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Thomas H. Connor - One of the best experts on this subject based on the ideXlab platform.

Timothy G Tyler - One of the best experts on this subject based on the ideXlab platform.

Shinji Kumagai - One of the best experts on this subject based on the ideXlab platform.

  • Association between Occupational Exposure and Control Measures for Antineoplastic Drugs in a Pharmacy of a Hospital
    The Annals of occupational hygiene, 2012
    Co-Authors: Jin Yoshida, Genshin Tei, Shigeki Koda, Shozo Nishida, Hiroyuki Nakano, Shinji Kumagai
    Abstract:

    OBJECTIVES To investigate the association between occupational contamination and exposure levels to Antineoplastic Drugs and the application of control measures in a hospital work environment. METHODS Wipe samples of equipments were collected at a hospital in Osaka Prefecture, Japan, from 2007 to 2011. These samples were subjected to measurements of cyclophosphamide (CP), gemcitabine (GEM), platinum-containing Drugs (Pt), and fluorouracil (5FU). Additionally, 24-h urine samples were collected from pharmacists who handled Antineoplastic Drugs, which were analyzed for CP and alpha-fluoro-beta-alanine (AFBA). The application of control measures was scored according to a checklist, which consisted of the following five items: safety equipment and maintenance, training and documentation, devices for safe handling, personal protective equipment, and emergency care. The aim was to obtain a score of 80%. RESULTS The median CP, GEM, and 5FU concentrations of all wipe samples were significantly lower during the period when the mean score was >80% (attainment period) versus when the mean score was ≤80% (nonattainment period; all P < 0.001, Mann-Whitney's U-test). Additionally, the median urinary CP and AFBA concentrations of pharmacists during the attainment period tended to be lower than that of those during the nonattainment period (P = 0.061 and 0.061, respectively, using Mann-Whitney's U-test). CONCLUSIONS Contamination and levels of exposure to Antineoplastic Drugs decreased with a score higher than 80%. The scores of the items on the checklist appeared to adequately reflect the condition of the control measures, as increases in all five items were associated with reductions in the contamination by and levels of exposure to all Drugs.

  • association between occupational exposure levels of Antineoplastic Drugs and work environment in five hospitals in japan
    Journal of Oncology Pharmacy Practice, 2011
    Co-Authors: Jin Yoshida, Shigeki Koda, Shozo Nishida, Toshiaki Yoshida, Keiko Miyajima, Shinji Kumagai
    Abstract:

    Purpose. The aim of the present study was to evaluate the measurement of contamination by Antineoplastic Drugs for safer handling of such Drugs by medical workers. We investigated the relationship between the contamination level of Antineoplastic Drugs and the conditions of their handling.Methods. Air samples and wipe samples were collected from equipment in the preparation rooms of five hospitals (hospitals A—E). These samples were subjected to measurement of the amounts of cyclophosphamide (CPA), fluorouracil (5FU), gemcitabine (GEM), and platinum-containing Drugs (Pt). Twenty-four-hour urine samples were collected from the pharmacists who handled or audited, the Antineoplastic Drugs were analyzed for CPA and Pt.Results. Pt was detected from air samples inside BSC in hospital B. Antineoplastic Drugs were detected from wipe samples of the BSC in hospitals A, B, D, and E and of other equipment in the preparation rooms in hospitals A, B, C, and D. Cyclophosphamide and 5FU were detected from wipe samples of...

  • Use of a closed system device to reduce occupational contamination and exposure to Antineoplastic Drugs in the hospital work environment
    Annals of Occupational Hygiene, 2009
    Co-Authors: Jin Yoshida, Genshin Tei, Yoshie Masu, Chie Mochizuki, Shin-ichi Koda, Shinji Kumagai
    Abstract:

    OBJECTIVES: The aim of the preset study was to evaluate the applicability of a closed system device to protect against occupational contamination and exposure to Antineoplastic Drugs in the work environment of a hospital. METHODS: We compared the contamination by and exposure to cyclophosphamide (CPA) between a conventional mixing method and a mixing method using a closed system device. Wipe samples in the preparation room, gloves samples and 24-h urine samples of pharmacists preparing Antineoplastic Drugs were collected. Working surfaces inside the biological safety cabinet (BSC), front side of the air grilles of the BSC, stainless steel trays, working table and floor were wiped. At first, sample collection was done on 5 days over an interval of 2 weeks using the conventional mixing method. After 2 weeks training for using the closed system device, sample collection was done 5 days over an interval of 2 weeks using the closed system device. RESULTS: When pharmacists prepared Antineoplastic Drugs by the conventional method, CPA was detected from all wipe samples, and the mean and median concentrations of CPA were 1.0 and 0.16 ng cm(-2), respectively (range was from 0.0095 to 27 ng cm(-2)). When pharmacists prepared Antineoplastic Drugs with a closed system device, CPA was detected from 75% of the wipe samples at mean and median concentrations of 0.18 and 0.0013 ng cm(-2), respectively (the range was from lower than detection limit to 4.4 ng cm(-2)). Using the closed system device significantly reduced the surface contamination of CPA for all wipe sampling points in the preparation room (Mann-Whitney's U-test). The range of CPA of glove samples used in the conventional method and closed system device ranged from lower than detection limit to 3200 ng per glove-pair and from lower than detection limit to 740 ng per glove-pair, respectively. Using the closed system device significantly reduced the gloves contamination of CPA (Mann-Whitney's U-test). The range of urinary CPA of six pharmacists preparing the Antineoplastic Drugs with the conventional method and closed system device ranged from lower than detection limit to 170 ng day(-1) and from lower than detection limit to 15 ng day(-1), respectively. Using the closed system device significantly reduced the amount of urinary CPA in pharmacists preparing the Antineoplastic Drugs (Wilcoxon's signed ranks test). CONCLUSIONS: We concluded that a closed system device can reduce occupational contamination and exposure to Antineoplastic Drugs in the hospital work environment.

  • genotoxic risks to nurses from contamination of the work environment with Antineoplastic Drugs in japan
    Journal of Occupational Health, 2006
    Co-Authors: Jin Yoshida, Hiroshi Kosaka, Kimiko Tomioka, Shinji Kumagai
    Abstract:

    The aims of the present study were to clarify the work environment contamination by Antineoplastic Drugs in a hospital ward and to assess the genotoxic risks to nurses who routinely handle Antineoplastic Drugs in Japan. The exposed group consisted of 19 female nurses who routinely handled Antineoplastic Drugs. The control group consisted of 18 female nurses who did not handle Antineoplastic Drugs in the same hospital as the exposed group. The genotoxicity of the 19 Antineoplastic Drugs used in the hospital ward and 8 wipe samples of the workbench after handling of Antineoplastic Drugs were measured using the umu assay. Lymphocyte DNA damage (tail length) was measured with alkaline methods of the single cell gel electrophoresis assay (comet assay). Of the 19 Antineoplastic Drugs, dacarbazine, bleomycin, daunorubicin, doxorubicin, pirarubicin, carboplatin, cisplatin and etoposide induced genotoxicity. Of the 8 sampling d, the umu activity of the wipe sample was positive on 3 d. Contamination of the workbench was found when the nurses handled more Drugs than on other days. The medians of the tail length in the comet assay were 8.5 and 5.1 microm, respectively, for the exposed and control groups, with a significant difference (p=0.004 by Mann-Whitney's U-test). In the present study, the nurses of the exposed group were considered to have been exposed to Antineoplastic Drugs and lymphocyte DNA damage of the exposed group was suggested to be induced by Antineoplastic Drugs.

Chunyip Hon - One of the best experts on this subject based on the ideXlab platform.

  • the application of novel field measurement and field evaluation protocols for assessing health care workers exposure risk to Antineoplastic Drugs
    Journal of Occupational and Environmental Hygiene, 2020
    Co-Authors: George Astrakianakis, Matthew Jeronimo, Andrea Griffiths, Manuel Colombo, Desre Kramer, Paul A Demers, Chunyip Hon
    Abstract:

    Contamination of multiple Antineoplastic Drugs (ADs) on work surfaces presents an exposure concern for health care workers. Surface wipe sampling is a recognized method to evaluate the degree of co...

  • wipe sampling method and evaluation of environmental variables for assessing surface contamination of 10 Antineoplastic Drugs by liquid chromatography tandem mass spectrometry
    Annals of Work Exposures and Health, 2017
    Co-Authors: Manuel Colombo, George Astrakianakis, Matthew Jeronimo, Chirag Apte, Chunyip Hon
    Abstract:

    This paper describes a novel wipe sampling and high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method capable of simultaneously detecting 10 Antineoplastic Drugs (5-fluorouracil, oxaliplatin, methotrexate, vindesine, ifosfamide, cyclophosphamide, vincristine, vinblastine, docetaxel, and paclitaxel). The good overall recoveries and sensitivity values of this method along with the comparatively short run time (8 min) allows for its use in routine monitoring in health care facilities. The long-term behavior of the studied Drugs on contaminated surfaces and the effect of surface roughness on drug recoveries were studied to gain insights about how these environmental variables influence the detection, cleaning, and occupational exposure of these Drugs. Surfaces with higher roughness parameter (Ra) values (rougher) had the lowest recoveries while those with lower Ra (smoother) presented the highest recoveries. Long-term assessments evidence distinctive drug behaviors with oxaliplatin, vindesine, vincristine, and vinblastine being the less persistent Drugs (~20% was recovered after 24 h) and docetaxel and paclitaxel the most persistent Drugs with recoveries of 40% and 80% after 1 month. This information indicates the importance of collecting ancillary information about drug usage (throughput, timing, cleaning procedures, etc.) to interpret the results in the context of potential exposure. Finally, the method was successfully applied to evaluate trace surface contamination down to the single picogram per square centimeter in multiple work areas within three local health care centers on Vancouver Island, Canada.

  • health care workers knowledge perceptions and behaviors regarding Antineoplastic Drugs survey from british columbia canada
    Journal of Occupational and Environmental Hygiene, 2015
    Co-Authors: Chunyip Hon, Kay Teschke, Hui Shen
    Abstract:

    Although nurses are knowledgeable regarding the risk of exposure to Antineoplastic Drugs, they often do not adhere with safe work practices. However, the knowledge, perceptions, and behavior of other health care job categories at risk of exposure has yet to be determined. This study aimed to survey a range of health care workers from British Columbia, Canada about their knowledge, perceptions, and behaviors regarding Antineoplastic Drugs. A self-administered questionnaire was sent to participants querying the degree of contact with Antineoplastics, knowledge of risks associated with Antineoplastics, perceptions of personal risk, previous training with respect to Antineoplastics, and safe work practices. Subjects were recruited from health care facilities in and around Vancouver. Fisher's exact tests were performed to ascertain whether there were differences in responses between job categories. We received responses from 120 participants representing seven different job categories. Pharmacists, pharmacy te...

  • a surface wipe sampling and lc ms ms method for the simultaneous detection of six Antineoplastic Drugs commonly handled by healthcare workers
    Analytical and Bioanalytical Chemistry, 2015
    Co-Authors: Matthew Jeronimo, George Astrakianakis, Manuel Colombo, Chunyip Hon
    Abstract:

    An effective wipe sampling and LC–MS/MS method was developed to simultaneously analyze six commonly administered Antineoplastic Drugs in stainless steel surface. The analyzed Drugs were methotrexate, paclitaxel, cyclophosphamide, 5-fluorouracil, vincristine, and oxaliplatin, a frequently prepared Antineoplastic drug that has not been included among any of the published simultaneous detection methods. The established method was used to evaluate the recoveries of Antineoplastic Drugs on brand new and worn stainless steel surfaces by wiping the plates with a Whatman filter paper wetted with 0.5 mL of water/methanol (20:80) with 0.1 % formic acid followed by LC–MS/MS before desorbing the filter with a water/methanol (50:50) solution. A significant decrease in the recovery of all evaluated Drugs was found when worn plates were used. Additionally, the inter-personnel variability on drug recoveries during wiping procedures was evaluated. Significantly higher recoveries were achieved by the personnel with more training and experience versus personnel without prior experience. Finally, a laboratory stability test was developed to assess the degradation of the Antineoplastic Drugs during replicated shipping conditions. With the exception of vincristine sulfate which exhibited a significant (p < 0.05) degradation after 48 h, all evaluated Drugs were stable during the first 24–48 h. However, after 144 h, an increase in the degradation of all evaluated Drugs was observed, with oxaliplatin and 5-fluorouracil exhibiting the most degradation.

  • examining factors that influence the effectiveness of cleaning Antineoplastic Drugs from drug preparation surfaces a pilot study
    Journal of Oncology Pharmacy Practice, 2014
    Co-Authors: Chunyip Hon, Prescillia Ps Chua, Quinn Danyluk, George Astrakianakis
    Abstract:

    Occupational exposure to Antineoplastic Drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels...

Rafael Morenosanchez - One of the best experts on this subject based on the ideXlab platform.

  • cardiotoxicity of copper based Antineoplastic Drugs casiopeinas is related to inhibition of energy metabolism
    Toxicology and Applied Pharmacology, 2006
    Co-Authors: Luz Hernandezesquivel, Alvaro Marinhernandez, Natalia Pavon, Karla Carvajal, Rafael Morenosanchez
    Abstract:

    Abstract Isolated rat hearts were perfused with glucose, octanoate or glucose + octanoate and different concentrations of the copper-based Antineoplastic Drugs casiopeina II-gly (CSII) or casiopeina III-i-a (CSIII). In isolated perfused hearts with glucose + octanoate, both casiopeinas induced diminution in cardiac work and O2 consumption with half-maximal inhibitory concentrations (IC50) of 4 (CSII) and 4.6 (CSIII) μM, after 1 h of perfusion. Strong inhibition of the pyruvate and 2-oxoglutarate dehydrogenases as well as total creatine kinase by casiopeinas suggested that ATP generation by oxidative phosphorylation and its transfer towards myofibrils were targets for these Drugs. In consequence, the cellular contents of ATP and phosphocreatine were also lowered by casiopeinas. Remarkably, casiopeinas were less toxic than adriamycin (IC50 = 2.6 μM), a well-known potent cardiotoxic and Antineoplastic drug, which has a wide clinical use. In an open-chest animal, which is a more physiological model than the isolated heart, femoral administration of 1 μM drug revealed that CSII was innocuous very likely due to strong binding to serum albumin, whereas adriamycin induced again a potent cardiotoxic effect (diminution in heart rate and severe depression of systolic blood pressure). Thus, it seems that casiopeinas are a group of new Antineoplastic Drugs with milder secondary toxic effects than proven Drugs such as adriamycin.

  • toxic effects of copper based Antineoplastic Drugs casiopeinas on mitochondrial functions
    Biochemical Pharmacology, 2003
    Co-Authors: Alvaro Marinhernandez, Isabel Graciamora, Lena Ruizramirez, Rafael Morenosanchez
    Abstract:

    Abstract To elucidate some of the subcellular and biochemical mechanisms of toxicity of metal-based Antineoplastic Drugs, mitochondria and cells were exposed to Casiopeinas®, a new class of copper-based compounds with high Antineoplastic activity. The rates of respiration and swelling, the H+ gradient, and the activities of succinate (SDH) and 2-oxoglutarate dehydrogenases (2-OGDH) and ATPase were measured in mitochondria isolated from rat liver, kidney, heart, and hepatoma AS-30D. Also, oligomycin-sensitive respiration and ATP content in hepatoma AS-30D cells were determined. Casiopeinas® (CS) II-gly and III-i inhibited the rates of state 3 and uncoupled respiration in mitochondria. CS II was 10 times more potent than CS III. The sensitivity to CS II was 4–5-fold higher in mitochondria incubated with 2-OG than with succinate. Thus, at low concentrations (≤10 nmol (mg protein)−1; 10 μM), CS II disturbed mitochondrial functions only when 2-OG was present, due to a specific inhibition of 2-OGDH. At high concentrations (≥15 nmol (mg protein)−1), CS II-induced stimulation of basal respiration, followed by a strong inhibition, which correlated with K+-dependent swelling and cytochrome c release, respectively; K+-channel openers induce a similar mitochondrial response. Mitochondria from liver, kidney and hepatoma showed a similar sensitivity towards CS II, whereas heart mitochondria were more resistant. Oxidative phosphorylation and ATP content were also decreased in tumor cells by CS II. The data suggested that CS affected several different mitochondrial sites, bringing about inhibition of respiration and ATP synthesis, which could compromise energy-dependent processes such as cellular duplication.