scattering and nuclear reactions below 140 MeV, as well as photons from electromagnetic cascades. The obtained ratio of the photon dose to the neutron dose equivalent varies from 8% to 20% and it well compares with measurements performed recently at DESY giving a mean ratio of 14%. (orig.)

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)

Epithelial regeneration of transposed intestine after high doses of X irradiation

Energy Technology Data Exchange (ETDEWEB)

Both, N.J. de; Vermey, M [Erasmus Universiteit, Rotterdam (Netherlands)

1976-01-01

The regeneration capacities of normal and transposed small bowel epithelium were compared in rats after applying high doses of x irradiation. It has been shown that the potency of the mucosa to regenerate was much higher than assumed and that the mucosa could regenerate after single doses varying from 2000 to 5000 R. Even in the villus epithelium and in flat epithelium covering infiltrates of the lamina propria cells survived, which were still able to resume proliferative activity several days after irradiation.

Epithelial regeneration of transposed intestine after high doses of X-irradiation

International Nuclear Information System (INIS)

Both, N.J. de; Vermey, M.

1976-01-01

The regeneration capacities of normal and transposed small bowel epithelium were compared in rats after applying high doses of X-irradiation. It has been shown that the potency of the mucosa to regenerate was much higher than assumed and that the mucosa could regenerate after single doses varying from 2000 to 5000 R. Even in the villus epithelium and in flat epithelium covering infiltrates of the lamina propria cells survived, which were still able to resume proliferative activity several days after irradiation. (author)

Evaluation of organ doses and specific k effective dose of 64-slice CT thorax examination using an adult anthropomorphic phantom

International Nuclear Information System (INIS)

Hashim, S.; Karim, M.K.A.; Bakar, K.A.; Sabarudin, A.; Chin, A.W; Saripan, M.I.; Bradley, D.A.

2016-01-01

The magnitude of radiation dose in computed tomography (CT) depends on the scan acquisition parameters, investigated herein using an anthropomorphic phantom (RANDO®) and thermoluminescence dosimeters (TLD). Specific interest was in the organ doses resulting from CT thorax examination, the specific k coefficient for effective dose estimation for particular protocols also being determined. For measurement of doses representing five main organs (thyroid, lung, liver, esophagus and skin), TLD-100 (LiF:Mg, Ti) were inserted into selected holes in a phantom slab. Five CT thorax protocols were investigated, one routine (R1) and four that were modified protocols (R2 to R5). Organ doses were ranked from greatest to least, found to lie in the order: thyroid>skin>lung>liver>breast. The greatest dose, for thyroid at 25 mGy, was that in use of R1 while the lowest, at 8.8 mGy, was in breast tissue using R3. Effective dose (E) was estimated using three standard methods: the International Commission on Radiological Protection (ICRP)-103 recommendation (E103), the computational phantom CT-EXPO (E(CTEXPO)) method, and the dose-length product (DLP) based approach. E103 k factors were constant for all protocols, ~8% less than that of the universal k factor. Due to inconsistency in tube potential and pitch factor the k factors from CTEXPO were found to vary between 0.015 and 0.010 for protocols R3 and R5. With considerable variation between scan acquisition parameters and organ doses, optimization of practice is necessary in order to reduce patient organ dose. - Highlights: • Using TLD-100 dosimeters and a RANDO phantom 5 CT thorax protocol organ doses were assessed. • The specific k coefficient for effective dose estimation of protocols differed with approach. • Organ dose was observed to decrease in the order: thyroid>skin>lung>liver>breast. • E103 k factors were constant for all protocols, lower by ~8% compared to the universal k factor.

Impact of cytochrome p450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients.

Science.gov (United States)

Thervet, Eric; Anglicheau, Dany; King, Barry; Schlageter, Marie-Hélène; Cassinat, Bruno; Beaune, Philippe; Legendre, Christophe; Daly, Ann K

2003-10-27

Tacrolimus pharmacokinetic characteristics vary greatly among individuals. Tacrolimus is a substrate of cytochrome p450 (CYP), of subfamily CYP3A. CYP3A activity is the sum of the activities of the family of CYP3A genes, including CYP3A5. Subjects with the CYP3A5*1/*1 genotype express large amounts of CYP3A5. Heterozygotes (genotype CYP3A5*1/*3) also express the enzyme. We postulated that CYP3A5 polymorphism is associated with tacrolimus pharmacokinetic variations. CYP3A5 genotype was evaluated in 80 renal transplant recipients and correlated with the daily tacrolimus dose and concentration-to-dose ratio. The frequency of the homozygous CYP3A5*1 genotype (CYP3A5*1/*1) was 5%, and 11% of subjects were heterozygous (CYP3A5*1/*3). The mean doses required to obtain the targeted concentration-to-dose ratio were significantly lower in patients with the CYP3A5*1/*1 genotype. Determination of CYP3A5 genotype is predictive of the dose of tacrolimus in renal transplant recipients and may help to determine the initial daily dose needed by individual patients for adequate immunosuppression without excess nephrotoxicity.

High dose rate (HDR) and low dose rate (LDR) interstitial irradiation (IRT) of the rat spinal cord

International Nuclear Information System (INIS)

Pop, Lucas A.M.; Plas, Mirjam van der; Skwarchuk, Mark W.; Hanssen, Alex E.J.; Kogel, Albert J. van der

1997-01-01

�/β ratio varies between 1.46 (0.06-3.08 CL) and 2.17 Gy (0.08-4.61). The half time of repair during continuous irradiation is 1.76 h (1.33-2.64), while no indication is found for a biphasic pattern of the kinetics of repair. Conclusion: The implantation technique in our study has shown to be a reliable model to compare the effectiveness of HDR- and LDR-interstitial continuous irradiation at different dose rates

Influence of image slice thickness on rectal dose-response relationships following radiotherapy of prostate cancer

Science.gov (United States)

Olsson, C.; Thor, M.; Liu, M.; Moissenko, V.; Petersen, S. E.; Høyer, M.; Apte, A.; Deasy, J. O.

2014-07-01

When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness

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

Local organ dose conversion coefficients for angiographic examinations of coronary arteries

International Nuclear Information System (INIS)

Schlattl, H; Zankl, M; Hausleiter, J; Hoeschen, C

2007-01-01

New organ dose conversion coefficients for coronary angiographic interventions are presented, as well as dose distributions and resulting maximal local dose conversion coefficients in the relevant organs. For the Monte Carlo based simulations, voxel models of the human anatomy were employed which represent the average Caucasian adult man and woman as defined by the International Commission on Radiological Protection. In the 21 investigated projections, the mean organ dose conversion coefficients vary from a few 0.01 to 2 mGy(Gy cm 2 ) -1 , depending on the projections. However, especially in portions of the lungs and the active bone marrow, the conversion coefficients can locally amount up to 10 mGy(Gy cm 2 ) -1 , which is half the average conversion coefficient of the skin at the field entrance. In addition to the dose conversion coefficients, the dependence of the patient dose on the projection has been estimated. It could be shown that the patient doses are highest for left anterior oblique views with strong caudal or cranial orientation. Nevertheless, for a large range of image-intensifier positions no significant dose differences could be found

Organ dose evaluation for CT scans based on in-phantom measurements

International Nuclear Information System (INIS)

Liu Haikuan; Zhuo Weihai; Chen Bo; Yi Yanling; Li Dehong

2009-01-01

Objective: To explore the organ doses and their distributions in different projections of CT scans. Methods: The CT values were measured and the linear absorption coefficients were derived for the main organs of the anthropomorphic phantom to compare with the normal values of human beings. The radiophotoluminescent glass dosimeters were set into various tissues or organs of the phantom for mimic measurements of the organ doses undergoing the head, chest, abdomen and pelvis CT scans, respectively. Results: The tissue equivalence of the phantom used in this study was good. The brain had the largest organ dose undergoing the head CT scan. The organ doses in thyroid, breast, lung and oesophagus were relatively large in performing the chest CT scan, while the liver, stomach, colon and lung had relatively hrge organ doses in abdomen CT practice. The doses in bone surface and colon exceeded by 50 mGy in a single pelvis CT scan. Conclusions: The organ doses and their distributions largely vary with different projections of CT scans. The organ doses of colon, bone marrow,gonads and bladder are fairly large in performing pelvis CT scan, which should be paid attention in the practice. (authors)

Study of radiation dose reduction of buildings of different sizes and materials

International Nuclear Information System (INIS)

Furuta, Takuya; Takahashi, Fumiaki

2015-01-01

The dependence of radiation dose reduction on the sizes and materials of buildings was studied by numerical analyses using the Monte Carlo simulation code, PHITS. The dose rates inside the buildings were calculated by simulating gamma-ray transport from radioactive cesium deposited at the ground surface. Three building models were developed: the wooden house, the open-space concrete building, and the thin-wall building, to study the effect of building size and construction material on dose reduction inside these structures. Here the floor-area sizes of the building models were varied to clarify the influence of building configuration on dose reduction. The results demonstrated that the dose rates inside the buildings linearly decreased with increasing floor area on a logarithmic scale for all types of buildings considered. The calculated dose distribution inside a building indicated that the distance from the outer walls was a determining factor for the dose rate at each position in the building. The obtained tendency was verified by comparison with data reflecting the dose reduction of typical buildings in Japan. (author)

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

TH-C-19A-03: Characterization of the Dose Per Pulse Dependence of Various Detectors Used in Quality Assurance of FFF Treatment Plans

Energy Technology Data Exchange (ETDEWEB)

Karan, T [Stronach Regional Cancer Center, Newmarket, ON (Canada); Viel, F; Atwal, P; Gete, E; Camborde, M; Horwood, R; Strgar, V; Duzenli, C [British Columbia Cancer Agency, Vancouver, BC (Canada)

2014-06-15

Purpose: To present the dose per pulse dependence of various QA devices under Flattening Filter Free (FFF) conditions. Methods: Air and liquid filled ion chamber arrays, diode arrays, radiochromic film and optically stimulated luminescence detectors were investigated. All detectors were irradiated under similar conditions of varying dose per pulse on a TrueBeam linac. Dose per pulse was controlled by varying SSD from 70 to 160 cm providing a range from ~0.5 to ~3 mGy per pulse. MU rates of up to 2400 MU/min for 10X FFF and 1400 MU/min for the 6X FFF beam were used. Beam pulses were counted using the Profiler™ diode array and pulse timing was confirmed by examining linac node files. Delivered doses were calculated with the Eclipse™ treatment planning system. Results: The detectors show a range of behaviors depending on the detector type, as expected. Diode arrays show up to 4% change in sensitivity (sensitivity increases with increasing dose per pulse) over the range tested. Air and liquid ion chambers arrays show a change in sensitivity of up to 3% (air) and 6% (liquid) (sensitivity decreases with increasing dose per pulse) while film and OSLD do not demonstrate a dependence on dose per pulse. Conclusion: Dependence of detector response on dose per pulse varies considerably depending on detector design. Interplay between dose per pulse and MU rate also exists for some detectors. Due diligence is required to characterize detector response prior to implementation of a QA protocol for FFF treatment delivery. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. We intend to further investigate the implications of this for VMAT FFF patient specific quality assurance. T Karan and F Viel have received partial funding through the Varian Research program.

TH-C-19A-03: Characterization of the Dose Per Pulse Dependence of Various Detectors Used in Quality Assurance of FFF Treatment Plans

International Nuclear Information System (INIS)

Karan, T; Viel, F; Atwal, P; Gete, E; Camborde, M; Horwood, R; Strgar, V; Duzenli, C

2014-01-01

Purpose: To present the dose per pulse dependence of various QA devices under Flattening Filter Free (FFF) conditions. Methods: Air and liquid filled ion chamber arrays, diode arrays, radiochromic film and optically stimulated luminescence detectors were investigated. All detectors were irradiated under similar conditions of varying dose per pulse on a TrueBeam linac. Dose per pulse was controlled by varying SSD from 70 to 160 cm providing a range from ~0.5 to ~3 mGy per pulse. MU rates of up to 2400 MU/min for 10X FFF and 1400 MU/min for the 6X FFF beam were used. Beam pulses were counted using the Profiler™ diode array and pulse timing was confirmed by examining linac node files. Delivered doses were calculated with the Eclipse™ treatment planning system. Results: The detectors show a range of behaviors depending on the detector type, as expected. Diode arrays show up to 4% change in sensitivity (sensitivity increases with increasing dose per pulse) over the range tested. Air and liquid ion chambers arrays show a change in sensitivity of up to 3% (air) and 6% (liquid) (sensitivity decreases with increasing dose per pulse) while film and OSLD do not demonstrate a dependence on dose per pulse. Conclusion: Dependence of detector response on dose per pulse varies considerably depending on detector design. Interplay between dose per pulse and MU rate also exists for some detectors. Due diligence is required to characterize detector response prior to implementation of a QA protocol for FFF treatment delivery. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. We intend to further investigate the implications of this for VMAT FFF patient specific quality assurance. T Karan and F Viel have received partial funding through the Varian Research program

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)

Reduced antituberculosis drug concentrations in HIV-infected patients who are men or have low weight: implications for international dosing guidelines.

Science.gov (United States)

McIlleron, Helen; Rustomjee, Roxana; Vahedi, Mahnaz; Mthiyane, Thuli; Denti, Paolo; Connolly, Catherine; Rida, Wasima; Pym, Alexander; Smith, Peter J; Onyebujoh, Philip C

2012-06-01

Reduced antituberculosis drug concentrations may contribute to unfavorable treatment outcomes among HIV-infected patients with more advanced immune suppression, and few studies have evaluated pharmacokinetics of the first-line antituberculosis drugs in such patients given fixed-dose combination tablets according to international guidelines using weight bands. In this study, pharmacokinetics were evaluated in 60 patients on 4 occasions during the first month of antituberculosis therapy. Multilevel linear mixed-effects regression analysis was used to examine the effects of age, sex, weight, drug dose/kilogram, CD4(+) lymphocyte count, treatment schedule (5 versus 7 days/week), and concurrent antiretrovirals (efavirenz plus lamivudine plus zidovudine) on the area under the concentration-time curve from 0 to 12 h (AUC(0-12)) of the respective antituberculosis drugs and to compare AUC(0-12)s at day 8, day 15, and day 29 with the day 1 AUC(0-12). Median (range) age, weight, and CD4(+) lymphocyte count were 32 (18 to 47) years, 55.2 (34.4 to 98.7) kg, and 252 (12 to 500)/μl. For every 10-kg increase in body weight, the predicted day 29 AUC(0-12) increased by 14.1% (95% confidence interval [CI], 7.5, 20.8), 14.1% (95% CI, -0.7, 31.1), 6.1% (95% CI, 2.7, 9.6) and 6.0% (95% CI, 0.8, 11.3) for rifampin, isoniazid, pyrazinamide, and ethambutol, respectively. Males had day 29 AUC(0-12)s 19.3% (95% CI, 3.6, 35.1) and 14.0% (95% CI, 5.6, 22.4) lower than females for rifampin and pyrazinamide, respectively. Level of immune suppression and concomitant antiretrovirals had little effect on the concentrations of the antituberculosis agents. As they had reduced drug concentrations, it is important to review treatment responses in patients in the lower weight bands and males to inform future treatment guidelines, and revision of doses in these patients should be considered.

Radiation dose and radiation risk to foetuses and newborns during X-ray examinations

Energy Technology Data Exchange (ETDEWEB)

Kettunen, A. [Oulu Univ. (Finland)

2004-05-01

to a foetus was not calculated either before or after the pelvic x-ray examination of an expectant mother. The responsibility for counselling an expectant mother about the risk of a radiation dose to the foetus was not determined. In conventional pelvic x-ray examinations, the dose to the foetus varied from 1 to 2 mSv/exposure. A proposal for a guide to good practices in the pelvic x-ray examination of women of reproductive age is given. The effective doses of 118 chest x-ray examinations to 43 newborns (gestational age from 26 to 42 weeks) were estimated. The effective dose from one chest radiograph varied from 7.5 {mu}Sv to 54 {mu}Sv. Retrospectively, the total number of radiation examinations to these newborns totalled 399 during the study; the mean was 9.3 (range 1-40). 98% of the examinations were produced during the first treatment period after birth. The total effective dose per child varied from 0.31 mSv to 3.7 mSv. The radiation risk of fatal childhood cancer due to the mean dose of 0.37 mSv is 3.7*10 -5. (orig.)

Radiation dose and radiation risk to foetuses and newborns during X-ray examinations

International Nuclear Information System (INIS)

Kettunen, A.

2004-05-01

foetus was not calculated either before or after the pelvic x-ray examination of an expectant mother. The responsibility for counselling an expectant mother about the risk of a radiation dose to the foetus was not determined. In conventional pelvic x-ray examinations, the dose to the foetus varied from 1 to 2 mSv/exposure. A proposal for a guide to good practices in the pelvic x-ray examination of women of reproductive age is given. The effective doses of 118 chest x-ray examinations to 43 newborns (gestational age from 26 to 42 weeks) were estimated. The effective dose from one chest radiograph varied from 7.5 μSv to 54 μSv. Retrospectively, the total number of radiation examinations to these newborns totalled 399 during the study; the mean was 9.3 (range 1-40). 98% of the examinations were produced during the first treatment period after birth. The total effective dose per child varied from 0.31 mSv to 3.7 mSv. The radiation risk of fatal childhood cancer due to the mean dose of 0.37 mSv is 3.7*10 -5. (orig.)

The clinical demand for information and the radiation dose in pelvimetry and amniography

International Nuclear Information System (INIS)

Wilbrand, H.F.; Lindmark, G.; Ytterbergh, C.

1982-01-01

Radiographic measurements are an important part of antenatal care and are in fact used to a great extent in nulliparous women. In view of this clinical background and also for ethical reasons, reduction of the radiation doses is mandatory. As radiographic pelvimetry is used in so many pregnant women, it is of importance that no higher radiation doses are applied than are absolutely needed to guarantee correct and necessary information. Dose reduction is afforded in two different ways - by optimizing the imaging techniques and by closing a suitable film-screen combination. Measurement of absorbed doses in patients was carried out with highly sensitive lithium fluoride thermoluminiscence dosimeters (TLD) with a dimension of 3x3x0.9 mm (Harshaw type TLD-100). All TLD probes were calibrated with Co60 radiation between the measurement series. Absorbed radiation doses were measured in the rectum for different film-screen combinations. Depending on the position of the fetus in relation to the maternal pelvis, it is obvious that in any individual case varying parts of the fetus will lie directly in the radiation beam. In amniography the absorbed radiation doses will vary from case to case depending on the number of exposures, which should not exceed six, and the duration of fluoroscopy, which should be no longer than 1 min. With the use of lanex Regular screens and highly coned images the radiation dose will not exceed 3.0 mGy. Since a high image quality is mandatory for evaluation of disorders in the fetal skeleton, measurements were not performed with other high-speed screens. The MR 800 screen appears to provide further reduction of the radiation dose in this type of examination. (orig./MG)

Liver toxicity associated with tuberculosis chemotherapy in the REMoxTB study.

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Tweed, Conor Duncan; Wills, Genevieve Helen; Crook, Angela M; Dawson, Rodney; Diacon, Andreas H; Louw, Cheryl E; McHugh, Timothy D; Mendel, Carl; Meredith, Sarah; Mohapi, Lerato; Murphy, Michael E; Murray, Stephen; Murthy, Sara; Nunn, Andrew J; Phillips, Patrick P J; Singh, Kasha; Spigelman, M; Gillespie, S H

2018-03-28

Drug-induced liver injury (DILI) is a common complication of tuberculosis treatment. We utilised data from the REMoxTB clinical trial to describe the incidence of predisposing factors and the natural history in patients with liver enzyme levels elevated in response to tuberculosis treatment. Patients received either standard tuberculosis treatment (2EHRZ/4HR), or a 4-month regimen in which moxifloxacin replaced either ethambutol (isoniazid arm, 2MHRZ/2MHR) or isoniazid (ethambutol arm, 2EMRZ/2MR). Hepatic enzymes were measured at 0, 2, 4, 8, 12 and 17 weeks and as clinically indicated during reported adverse events. Patients included were those receiving at least one dose of drug and with two or more hepatic enzyme measurements. A total of 1928 patients were included (639 2EHRZ/4HR, 654 2MHRZ/2MHR and 635 2EMRZ/2MR). DILI was defined as peak alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal (5 × ULN) or ALT ≥ 3 × ULN with total bilirubin > 2 × ULN. DILI was identified in 58 of the 1928 (3.0%) patients at a median time of 28 days (interquartile range IQR 14-56). Of 639 (6.4%) patients taking standard tuberculosis therapy, 41 experienced clinically significant enzyme elevations (peak ALT ≥ 3 × ULN). On standard therapy, 21.1% of patients aged >55 years developed a peak ALT/aspartate aminotransferase (AST) ≥ 3 × ULN (p = 0.01) and 15% of HIV-positive patients experienced a peak ALT/AST ≥ 3 × ULN compared to 9% of HIV-negative patients (p = 0.160). The median peak ALT/AST was higher in isoniazid-containing regimens vs no-isoniazid regimens (p tuberculosis patients on standard treatment. Older patients on standard therapy, HIV-positive patients, Asian patients and those receiving isoniazid were at higher risk of elevated enzyme levels. Monitoring hepatic enzymes during the first 2 months of standard therapy detected approximately 75% of patients with a peak enzyme elevation ≥3 × ULN, suggesting this should be a standard of care. These

The sensitivity of calculated doses to critical assumptions for the offsite consequences of nuclear power reactor accidents

International Nuclear Information System (INIS)

Moeller, M.P.; Scherpelz, R.I.; Desrosiers, A.E.

1982-01-01

This work analyzes the sensitivity of calculated doses to critical assumptions for offsite consequences following a PWR-2 accident at a nuclear power reactor. The calculations include three radiation dose pathways: internal dose resulting from inhalation, external doses from exposure to the plume, and external doses from exposure to contaminated ground. The critical parameters are the time period of integration for internal dose commitment and the duration of residence on contaminated ground. The data indicate the calculated offsite whole body dose will vary by as much as 600% depending upon the parameters assumed. When offsite radiation doses determine the size of emergency planning zones, this uncertainty has significant effect upon the resources allocated to emergency preparedness

Beta dose due to monazite sands of Kerala

International Nuclear Information System (INIS)

Massand, O.P.; Venkataraman, G.; Dhairyawan, M.P.

1977-01-01

The heavy black mineral sands of the sea coast of Kerala in India contain patches of monazite in concentrations varying between 0.5 to 5%. Monazite contains about 9.5% of thorium oxide (ThO 2 ) and 0.35% of uranium oxide (U 3 O 8 ). The high natural background radiation of this area had been a matter of concern and reports on the measured gamma radiation levels have appeared. The dose contribution due to beta rays emitted by the materials in the sand has been calculated using Loevinger's formula. The annual beta dose is of the order of 4200 mrad and 740 mrad at a height of 5 and 200 cm respectively from ground level. (author)

Evaluation of absorbed radiation dose rate in a didactic X-ray equipment; Avaliacao da taxa de dose absorvida em um equipamento de raios-X didatico

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Costa, Phelipe Amaral Ferreira; Perini, Ana Paula; Neves, Lucio Pereira, E-mail: lucio.neves@ufu.br [Universidade Federal de Uberlandia (UFU), MG (Brazil). Instituto de Fisica

2016-07-01

This work was performed in order to create a new didactic experiment in the X-ray apparatus of PHYWE, where the saturation current was obtained through a free air ionization chamber. The values of saturation currents were obtained in two ways. Initially, the anodic DDP was kept constant and the anodic current was varied. In the second way, the anodic current was kept constant while the anodic DDP was varied. Therefore, we were able to evaluate the dependence of the absolved dose rate in relation to the DDP and the tube current. (author)

Efavirenz, tenofovir and emtricitabine combined with first-line tuberculosis treatment in tuberculosis-HIV-coinfected Tanzanian patients: a pharmacokinetic and safety study.

Science.gov (United States)

Semvua, Hadija H; Mtabho, Charles M; Fillekes, Quirine; van den Boogaard, Jossy; Kisonga, Riziki M; Mleoh, Liberate; Ndaro, Arnold; Kisanga, Elton R; van der Ven, Andre; Aarnoutse, Rob E; Kibiki, Gibson S; Boeree, Martin J; Burger, David M

2013-01-01

To evaluate the effect of rifampicin-based tuberculosis (TB) treatment on the pharmacokinetics of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet, and vice versa, in Tanzanian TB-HIV-coinfected patients. This was a Phase II open-label multiple dose pharmacokinetic and safety study. This study was conducted in TB-HIV-coinfected Tanzanian patients who started TB treatment (rifampicin/isoniazid/pyrazinamide/ethambutol) at week 1 to week 8 and continued with rifampicin and isoniazid for another 16 weeks. Antiretroviral treatment (ART) of efavirenz/tenofovir/emtricitabine in a fixed-dose combination tablet was started at week 4 after initiation of TB treatment. A 24-h pharmacokinetic sampling curve was recorded at week 8 (with TB treatment) and week 28 (ART alone). For TB drugs, blood samples at 2 and 5 h post-dose were taken at week 3 (TB treatment alone) and week 8 (with ART). A total of 25 patients (56% male) completed the study; 21 had evaluable pharmacokinetic profiles. The area under the concentration-time curve 0-24 h post-dose of efavirenz, tenofovir and emtricitabine were slightly higher when these drugs were coadministered with TB drugs; geometric mean ratios (90% CI) were 1.08 (0.90, 1.30), 1.13 (0.93, 1.38) and 1.05 (0.85, 1.29), respectively. For TB drugs, equivalence was suggested for peak plasma concentrations when administered with and without efavirenz/tenofovir/emtricitabine. Adverse events were mostly mild and no serious adverse events or drug discontinuations were reported. Coadministration of efavirenz, tenofovir and emtricitabine with a standard first-line TB treatment regimen did not significantly alter the pharmacokinetic parameters of these drugs and was tolerated well by Tanzanian TB patients who are coinfected with HIV.

Radiation doses from medical diagnostic procedures in Canada

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Aldrich, J E; Lentle, B C; Vo, C [British Columbia Univ., Vancouver, BC (Canada). Dept. of Radiology

1997-03-01

This document sets out to record and analyze the doses incurred in Canada from medical procedures involving the use of ionizing radiation in a typical year. Excluded are those doses incurred during therapeutic irradiation, since they differ in scale to such a large degree and because they are used almost exclusively in treating cancer. In this we are following a precedent set by the United Nations Scientific Committee on the Effects of Ionizing Radiation. Although the International Commission on Radiological Protection (ICRP) notes that dose limits should not be applied to medical exposures, it also observes that doses in different settings for the same procedure may vary by as much as two orders of magnitude, and that there are considerable opportunities for dose reductions in diagnostic radiology. Because these data do not stand in isolation the report also encompasses a review of the relevant literature and some background comment on the evolving technology of the radiological sciences. Because there is a somewhat incomplete perception of the changes taking place in diagnostic methods we have also provided some introductory explanations of the relevant technologies. In addition, there is an analysis of at least some of the limitations on the completeness of the data which are reported here. (author).

Radiation doses from medical diagnostic procedures in Canada

International Nuclear Information System (INIS)

Aldrich, J.E.; Lentle, B.C.; Vo, C.

1997-03-01

This document sets out to record and analyze the doses incurred in Canada from medical procedures involving the use of ionizing radiation in a typical year. Excluded are those doses incurred during therapeutic irradiation, since they differ in scale to such a large degree and because they are used almost exclusively in treating cancer. In this we are following a precedent set by the United Nations Scientific Committee on the Effects of Ionizing Radiation. Although the International Commission on Radiological Protection (ICRP) notes that dose limits should not be applied to medical exposures, it also observes that doses in different settings for the same procedure may vary by as much as two orders of magnitude, and that there are considerable opportunities for dose reductions in diagnostic radiology. Because these data do not stand in isolation the report also encompasses a review of the relevant literature and some background comment on the evolving technology of the radiological sciences. Because there is a somewhat incomplete perception of the changes taking place in diagnostic methods we have also provided some introductory explanations of the relevant technologies. In addition, there is an analysis of at least some of the limitations on the completeness of the data which are reported here. (author)

Isoniazid

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... 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 ...

Investigation on radiation doses to patients in digital radiography

International Nuclear Information System (INIS)

Qiu Zhengshuai; Deng Daping; Li Quantai; Song Gang; Su Xu

2014-01-01

Objective: To investigate the patients' radiation dose received in digital radiography(DR) and provide basic data for developing diagnostic reference levels. Methods: The patient's ESD was estimated using the TLDs and DAP was measured by the dose-area product meter. The E values were then calculated by the DAP using Monte Carlo data and RefDose software. Measurements were made for twelve types of examination: skull PA, skull LAT, chest PA, chest LAT, abdomen AP, pelvis AP, cervix spine PA, cervix spine LAT, thoracic spine PA, thoracic spine LAT, lumber spine PA and lumber spine LAT. Results: Both kV and mAs varied in the same type of examination for ESD, DAP and E(F = 33.47, 24.68, 43.19, P < 0.05). The dose each time for lumber spine LAT was the highest, reached 4.62 mGy in ESD and 2.26 Gy·cm 2 in DAP, respectively. The E of abdomen AP averaged as 0.59 mSv, higher than that of lumber spine LAT. Even for the same type of examination, the dose from each equipment was different. Conclusions: DR has the potential to reduce the patients' radiation doses. The guidance levels suitable for Chinese population should be established as soon as possible. (authors)

Super-low dose endotoxin pre-conditioning exacerbates sepsis mortality.

Science.gov (United States)

Chen, Keqiang; Geng, Shuo; Yuan, Ruoxi; Diao, Na; Upchurch, Zachary; Li, Liwu

2015-04-01

Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditionings with super-low or low dose endotoxin lipopolysaccharide (LPS) cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP). This is in opposite to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET) in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a novel mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.

Super-low Dose Endotoxin Pre-conditioning Exacerbates Sepsis Mortality

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Keqiang Chen

2015-04-01

Full Text Available Sepsis mortality varies dramatically in individuals of variable immune conditions, with poorly defined mechanisms. This phenomenon complements the hypothesis that innate immunity may adopt rudimentary memory, as demonstrated in vitro with endotoxin priming and tolerance in cultured monocytes. However, previous in vivo studies only examined the protective effect of endotoxin tolerance in the context of sepsis. In sharp contrast, we report herein that pre-conditioning with super-low or low dose endotoxin lipopolysaccharide (LPS cause strikingly opposite survival outcomes. Mice pre-conditioned with super-low dose LPS experienced severe tissue damage, inflammation, increased bacterial load in circulation, and elevated mortality when they were subjected to cecal-ligation and puncture (CLP. This is in contrast to the well-reported protective phenomenon with CLP mice pre-conditioned with low dose LPS. Mechanistically, we demonstrated that super-low and low dose LPS differentially modulate the formation of neutrophil extracellular trap (NET in neutrophils. Instead of increased ERK activation and NET formation in neutrophils pre-conditioned with low dose LPS, we observed significantly reduced ERK activation and compromised NET generation in neutrophils pre-conditioned with super-low dose LPS. Collectively, our findings reveal a mechanism potentially responsible for the dynamic programming of innate immunity in vivo as it relates to sepsis risks.

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)

Influence of dose, dose rate, and radiation quality on radiation carcinogenesis and life shortening in RFM and BALB/C mice

International Nuclear Information System (INIS)

Ullrich, R.L.; Storer, J.B.

1978-01-01

The effects produced by 137 Cs gamma rays delivered at a high (45 rads/min) or intermediate (8.2 rads/day) dose rate and the effect of fission neutrons at a high (25 rads/min) and low (1 rad/day) rate in a population of nearly 30,000 RFM and 11,000 BALB/c mice have been studied. Gamma ray doses ranged from 10 to 400 rads with the RFM's and from 50-400 rads with the BALB/c's, while neutron doses ranged from 5 to 200 rads with both strains. The present paper will present an overview of these data and the general findings while subsequent publications will present detailed analyses of each aspect. A variety of neoplasms were sensitive to induction after radiation exposure, including tumors of both reticular tissue origin (leukemia, lymphoma, etc.) and solid tumors. For the RFM, thymic lymphomas were the dominant reticular tissue neoplasm while the majority of solid tumors were either lung adenomas or fit into the broad category of endocrine related tumors, including ovarian, pituitary, harderian, and uterine tumors. The BALB/c was much less sensitive to induction of reticular tissue neoplasms. The tumors that were most sensitive to induction included malignant lung carcinomas, mammary adenocarcinomas and ovarian tumors. In general for both life shortening and tumor induction after gamma ray exposures, when the low to intermediate dose range was sufficiently defined, linearity could be rejected and a dose squared or linear-dose squared relationship adequately fit the data. For neutron exposures, on the other hand, linear relationships were the general finding. The RBE for neutrons varied with tumor type and total dose level. For gamma ray irradiation, the intermediate dose rate resulted in a decreased effectiveness in all cases, while for neutron exposures the dose rate relationships were more complex

A blinded, randomized, controlled trial of three doses of high-dose insulin in poison-induced cardiogenic shock.

Science.gov (United States)

Cole, J B; Stellpflug, S J; Ellsworth, H; Anderson, C P; Adams, A B; Engebretsen, K M; Holger, J S

2013-05-01

High dose insulin (HDI) has proven superior to glucagon and catecholamines in the treatment of poison-induced cardiogenic shock (PICS) in previous animal studies. Standard recommendations for dosing of insulin vary and the optimal dose of HDI in PICS has not been established. Our hypothesis was a dose of 10 U/kg/hr of HDI would be superior to 1 U/kg/hr with cardiac output (CO) as our primary outcome measure in pigs with propranolol-induced PICS. This was a blinded, prospective, randomized trial with 4 arms consisting of 4 pigs in each arm. The arms were as follows: placebo (P), 1 U/kg/hr (HDI-1), 5 U/kg/hr (HDI-5), and 10 U/kg/hr (HDI-10). Cardiogenic shock was induced with a bolus of 0.5 mg/kg of propranolol followed by an infusion of 0.25 mg/kg/min until the point of toxicity, defined as 0.75 x (HR x MAP) was reached. At this point the propranolol infusion was decreased to 0.125 mg/kg/min and a 20 mL/kg bolus of normal saline (NS) was administered. The protocol was continued for 6 hours or until the animals died. 2 pigs died in the P arm, 1 pig died each in the HDI-1 and HDI-5 arms, and all pigs lived in the HDI-10 arm. There was a statistically significant difference in dose by time interaction on CO of 1.13 L/min over the 6 hr study period (p = < 0.001). There was also a statistically significant difference in dose by time interaction on MAP, HR, and systemic vascular resistance (SVR). No statistically significant difference was found between any of the arms regarding glucose utilization. HDI was statistically and clinically significantly superior to placebo in this propranolol model of PICS. Furthermore a dose response over time was found where CO increased corresponding to increases in doses of HDI.

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

Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013

International Nuclear Information System (INIS)

Taylor, Carolyn W.; Wang, Zhe; Macaulay, Elizabeth; Jagsi, Reshma; Duane, Frances; Darby, Sarah C.

2015-01-01

Purpose: Breast cancer radiation therapy cures many women, but where the heart is exposed, it can cause heart disease. We report a systematic review of heart doses from breast cancer radiation therapy that were published during 2003 to 2013. Methods and Materials: Eligible studies were those reporting whole-heart dose (ie, dose averaged over the whole heart). Analyses considered the arithmetic mean of the whole-heart doses for the CT plans for each regimen in each study. We termed this “mean heart dose.” Results: In left-sided breast cancer, mean heart dose averaged over all 398 regimens reported in 149 studies from 28 countries was 5.4 Gy (range, <0.1-28.6 Gy). In regimens that did not include the internal mammary chain (IMC), average mean heart dose was 4.2 Gy and varied with the target tissues irradiated. The lowest average mean heart doses were from tangential radiation therapy with either breathing control (1.3 Gy; range, 0.4-2.5 Gy) or treatment in the lateral decubitus position (1.2 Gy; range, 0.8-1.7 Gy), or from proton radiation therapy (0.5 Gy; range, 0.1-0.8 Gy). For intensity modulated radiation therapy mean heart dose was 5.6 Gy (range, <0.1-23.0 Gy). Where the IMC was irradiated, average mean heart dose was around 8 Gy and varied little according to which other targets were irradiated. Proton radiation therapy delivered the lowest average mean heart dose (2.6 Gy, range, 1.0-6.0 Gy), and tangential radiation therapy with a separate IMC field the highest (9.2 Gy, range, 1.9-21.0 Gy). In right-sided breast cancer, the average mean heart dose was 3.3 Gy based on 45 regimens in 23 studies. Conclusions: Recent estimates of typical heart doses from left breast cancer radiation therapy vary widely between studies, even for apparently similar regimens. Maneuvers to reduce heart dose in left tangential radiation therapy were successful. Proton radiation therapy delivered the lowest doses. Inclusion of the IMC doubled typical heart dose.

Prospective ECG triggering versus low-dose retrospective ECG-gated 128-channel CT coronary angiography: comparison of image quality and radiation dose

International Nuclear Information System (INIS)

Feng, Q.; Yin, Y.; Hua, X.; Zhu, R.; Hua, J.; Xu, J.

2010-01-01

Aim: To evaluate image quality and radiation dose for 128-detector prospective electrocardiogram (ECG)-gated computed tomography coronary angiography (CTCA) compared with a low-dose retrospective ECG-gated imaging protocol. Materials and methods: Thirty-one and 47 patients suspected of having coronary artery disease were enrolled into groups examined using prospective and low-dose retrospective ECG-gated CT protocols respectively. All examinations were performed on a 128-detector CT system (Definition AS, Siemens Healthcare, Forchheim, Germany). Prospective CTCA was performed using following parameters: tube voltage 100 kV; tube current 205 mAs; centre of acquisition window 70% of the RR interval. The tube current for low-dose retrospective ECG-gated CTCA was full dose during 40-70% of the RR interval and partial dose for the rest of RR interval. The pitch varied between 0.2 and 0.5 depending on heart rate and patient size. Image quality of coronary arteries was evaluated using a four-point grading scale. The signal-to-noise ratios (SNRs) of enhanced arteries and myocardium were also measured, corresponding contrast-to-noise ratios (CNRs) were calculated, and the radiation doses received were recorded. Results: There was a significant difference in the image quality scores between the retrospective and prospective gating protocols (Chi-square = 15.331, p = 0.009). There was no significant difference between the SNRs of the contrasted artery and myocardium in these two groups, but the CNRs were increased in the prospective group. The mean radiation dose of prospective gating group was 2.71 ± 0.67 mSv (range, 1.67-3.59 mSv), which was significantly lower than that of the retrospective group (p < 0.001). Conclusion: Prospective CT angiography can achieve lower radiation dose than that of low-dose retrospective CT angiography, with preserved image quality.

Prospective ECG triggering versus low-dose retrospective ECG-gated 128-channel CT coronary angiography: comparison of image quality and radiation dose

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Feng, Q.; Yin, Y.; Hua, X.; Zhu, R.; Hua, J. [Department of Radiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Xu, J., E-mail: xujianr@hotmail.co [Department of Radiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China)

2010-10-15

Aim: To evaluate image quality and radiation dose for 128-detector prospective electrocardiogram (ECG)-gated computed tomography coronary angiography (CTCA) compared with a low-dose retrospective ECG-gated imaging protocol. Materials and methods: Thirty-one and 47 patients suspected of having coronary artery disease were enrolled into groups examined using prospective and low-dose retrospective ECG-gated CT protocols respectively. All examinations were performed on a 128-detector CT system (Definition AS, Siemens Healthcare, Forchheim, Germany). Prospective CTCA was performed using following parameters: tube voltage 100 kV; tube current 205 mAs; centre of acquisition window 70% of the RR interval. The tube current for low-dose retrospective ECG-gated CTCA was full dose during 40-70% of the RR interval and partial dose for the rest of RR interval. The pitch varied between 0.2 and 0.5 depending on heart rate and patient size. Image quality of coronary arteries was evaluated using a four-point grading scale. The signal-to-noise ratios (SNRs) of enhanced arteries and myocardium were also measured, corresponding contrast-to-noise ratios (CNRs) were calculated, and the radiation doses received were recorded. Results: There was a significant difference in the image quality scores between the retrospective and prospective gating protocols (Chi-square = 15.331, p = 0.009). There was no significant difference between the SNRs of the contrasted artery and myocardium in these two groups, but the CNRs were increased in the prospective group. The mean radiation dose of prospective gating group was 2.71 {+-} 0.67 mSv (range, 1.67-3.59 mSv), which was significantly lower than that of the retrospective group (p < 0.001). Conclusion: Prospective CT angiography can achieve lower radiation dose than that of low-dose retrospective CT angiography, with preserved image quality.

Dose-image quality study in digital chest radiography using Monte Carlo simulation

International Nuclear Information System (INIS)

Correa, S.C.A.; Souza, E.M.; Silva, A.X.; Lopes, R.T.; Yoriyaz, H.

2008-01-01

One of the main preoccupations of diagnostic radiology is to guarantee a good image-sparing dose to the patient. In the present study, Monte Carlo simulations, with MCNPX code, coupled with an adult voxel female model (FAX) were performed to investigate how image quality and dose in digital chest radiography vary with tube voltage (80-150 kV) using air-gap technique and a computed radiography system. Calculated quantities were normalized to a fixed value of entrance skin exposure (ESE) of 0.0136 R. The results of the present analysis show that the image quality for chest radiography with imaging plate is improved and the dose reduced at lower tube voltage

Australian high-dose-rate brachytherapy protocols for gynaecological malignancy

International Nuclear Information System (INIS)

MacLeod, C.; Dally, M.; Stevens, M.; Thornton, D.; Carruthers, S.; Jeal, P.

2001-01-01

There is no consensus over the optimal dose fractionation schedules for high-dose-rate (HDR) brachytherapy used for gynaecological malignancy. In Australian public hospital departments of radiation oncology, HDR brachytherapy for gynaecological cancer is being more commonly used. A survey of public departments that are using this technology, or that plan to introduce this technology, was performed. Their current protocols are presented. In general, protocols are similar biologically; however, the practical aspects such as the number of fractions given do vary and may reflect resource restrictions or, alternatively, differences in interpretations of the literature and of the best protocols by clinicians. Copyright (2001) Blackwell Science Pty Ltd

Doses of radioiodine administered for hyperthyroidism: a sampling of Belgian nuclear medicine physician's attitudes

International Nuclear Information System (INIS)

Tondeur Dejonckheere, Marianne; Glinoer, Daniel; Verelst, Jean; Sand, Alain; Ham, Hamphrey

2005-01-01

Full text: While radioiodine (RI) is a well established treatment for hyperthyroidism, there is no consensus regarding the administration of fixed or calculated doses. Guidelines from scientific societies do not specify the preferable approach, nor the parameters to be used in order to calculate the latter. Therefore, the doses might, for the same patient, be different with regard to the chosen procedure. This study was undertaken to assess the variability of RI amounts administered in Belgium in various cases of hyperthyroidism. 21 Belgian nuclear medicine physicians issued from different departments and universities participated into the study. They received a file with clinical and biological data, iodine turnover rate, scintigraphic images and calculated thyroid surfaces from 10 patients (8 females, 2 males), 30-77 yrs suffering from hyperthyroidism of various etiologies: 7 patients had clinically overt hyperthyroidism and 3 subclinical hyperthyroidism; 7 patients had toxic goiters of various size (Graves' disease), 2 multi nodular goiter and 1 toxic nodule. None suffered from cardiac anomalies or ophthalmopathy. Participants were asked to define the amount of RI they would give in each case. Answers were received during a 8-week period. Analysing data from case 1 to case 10, the ranges of the proposed doses varied between 8 and 22 milli Curies (mCi) (sd : 2.4 - 6.07). Considering all the patients, the proposed doses varied between 2 mCi and 25 mCi. Analysing answers among the 21 participants, mean proposed doses varied between 4.5 and 17.3 mCi (sd: 0.69 - 7.99). Conclusion: These results demonstrate a wide variability among nuclear medicine physicians in the proposed RI doses and confirm that in Belgium there is no uniformity in the procedure used to determine the amount of RI to administer for various causes of hyperthyroidism. This emphasizes the notion that the determination of the amount of RI to be administered remains a matter of debate. (author)

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.

Biological UV-doses and the effect on an ozone layer depletion

International Nuclear Information System (INIS)

Dahlback, A.; Henriksen, T.

1988-08-01

Effective UV-doses were calculated based on the integrated product of the biological action spectrum and the solar radiation. The calculations included absorption and scattering of UV-radiation in the atmosphere, both for normal ozone conditions as well as for a depleted ozone layer. The effective annual UV-dose increases by approximately 4% per degree of latitude towards the equator. An ozone depletion of 1% increases the annual UV-dose by approximately 1% at 60 o N. A large depletion of 50% over Scandinavia (60 o N) would give this region an effective UV-dose similar to that obtained, with normal ozone conditions, at a latitude of 40 o N (California or the Mediterranean countries). The Antarctic ozone hole increases the annual UV-dose by 20 to 25% which is a similar increase as that attained by moving 5 to 6 degrees of latitude nearer the equator. The annual UV-dose on higher latitudes is mainly determined by the summer values of ozone. Both the ozone values and the effective UV-doses vary from one year to another (within ±4%). No positive or negative trend is observed for Scandinavia from 1978 to 1988

Preparation of labelled antituberculotics for clarifying specific problems in therapy optimization. 1

International Nuclear Information System (INIS)

Winsel, K.; Iwainsky, H.; Mittag, E.; Kiessling, M.; Koehler, H.

1985-01-01

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. (author)

Radiation absorbed doses from iron-52, iron-55, and iron-59 used to study ferrokinetics

International Nuclear Information System (INIS)

Robertson, J.S.; Price, R.R.; Budinger, T.F.; Fairbanks, V.F.; Pollycove, M.

1983-01-01

Biological data obtained principally with Fe-59 citrate are used with physical data to calculate radiation absorbed doses for ionic or weak chelate forms of Fe-52, Fe-55, and Fe-59, administered by intravenous injection. Doses are calculated for normal subjects, primary hemochromatosis (also called idiopathic or hereditary hemochromatosis), pernicious anemia in relapse, iron-deficiency anemia, and polycythemia vera. The Fe-52 doses include the dose from the Mn-52m daughter generated after injection of Fe-52. Special attention has been given to the dose to the spleen, which has a relatively high concentration of RBCs and therefore of radioiron, and which varies significantly in size in both health and disease

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.

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

A Phase 2 Randomized Trial of a Rifapentine plus Moxifloxacin-Based Regimen for Treatment of Pulmonary Tuberculosis.

Directory of Open Access Journals (Sweden)

Marcus B Conde

Full Text Available The combination of rifapentine and moxifloxacin administered daily with other anti-tuberculosis drugs is highly active in mouse models of tuberculosis chemotherapy. The objective of this phase 2 clinical trial was to determine the bactericidal activity, safety, and tolerability of a regimen comprised of rifapentine, moxifloxacin, isoniazid, and pyrazinamide administered daily during the first 8 weeks of pulmonary tuberculosis treatment.Adults with sputum smear-positive pulmonary tuberculosis were randomized to receive either rifapentine (approximately 7.5 mg/kg plus moxifloxacin (investigational arm, or rifampin (approximately 10 mg/kg plus ethambutol (control daily for 8 weeks, along with isoniazid and pyrazinamide. The primary endpoint was sputum culture status at completion of 8 weeks of treatment.121 participants (56% of accrual target were enrolled. At completion of 8 weeks of treatment, negative cultures using Löwenstein-Jensen (LJ medium occurred in 47/60 (78% participants in the investigational arm vs. 43/51 (84%, p = 0.47 in the control arm; negative cultures using liquid medium occurred in 37/47 (79% in the investigational arm vs. 27/41 (66%, p = 0.23 in the control arm. Time to stable culture conversion was shorter for the investigational arm vs. the control arm using liquid culture medium (p = 0.03, but there was no difference using LJ medium. Median rifapentine area under the concentration-time curve (AUC0-24 was 313 mcg*h/mL, similar to recent studies of rifapentine dosed at 450-600 mg daily. Median moxifloxacin AUC0-24 was 28.0 mcg*h/mL, much lower than in trials where rifapentine was given only intermittently with moxifloxacin. The proportion of participants discontinuing assigned treatment for reasons other than microbiological ineligibility was higher in the investigational arm vs. the control arm (11/62 [18%] vs. 3/59 [5%], p = 0.04 although the proportions of grade 3 or higher adverse events were similar (5/62 [8%] in the

The MLC tongue-and-groove effect on IMRT dose distributions

Energy Technology Data Exchange (ETDEWEB)

Deng Jun [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305 (United States). E-mail: jun@reyes.stanford.edu; Pawlicki, Todd; Chen Yan; Li Jinsheng; Jiang, Steve B.; Ma, C.-M. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305 (United States)

2001-04-01

We have investigated the tongue-and-groove effect on the IMRT dose distributions for a Varian MLC. We have compared the dose distributions calculated using the intensity maps with and without the tongue-and-groove effect. Our results showed that, for one intensity-modulated treatment field, the maximum tongue-and-groove effect could be up to 10% of the maximum dose in the dose distributions. For an IMRT treatment with multiple gantry angles ({>=} 5), the difference between the dose distributions with and without the tongue-and-groove effect was hardly visible, less than 1.6% for the two typical clinical cases studied. After considering the patient setup errors, the dose distributions were smoothed with reduced and insignificant differences between plans with and without the tongue-and-groove effect. Therefore, for a multiple-field IMRT plan ({>=} 5), the tongue-and-groove effect on the IMRT dose distributions will be generally clinically insignificant due to the smearing effect of individual fields. The tongue-and-groove effect on an IMRT plan with small number of fields (<5) will vary depending on the number of fields in a plan (coplanar or non-coplanar), the MLC leaf sequences and the patient setup uncertainty, and may be significant (>5% of maximum dose) in some cases, especially when the patient setup uncertainty is small ({<=} 2 mm). (author)

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.

Assessment of Effective Dose Equivalent of Indoor 222Rn Daughters in Inchass

International Nuclear Information System (INIS)

Ali, E.M.; Taha, T.M.; Gomaa, M.A.; El-Hussein, A.M.; Ahmad, A.A.

2000-01-01

The dominant component of natural radiation dose for the general population comes from the radon gas 222 Rn and its short-lived decay products, Ra A ( 214 Po), Ra B ( 214 Pb), Ra C ( 214 Bi), Ra C( 214 Po) in the breathing air. The objective of the present work is to assess the affective dose equivalent of the inhalation exposure of indoor 222 Rn for occupational workers. Average indon concentrations (Bqm -3 ) were monitored in several departments in Nuclear Research Center by radon monitor. We have calculated the lung dose equivalent and the effective dose equivalent for the Egyptian workers due to inhalation exposure of an equilibrium equivalent concentrations of radon daughters which varies from 0.27 to 2.5 mSvy -1 and 0.016 to 0.152mSvy -1 respectively. The annual effective doses obtained are within the accepted range of ICRP recommendations

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

Effect of low doses gamma irradiation of cotton seeds

International Nuclear Information System (INIS)

Al-Oudat, M.; Khalifa, Kh.

1996-01-01

Field experiments and then large scale application of irradiated cotton seeds (C.V. Aleppo-40) were carried out during three seasons (1986, 1987 and 1988) for field experiment at ACSAD Station in Dier-Ezzor and 1988, 1989 and 1990 for large scale application at Euphrate's Basin, Al-Ghab and Salamia, farmers farms. The above areas were selected as they represent major cotton production areas in Syria. The aims of the experiments were to study the effect of low doses of gamma irradiation 0, 5, 10, 20, 30, 40 and 50 Gy on cotton yield and to look for the optimum dose of gamma irradiation to obtain best results. The results show that, there were positive effect (P<0.95) for doses 5-30 Gy in increasing cotton yield. The highest increase was at dose of 10 Gy. which as 19.5% higher than control. For the large scale application using 10 Gy the increase in cotton yield varied from 10-39% compared to control. (author). 11 refs., 6 figs

Non-linear dose response of a few plant taxa to acute gamma radiation

International Nuclear Information System (INIS)

George, J.T.; Patel, B.B.; Pius, J.; Narula, B.; Shankhadarwar, S.; Rane, V.A.; Venu-Babu, P.; Eapen, S.; Singhal, R.K.

2014-01-01

Micronuclei induction serves as an essential biomarker of radiation stress in a living system, and the simplicity of its detection technique has made it a widely used indicator of radiation damage. The present study was conducted to reveal the cytological dose-response of a few plant taxa, viz., Allium cepa var. aggregatum Linn., Allium sativum Linn., Chlorophytum comosum (Thunb.) Jacques and Eichhornia crassipes (Mart.) Solms, to low LET gamma radiation with special emphasis on the pattern of micronuclei induced across low and high dose regimes. A tri-phasic non-linear dose-response pattern was observed in the four taxa studied, characterized by a low dose linear segment, a plateau and a high dose linear segment. Despite a similar response trend, the critical doses where the phase transitions occurred varied amongst the plant taxa, giving an indication to their relative radiosensitivities. E. crassipes and A. sativum, with their lower critical doses for slope modifications of phase transitions, were concluded as being more radiosensitive as compared to C. comosum and A. cepa, which had relatively higher critical doses. (author)

Estimating Effective Dose of Radiation From Pediatric Cardiac CT Angiography Using a 64-MDCT Scanner: New Conversion Factors Relating Dose-Length Product to Effective Dose.

Science.gov (United States)

Trattner, Sigal; Chelliah, Anjali; Prinsen, Peter; Ruzal-Shapiro, Carrie B; Xu, Yanping; Jambawalikar, Sachin; Amurao, Maxwell; Einstein, Andrew J

2017-03-01

The purpose of this study is to determine the conversion factors that enable accurate estimation of the effective dose (ED) used for cardiac 64-MDCT angiography performed for children. Anthropomorphic phantoms representative of 1- and 10-year-old children, with 50 metal oxide semiconductor field-effect transistor dosimeters placed in organs, underwent scanning performed using a 64-MDCT scanner with different routine clinical cardiac scan modes and x-ray tube potentials. Organ doses were used to calculate the ED on the basis of weighting factors published in 1991 in International Commission on Radiological Protection (ICRP) publication 60 and in 2007 in ICRP publication 103. The EDs and the scanner-reported dose-length products were used to determine conversion factors for each scan mode. The effect of infant heart rate on the ED and the conversion factors was also assessed. The mean conversion factors calculated using the current definition of ED that appeared in ICRP publication 103 were as follows: 0.099 mSv · mGy -1 · cm -1 , for the 1-year-old phantom, and 0.049 mSv · mGy -1 · cm -1 , for the 10-year-old phantom. These conversion factors were a mean of 37% higher than the corresponding conversion factors calculated using the older definition of ED that appeared in ICRP publication 60. Varying the heart rate did not influence the ED or the conversion factors. Conversion factors determined using the definition of ED in ICRP publication 103 and cardiac, rather than chest, scan coverage suggest that the radiation doses that children receive from cardiac CT performed using a contemporary 64-MDCT scanner are higher than the radiation doses previously reported when older chest conversion factors were used. Additional up-to-date pediatric cardiac CT conversion factors are required for use with other contemporary CT scanners and patients of different age ranges.

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.)

SU-F-T-93: Breast Surface Dose Enhancement Using a Clinical Prone Breast Board

International Nuclear Information System (INIS)

Guerra, M; Jozsef, G

2016-01-01

Purpose: The use of specialized patient set-up devices in radiotherapy, such as prone breast boards, may have unwanted dosimetric effects. The goal of this study was to evaluate the effect of a clinically used prone breast board on skin dose due to buildup. Methods: GafChromic film (EBT3) was used for dose measurements on the surface of a solid water phantom shaped to mimic the curvature of the breast. We investigated two setup scenarios: the medial field border placed at the medial edge of the board and 1 cm contralaterally from that edge. A strip of film was taped to the medial surface of the phantom. Gantry angles varied from 10 to 30 degrees below the lateral gantry position, representing anterior oblique fields. The measurements were performed with and without the presence of the board; the ratio of their corresponding doses (dose enhancement) was evaluated. Results: For the cases where the field edge is at the edge of the board, the dose enhancement is negligible for all the tested angles. When the field edge is 1 cm inside the board, the maximum surface dose enhancement varies depending on the gantry angle between 2.2 for 30 degrees and 3.2 for 20 degrees. The length on the film at which the presence of the board is detectable (i.e. where there is dose enhancement) is longer for the shallower angles. Conclusion: Even the low-density, thin carbon fiber board with a thin soft foam pad on the top can produce significant dose enhancement on the skin in prone breast treatment due to loss of buildup. However, it happens only when the patient mid-sternum is over the board, i.e. the medial edge of the field traverses through the board and pad. Even then, the effect occurs only at the field edge, i.e. the penumbral region.

High dose-per-pulse electron beam dosimetry - A model to correct for the ion recombination in the Advanced Markus ionization chamber.

Science.gov (United States)

Petersson, Kristoffer; Jaccard, Maud; Germond, Jean-François; Buchillier, Thierry; Bochud, François; Bourhis, Jean; Vozenin, Marie-Catherine; Bailat, Claude

2017-03-01

The purpose of this work was to establish an empirical model of the ion recombination in the Advanced Markus ionization chamber for measurements in high dose rate/dose-per-pulse electron beams. In addition, we compared the observed ion recombination to calculations using the standard Boag two-voltage-analysis method, the more general theoretical Boag models, and the semiempirical general equation presented by Burns and McEwen. Two independent methods were used to investigate the ion recombination: (a) Varying the grid tension of the linear accelerator (linac) gun (controls the linac output) and measuring the relative effect the grid tension has on the chamber response at different source-to-surface distances (SSD). (b) Performing simultaneous dose measurements and comparing the dose-response, in beams with varying dose rate/dose-per-pulse, with the chamber together with dose rate/dose-per-pulse independent Gafchromic™ EBT3 film. Three individual Advanced Markus chambers were used for the measurements with both methods. All measurements were performed in electron beams with varying mean dose rate, dose rate within pulse, and dose-per-pulse (10 -2  ≤ mean dose rate ≤ 10 3 Gy/s, 10 2  ≤ mean dose rate within pulse ≤ 10 7  Gy/s, 10 -4  ≤ dose-per-pulse ≤ 10 1  Gy), which was achieved by independently varying the linac gun grid tension, and the SSD. The results demonstrate how the ion collection efficiency of the chamber decreased as the dose-per-pulse increased, and that the ion recombination was dependent on the dose-per-pulse rather than the dose rate, a behavior predicted by Boag theory. The general theoretical Boag models agreed well with the data over the entire investigated dose-per-pulse range, but only for a low polarizing chamber voltage (50 V). However, the two-voltage-analysis method and the Burns & McEwen equation only agreed with the data at low dose-per-pulse values (≤ 10 -2 and ≤ 10 -1  Gy, respectively). An empirical

Dose reduction in pediatric abdominal CT: use of iterative reconstruction techniques across different CT platforms

International Nuclear Information System (INIS)

Khawaja, Ranish Deedar Ali; Singh, Sarabjeet; Otrakji, Alexi; Padole, Atul; Lim, Ruth; Nimkin, Katherine; Westra, Sjirk; Kalra, Mannudeep K.; Gee, Michael S.

2015-01-01

Dose reduction in children undergoing CT scanning is an important priority for the radiology community and public at large. Drawbacks of radiation reduction are increased image noise and artifacts, which can affect image interpretation. Iterative reconstruction techniques have been developed to reduce noise and artifacts from reduced-dose CT examinations, although reconstruction algorithm, magnitude of dose reduction and effects on image quality vary. We review the reconstruction principles, radiation dose potential and effects on image quality of several iterative reconstruction techniques commonly used in clinical settings, including 3-D adaptive iterative dose reduction (AIDR-3D), adaptive statistical iterative reconstruction (ASIR), iDose, sinogram-affirmed iterative reconstruction (SAFIRE) and model-based iterative reconstruction (MBIR). We also discuss clinical applications of iterative reconstruction techniques in pediatric abdominal CT. (orig.)

Dose reduction in pediatric abdominal CT: use of iterative reconstruction techniques across different CT platforms

Energy Technology Data Exchange (ETDEWEB)

Khawaja, Ranish Deedar Ali; Singh, Sarabjeet; Otrakji, Alexi; Padole, Atul; Lim, Ruth; Nimkin, Katherine; Westra, Sjirk; Kalra, Mannudeep K.; Gee, Michael S. [MGH Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA (United States)

2015-07-15

Dose reduction in children undergoing CT scanning is an important priority for the radiology community and public at large. Drawbacks of radiation reduction are increased image noise and artifacts, which can affect image interpretation. Iterative reconstruction techniques have been developed to reduce noise and artifacts from reduced-dose CT examinations, although reconstruction algorithm, magnitude of dose reduction and effects on image quality vary. We review the reconstruction principles, radiation dose potential and effects on image quality of several iterative reconstruction techniques commonly used in clinical settings, including 3-D adaptive iterative dose reduction (AIDR-3D), adaptive statistical iterative reconstruction (ASIR), iDose, sinogram-affirmed iterative reconstruction (SAFIRE) and model-based iterative reconstruction (MBIR). We also discuss clinical applications of iterative reconstruction techniques in pediatric abdominal CT. (orig.)

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)

Doses of external exposure in Jordan house due to gamma-emitting natural radionuclides in building materials.

Science.gov (United States)

Al-Jundi, J; Ulanovsky, A; Pröhl, G

2009-10-01

The use of building materials containing naturally occurring radionuclides as (40)K, (232)Th, and (238)U and their progeny results in external exposures of the residents of such buildings. In the present study, indoor dose rates for a typical Jordan concrete room are calculated using Monte Carlo method. Uniform chemical composition of the walls, floor and ceiling as well as uniform mass concentrations of the radionuclides in walls, floor and ceiling are assumed. Using activity concentrations of natural radionuclides typical for the Jordan houses and assuming them to be in secular equilibrium with their progeny, the maximum annual effective doses are estimated to be 0.16, 0.12 and 0.22 mSv a(-1) for (40)K, (232)Th- and (238)U-series, respectively. In a total, the maximum annual effective indoor dose due to external gamma-radiation is 0.50 mSv a(-1). Additionally, organ dose coefficients are calculated for all organs considered in ICRP Publication 74. Breast, skin and eye lenses have the maximum equivalent dose rate values due to indoor exposures caused by the natural radionuclides, while equivalent dose rates for uterus, colon (LLI) and small intestine are found to be the smallest. More specifically, organ dose rates (nSv a(-1)per Bq kg(-1)) vary from 0.044 to 0.060 for (40)K, from 0.44 to 0.60 for radionuclides from (238)U-series and from 0.60 to 0.81 for radionuclides from (232)Th-series. The obtained organ and effective dose conversion coefficients can be conveniently used in practical dose assessment tasks for the rooms of similar geometry and varying activity concentrations and local-specific occupancy factors.

Cancer and low dose responses in vivo: implications for radiation protection

International Nuclear Information System (INIS)

Mitchel, R.E.J.

2006-01-01

Full text: Radiation protection practices assume that cancer risk is linearly proportional to total dose, without a threshold, both for people with normal cancer risk and for people who may be genetically cancer prone. Mice heterozygous for the Tp 53 gene are cancer prone, and their increased risk from high doses was not different from Tp 53 normal mice. However, in either Tp 53 normal or heterozygous mice, a single low dose of low LET radiation given at low dose rate protected against both spontaneous and radiation-induced cancer by increasing tumor latency. Increased tumor latency without a cancer frequency change implies that low doses in vivo primarily slow the process of genomic instability, consistent with the elevated capacity for correct DSB rejoining seen in low dose exposed cells. The in vivo animal data indicates that, for low doses and low dose rates in both normal and cancer prone adult mice, risk does not increase linearly with dose, and dose thresholds for increased risk exist. Below those dose thresholds (which are influenced by Tp 53 function) overall risk is reduced below that of unexposed control mice, indicating that Dose Rate Effectiveness Factors (DREF) may approach infinity, rather than the current assumption of 2. However, as dose decreases, different tissues appear to have different thresholds at which detriment turns to protection, indicating that individual tissue weighting factors (Wt) are also not constant, but vary from positive values to zero with decreasing dose. Measurements of Relative Biological Effect between high and low LET radiations are used to establish radiation weighting factors (Wr) used in radiation protection, and these are also assumed to be constant with dose. However, since the risk from an exposure to low LET radiation is not constant with dose, it would seem unlikely that radiation-weighting factors for high LET radiation are actually constant at low dose and dose rate

Effect of variable consumption habits in the Nordic populations on ECOSYS model predictions of ingestion dose

International Nuclear Information System (INIS)

Nielsen, Sven P.; Andersson, Kasper G.; Hansen, Hanne S.; Thoerring, Haavard; Joensen, Hans P.; Isaksson, Mats; Kostiainen, Eila; Suolanen, Vesa; Sigurgeirsson, Magnus A.; Palsson, Sigurour E.

2008-01-01

Full text: The two European standard decision support systems, ARGOS and RODOS, have in recent years become increasingly integrated in the Nordic preparedness against nuclear and radiological accidents and incidents. In the event of an emergency, decision making will rest heavily on the reliability of these tools. The ECOSYS model is the ingestion dose module in both decision support systems. This module is highly sensitive to variation in a number of input parameters, food production patterns, diets and environmental transfer data. With regard to for instance consumption habits, the ECOSYS default values, based on data from Southern Germany, have shown to be inadequate for Nordic conditions. We have thus collected recent data describing the human diets for four different age groups in each of the Nordic countries. Also the fractions of the consumed food items that have national origin and the animal feeding regimes in each of the Nordic countries have been examined. For a particular contamination scenario of atmospheric deposition of caesium-137, country specific data regarding consumption habits were used for dose calculations. Resulting 'country specific' doses were then compared among the participating countries and with the doses calculated using the default values of the parameters.The collected data for diets demonstrated that the average consumption of milk varied by a factor of 4-5 among the Nordic countries, and consumption of leafy vegetables varied by a factor of almost 4. Calculated ingestion doses based on country specific data for diets, with all other parameters being default values, varied by a factor of 1.8 among the countries. When also the import fractions were taken into account the calculated doses varied by a factor of 2. Due to the differences in the climate among the Nordic countries, and between these countries and Southern Germany, there were also very significant differences in the production regimes of some food items. In countries in