Microgravity

NASA Image and Video Library

2000-07-01

Engineering bench system hardware for the Mechanics of Granular Materials (MGM) experiment is tested on a lab bench at the University of Colorado in Boulder. This is done in a horizontal arrangement to reduce pressure differences so the tests more closely resemble behavior in the microgravity of space. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. MGM experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: University of Colorado at Boulder).

MGM - MS Reilly holds a container used in the MGM experiment

NASA Image and Video Library

1998-03-04

S89-E-5328 (27 Jan 1998) --- This Electronic Still Camera (ESC) image shows astronaut James F. Reilly, mission specialist, holding the Mechanics of Granular Materials (MGM) experiment. The MGM experiment is aimed at understanding the behavior of granular materials, such as sand or salt, under very low confining pressure. This pressure is the force that keeps a granular material ?sticking together?. The experiment has applications in a wide range of fields, including earthquake engineering; coastal and off-shore engineering; mining; transportation of granular materials; soil erosion; the handling of granular materials such as grains and powders; off-road vehicles; geology of the Earth; and planetary geology and exploration. Findings from the experiment may lead to improved selection and preparation of building sites, better management of undeveloped land, and improved handling of materials in chemical, agricultural and other industries.

Microgravity

NASA Image and Video Library

1996-09-18

Astronaut Jay Apt installs Mechanics of Granular Materials (MGM0 test cell on STS-79. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. MGM experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: NASA/John Space Center).

Microgravity

NASA Image and Video Library

2000-07-01

Mechanics of Granular Materials (MGM) flight hardware takes two twin double locker assemblies in the Space Shuttle middeck or the Spacehab module. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. MGM experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: NASA/MSFC).

Microgravity

NASA Image and Video Library

1996-09-18

Astronaut Carl Walz installs Mechanics of Granular Materials (MGM) test cell on STS-79. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: NASA/John Space Center

Mechanics of Granular Materials labeled hardware

NASA Technical Reports Server (NTRS)

2000-01-01

Mechanics of Granular Materials (MGM) flight hardware takes two twin double locker assemblies in the Space Shuttle middeck or the Spacehab module. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. MGM experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: NASA/MSFC).

Mechanics of Granular Materials (MGM) Cell

NASA Technical Reports Server (NTRS)

1996-01-01

One of three Mechanics of Granular Materials (MGM) test cells after flight on STS-79 and before impregnation with resin. Note that the sand column has bulged in the middle, and that the top of the column is several inches lower than the top of the plastic enclosure. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: University of Colorado at Boulder

Khalid Alshibli shows a child MGM apparatus at outreach event

NASA Technical Reports Server (NTRS)

2002-01-01

Khalid Alshibli of Louisiana State University, project scientist for the Mechanics of Granular Materials (MGM-III) experiment, uses a jar of sand and a training model of the MGM apparatus to explain the experiment to two young Virginia students. The activity was part of the Space Research and You education event held by NASA's Office of Biological and Physical Research on June 25, 2002, in Arlington, VA, to highlight the research that will be conducted on STS-107.

Khalid Alshibli explains MGM to Sean O'Keefe

NASA Technical Reports Server (NTRS)

2002-01-01

Khalid Alshibli of Louisiana State University, project scientist for the Mechanics of Granular Materials (MGM-III) experiment, uses a jar of sand as he explains MGM to NASA Administrator Sean O'Keefe. A training model of an MGM test cell is in the foreground. The activity was part of the Space Research and You education event held by NASA's Office of Biological and Physical Research on June 25, 2002, in Arlington, VA, to highlight the research that will be conducted on STS-107.

Microgravity

NASA Image and Video Library

1996-09-18

One of three Mechanics of Granular Materials (MGM) test cells after flight on STS-79 and before impregnation with resin. Note that the sand column has bulged in the middle, and that the top of the column is several inches lower than the top of the plastic enclosure. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: University of Colorado at Boulder

Microgravity

NASA Image and Video Library

2000-07-01

What appear to be boulders fresh from a tumble down a mountain are really grains of Ottawa sand, a standard material used in civil engineering tests and also used in the Mechanics of Granular Materials (MGM) experiment. The craggy surface shows how sand grans have faces that can cause friction as they roll and slide against each other, or even causing sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. MGM uses the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. These images are from an Electron Spectroscopy for Chemical Analysis (ESCA) study conducted by Dr. Binayak Panda of IITRI for Marshall Space Flight Center (MSFC). (Credit: NASA/MSFC)

Material Science

NASA Image and Video Library

2002-08-06

Khalid Alshibli of Louisiana State University, project scientist for the Mechanics of Granular Materials (MGM-III) experiment, uses a jar of sand as he explains MGM to NASA Administrator Sean O'Keefe. A training model of an MGM test cell is in the foreground. The activity was part of the Space Research and You education event held by NASA's Office of Biological and Physical Research on June 25, 2002, in Arlington, VA, to highlight the research that will be conducted on STS-107.

CT Scans of Soil Specimen Processed in Space

NASA Technical Reports Server (NTRS)

1998-01-01

CT scans of the spcimens on STS-79 reveal internal cone-shaped features and radial patterns not seen in specimens processed on the ground. The lighter areas are the densest in these images. CT scans produced richly detailed images allowing scientists to build 3D models of the interior of the specimens that can be compared with microscopic examination of thin slices. This view is made from a series of horizontal slices. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: Los Alamos National Laboratory and the University of Colorado at Boulder.

CT Scans of Soil Specimen Processed in Space

NASA Technical Reports Server (NTRS)

1998-01-01

CT scans of the specimens on STS-79 reveal internal cone-shaped features and radial patterns not seen in specimens processed on the ground. The lighter areas are the densest in these images. CT scans produced richly detailed images allowing scientists to build 3D models of the interior of the specimens that can be compared with microscopic examination of thin slices. This view is made from three orthogonal slices. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: Los Alamos National Laboratory and the University of Colorado at Boulder).

CT Scans of Soil Specimen Processed in Space

NASA Technical Reports Server (NTRS)

1998-01-01

CT scans of the spcimens on STS-79 reveal internal cone-shaped features and radial patterns not seen in specimens processed on the ground. The lighter areas are the densest in these images. CT scans produced richly detailed images allowing scientists to build 3D models of the interior of the specimens that can be compared with microscopic examination of thin slices. This view depict horizontal slices from top to bottom of a flight specimen. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: Los Alamos National Laboratory and the University of Colorado at Boulder.

CT Scans of Soil Specimen Processed in Space

NASA Technical Reports Server (NTRS)

1998-01-01

CT scans of the spcimens on STS-79 reveal internal cone-shaped features and radial patterns not seen in specimens processed on the ground. The lighter areas are the densest in these images. CT scans produced richly detailed images allowing scientists to build 3D models of the interior of the specimens that can be compared with microscopic examination of thin slices. These views depict vertical slices from side to middle of a flight specimen. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: Los Alamos National Laboratory and the University of Colorado at Boulder.

Multi-Gas Monitor (MGM)

NASA Technical Reports Server (NTRS)

Pilgrim, Jeff; Limero, Thomas

2015-01-01

Multi-Gas Monitor is a flight experiment, a technology demonstration to test the ability of tunable diode laser spectroscopy based instrument to stay in calibration long term and follow events and dynamics occurring with the cabin atmosphere. MGM measures 4 gases: oxygen, carbon monoxide, ammonia and water vapor, as well as temperature and pressure. This month marked one year of successful and continuous MGM operation on ISS. The crew successfully tested the ammonia channel using a commercially available inhalant. MGM has detected some interesting dynamics inside Japanese Experiment Module (JEM) as a result of CO2 thruster firings from the SPHERES/RINGS payload and water spikes from dry out cycling of the JEM heat exchangers. Results to date have given us high confidence in the technology such that we believe this could have applications in the energy and medical sectors. This presentation will summarize the testing and results of the unit on ISS and suggest areas of use within the energy and medical arenas.

Mechanics of Granular Materials (MGM)

NASA Technical Reports Server (NTRS)

2000-01-01

The packing of particles can change radically during cyclic loading such as in an earthquake or when shaking a container to compact a powder. A large hole (1) is maintained by the particles sticking to each other. A small, counterclockwise strain (2) collapses the hole, and another large strain (3) forms more new holes which collapse when the strain reverses (4). Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. MGM experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (after T.L. Youd, Packing Changes and Liquefaction Susceptibility, Journal of the Geotechnical Engieering Division, 103: GT8,918-922, 1977)(Credit: NASA/Marshall Space Flight Center.)(Credit: University of Colorado at Boulder).

Material Science

NASA Image and Video Library

2002-08-06

Khalid Alshibli of Louisiana State University, project scientist for the Mechanics of Granular Materials (MGM-III) experiment, uses a jar of sand and a training model of the MGM apparatus to explain the experiment to two young Virginia students. The activity was part of the Space Research and You education event held by NASA's Office of Biological and Physical Research on June 25, 2002, in Arlington, VA, to highlight the research that will be conducted on STS-107.

Total fume and metal concentrations during welding in selected factories in Jeddah, Saudi Arabia.

PubMed

Balkhyour, Mansour Ahmed; Goknil, Mohammad Khalid

2010-07-01

Welding is a major industrial process used for joining metals. Occupational exposure to welding fumes is a serious occupational health problem all over the world. The degree of risk to welder's health from fumes depends on composition, concentration, and the length of exposure. The aim of this study was to investigate workers' welding fume exposure levels in some industries in Jeddah, Saudi Arabia. In each factory, the air in the breathing zone within 0.5 m from welders was sampled during 8-hour shifts. Total particulates, manganese, copper, and molybdenum concentrations of welding fumes were determined. Mean values of eight-hour average particulate concentrations measured during welding at the welders breathing zone were 6.3 mg/m(3) (Factory 1), 5.3 mg/m(3) (Factory 2), 11.3 mg/m(3) (Factory 3), 6.8 mg/m(3) (Factory 4), 4.7 mg/m(3) (Factory 5), and 3.0 mg/m(3) (Factory 6). Mean values of airborne manganese, copper, and molybdenum levels measured during welding were in the range of 0.010 mg/m(3)-0.477 mg/m(3), 0.001 mg/m(3)-0.080 mg/m(3) and 0.001 mg/m(3)-0.058 mg/m(3) respectively. Mean values of calculated equivalent exposure values were: 1.50 (Factory 1), 1.56 (Factory 2), 5.14 (Factory 3), 2.21 (Factory 4), 2.89 (Factory 5), and 1.20 (Factory 6). The welders in factories 1, 2, 3, and 4 were exposed to welding fume concentration above the SASO limit value, which may increase the risk of respiratory health problems.

Nitrogen and Phosphorus Pollutants in Cosmetics Wastewater and Its Treatment Process of a Certain Brand

NASA Astrophysics Data System (ADS)

Ma, Guosheng; Chen, Juan

2018-02-01

Cosmetics wastewater is one of the sources of nitrogen and phosphorus pollutants that cause eutrophication of water bodies. This paper is to test the cosmetics wastewater in the production process with American Hach method, and the pH and other indicators would be detected during a whole production cycle. The results show that the pH value in wastewater is 8.6~8.7 (average 8.67), SS 880~1090 mg. L-1 (average 968.57), TN 65.2~100.4 mg.m-3 (average 80.50), TP 6.6~11.4 mg.m-3 (average 9.84), NH3-N 44.2~77.0 mg.m-3 (average 55.61), COD 4650~5900 mg.m-3 (average 5490). After pollutant treatment, the nitrogen and phosphorus pollutants in wastewater can reach the standard discharge.

Material Science

NASA Image and Video Library

2002-08-06

Khalid Alshibli of Louisiana State University, project scientist for the Mechanics of Granular Materials (MGM-III) experiment, explains the MGM experiment to Kristen Erickson, acting deputy associate administrator in NASA's Office of Biological and Physical Research. A training model of the test cell is at right. The activity was part of the Space Research and You education event held by NASA's Office of Biological and Physical Research on June 25, 2002, in Arlington, VA, to highlight the research that will be conducted on STS-107.

Water-soluble polysaccharides from agro-industrial by-products: functional and biological properties.

PubMed

Sila, Assaâd; Bayar, Nadia; Ghazala, Imen; Bougatef, Ali; Ellouz-Ghorbel, Raoudha; Ellouz-Chaabouni, Semia

2014-08-01

Water-soluble polysaccharides were isolated from almond (AWSP) and pistachio (PWSP) juice processing by-products. Their chemical and physical characteristics were determined using NMR and Infrared spectroscopic analysis. The complexities of the spectra reflected the heterogeneity of these polysaccharides. The ACE inhibitory activities (IC50 AWSP=2.81mgmL(-1) and IC50 PWSP=2.59mgmL(-1)) and antioxidant properties of AWSP and PWSP were investigated based on the DPPH radical-scavenging capacity assay (IC50 AWSP=2.87mgmL(-1) and IC50 PWSP=1.61mgmL(-1)). Reducing power, β-carotene bleaching inhibition (IC50AWSP=4.46mgmL(-1) and IC50 PWSP=3.39mgmL(-1)), and ferrous chelating assays (IC50 AWSP=0.22mgmL(-1) and IC50 PWSP=0.19mgmL(-1)) were also performed. The findings revealed that water-soluble polysaccharides exhibited antioxidant and antihypertensive activities. AWSP and PWSP showed excellent interfacial concentration-dependent properties. Overall, the results suggested that both AWSP and PWSP are promising sources of natural antioxidants and ACE inhibitory agents and could, therefore, be used as alternative additives in food, pharmaceutical and cosmetic preparations. Copyright © 2014 Elsevier B.V. All rights reserved.

Microgravity

NASA Image and Video Library

1998-01-25

CT scans of the spcimens on STS-79 reveal internal cone-shaped features and radial patterns not seen in specimens processed on the ground. The lighter areas are the densest in these images. CT scans produced richly detailed images allowing scientists to build 3D models of the interior of the specimens that can be compared with microscopic examination of thin slices. These views depict vertical slices from side to middle of a flight specimen. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: Los Alamos National Laboratory and the University of Colorado at Boulder.

Microgravity

NASA Image and Video Library

1998-01-25

CT scans of the spcimens on STS-79 reveal internal cone-shaped features and radial patterns not seen in specimens processed on the ground. The lighter areas are the densest in these images. CT scans produced richly detailed images allowing scientists to build 3D models of the interior of the specimens that can be compared with microscopic examination of thin slices. This view depict horizontal slices from top to bottom of a flight specimen. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: Los Alamos National Laboratory and the University of Colorado at Boulder.

Microgravity

NASA Image and Video Library

1998-01-25

CT scans of the spcimens on STS-79 reveal internal cone-shaped features and radial patterns not seen in specimens processed on the ground. The lighter areas are the densest in these images. CT scans produced richly detailed images allowing scientists to build 3D models of the interior of the specimens that can be compared with microscopic examination of thin slices. This view is made from a series of horizontal slices. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: Los Alamos National Laboratory and the University of Colorado at Boulder.

Microgravity

NASA Image and Video Library

1998-01-25

CT scans of the specimens on STS-79 reveal internal cone-shaped features and radial patterns not seen in specimens processed on the ground. The lighter areas are the densest in these images. CT scans produced richly detailed images allowing scientists to build 3D models of the interior of the specimens that can be compared with microscopic examination of thin slices. This view is made from three orthogonal slices. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: Los Alamos National Laboratory and the University of Colorado at Boulder).

Microgravity

NASA Image and Video Library

1998-01-01

On STS-89, three Mechanics of Granular Materials (MGM) test cells were subjected to five cycles of compression and relief (left) and three were subjected to shorter displacement cycles that simulate motion during an earthquake (right). In the compression/relief tests, the sand particles rearranged themselves and slightly re-expanded the column during relief. In the short displacement tests, the specimen's resistance to compression decreases, even though the displacement remains the same. The specimens were cycled up to 100 times or until the resistive force was less than 1% that of the previous cycle. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: NASA/Marshall Space Flight Center (MSFC)

Graphs of Soil Mechanics Tests in Orbit

NASA Technical Reports Server (NTRS)

1998-01-01

On STS-89, three Mechanics of Granular Materials (MGM) test cells were subjected to five cycles of compression and relief (left) and three were subjected to shorter displacement cycles that simulate motion during an earthquake (right). In the compression/relief tests, the sand particles rearranged themselves and slightly re-expanded the column during relief. In the short displacement tests, the specimen's resistance to compression decreases, even though the displacement remains the same. The specimens were cycled up to 100 times or until the resistive force was less than 1% that of the previous cycle. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: NASA/Marshall Space Flight Center (MSFC)

Microgravity

NASA Image and Video Library

1989-10-17

An automobile lies crushed under the third story of this apartment building in the Marina District after the Oct. 17, 1989, Loma Prieta earthquake. The ground levels are no longer visible because of structural failure and sinking due to liquefaction. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: J.K. Nakata, U.S. Geological Survey.

Housing Damage Following Earthquake

NASA Technical Reports Server (NTRS)

1989-01-01

An automobile lies crushed under the third story of this apartment building in the Marina District after the Oct. 17, 1989, Loma Prieta earthquake. The ground levels are no longer visible because of structural failure and sinking due to liquefaction. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: J.K. Nakata, U.S. Geological Survey.

Mechanics of Granular Materials-3 (MGM-3)

NASA Technical Reports Server (NTRS)

Sture, Stein; Alshibi, Khalid; Guynes, Buddy (Technical Monitor)

2002-01-01

Scientists are going to space to understand how earthquakes and other forces disturb grains of soil and sand. They will examine how the particle arrangement and structure of soils, grains and powders are changed by external forces and gain knowledge about the strength, stiffness and volume changes properties of granular materials at low pressures. The Mechanics of Granular Materials (MGM) experiment uses the microgravity of orbit to test sand columns under conditions that cannot be obtained in experiments on Earth. Research can only go so far on Earth because gravity-induced stresses complicate the analysis and change loads too quickly for detailed analysis. This new knowledge will be applied to improving foundations for buildings, managing undeveloped land, and handling powdered and granular materials in chemical, agricultural, and other industries. NASA wants to understand the way soil behaves under different gravity levels so that crews can safely build habitats on Mars and the Moon. Future MGM experiments will benefit from extended tests aboard the International Space Station, including experiments under simulated lunar and Martian gravity in the science centrifuge.

Gravimetric and analytical evaluation of welding fume in an automobile part manufacturing factory.

PubMed

Mansouri, N; Atbi, F; Moharamnezhad, N; Rahbaran, D A; Alahiari, M

2008-12-28

Welding is one of the most exercised industrial processes which welders are exposed to chemical and physical Hazardous agents. This study was conducted to evaluate occupational and environmental exposures to aerosols generated by welding processes in a factory. A total of 28 samples of aerosols were collected at 4 different locations including indoor, outdoor, source of welding and the stacks using a high volume pump with a volumetric flow rate of 112 lit/min calibrated with a dry gas meter. The samples were collected on round 110 mm fiber glass filters, measured gravimetrically, extracted using nitric acid and analyzed with atomic absorption spectroscopy method for heavy metals including Fe, Mn, Ni, Cr3+, Cr+6, Co, and Zn. Gravimetric measuring has shown the mean values of indoor air: 1.33 mg/m3, breathing zone of the welders using coated electrodes and CO2: 7.25 mg/m3 and 6.45 mg/m3 respectively and in ventilation exhausts: 95.07 mg/m3. The mean values of Fe, Mn, and Ni were 0.8, 0.041, and 0.00 mg/m3 in indoor air, 2.7, 0.18, and 0.15 mg/m3 in breathing zone of welders used coated electrodes, and 1.75, 0.08, and 0.22 mg/m3 in breathing zone of welders used CO2 welding respectively. The concentrations of Cr3+, Cr+6, Co, and Zn were too low to be detected. The welders were exposed to high concentration of metallic fumes, which raise the risk of pulmonary dysfunction and other health disorders. Using suitable respiratory masks and Appling the effective local ventilation system may improve the working condition.

Study on the traffic air pollution inside and outside a road tunnel in Shanghai, China.

PubMed

Zhou, Rui; Wang, Shanshan; Shi, Chanzhen; Wang, Wenxin; Zhao, Heng; Liu, Rui; Chen, Limin; Zhou, Bin

2014-01-01

To investigate the vehicle induced air pollution situations both inside and outside the tunnel, the field measurement of the pollutants concentrations and its diurnal variations was performed inside and outside the Xiangyin tunnel in Shanghai from 13:00 on April 24th to 13:00 on April 25th, 2013. The highest hourly average concentrations of pollutants were quantified that CO, NO, NO2 and NOX inside the tunnel were 13.223 mg/m3, 1.829 mg/m3, 0.291 mg/m3 and 3.029 mg/m3, respectively, while the lowest ones were 3.086 mg/m3, 0.344 mg/m3, 0.080 mg/m3 and 0.619 mg/m3. Moreover, the concentrations of pollutants were higher during the daytime, and lower at night, which is relevant to the traffic conditions inside the tunnel. Pollutants concentrations inside the tunnel were much higher than those outside the tunnel. Then in a case of slow wind, the effect of wind is much smaller than the impact of pollution sources. Additionally, the PM2.5 concentrations climbed to the peak sharply (468.45 µg/m3) during the morning rush hours. The concentrations of organic carbon (OC) and elemental carbon (EC) in PM2.5 inside the tunnel were 37.09-99.06 µg/m3 and 22.69-137.99 µg/m3, respectively. Besides, the OC/EC ratio ranged from 0.72 to 2.19 with an average value of 1.34. Compared with the results of other tunnel experiments in Guangzhou and Shenzhen, China, it could be inferred that the proportion of HDVs through the Xiangyin tunnel is relatively lower.

Study on the Traffic Air Pollution inside and outside a Road Tunnel in Shanghai, China

PubMed Central

Zhou, Rui; Wang, Shanshan; Shi, Chanzhen; Wang, Wenxin; Zhao, Heng; Liu, Rui; Chen, Limin; Zhou, Bin

2014-01-01

To investigate the vehicle induced air pollution situations both inside and outside the tunnel, the field measurement of the pollutants concentrations and its diurnal variations was performed inside and outside the Xiangyin tunnel in Shanghai from 13:00 on April 24th to 13:00 on April 25th, 2013. The highest hourly average concentrations of pollutants were quantified that CO, NO, NO2 and NOX inside the tunnel were 13.223 mg/m3, 1.829 mg/m3, 0.291 mg/m3 and 3.029 mg/m3, respectively, while the lowest ones were 3.086 mg/m3, 0.344 mg/m3, 0.080 mg/m3 and 0.619 mg/m3. Moreover, the concentrations of pollutants were higher during the daytime, and lower at night, which is relevant to the traffic conditions inside the tunnel. Pollutants concentrations inside the tunnel were much higher than those outside the tunnel. Then in a case of slow wind, the effect of wind is much smaller than the impact of pollution sources. Additionally, the PM2.5 concentrations climbed to the peak sharply (468.45 µg/m3) during the morning rush hours. The concentrations of organic carbon (OC) and elemental carbon (EC) in PM2.5 inside the tunnel were 37.09–99.06 µg/m3 and 22.69–137.99 µg/m3, respectively. Besides, the OC/EC ratio ranged from 0.72 to 2.19 with an average value of 1.34. Compared with the results of other tunnel experiments in Guangzhou and Shenzhen, China, it could be inferred that the proportion of HDVs through the Xiangyin tunnel is relatively lower. PMID:25386920

Mgm101 is a Rad52-related protein required for mitochondrial DNA recombination.

PubMed

Mbantenkhu, MacMillan; Wang, Xiaowen; Nardozzi, Jonathan D; Wilkens, Stephan; Hoffman, Elizabeth; Patel, Anamika; Cosgrove, Michael S; Chen, Xin Jie

2011-12-09

Homologous recombination is a conserved molecular process that has primarily evolved for the repair of double-stranded DNA breaks and stalled replication forks. However, the recombination machinery in mitochondria is poorly understood. Here, we show that the yeast mitochondrial nucleoid protein, Mgm101, is related to the Rad52-type recombination proteins that are widespread in organisms from bacteriophage to humans. Mgm101 is required for repeat-mediated recombination and suppression of mtDNA fragmentation in vivo. It preferentially binds to single-stranded DNA and catalyzes the annealing of ssDNA precomplexed with the mitochondrial ssDNA-binding protein, Rim1. Transmission electron microscopy showed that Mgm101 forms large oligomeric rings of ∼14-fold symmetry and highly compressed helical filaments. Specific mutations affecting ring formation reduce protein stability in vitro. The data suggest that the ring structure may provide a scaffold for stabilization of Mgm101 by preventing the aggregation of the otherwise unstable monomeric conformation. Upon binding to ssDNA, Mgm101 is remobilized from the rings to form distinct nucleoprotein filaments. These studies reveal a recombination protein of likely bacteriophage origin in mitochondria and support the notion that recombination is indispensable for mtDNA integrity.

Lunar Crater Slumping Caused by Soil Grain Motion

NASA Technical Reports Server (NTRS)

1966-01-01

Lunar Orbiter 2 oblique northward view towards Copernicus crater on the Moon shows crater wall slumping caused by soil liquefaction following the impact that formed the crater. The crater is about 100 km in diameter. The central peaks are visible towards the top of the image, rising about 400 m above the crater floor, and stretching for about 15 km. The northern wall of the crater is in the background. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. MGM experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: University of Colorado at Boulder).

Road Damage Following Earthquake

NASA Technical Reports Server (NTRS)

1989-01-01

Ground shaking triggered liquefaction in a subsurface layer of water-saturated sand, producing differential lateral and vertical movement in a overlying carapace of unliquified sand and slit, which moved from right to left towards the Pajaro River. This mode of ground failure, termed lateral spreading, is a principal cause of liquefaction-related earthquake damage caused by the Oct. 17, 1989, Loma Prieta earthquake. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: S.D. Ellen, U.S. Geological Survey

Sand Volcano Following Earthquake

NASA Technical Reports Server (NTRS)

1989-01-01

Sand boil or sand volcano measuring 2 m (6.6 ft.) in length erupted in median of Interstate Highway 80 west of the Bay Bridge toll plaza when ground shaking transformed loose water-saturated deposit of subsurface sand into a sand-water slurry (liquefaction) in the October 17, 1989, Loma Prieta earthquake. Vented sand contains marine-shell fragments. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: J.C. Tinsley, U.S. Geological Survey)

Microgravity

NASA Image and Video Library

1989-10-17

Sand boil or sand volcano measuring 2 m (6.6 ft.) in length erupted in median of Interstate Highway 80 west of the Bay Bridge toll plaza when ground shaking transformed loose water-saturated deposit of subsurface sand into a sand-water slurry (liquefaction) in the October 17, 1989, Loma Prieta earthquake. Vented sand contains marine-shell fragments. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: J.C. Tinsley, U.S. Geological Survey)

Microgravity

NASA Image and Video Library

1989-10-17

Ground shaking triggered liquefaction in a subsurface layer of water-saturated sand, producing differential lateral and vertical movement in a overlying carapace of unliquified sand and slit, which moved from right to left towards the Pajaro River. This mode of ground failure, termed lateral spreading, is a principal cause of liquefaction-related earthquake damage caused by the Oct. 17, 1989, Loma Prieta earthquake. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. Mechanics of Granular Materials (MGM) experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditons that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. Credit: S.D. Ellen, U.S. Geological Survey

Microgravity

NASA Image and Video Library

1966-11-24

Lunar Orbiter 2 oblique northward view towards Copernicus crater on the Moon shows crater wall slumping caused by soil liquefaction following the impact that formed the crater. The crater is about 100 km in diameter. The central peaks are visible towards the top of the image, rising about 400 m above the crater floor, and stretching for about 15 km. The northern wall of the crater is in the background. Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. MGM experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (Credit: University of Colorado at Boulder).

2012 National Park visitor spending effects: economic contributions to local communities, states, and the nation

USGS Publications Warehouse

Cullinane Thomas, Catherine; Huber, Christopher C.; Koontz, Lynne

2014-01-01

This 2012 analysis marks a major revision to the NPS visitor spending effects analyses, with the development of a new visitor spending effects model (VSE model) that replaces the former Money Generation Model (MGM2). Many of the hallmarks and processes of the MGM2 model are preserved in the new VSE model, but the new model makes significant strides in improving the accuracy and transparency of the analysis. Because of this change from the MGM2 model to the VSE model, estimates from this year’s analysis are not directly comparable to previous analyses.

A new process for NOx reduction in combustion systems for the generation of energy from waste.

PubMed

Gohlke, Oliver; Weber, Toralf; Seguin, Philippe; Laborel, Yann

2010-07-01

In the EU, emissions from energy from waste plants are largely reduced by applying the Waste Incineration Directive with its limit of 200 mg/m3(s) for NO(x) emissions. The need for further improvement is reflected by new German legislation effective as of 27 January 2009, requiring 100 mg/m3(s). Other countries are expected to follow this example due to the national emission ceilings of the Gothenburg protocol and the concluding EU directive 2001/81/EC. On the other hand, an increase in energy efficiency will be encouraged by the EU Waste Framework Directive. This is why there is a need for new technologies that make it possible to reconcile both requirements: reduced emissions and increased energy efficiency. A new process combining the internal recirculation of flue gas with ammonia or urea injection in order to achieve less then 80 mg/m3(s) of NO(x) is described. Important additional features of the process are an R1 efficiency above the required 0.65 of the EU Waste Framework Directive even with standard steam parameters of 40 bar/380 degrees C as well as low ammonia slip in the flue gas at the boiler outlet of below 10 mg/m3(s). Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Computer-aided analysis for the Mechanics of Granular Materials (MGM) experiment

NASA Technical Reports Server (NTRS)

Parker, Joey K.

1986-01-01

The Mechanics of Granular Materials (MGM) program is planned to provide experimental determinations of the mechanics of granular materials under very low gravity conditions. The initial experiments will use small glass beads as the granular material, and a precise tracking of individual beads during the test is desired. Real-time video images of the experimental specimen were taken with a television camera, and subsequently digitized by a frame grabber installed in a microcomputer. Easily identified red tracer beads were randomly scattered throughout the test specimen. A set of Pascal programs was written for processing and analyzing the digitized images. Filtering the image with Laplacian, dilation, and blurring filters when using a threshold function produced a binary (black on white) image which clearly identified the red beads. The centroids and areas for each bead were then determined. Analyzing a series of the images determined individual red bead displacements throughout the experiment. The system can provide displacement accuracies on the order of 0.5 to 1 pixel is the image is taken directly from the video camera. Digitizing an image from a video cassette recorder introduces an additional repeatability error of 0.5 to 1 pixel. Other programs were written to provide hardcopy prints of the digitized images on a dot-matrix printer.

Exposure to grain dust in Great Britain.

PubMed

Spankie, Sally; Cherrie, John W

2012-01-01

Airborne grain dust is a complex mixture of fragments of organic material from grain, plus mineral matter from soil, and possible insect, fungal, or bacterial contamination or their toxic products, such as endotoxin. In the 1990s, grain workers in Britain were frequently exposed to inhalable dust >10 mg.m(-3) (8 h), with particularly high exposures being found at terminals where grain was imported or exported and in drying operations (personal exposure typically approximately 20 mg.m(-3)). Since then, the industry has made substantial progress in improving the control of airborne dust through better-designed processes, increased automation, and an improved focus on product quality. We have used information from the published scientific literature and a small survey of industry representatives to estimate current exposure levels. These data suggest that current long-term exposure to inhalable dust for most workers is on average less than approximately 3 mg.m(-3), with perhaps 15-20% of individual personal exposures being >10 mg.m(-3). There are no published data from Britain on short-term exposure during cleaning and other tasks. We have estimated average levels for a range of tasks and judge that the highest levels, for example during some cleaning activities and certain process tasks such as loading and packing, are probably approximately10 mg.m(-3). Endotoxin levels were judged likely to be <10⁴ EU m(-3) throughout the industry provided inhalable dust levels are <10 mg.m(-3). There are no published exposure data on mycotoxin, respirable crystalline silica, and mite contamination but these are not considered to present widespread problems in the British industry. Further research should be carried out to confirm these findings.

Laser Spectroscopy Multi-Gas Monitor: Results of Technology Demonstration on ISS

NASA Technical Reports Server (NTRS)

Mudgett, Paul D.; Pilgrim, Jeffrey S.

2015-01-01

Tunable diode laser spectroscopy (TDLS) is an up and coming trace and major gas monitoring technology with unmatched selectivity, range and stability. The technology demonstration of the 4 gas Multi-Gas Monitor (MGM), reported at the 2014 ICES conference, operated continuously on the International Space Station (ISS) for nearly a year. The MGM is designed to measure oxygen, carbon dioxide, ammonia and water vapor in ambient cabin air in a low power, relatively compact device. While on board, the MGM experienced a number of challenges, unplanned and planned, including a test of the ammonia channel using a commercial medical ammonia inhalant. Data from the unit was downlinked once per week and compared with other analytical resources on board, notably the Major Constituent Analyzer (MCA), a magnetic sector mass spectrometer. MGM spent the majority of the time installed in the Nanoracks Frame 2 payload facility in front breathing mode (sampling the ambient environment of the Japanese Experiment Module), but was also used to analyze recirculated rack air. The capability of the MGM to be operated in portable mode (via internal rechargeable lithium ion polymer batteries or by plugging into any Express Rack 28VDC connector) was a part of the usability demonstration. Results to date show unprecedented stability and accuracy of the MGM vs. the MCA for oxygen and carbon dioxide. The ammonia challenge (approx. 75 ppm) was successful as well, showing very rapid response time in both directions. Work on an expansion of capability in a next generation MGM has just begun. Combustion products and hydrazine are being added to the measurable target analytes. An 8 to 10 gas monitor (aka Gas Tricorder 1.0) is envisioned for use on ISS, Orion and Exploration missions.

Microgravity

NASA Image and Video Library

2000-07-01

The packing of particles can change radically during cyclic loading such as in an earthquake or when shaking a container to compact a powder. A large hole (1) is maintained by the particles sticking to each other. A small, counterclockwise strain (2) collapses the hole, and another large strain (3) forms more new holes which collapse when the strain reverses (4). Sand and soil grains have faces that can cause friction as they roll and slide against each other, or even cause sticking and form small voids between grains. This complex behavior can cause soil to behave like a liquid under certain conditions such as earthquakes or when powders are handled in industrial processes. MGM experiments aboard the Space Shuttle use the microgravity of space to simulate this behavior under conditions that carnot be achieved in laboratory tests on Earth. MGM is shedding light on the behavior of fine-grain materials under low effective stresses. Applications include earthquake engineering, granular flow technologies (such as powder feed systems for pharmaceuticals and fertilizers), and terrestrial and planetary geology. Nine MGM specimens have flown on two Space Shuttle flights. Another three are scheduled to fly on STS-107. The principal investigator is Stein Sture of the University of Colorado at Boulder. (after T.L. Youd, Packing Changes and Liquefaction Susceptibility, Journal of the Geotechnical Engieering Division, 103: GT8,918-922, 1977)(Credit: NASA/Marshall Space Flight Center.)(Credit: University of Colorado at Boulder).

Airborne concentrations of methylene diphenyl diisocyanate (MDI) in North American wood mills during the manufacturing of oriented strand board (OSB).

PubMed

Karoly, William J; Flatley, John J; Stevenson, Ralph D; Bowers, John D

2004-12-01

Air monitoring data were collected from industrial hygiene surveys over an 8-year period in oriented strand board (OSB) mills. Personal samples were taken to evaluate potential employee exposures to MDI. Area samples were taken to determine the effectiveness of control measures used in the mills to prevent fugitive emissions of wood dust, MDI, and MDI-coated wood dust from the OSB manufacturing process. Personal sampling results (578 samples covering 11 different job categories) ranged from 0.0002-0.524 mg/m3, with a GM = 0.001 and GSD = 3.71. Area sampling results (1657 samples covering 14 stationary locations in the mills) ranged from 0.0002-2.5 mg/m3, with a GM = 0.004 and GSD = 5.52. The statistical range of the data suggests high variability. While exposures to MDI above the established limits (0.051 mg/m3, 8-hour time-weighted average, 0.2 mg/m3, ceiling) can and do occur when engineering controls are not maintained and/or proper work practices and personal protective equipment are not followed/used for certain high exposure potential tasks, the data indicate that over 97% of the personal and 92% of the area sampling results are less than 0.051 mg/m3. Wipe testing was performed to determine the presence of removable, unreacted diisocyanates (NCO functional groups)from various surfaces. Positive results were found in about 13% of the wipe tests on surfaces confined to the blender, forming line, and hopper deck process areas.

Weekly infusional high-dose 5-fluorouracil and leucovorin and biweekly cisplatin: a convenient treatment option in advanced gastric cancer.

PubMed

Kundel, Yulia; Purim, Ofer; Figer, Arie; Stemmer, Salomon M; Tichler, Thomas; Sulkes, Jaqueline; Sulkes, Aaron; Brenner, Baruch

2008-04-01

To summarize our experience using a regimen of weekly 5-FU and leucovorin (LV) and biweekly cisplatin (CDDP) in advanced gastric cancer (AGC). Patients had previously untreated histologically confirmed AGC. Treatment consisted of intravenous weekly infusional 5-FU and LV and biweekly CDDP, given for 6 weeks followed by a 2-week rest. Initially, a lower dose level was used (5-FU 2000 mg/m(2), LV 500 mg/m(2), CDDP 40 mg/m(2)), which was later increased (5-FU 2600 mg/m(2), LV 500 mg/m(2), CDDP 50 mg/m(2)). Forty-five patients were treated, 18 at the lower dose level and 27 at the higher dose level. The median age was 67 years and 55% were male. Grade > or =3 toxicity was documented in 37% of patients but toxicity related hospitalizations or treatment discontinuation occurred in only 22% and 13%, respectively. There were no toxic deaths. The most common hematological toxicities were anemia and neutropenia and the most common non-hematological toxicities were nausea, vomiting and fatigue. Of the 39 patients evaluable for response, 13 (33%) had partial response (PR) and 11 (28%) had stable disease (SD). Control of disease (PR+SD) was achieved in 61%. The higher dose level was associated with a higher response rate (p=0.07) and an increased toxicity (p=0.01), mostly hematological and gastrointestinal. Median progression-free survival and overall survival were 3.5 and 9.2 months, respectively. This regimen appears safe, with a manageable toxicity profile. Efficacy data resemble those reported for more complex and toxic regimens. The higher dose level had enhanced activity, at the expense of increased toxicity.

STS-107 Crew Interviews: Kalpana Chawla MS2

NASA Technical Reports Server (NTRS)

2002-01-01

STS-107 Mission Specialist 2 Kalpana Chawla is seen during this preflight interview where she gives a quick overview of the mission before answering questions about her inspiration to become an astronaut and her career path. Chawla outlines her role in the mission in general, and specifically in conducting the on-board science experiments. She discusses the following experiments in detail: MEIDEX (Mediterranean Israel Dust Experiment), CM2 (Combustion Module 2), MIST (Water Mist Fire Suppression), SOFBALL (Structures of Flame Balls at Low Lewis-Number), LSP (Laminar Soot Processes), MGM (Mechanics of Granular Materials) and BDS (Biotechnology Demonstration System). She also discusses the potential benefits of space research, the dual-work shift of the mission and the rewards of international cooperation.

Assessment of environmental impact on air quality by cement industry and mitigating measures: a case study.

PubMed

Kabir, G; Madugu, A I

2010-01-01

In this study, environmental impact on air quality was evaluated for a typical Cement Industry in Nigeria. The air pollutants in the atmosphere around the cement plant and neighbouring settlements were determined using appropriate sampling techniques. Atmospheric dust and CO2 were prevalent pollutants during the sampling period; their concentrations were recorded to be in the range of 249-3,745 mg/m3 and 2,440-2,600 mg/m3, respectively. Besides atmospheric dust and CO2, the air pollutants such as NOx, SOx and CO were in trace concentrations, below the safe limits approved by FEPA that are 0.0062-0.093 mg/m3 NOx, 0.026 mg/m3 SOx and 114.3 mg/m3 CO, respectively. Some cost-effective mitigating measures were recommended that include the utilisation of readily available and low-cost pozzolans material to produce blended cement, not only could energy efficiency be improved, but carbon dioxide emission could also be minimised during clinker production; and the installation of an advance high-pressure grinding rolls (clinker-roller-press process) to maximise energy efficiency to above what is obtainable from the traditional ball mills and to minimise CO2 emission from the power plant.

Microgravity

NASA Image and Video Library

2004-04-15

Computed tomography (CT) images of resin-impregnated Mechanics of Granular Materials (MGM) specimens are assembled to provide 3-D volume renderings of density patterns formed by dislocation under the external loading stress profile applied during the experiments. Experiments flown on STS-79 and STS-89. Principal Investigator: Dr. Stein Sture

Therapeutic and neurotoxic effects of 2-chlorodeoxyadenosine in adults with acute myeloid leukemia.

PubMed

Vahdat, L; Wong, E T; Wile, M J; Rosenblum, M; Foley, K M; Warrell, R P

1994-11-15

Despite expectations that 2-chlorodeoxyadenosine (2-CdA) would prove active primarily in lymphoproliferative diseases, early reports suggested unexpected high activity of this drug in heavily pretreated children with acute myeloblastic leukemia (AML) at a maximally tolerated dose of 8.9 mg/m2/day for 5 days. In view of these findings, we conducted an escalating dose trial of 2-CdA in adult patients with relapsed or resistant AML. Thirty-six patients who had received extensive prior therapy were treated at 9 dose levels of 2-CdA at daily doses ranging from 5 to 21 mg/m2 for 5 days. 2-CdA eliminated leukemic blasts from the peripheral blood in 32 of 36 cases; however, bone marrow hypoplasia was seen only at daily dose levels > or = 15 mg/m2. We observed a total of 3 complete remissions: 1 at the 15 mg/m2/d dose level and 2 at the 21 mg/m2/d dose level; these responses persisted for 3, 2, and 3 months, respectively. Although prolonged myelosuppression would have been dose-limiting at 21 mg/m2/d for 5 days, the most important adverse effect was the development of a sensorimotor peripheral neuropathy. This reaction, whose onset was substantially delayed after completion of drug treatment, was observed in 2 of 5 patients at the 19 mg/m2/d level and in 4 of 4 evaluable patients at the 21 mg/m2/d level. Pathologically, this process was characterized by axonal degeneration and secondary demyelination. Other side effects included reactivation of a posttransplant Epstein-Barr virus-related lymphoma in 1 patient and tumor lysis syndrome. We conclude that the maximally tolerable dose of 2-CdA in adult patients (17 mg/m2/d for 5 days) in approximately twofold in excess of that previously reported in children and that the limiting toxic effect is a degenerative neuropathic disorder. We confirm that this drug has definite activity in AML, but the magnitude of this effect needs to be determined in larger numbers of patients who have received less extensive therapy. This agent deserves further evaluation in patients with both AML and acute lymphoblastic leukemia at these higher doses and perhaps as part of a preparative regimen for patients undergoing bone marrow transplantation.

Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m2 every 21 days in patients with cancer

PubMed Central

Iyengar, Tara; Ramanathan, Ramesh K.; Lewandowski, Karen; Anthony, Stephen P.; Donehower, Ross C.; Westin, Eric; Hurt, Karla; Hynes, Scott M.; McKane, Scott

2013-01-01

Summary Purpose This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. Experimental design This was an open-label, multicenter, dose-escalation study in patients with advanced solid tumors. Increasing doses of LY2603618 (40–195 mg/m2) were combined with 500 mg/m2 of pemetrexed. LY2603618 was administered on Days 1 and 9 and pemetrexed on Day 8 in a 28-day cycle. For all subsequent 21-day cycles, pemetrexed was administered on Day 1 and LY2603618 on Day 2. Anti-tumor activity was evaluated as per Response Evaluation Criteria in Solid Tumors 1.0. Results A total of 31 patients were enrolled into six cohorts (three at 40 mg/m2 over 4.5-hour infusion, 1-hour infusion in subsequent cohorts: three each at 40 mg/m2, 70 mg/m2, and 195 mg/m2; 13 at 105 mg/m2; six at 150 mg/m2). Four patients experienced a dose-limiting toxicity: diarrhea (105 mg/m2); reversible infusion-related reaction (150 mg/m2); thrombocytopenia (195 mg/m2); and fatigue (195 mg/m2). The maximum tolerated dose was defined as 150 mg/m2. The pharmacokinetic data demonstrated that the exposure of LY2603618 increased in a dose-dependent manner, displayed a suitable half-life for maintaining required human exposures while minimizing the intra- and inter-cycle accumulation, and was unaffected by the pemetrexed administration. The pharmacokinetic-defined biologically efficacious dose was achieved at doses ≥105 mg/m2. Conclusion LY2603618 administered approximately 24 h after pemetrexed showed acceptable safety and pharmacokinetic profiles. PMID:22492020

Comparative inhalation toxicity of multi-wall carbon nanotubes, graphene, graphite nanoplatelets and low surface carbon black.

PubMed

Ma-Hock, Lan; Strauss, Volker; Treumann, Silke; Küttler, Karin; Wohlleben, Wendel; Hofmann, Thomas; Gröters, Sibylle; Wiench, Karin; van Ravenzwaay, Bennard; Landsiedel, Robert

2013-06-17

Carbon nanotubes, graphene, graphite nanoplatelets and carbon black are seemingly chemically identical carbon-based nano-materials with broad technological applications. Carbon nanotubes and carbon black possess different inhalation toxicities, whereas little is known about graphene and graphite nanoplatelets. In order to compare the inhalation toxicity of the mentioned carbon-based nanomaterials, male Wistar rats were exposed head-nose to atmospheres of the respective materials for 6 hours per day on 5 consecutive days. Target concentrations were 0.1, 0.5, or 2.5 mg/m3 for multi-wall carbon nanotubes and 0.5, 2.5, or 10 mg/m3 for graphene, graphite nanoplatelets and low-surface carbon black. Toxicity was determined after end of exposure and after three-week recovery using broncho-alveolar lavage fluid and microscopic examinations of the entire respiratory tract. No adverse effects were observed after inhalation exposure to 10 mg/m3 graphite nanoplatelets or relatively low specific surface area carbon black. Increases of lavage markers indicative for inflammatory processes started at exposure concentration of 0.5 mg/m3 for multi-wall carbon nanotubes and 10 mg/m3 for graphene. Consistent with the changes in lavage fluid, microgranulomas were observed at 2.5 mg/m3 multi-wall carbon nanotubes and 10 mg/m3 graphene. In order to evaluate volumetric loading of the lung as the key parameter driving the toxicity, deposited particle volume was calculated, taking into account different methods to determine the agglomerate density. However, the calculated volumetric load did not correlate to the toxicity, nor did the particle surface burden of the lung. The inhalation toxicity of the investigated carbon-based materials is likely to be a complex interaction of several parameters. Until the properties which govern the toxicity are identified, testing by short-term inhalation is the best option to identify hazardous properties in order to avoid unsafe applications or select safer alternatives for a given application.

A pilot study of addition of amifostine to melphalan, carboplatin, etoposide, and cyclophosphamide with autologous hematopoietic stem cell transplantation in pediatric solid tumors-A pediatric blood and marrow transplant consortium study.

PubMed

Ozkaynak, M Fevzi; Sahdev, Indira; Gross, Thomas G; Levine, John E; Cheerva, Alexandra C; Richards, Michael K; Rozans, Marta K; Shaw, Peter J; Kadota, Richard P

2008-03-01

Limited information is available regarding the use of amifostine in pediatric hematopoietic stem cell transplant (HSCT) patients. Melphalan, carboplatin, etoposide +/- cyclophosphamide is a commonly used preparatory regimen in pediatric solid tumor HSCT. Therefore, we decided to determine the feasibility of the addition of amifostine (750 mg/m b.i.d. x 4 d) to melphalan (200 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) (level 1) and escalating doses of cyclophosphamide (3000 mg/m and 3800 mg/m, levels 2 and 3, respectively) followed by autologous HSCT. Thirty-two patients with a variety of pediatric solid tumors were studied. Seventeen patients were accrued at level 1, 9 at level 2, and 6 at level 3. Major toxicities during the administration of the preparatory regimen were hypocalcemia, emesis, and hypotension. Hypocalcemia required aggressive calcium supplementation during the conditioning phase. No dose limiting toxicities were encountered at level 3. Amifostine at 750 mg/m b.i.d. for 4 days can be administered with a double alkylator regimen consisting of melphalan (200 mg/m), cyclophosphamide (up to 3800 mg/m), carboplatin (1200 mg/m), and etoposide (800 mg/m) with manageable toxicities.

Exposure to bioaerosols in the selected agricultural facilities of the Ukraine and Poland - a review.

PubMed

Tsapko, Valentin G; Chudnovets, Alla J; Sterenbogen, Marina J; Papach, Vladimir V; Dutkiewicz, Jacek; Skórska, Czesława; Krysińska-Traczyk, Ewa; Golec, Marcin

2011-01-01

The aim of this work was to review the studies on bioaerosols which were carried out in the years 1972-2009 in following branches of agricultural industry in the Ukraine and Poland: animal farms for cows and pigs, animal feed facilities, production of biofuel from rape, herb farms and herb processing facilities. In all facilities were determined: concentration of dust and microorganisms in the air and species composition of microflora. Moreover, in Polish animal farms, herb farms and herb processing facilities, as well as in the Ukrainian animal feed facilities, was determined the concentration of bacterial endotoxin in the air. Dust concentrations in animal farms located in the Ukraine and Poland ranged from 6-200 mg/m(3) and from 0.25-14.05 mg/m(3), respectively, while in animal feed facilities they ranged from 35-306 mg/m(3) and from 3.8-405 mg/m(3), respectively. Dust concentrations in the facilities producing biofuel from rape in the Ukraine were in the range 3.6-28 mg/m(3), whereas on herb farms and in herb processing facilities in Poland they were in the range 0.8- 1,319.6 mg/m(3), and 2.2-946 mg/m(3), respectively. The determined values exceeded in most cases the maximal acceptable concentration (MAC) which in the Ukraine and Poland is equal to 4 mg/m(3). The concentrations of microorganisms on animal farms located in the Ukraine and Poland ranged from 5.5 x 10(4)- 1.9 x 10(7) cfu/m(3) and from 4.7 x 10(4)-1.5 x 10(6) cfu/m(3), respectively, while in animal feed facilities they ranged from 2.7 x 10(4)-2.6 x 10(9) cfu/m(3) and from 1.7 x 10(3)-2.0 x 10(6) cfu/m(3), respectively. Concentrations of microorganisms in the facilities producing biofuel from rape in the Ukraine were in the range 1.5 x 10(3)-5.7 x 10(6) cfu/m(3), whereas on herb farms and in herb processing facilities in Poland they were in the ranges of 8.8 x 10(2)-8.0 x 10(6) cfu/m(3), and 9.7 x 10(3)-6.3 x 10(5) cfu/m(3), respectively. The determined values exceeded in most cases the maximal acceptable concentration (MAC) which in the Ukraine is equal to 5.0 x 10(4) cfu/m(3). The concentrations of endotoxin in Polish animal houses were in the range 0.00125-75.0 ug/m(3), whereas on herb farms and herb processing facilities they were in the ranges of 0.0045- 2,448.8 ug/m(3) and 0.2-681.0 ug/m(3), respectively, and in the Ukrainian animal feed facilities were within the range 0.008-240.0 ug/m(3). They exceeded in most cases the level of 0.2 ug/m(3) proposed as a threshold. In the air microflora of examined facilities prevailed Gram-positive bacteria (corynebacteria, cocci, spore-forming bacilli, actinomycetes) of which some (Arthrobacter spp., thermophilic actinomycetes) could be a cause of allergic alveolitis (hypersensitivity pneumonitis). Among Gram-negative bacteria isolated from the air of agricultural settings dominated the epiphytic species Pantoea agglomerans, possessing potent allergenic and endotoxic properties. Fungi were abundant in the air of the Ukrainian agricultural settings and comprised species able to produce harmful mycotoxins. In conclusion, the airborne biological factors in stated concentrations may exert harmful effects on the state of the health of exposed workers. Formation of the bioaerosol depends on the specificity of the setting, kind of technological operations, degree of mechanization, properties of processed materials, temperature and humidity, and concentration of dust in the air.

Role of Transient Receptor Potential Ion Channels and Evoked Levels of Neuropeptides in a Formaldehyde-Induced Model of Asthma in Balb/c Mice

PubMed Central

Wu, Yang; You, Huihui; Ma, Ping; Li, Li; Yuan, Ye; Li, Jinquan; Ye, Xin; Liu, Xudong; Yao, Hanchao; Chen, Ruchong; Lai, Kefang; Yang, Xu

2013-01-01

Objective Asthma is a complex pulmonary inflammatory disease characterized by the hyper-responsiveness, remodeling and inflammation of airways. Formaldehyde is a common indoor air pollutant that can cause asthma in people experiencing long-term exposure. The irritant effect and adjuvant effect are the two possible pathways of formaldehyde promoted asthma. Methodology/Principal Findings To explore the neural mechanisms and adjuvant effect of formaldehyde, 48 Balb/c mice in six experimental groups were exposed to (a) vehicle control; (b) ovalbumin; (c) formaldehyde (3.0 mg/m3); (d) ovalbumin+formaldehyde (3.0 mg/m3); (e) ovalbumin+formaldehyde (3.0 mg/m3)+HC-030031 (transient receptor potential ankyrin 1 antagonist); (f) ovalbumin+formaldehyde (3.0 mg/m3)+ capsazepine (transient receptor potential vanilloid 1 antagonist). Experiments were conducted after 4 weeks of combined exposure and 1-week challenge with aerosolized ovalbumin. Airway hyper-responsiveness, pulmonary tissue damage, eosinophil infiltration, and increased levels of interleukin-4, interleukin-6, interleukin-1β, immunoglobulin E, substance P and calcitonin gene-related peptide in lung tissues were found in the ovalbumin+formaldehyde (3.0 mg/m3) group compared with the values seen in ovalbumin -only immunized mice. Except for interleukin-1β levels, other changes in the levels of biomarker could be inhibited by HC-030031 and capsazepine. Conclusions/Significance Formaldehyde might be a key risk factor for the rise in asthma cases. Transient receptor potential ion channels and neuropeptides have important roles in formaldehyde promoted-asthma. PMID:23671638

Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer.

PubMed

Weiss, Glen J; Donehower, Ross C; Iyengar, Tara; Ramanathan, Ramesh K; Lewandowski, Karen; Westin, Eric; Hurt, Karla; Hynes, Scott M; Anthony, Stephen P; McKane, Scott

2013-02-01

This phase I study aims at assessing the safety and tolerability of LY2603618, a selective inhibitor of Checkpoint Kinase 1, in combination with pemetrexed and determining the maximum tolerable dose and the pharmacokinetic parameters. This was an open-label, multicenter, dose-escalation study in patients with advanced solid tumors. Increasing doses of LY2603618 (40-195 mg/m(2)) were combined with 500 mg/m(2) of pemetrexed. LY2603618 was administered on Days 1 and 9 and pemetrexed on Day 8 in a 28-day cycle. For all subsequent 21-day cycles, pemetrexed was administered on Day 1 and LY2603618 on Day 2. Antitumor activity was evaluated as per Response Evaluation Criteria in Solid Tumors 1.0. A total of 31 patients were enrolled into six cohorts (three at 40 mg/m(2) over 4.5-hour infusion, 1-hour infusion in subsequent cohorts: three each at 40 mg/m(2), 70 mg/m(2), and 195 mg/m(2); 13 at 105 mg/m(2); six at 150 mg/m(2)). Four patients experienced a dose-limiting toxicity: diarrhea (105 mg/m(2)); reversible infusion-related reaction (150 mg/m(2)); thrombocytopenia (195 mg/m(2)); and fatigue (195 mg/m(2)). The maximum tolerated dose was defined as 150 mg/m(2). The pharmacokinetic data demonstrated that the exposure of LY2603618 increased in a dose-dependent manner, displayed a suitable half-life for maintaining required human exposures while minimizing the intra- and inter-cycle accumulation, and was unaffected by the pemetrexed administration. The pharmacokinetic-defined biologically efficacious dose was achieved at doses ≥105 mg/m(2). LY2603618 administered approximately 24 h after pemetrexed showed acceptable safety and pharmacokinetic profiles.

Characterization of Aerosols of Titanium Dioxide Nanoparticles Following Three Generation Methods Using an Optimized Aerosolization System Designed for Experimental Inhalation Studies

PubMed Central

Pujalté, Igor; Serventi, Alessandra; Noël, Alexandra; Dieme, Denis; Haddad, Sami; Bouchard, Michèle

2017-01-01

Nanoparticles (NPs) can be released in the air in work settings, but various factors influence the exposure of workers. Controlled inhalation experiments can thus be conducted in an attempt to reproduce real-life exposure conditions and assess inhalation toxicology. Methods exist to generate aerosols, but it remains difficult to obtain nano-sized and stable aerosols suitable for inhalation experiments. The goal of this work was to characterize aerosols of titanium dioxide (TiO2) NPs, generated using a novel inhalation system equipped with three types of generators—a wet collision jet nebulizer, a dry dust jet and an electrospray aerosolizer—with the aim of producing stable aerosols with a nano-diameter average (<100 nm) and monodispersed distribution for future rodent exposures and toxicological studies. Results showed the ability of the three generation systems to provide good and stable dispersions of NPs, applicable for acute (continuous up to 8 h) and repeated (21-day) exposures. In all cases, the generated aerosols were composed mainly of small aggregates/agglomerates (average diameter <100 nm) with the electrospray producing the finest (average diameter of 70–75 mm) and least concentrated aerosols (between 0.150 and 2.5 mg/m3). The dust jet was able to produce concentrations varying from 1.5 to 150 mg/m3, and hence, the most highly concentrated aerosols. The nebulizer collision jet aerosolizer was the most versatile generator, producing both low (0.5 mg/m3) and relatively high concentrations (30 mg/m3). The three optimized generators appeared suited for possible toxicological studies of inhaled NPs. PMID:29051446

Randomized trial comparing adriamycin vincristine (av) cyclophosphamide methotrexate 5-Fluorouracil prednisone (cmfp) hybrid versus av-cmfp monthly alternated in metastatic breast-cancer.

PubMed

Vallejo, C; Bianco, A; Perez, J; Machiavelli, M; Leone, B; Romero, A; Rabinovich, M; Alvarez, L; Rodriguez, R; Cuevas, M; Hannois, A; Lacava, J

1993-03-01

194 metastatic breast cancer patients with no prior chemotherapy for advanced disease were randomized to one of two alternating schedules, fulfilling the requisites of Goldie and Coldman's hypothesis to evaluate if the earlier alternation of two non-cross resistant regimens is superior in terms of response (R), duration of R (DR), and survival (SV). arm A: Adriamycin (A) 60 mg/m2 IV day (d) 1 and vincristine (V) 1.4 mg/m2 IV d 1 and 8 monthly alternated with cyclophosphamide (C) 100 mg/m2 p.o. d 1-14; methotrexate (M) 30 mg/m2 IV d 1 and 8; 5-fluorouracil (F) 600 mg/m2 IV d 1 and 8 and prednisone (Pr) 40 mg/m2 p.o. d 1-14. Arm B (hybrid): A 60 mg/m2 IV d 1; V 1.4 mg/m2 IV d 1; C 100 mg/m2 p.o. d 8-14; M 30 mg/m2 IV d 8; F 600 mg/m2 IV d 8 and Pr 40 mg/m2 p.o. d 8-14. 87 and 89 patients are evaluable for R. Arm A: R= 59% (51/87); median DR= 13 months (m); median SV= 25 m. Arm B: R= 69% (61/89); median DR= 15 m.; median SV= 29 m. Myelosuppression was slightly more marked in arm B. Three patients had toxic-related deaths (arm A: 1; arm B: 2). a trend favoring an earlier alternation and higher dose intensity (DI) was found regarding to R, DR and SV. However, differences were not statistically significant.

Characteristics and risks of secondary pollutants generation during compression and transfer of municipal solid waste in Shanghai.

PubMed

Wang, Xiaoyuan; Xie, Bing; Wu, Dong; Hassan, Muhammad; Huang, Changying

2015-09-01

The generation and seasonal variations of secondary pollutants were investigated during three municipal solid waste (MSW) compression and transfer in Shanghai, China. The results showed that the raw wastewater generated from three MSW transfer stations had pH of 4.2-6.0, COD 40,000-70,000mg/L, BOD5 15,000-25,000mg/L, ammonia nitrogen (NH3-N) 400-700mg/L, total nitrogen (TN) 600-1500mg/L, total phosphorus (TP) 50-200mg/L and suspended solids (SS) 1000-80,000mg/L. The pH, COD, BOD5 and NH3-N did not show regular change throughout the year while the concentration of TN, TP and SS were higher in summer and autumn. The animal and vegetable oil content was extremely high. The average produced raw wastewater of three transfer stations ranged from 2.3% to 8.4% of total refuse. The major air pollutants of H2S 0.01-0.17mg/m(3), NH3 0.75-1.8mg/m(3) in transfer stations, however, the regular seasonal change was not discovered. During the transfer process, the generated leachate in container had pH of 5.7-6.4, SS of 9120-32,475mg/L. The COD and BOD5 were 41,633-89,060mg/L and 18,116-34,130mg/L respectively, higher than that in the compress process. The concentration of NH3-N and TP were 587-1422mg/L and 80-216mg/L, respectively, and both increased during transfer process. H2S, VOC, CH4 and NH3 were 0.4-4mg/m(3), 7-19mg/m(3), 0-3.4% and 1-4mg/m(3), respectively. The PCA analysis showed that the production of secondary pollutants is closely related to temperature, especially CH4. Therefore, avoiding high temperature is a key means of reducing the production of gaseous pollutants. And above all else, refuse classification in source, deodorization and anti-acid corrosion are the important processes to control the secondary pollutants during compression and transfer of MSW. Copyright © 2015 Elsevier Ltd. All rights reserved.

The structure and DNA-binding properties of Mgm101 from a yeast with a linear mitochondrial genome

PubMed Central

Pevala, Vladimír; Truban, Dominika; Bauer, Jacob A.; Košťan, Július; Kunová, Nina; Bellová, Jana; Brandstetter, Marlene; Marini, Victoria; Krejčí, Lumír; Tomáška, Ľubomír; Nosek, Jozef; Kutejová, Eva

2016-01-01

To study the mechanisms involved in the maintenance of a linear mitochondrial genome we investigated the biochemical properties of the recombination protein Mgm101 from Candida parapsilosis. We show that CpMgm101 complements defects associated with the Saccharomyces cerevisiae mgm101–1ts mutation and that it is present in both the nucleus and mitochondrial nucleoids of C. parapsilosis. Unlike its S. cerevisiae counterpart, CpMgm101 is associated with the entire nucleoid population and is able to bind to a broad range of DNA substrates in a non-sequence specific manner. CpMgm101 is also able to catalyze strand annealing and D-loop formation. CpMgm101 forms a roughly C-shaped trimer in solution according to SAXS. Electron microscopy of a complex of CpMgm101 with a model mitochondrial telomere revealed homogeneous, ring-shaped structures at the telomeric single-stranded overhangs. The DNA-binding properties of CpMgm101, together with its DNA recombination properties, suggest that it can play a number of possible roles in the replication of the mitochondrial genome and the maintenance of its telomeres. PMID:26743001

Occupational exposure to hydrogen cyanide during large-scale cassava processing, in Alagoas State, Brazil.

PubMed

Zacarias, Cyro Hauaji; Esteban, Claudia; Rodrigues, Gilson Lucio; Nascimento, Elizabeth de Souza

2017-07-27

The cassava roots used for flour production contain high amounts of cyanogenic glycosides and are, therefore, potential hydrogen cyanide (HCN) releasers. This fact is the cause of an increasing health concern in the sector of cassava processing. Brazilian workers engaged in the flour production may be chronically exposed to HCN in levels above the safety limits. This hypothesis is based on the drastic reduction in cyanide content of cassava roots during a traditional Brazilian method of processing and in the physical properties of the compound, which makes it very susceptible to volatilization and air contamination. As an attempt to explore this issue, HCN exposure in Brazilian "flour houses" was evaluated in this study through environmental and biological monitoring. Four flour houses placed in Alagoas State, Brazil, were investigated. The results indicated that the cassava processors are chronically exposed to HCN at average levels between 0.464 and 3.328mg/m3 (TWA), in the work environment. This range is below the TLV-C of 5mg/m3 but not below the Action Level of 2.5mg/m3. These data may be interpreted as a possible risk to susceptible individuals. Additionally, the biological monitoring indicated a high cyanide exposure in the population study, considering urinary thiocyanate (SCN-) levels.

Exposure to airborne microorganisms, dust and endotoxin during processing of peppermint and chamomile herbs on farms.

PubMed

Skórska, Czesława; Sitkowska, Jolanta; Krysińska-Traczyk, Ewa; Cholewa, Grazyna; Dutkiewicz, Jacek

2005-01-01

The aim of this study was to determine the levels of microorganisms, dust and endotoxin in the air during processing of peppermint (Mentha piperita) and chamomile (Matricaria recutita) by herb farmers, and to examine the species composition of airborne microflora. Air samples were collected on glass fibre filters by use of personal samplers on 13 farms owned by herb cultivating farmers, located in Lublin province (eastern Poland). The concentrations of total viable microorganisms (bacteria + fungi) in the farm air during processing of peppermint herb were large, within a range from 895.1-6,015.8 x 10(3) cfu/m(3) (median 1,055.3 x 10(3) cfu/m(3)). During processing of chamomile herb they were much lower and varied within a range from 0.88-295.6 x 10(3) cfu/m(3) (median 27.3 x 10(3) cfu/m(3)). Gram-negative bacteria distinctly prevailed during processing of peppermint leaves, forming 46.4-88.5 % of the total airborne microflora. During processing of chamomile herb, Gram-negative bacteria were dominant at 3 out of 6 sampling sites forming 54.7-75.3 % of total microflora, whereas at the remaining 3 sites the most common were fungi forming 46.2-99.9 % of the total count. The species Pantoea agglomerans (synonyms: Erwinia herbicola, Enterobacter agglomerans ), having strong allergenic and endotoxic properties, distinctly prevailed among Gram-negative isolates. Among fungi, the most common species was Alternaria alternata. The concentrations of airborne dust and endotoxin determined on the examined herb farms were large. The concentrations of airborne dust during peppermint and chamomile processing ranged from 86.7-958.9 mg/m(3), and from 1.1-499.2 mg/m(3), respectively (medians 552.3 mg/m(3) and 12.3 mg/m(3)). The concentrations of airborne endotoxin determined during peppermint and chamomile processing were within a wide range 1.53-208.33 microg/m(3) and 0.005-2604.19 microg/m(3) respectively (medians 57.3 microg/m(3) and 0.96 microg/m(3)). In conclusion, farmers cultivating peppermint are exposed during processing of this herb to large concentrations of airborne microorganisms, dust and endotoxin posing a risk of work-related respiratory disease. The exposure to bioaerosols during processing of chamomile is lower; nevertheless, peak values create a respiratory risk for exposed farmers.

[Re-analysis of occupational hazards in foundry].

PubMed

Zhang, Min; Qi, Cheng; Chen, Wei-Hong; Lu, Yang; Du, Xie-Yi; Li, Wen-Jie; Meng, Chuan-San

2010-04-01

To analyze systematically the characteristics of occupational hazards in the foundry, and provide precise data for epidemiology studies and control of occupational hazards in the foundry. Data of airborne dust, chemical occupational hazards and physical occupational agents in environment in the foundry from 1978 to 2008 were dynamically collected. Mean concentration and intensity (geometric mean) of occupational hazards were calculated by job in different years. Main occupational hazards in the foundry were silica, metal fume, noise and heat stress. Silica existed in all of main jobs. The mean concentration of silica before 1986 was an extremely high level of 8.6 mg/m(3), and then remarkably dropped after 1986, with the level of 2.4 mg/m(3) from 1986 to 1989, 2.7 mg/m(3) from 1990 to 2002 and 2.7 mg/m(3) from 2003 to 2008. The trend of silica concentrations by job was consistent with that in general. Silica concentrations among jobs were significantly different, with highest level in melting (4.4 mg/m(3)), followed by cast shakeout and finishing (3.4 mg/m(3)), pouring (3.4 mg/m(3)), sand preparation (2.4 mg/m(3)), moulding (2.1 mg/m(3)) and core-making (1.7 mg/m(3)). Concentration of respirable dust in pouring was highest (2.76 mg/m(3)), followed by cast shakeout and finishing (1.14 mg/m(3)). Mean concentration of asbestos dust in melting was a relative high level of 2.0 mg/m(3). In core-making and sand preparation, there existed emission production of adhesive, with mean concentrations as followed, ammonia (5.84 mg/m(3)), formaldehyde (0.60 mg/m(3)), phenol (1.73 mg/m(3)) and phenol formaldehyde resin (1.3 mg/m(3)) also existed. Benzene and its homologues existed in cast shakeout and finishing, and the level of benzene, toluene, xylene was 0.2 mg/m(3), 0.1 mg/m(3) and 1.3 mg/m(3), respectively. In pouring and melting, there existed chemical occupational hazards, including benzo(a) pyrene, metal fume (lead, cadmium, manganese, nickel, chromium) and gas(hydrogen sulfide, phosphine, sulfur dioxide, carbon monoxide). Mean concentration of benzo(a) pyrene was a low level of 1.80 x 10(-4) microg/m(3). Physical occupational agents in the foundry were noise, heat stress and vibration. Intensity of heat stress was high in melting, pouring and cast shakeout and finishing, with the level of 30 degrees C, 29 degrees C and 26 degrees C, respectively. Noise was high in cast shakeout and finishing and core-making, with the level of 93.1 dB(A) and 89.5 dB(A), respectively. Vibration existed in core-making and cast shakeout and finishing. Compulsory postures included long standing, seating and bowing. Occupational hazards in environment of the foundry are diversified and their concentrations exceed permissible exposure limits stipulated by the national occupational hygienic standards. High-concentrations of dust, metal fume, low-concentrations of variety of chemicals, high-intensity of noise and vibration, heat stress, and harmful compulsory posture, and so on all co-exist in the foundry. Control and protective measures should be strengthened.

Initial experience with CMC-544 (inotuzumab ozogamicin) in pediatric patients with relapsed B-cell acute lymphoblastic leukemia.

PubMed

Rytting, Michael; Triche, Lisa; Thomas, Deborah; O'Brien, Susan; Kantarjian, Hagop

2014-02-01

Survival is poor in pediatric patients with relapsed or refractory acute B-cell lymphoblastic leukemia (ALL) and therapeutic options are limited. CMC-544 (inotuzumab ozogamicin) has shown significant activity in adult patients with relapsed and refractory ALL. We evaluated CMC-544 in pediatric patients with multiply relapsed ALL. Five children 4-15 years old with relapsed, CD 22 positive B-cell ALL were enrolled on a phase II non-randomized trial of CMC-544. CMC-544 was initially administered at 1.3 mg/m(2) every 3 weeks. The dose then increased to 1.8 mg/m(2) every 3 weeks. Subsequently, a weekly schedule of CMC-544 given as 0.8 mg/m(2) on day 1 followed by 0.5 mg/m(2) on days 8 and 15 was administered. All five patients had refractory relapsed B-cell ALL. Lymphoblasts for all patients highly expressed CD22. Four patients had two or more relapses before starting the study drug. One patient achieved a complete remission in the bone marrow and normal peripheral counts, and two patients achieved bone marrow morphologic remission with absolute neutrophils >1,000/µl but platelets <100,000/µl. Two patients had no response to the drug. Toxicities consisted of fever, sepsis, and liver enzyme elevation. Single agent CMC-544 given at the single dose of 1.8 mg/m(2) every 3 weeks or given as a split, weekly dose was generally well tolerated considering the inherent risks in this population of patients and showed promising activity in pediatric patients with relapsed and refractory ALL. © 2013 Wiley Periodicals, Inc.

Results of a Long-Term Demonstration of an Optical Multi-Gas Monitor on ISS

NASA Technical Reports Server (NTRS)

Mudgett, Paul; Pilgrim, Jeffrey S.

2015-01-01

Previously at SAMAP we reported on the development of tunable diode laser spectroscopy (TDLS) based instruments for measuring small gas molecules in real time. TDLS technology has matured rapidly over the last 5 years as a result of advances in low power diode lasers as well as better detection schemes. In collaboration with two small businesses Vista Photonics, Inc. and Nanoracks LLC, NASA developed a 4 gas TDLS based monitor for an experimental demonstration of the technology on the International Space Station (ISS). Vista invented and constructed the core TDLS sensor. Nanoracks designed and built the enclosure, and certified the integrated monitor as a payload. The device, which measures oxygen, carbon dioxide, ammonia and water vapor, is called the Multi-Gas Monitor (MGM). MGM measures the 4 gases every few seconds and records a 30 second moving average of the concentrations. The relatively small unit draws only 2.5W. MGM was calibrated at NASA-Johnson Space Center in July 2013 and launched to ISS on a Soyuz vehicle in November 2013. Installation and activation of MGM occurred in February 2014, and the unit has been operating nearly continuously ever since in the Japanese Experiment Module. Data is downlinked from ISS about once per week. Oxygen and carbon dioxide data is compared with that from the central Major Constituents Analyzer. Water vapor data is compared with dew point measurements made by sensors in the Columbus module. The ammonia channel was tested by the crew using a commercial ammonia inhalant. MGM is remarkably stable to date. Results of 18 months of operation are presented and future applications including combustion product monitoring are discussed.

77 FR 13357 - MGM Transport, et al.; Amended Notice of Revised Determination on Reconsideration

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-06

... DEPARTMENT OF LABOR Employment and Training Administration MGM Transport, et al.; Amended Notice of Revised Determination on Reconsideration TA-W-80,420 MGM Transport, 2550 Hickory Blvd., A Subsidiary Of Cf Holding Co. Inc., Lenoir, NC TA-W-80,420H MGM Transport, 501 North County Road, a Subsidiary...

Emission of Carbon Dioxide and Methane from Duckweed Ponds for Stormwater Treatment.

PubMed

Dai, Jingjing; Zhang, Chiqian; Lin, Chung-Ho; Hu, Zhiqiang

2015-09-01

This study determined the greenhouse gas emission from two laboratory-scale duckweed ponds for stormwater treatment. The rate of carbon dioxide (CO2) emission from the two duckweed systems was 1472 ± 721 mg/m(2)·d and 626 ± 234 mg/m(2)·d, respectively. After the removal of duckweeds, CO2 emissions decreased to 492 ± 281 mg/m(2)·d and 395 ± 53 mg/m(2)·d, respectively. The higher CO2 emissions in the duckweed systems were attributed to duckweed biomass decay on the pond soil surface. A thin-film model was able to predict the increasing CO2 concentrations in the closed static chamber during 2 weeks of sampling. The initial methane fluxes from the duckweed systems were 299 ± 74 mg/m(2)·d and 180 ± 91 mg/m(2)·d, respectively. After the removal of duckweeds, the flux increased to 559 ± 215 mg/m(2)·d and 328 ± 114 mg/m(2)·d, respectively.

The structure and DNA-binding properties of Mgm101 from a yeast with a linear mitochondrial genome.

PubMed

Pevala, Vladimír; Truban, Dominika; Bauer, Jacob A; Košťan, Július; Kunová, Nina; Bellová, Jana; Brandstetter, Marlene; Marini, Victoria; Krejčí, Lumír; Tomáška, Ľubomír; Nosek, Jozef; Kutejová, Eva

2016-03-18

To study the mechanisms involved in the maintenance of a linear mitochondrial genome we investigated the biochemical properties of the recombination protein Mgm101 from Candida parapsilosis. We show that CpMgm101 complements defects associated with the Saccharomyces cerevisiae mgm101-1(ts) mutation and that it is present in both the nucleus and mitochondrial nucleoids of C. parapsilosis. Unlike its S. cerevisiae counterpart, CpMgm101 is associated with the entire nucleoid population and is able to bind to a broad range of DNA substrates in a non-sequence specific manner. CpMgm101 is also able to catalyze strand annealing and D-loop formation. CpMgm101 forms a roughly C-shaped trimer in solution according to SAXS. Electron microscopy of a complex of CpMgm101 with a model mitochondrial telomere revealed homogeneous, ring-shaped structures at the telomeric single-stranded overhangs. The DNA-binding properties of CpMgm101, together with its DNA recombination properties, suggest that it can play a number of possible roles in the replication of the mitochondrial genome and the maintenance of its telomeres. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Sequential chemotherapy with dose-dense docetaxel, cisplatin, folinic acid and 5-fluorouracil (TCF-dd) followed by combination of oxaliplatin, folinic acid, 5-fluorouracil and irinotecan (COFFI) in metastatic gastric cancer: results of a phase II trial.

PubMed

Dalla Chiesa, Matteo; Tomasello, Gianluca; Buti, Sebastiano; Rovere, Rodrigo Kraft; Brighenti, Matteo; Lazzarelli, Silvia; Donati, Gianvito; Passalacqua, Rodolfo

2011-01-01

To evaluate a new strategy of two sequential, intensified chemotherapy regimens in metastatic gastric cancer. Chemo-naïve patients with metastatic gastric cancer were enrolled to receive 4 cycles of TCF-dd (docetaxel initially 85 mg/m(2) and cisplatin initially 75 mg/m(2) on day 1 [later modified due to toxicity: 70 and 60 mg/m(2) respectively], l-folinic acid 100 mg/m(2) on days 1 and 2, 5-fluorouracil 400 mg/m(2) bolus and then 600 mg/m(2) as a 22 h continuous infusion on day 1 and 2, every 14 days). Subsequently, patients with CR, PR or SD received 4 cycles of COFFI (oxaliplatin 85 mg/m(2), irinotecan 140 mg/m(2), l-folinic acid 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) on day 1 followed by 2,400 mg/m(2) as a 48 h continuous infusion, every 14 days). In both regimens pegfilgrastim 6 mg subcutaneously on day 3 was included. Forty consecutive patients were enrolled. TCF-dd regimen achieved an ORR of 55% (95% CI, 40-70). Twenty-three patients proceeded to COFFI. After this regimen the ORR was then increased to 60% (95% CI, 45-75). Among the 21 patients treated with TCF-dd after the protocol amendments, main grade 3-4 toxicities were: neutropenia (29%), thrombocytopenia (19%), asthenia (24%) and diarrhea (14%). COFFI caused grade 3-4 neutropenia (all not febrile) and diarrhea in 35% and 17% of patients respectively. A sequential strategy with TCF-dd followed by COFFI is very active and may be of special interest in selected patients.

Computer-aided analysis for the Mechanics of Granular Materials (MGM) experiment, part 2

NASA Technical Reports Server (NTRS)

Parker, Joey K.

1987-01-01

Computer vision based analysis for the MGM experiment is continued and expanded into new areas. Volumetric strains of granular material triaxial test specimens have been measured from digitized images. A computer-assisted procedure is used to identify the edges of the specimen, and the edges are used in a 3-D model to estimate specimen volume. The results of this technique compare favorably to conventional measurements. A simplified model of the magnification caused by diffraction of light within the water of the test apparatus was also developed. This model yields good results when the distance between the camera and the test specimen is large compared to the specimen height. An algorithm for a more accurate 3-D magnification correction is also presented. The use of composite and RGB (red-green-blue) color cameras is discussed and potentially significant benefits from using an RGB camera are presented.

Exposures and their determinants in radiographic film processing.

PubMed

Teschke, Kay; Chow, Yat; Brauer, Michael; Chessor, Ed; Hirtle, Bob; Kennedy, Susan M; Yeung, Moira Chan; Ward, Helen Dimich

2002-01-01

Radiographers process X-ray films using developer and fixer solutions that contain chemicals known to cause or exacerbate asthma. In a study in British Columbia, Canada, radiographers' personal exposures to glutaraldehyde (a constituent of the developer chemistry), acetic acid (a constituent of the fixer chemistry), and sulfur dioxide (a byproduct of sulfites, present in both developer and fixer solutions) were measured. Average full-shift exposures to glutaraldehyde, acetic acid, and sulfur dioxide were 0.0009 mg/m3, 0.09 mg/m3, and 0.08 mg/m3, respectively, all more than one order of magnitude lower than current occupational exposure limits. Local exhaust ventilation of the processing machines and use of silver recovery units lowered exposures, whereas the number of films processed per machine and the time spent near the machines increased exposures. Personnel in clinic facilities had higher exposures than those in hospitals. Private clinics were less likely to have local exhaust ventilation and silver recovery units. Their radiographers spent more time in the processor areas and processed more films per machine. Although exposures were low compared with exposure standards, there are good reasons to continue practices to minimize or eliminate exposures: glutaraldehyde and hydroquinone (present in the developer) are sensitizers; the levels at which health effects occur are not yet clearly established, but appear to be lower than current standards; and health effects resulting from the mixture of chemicals are not understood. Developments in digital imaging technology are making available options that do not involve wet-processing of photographic film and therefore could eliminate the use of developer and fixer chemicals altogether.

[Dust concentration analysis in non-coal mining. Exposure evaluation based on measurements performed by occupational hygiene laboratories in the years 2001-2005 in Poland].

PubMed

Bujak-Pietrek, Stella; Mikołajczyk, Urszula; Szadkowska-Stańczyk, Irena

2011-01-01

Non-coal mining includes the extraction of materials for construction (stone, gravel, sand and clay), chemical industry (salt and sulfur), metallurgy (metal ores, uranium and thorium) and other mining and quarrying. Regardless of the type of mining company one of the most common health hazards in this sector is exposure to high concentrations of dust occurring during the extraction of materials. Such activities as drilling, use of blasting agents, processing of raw material, its transportation and loading are the source of large amounts of dust containing crystalline silica. Data on exposure to dust, collected by industrial hygiene laboratories on the basis of dust concentration measurements in the work environment, were obtained from the sanitary inspection service. The analysis of dust concentrations at workplaces in non-coal mining covered the years 2001-2005. The average concentration of inhalable and respirable dust and the degree of results dispersion at workposts in different branches of non-coal mining (according to NACE rev1.1) were evaluated. Also there was estimated the percentage of surveys indicating dust concentrations above hygiene standards. Almost 5000 measurements of dust concentrations were performed in the years under study. The highest concentration of inhalable dust was noted for the production of salt (5.51 mg/m3), other mining and quarrying (4.30 mg/m3) and quarrying of slate (3.77 mg/m3). For respirable dust the highest concentrations were noted in other mining and quarrying (1.10 mg/m3), quarrying of slate (1.09 mg/m3) and quarrying of stone (0.81 mg/m3). Exposure to high concentrations of dust during the extraction of non-carbon is still an important hazard to human health. Almost for all workposts under study the excess of hygiene standards were observed.

Preparation of Diatomite Supported Nano Zinc Oxide Composite Photocatalytic Material and Study on its Formaldehyde Degradation

NASA Astrophysics Data System (ADS)

Xiao, Liguang; Pang, Bo

2017-09-01

This experiment used zinc nitrate as precursor, ethanol as solvent and polyethylene glycol as dispersant, diatomite as carrier, diatomite loaded nano Zinc Oxide was prepared by sol-gel method, in addition, the formaldehyde degradation was studied by two kinds of experimental methods: preparation and loading, preparation and post loading, The samples were characterized by SEM, XRD, BET and IR. Experimental results showed that: Diatomite based nano Zinc Oxide had a continuous adsorption and degradation of formaldehyde, formaldehyde gas with initial concentration was 0.7mg/m3, after 36h degradation, the concentration reached 0.238mg/m3, the degradation rate reached to 66%.

Mgm101p Is a Novel Component of the Mitochondrial Nucleoid That Binds DNA and Is Required for the Repair of Oxidatively Damaged Mitochondrial DNA

PubMed Central

Meeusen, Shelly; Tieu, Quinton; Wong, Edith; Weiss, Eric; Schieltz, David; Yates, John R.; Nunnari, Jodi

1999-01-01

Maintenance of mitochondrial DNA (mtDNA) during cell division is required for progeny to be respiratory competent. Maintenance involves the replication, repair, assembly, segregation, and partitioning of the mitochondrial nucleoid. MGM101 has been identified as a gene essential for mtDNA maintenance in S. cerevisiae, but its role is unknown. Using liquid chromatography coupled with tandem mass spectrometry, we identified Mgm101p as a component of highly enriched nucleoids, suggesting that it plays a nucleoid-specific role in maintenance. Subcellular fractionation, indirect immunofluorescence and GFP tagging show that Mgm101p is exclusively associated with the mitochondrial nucleoid structure in cells. Furthermore, DNA affinity chromatography of nucleoid extracts indicates that Mgm101p binds to DNA, suggesting that its nucleoid localization is in part due to this activity. Phenotypic analysis of cells containing a temperature sensitive mgm101 allele suggests that Mgm101p is not involved in mtDNA packaging, segregation, partitioning or required for ongoing mtDNA replication. We examined Mgm101p's role in mtDNA repair. As compared with wild-type cells, mgm101 cells were more sensitive to mtDNA damage induced by UV irradiation and were hypersensitive to mtDNA damage induced by gamma rays and H2O2 treatment. Thus, we propose that Mgm101p performs an essential function in the repair of oxidatively damaged mtDNA that is required for the maintenance of the mitochondrial genome. PMID:10209025

Semen quality of workers occupationally exposed to hydrocarbons.

PubMed

De Celis, R; Feria-Velasco, A; González-Unzaga, M; Torres-Calleja, J; Pedrón-Nuevo, N

2000-02-01

To determine whether occupational exposure of men to hydrocarbons has adverse effects on the quality of their semen. Comparative study. The rubber industry in Mexico City. Forty-eight workers who were exposed to hydrocarbons for 2-24 years and 42 unexposed workers. None. Environmental hydrocarbon concentrations were determined by continuous air monitoring in all areas of the factory. Analyses of semen samples were performed in accordance with World Health Organization criteria. Hydrocarbon concentrations were as follows: ethylbenzene, 220.7-234 mg/m3; benzene, 31.9-47.8 mg/m3; toluene, 189.7-212.5 mg/m3; and xylene, 47-56.4 mg/m3. The number of subjects with ejaculates that had normal characteristics was greater in the unexposed group (76%) than in the exposed group (17%). More abnormal characteristics were found in the semen of exposed workers than unexposed workers, including alterations in viscosity, liquefaction capacity, sperm count, sperm motility, and the proportion of sperm with normal morphology. Some abnormal characteristics correlated with the number of years of exposure to the hydrocarbons. Damage to the spermatogenic process resulting from hydrocarbon exposure was demonstrated by an increased rate of abnormalities in the semen of exposed workers compared with unexposed workers. This information may be useful for conducting future analyses of reproductive risks related to exposure to high concentrations of hydrocarbons.

Exposure of bakery and pastry apprentices to airborne flour dust using PM2.5 and PM10 personal samplers.

PubMed

Mounier-Geyssant, Estelle; Barthélemy, Jean-François; Mouchot, Lory; Paris, Christophe; Zmirou-Navier, Denis

2007-11-01

This study describes exposure levels of bakery and pastry apprentices to flour dust, a known risk factor of occupational asthma. Questionnaires on work activity were completed by 286 students. Among them, 34 performed a series of two personal exposure measurements using a PM2.5 and PM10 personal sampler during a complete work shift, one during a cold ("winter") period, and the other during a hot ("summer") period. Bakery apprentices experience greater average PM2.5 and PM10 exposures than pastry apprentices (p < 0.006). Exposure values for both particulate fractions are greater in winter (average PM10 values among bakers = 1.10 mg.m-3 [standard deviation: 0.83]) than in summer (0.63 mg.m-3 [0.36]). While complying with current European occupational limit values, these exposures exceed the ACGIH recommendations set to prevent sensitization to flour dust (0.5 mg.m-3). Over half the facilities had no ventilation system. Young bakery apprentices incur substantial exposure to known airways allergens, a situation that might elicit early induction of airways inflammation.

Customer exposure to MTBE, TAME, C6 alkyl methyl ethers, and benzene during gasoline refueling.

PubMed

Vainiotalo, S; Peltonen, Y; Ruonakangas, A; Pfäffli, P

1999-02-01

We studied customer exposure during refueling by collecting air samples from customers' breathing zone. The measurements were carried out during 4 days in summer 1996 at two Finnish self-service gasoline stations with "stage I" vapor recovery systems. The 95-RON (research octane number) gasoline contained approximately 2.7% methyl tert-butyl ether (MTBE), approximately 8.5% tert-amyl methyl ether (TAME), approximately 3.2% C6 alkyl methyl ethers (C6 AMEs), and 0.75% benzene. The individual exposure concentrations showed a wide log-normal distribution, with low exposures being the most frequent. In over 90% of the samples, the concentration of MTBE was higher (range <0.02-51 mg/m3) than that of TAME. The MTBE values were well below the short-term (15 min) threshold limits set for occupational exposure (250-360 mg/m3). At station A, the geometric mean concentrations in individual samples were 3.9 mg/m3 MTBE and 2. 2 mg/m3 TAME. The corresponding values at station B were 2.4 and 1.7 mg/m3, respectively. The average refueling (sampling) time was 63 sec at station A and 74 sec at station B. No statistically significant difference was observed in customer exposures between the two service stations. The overall geometric means (n = 167) for an adjusted 1-min refueling time were 3.3 mg/m3 MTBE and 1.9 mg/m3 TAME. Each day an integrated breathing zone sample was also collected, corresponding to an arithmetic mean of 20-21 refuelings. The overall arithmetic mean concentrations in the integrated samples (n = 8) were 0.90 mg/m3 for benzene and 0.56 mg/m3 for C6 AMEs calculated as a group. Mean MTBE concentrations in ambient air (a stationary point in the middle of the pump island) were 0.16 mg/m3 for station A and 0.07 mg/m3 for station B. The mean ambient concentrations of TAME, C6 AMEs, and benzene were 0.031 mg/m3, approximately 0.005 mg/m3, and approximately 0.01 mg/m3, respectively, at both stations. The mean wind speed was 1.4 m/sec and mean air temperature was 21 degreesC. Of the gasoline refueled during the study, 75% was 95 grade and 25% was 98/99 grade, with an oxygenate (MTBE) content of 12.2%.

Customer exposure to MTBE, TAME, C6 alkyl methyl ethers, and benzene during gasoline refueling.

PubMed Central

Vainiotalo, S; Peltonen, Y; Ruonakangas, A; Pfäffli, P

1999-01-01

We studied customer exposure during refueling by collecting air samples from customers' breathing zone. The measurements were carried out during 4 days in summer 1996 at two Finnish self-service gasoline stations with "stage I" vapor recovery systems. The 95-RON (research octane number) gasoline contained approximately 2.7% methyl tert-butyl ether (MTBE), approximately 8.5% tert-amyl methyl ether (TAME), approximately 3.2% C6 alkyl methyl ethers (C6 AMEs), and 0.75% benzene. The individual exposure concentrations showed a wide log-normal distribution, with low exposures being the most frequent. In over 90% of the samples, the concentration of MTBE was higher (range <0.02-51 mg/m3) than that of TAME. The MTBE values were well below the short-term (15 min) threshold limits set for occupational exposure (250-360 mg/m3). At station A, the geometric mean concentrations in individual samples were 3.9 mg/m3 MTBE and 2. 2 mg/m3 TAME. The corresponding values at station B were 2.4 and 1.7 mg/m3, respectively. The average refueling (sampling) time was 63 sec at station A and 74 sec at station B. No statistically significant difference was observed in customer exposures between the two service stations. The overall geometric means (n = 167) for an adjusted 1-min refueling time were 3.3 mg/m3 MTBE and 1.9 mg/m3 TAME. Each day an integrated breathing zone sample was also collected, corresponding to an arithmetic mean of 20-21 refuelings. The overall arithmetic mean concentrations in the integrated samples (n = 8) were 0.90 mg/m3 for benzene and 0.56 mg/m3 for C6 AMEs calculated as a group. Mean MTBE concentrations in ambient air (a stationary point in the middle of the pump island) were 0.16 mg/m3 for station A and 0.07 mg/m3 for station B. The mean ambient concentrations of TAME, C6 AMEs, and benzene were 0.031 mg/m3, approximately 0.005 mg/m3, and approximately 0.01 mg/m3, respectively, at both stations. The mean wind speed was 1.4 m/sec and mean air temperature was 21 degreesC. Of the gasoline refueled during the study, 75% was 95 grade and 25% was 98/99 grade, with an oxygenate (MTBE) content of 12.2%. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9924009

Determinants of dust exposure in tunnel construction work.

PubMed

Bakke, Berit; Stewart, Patricia; Eduard, Wijnand

2002-11-01

In tunnel construction work, dust is generated from rock drilling, rock bolting, grinding, scaling, and transport operations. Other important dust-generating activities are blasting rock and spraying wet concrete on tunnel walls for strength and finishing work. The aim of this study was to identify determinants of dust exposure in tunnel construction work and to propose control measures. Personal exposures to total dust, respirable dust, and alpha-quartz were measured among 209 construction workers who were divided into 8 job groups performing similar tasks: drill and blast workers, shaft drilling workers, tunnel boring machine workers, shotcreting operators, support workers, concrete workers, outdoor concrete workers, and electricians. Information on determinants was obtained from interviewing the workers, observation by the industrial hygienist responsible for the sampling, and the job site superintendent. Multivariate regression models were used to identify determinants associated with the dust exposures within the job groups. The geometric mean exposure to total dust, respirable dust, and alpha-quartz for all tunnel workers was 3.5 mg/m(3) (GSD = 2.6), 1.2 mg/m(3) (GSD = 2.4), and 0.035 mg/m(3) (GSD = 5.0), respectively. A total of 15 percent of the total dust measurements, 5 percent of the respirable dust, and 21 percent of the alpha-quartz exceeded the Norwegian OELs of 10 mg/m(3), 5 mg/m(3), and 0.1 mg/m(3), respectively. Job groups with highest geometric mean total dust exposure were shotcreting operators (6.8 mg/m(3)), tunnel boring machine workers (6.2 mg/m(3)), and shaft drilling workers (6.1 mg/m(3)). The lowest exposed groups to total dust were outdoor concrete workers (1.0 mg/m(3)), electricians (1.4 mg/m(3)), and support workers (1.9 mg/m(3)). Important determinants of exposure were job group, job site, certain tasks (e.g., drilling and scaling), the presence of a cab, and breakthrough of the tunnel. The use of ventilated, closed cabs appeared to be the single most important control measure for lowering exposures.

Mechanics of Granular Materials (MGM) Test Cell

NASA Technical Reports Server (NTRS)

2004-01-01

Test cells comprise specimen sand contained in a latex membrane (with a grid pattern for CCD cameras) between metal end plates and housed in a water-filled Lexan jacket. Experiment flown on STS-79 and STS-89. Principal Investigator: Dr. Stein Sture.

Decomposition of mixed malodorants in a wire-plate pulse corona reactor.

PubMed

Shi, Y; Ruan, J; Wang, X; Li, W; Tan, T

2005-09-01

Decomposition characteristics of two groups of representative mixed malodorants (1, ethanethiol + hydrogen sulfide; 2, ethanethiol + ammonia) in air were investigated employing a wire-plate pulse corona reactor. A new type of high-voltage pulse generator with a thyratron switch and a Blumlein pulse-forming network (BPFN) was used in our experiments. The experiments were conducted at a gas-flow rate of 13 m3/h. Important parameters, including peak voltage, chemical structures of malodorants, pulse frequency, and initial concentration, which influenced the removal efficiency, were investigated. The results showed that the mixed malodorants could be treated effectively by pulse corona. The removal efficiencies of 200 mg/m3 C2H5SH and 200 mg/m3 H2S for group 1 were 95.6% and 100%, respectively, which were almost equal to those of the two pollutants separately. The energy cost was about 65.1-81.4 J/L, which was 31.5-45.2% lower than for treating pollutants alone. The removal efficiencies of 105 mg/m3 C2HsSH and 40 mg/m3 NH3 for group 2 were 93.1% and almost 100%, and the energy cost was 65.1 J/L, 55.6% lower than that which was treated separately. In the case of two groups of mixed malodorants removal, NOx, 03, SO2, CO2, and CO were all observed. Moreover, some sulfur and white crystal ammonium nitrates were discovered adhering to the corona wires in the removal of groups 1 and 2, respectively. A dynamics model was developed to describe the relation of the removal efficiency with specific energy density and initial concentration. In the case of group 1 removal,the decomposition rate constants decreased as compared to the single treating. As for group 2 removal, the decomposition rate constants increased, especially for NH3. According to the results, the optimization design for the reactor and the matching of high pulse voltage source can be reckoned.

Case cluster of pneumoconiosis at a coal slag processing facility.

PubMed

Fagan, Kathleen M; Cropsey, Erin B; Armstrong, Jenna L

2015-05-01

During an inspection by the Occupational Safety and Health Administration (OSHA) of a small coal slag processing plant with 12 current workers, four cases of pneumoconiosis were identified among former workers. The OSHA investigation consisted of industrial hygiene sampling, a review of medical records, and case interviews. Some personal sampling measurements exceeded the OSHA Permissible Exposure Limit (PEL) for total dust exposures of 15 mg/m(3), and the measured respirable silica exposure of 0.043 mg/m(3), although below OSHA's current PEL for respirable dust containing silica, was above the American Conference of Governmental Industrial Hygienists' Threshold Limit Value (TLV). Chest x-rays for all four workers identified small opacities consistent with pneumoconiosis. This is the first known report of lung disease in workers processing coal slag and raises concerns for workers exposed to coal slag dust. © 2015 Wiley Periodicals, Inc.

The impact of total suspended particulate concentration on workers’ health at ceramic industry

NASA Astrophysics Data System (ADS)

Sintorini, M. M.

2018-01-01

Ceramic production process pollutes the air with particulate matter at high concentration and has negative impact on the workers. The objective of this research was to determine the particulate concentration in the air and to analyse its impact on the workers. This research used cross sectional method to correlate the particulate concentration, temperature, humidity, smoke level and level of workers’ compliance with safety regulations. Sampling was conducted from April to May 2012 in three locations, i.e. exposure area (Mass Preparation I, II) and non-exposure area (Forming area). In the exposure area (Mass Preparation I and II) where the particulate concentrations were 22.3673 mg/m3 and 14.8277 mg/m3, and 58.33%, the workers had bad health status. In the non-exposure area, where the particulate concentration was 3.2185 mg/m3 and 25% the workers had bad health status. The Odds Ratio among the workers in exposure area was 4.2 times higher than the workers in the non-exposure area.

Assessment of occupational exposure to gaseous peracetic acid.

PubMed

Dugheri, Stefano; Bonari, Alessandro; Pompilio, Ilenia; Colpo, Marco; Montalti, Manfredi; Mucci, Nicola; Arcangeli, Giulio

2018-02-07

In order to assess short-term exposure to peracetic acid (PAA) in disinfection processes, the Authors compared 4 industrial hygiene monitoring methods to evaluate their proficiency in measuring airborne PAA concentrations. An active sampling by basic silica gel impregnated with methyl p-tolyl sulfoxide (MTSO), a passive solid phase micro-extraction technique using methyl p-tolyl sulfide (MTS) as on-fiber derivatization reagent, an electrochemical direct-reading PAA monitor, and a novel visual test strip PAA detector doped with 2,2'-azino-bis (3-ethylbenzothiazoline)-6-sulfonate were evaluated and tested over the range of 0.06-16 mg/m3, using dynamically generated PAA air concentrations. The linear regression analysis of linearity and accuracy showed that the 4 methods were suitable for PAA monitoring. Peracetic acid monitoring in several use applications showed that the PAA concentration (1.8 mg/m3) was immediately dangerous to life or health as proposed by the National Institute of Occupational Safety and Health, and was frequently exceeded in wastewater treatment (up to 7.33 mg/m3), and sometimes during food and beverage processes and hospital high-level disinfection operations (up to 6.8 mg/m3). The methods were suitable for the quick assessment of acute exposure in PAA environmental monitoring and can assist in improving safety and air quality in the workplace where this disinfectant is used. These monitoring methods allowed the evaluation of changes to work out practices to reduce PAA vapor concentrations during the operations when workers are potentially overexposed to this strong antioxidant agent. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Dust exposure during small-scale mining in Tanzania: a pilot study.

PubMed

Bratveit, Magne; Moen, Bente E; Mashalla, Yohana J S; Maalim, Hatua

2003-04-01

Small-scale mining in developing countries is generally labour-intensive and carried out with low levels of mechanization. In the Mererani area in the northern part of Tanzania, there are about 15000 underground miners who are constantly subjected to a poor working environment. Gemstones are found at depths down to 500 m. The objectives of this pilot study were to monitor the exposure to dust during work processes, which are typical of small-scale mining in developing countries, and to make a rough estimation of whether there is a risk of chronic pulmonary diseases for the workers. Personal sampling of respirable dust (n = 15) and 'total' dust (n = 5) was carried out during three consecutive days in one mine, which had a total of 50 workers in two shifts. Sampling started immediately before the miners entered the shaft, and lasted until they reappeared at the mine entrance after 5-8 h. The median crystalline silica content and the combustible content of the respirable dust samples were 14.2 and 5.5%, respectively. When drilling, blasting and shovelling were carried out, the exposure measurements showed high median levels of respirable dust (15.5 mg/m(3)), respirable crystalline silica (2.4 mg/m(3)), respirable combustible dust (1.5 mg/m(3)) and 'total' dust (28.4 mg/m(3)). When only shovelling and loading of sacks took place, the median exposures to respirable dust and respirable crystalline silica were 4.3 and 1.1 mg/m(3). This study shows that the exposure to respirable crystalline silica was high during underground small-scale mining. In the absence of personal protective equipment, the miners in the Mererani area are presumably at a high risk of developing chronic silicosis.

[Preparation of ibuprofen/EC-PVP sustained-release composite particles by supercritical CO2 anti-solvent technology].

PubMed

Cai, Jin-Yuan; Huang, De-Chun; Wang, Zhi-Xiang; Dang, Bei-Lei; Wang, Qiu-Ling; Su, Xin-Guang

2012-06-01

Ibuprofen/ethyl-cellulose (EC)-polyvinylpyrrolidone (PVP) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading as the main evaluation index, orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles. The experiments such as encapsulation efficiency, particle size distribution, electron microscope analysis, infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 40 degrees C, crystallization pressure 12 MPa, PVP concentration 4 mgmL(-1), and CO2 velocity 3.5 Lmin(-1). Under the optimal conditions, the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%, and the average particle size of the particles was 27.621 microm. IR and DSC analysis showed that PVP might complex with EC. The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect. Experiment results showed that, ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in mice.

PubMed

Roberts, L G; Gray, T M; Marr, M C; Tyl, R W; Trimmer, G W; Hoffman, G M; Murray, F J; Clark, C R; Schreiner, C A

2014-11-01

CD-1 mice were exposed to baseline gasoline vapor condensate (BGVC) alone or to vapors of gasoline blended with methyl tertiary butyl ether (G/MTBE). Inhalation exposures were 6h/d on GD 5-17 at levels of 0, 2000, 10,000, and 20,000mg/m(3). Dams were evaluated for evidence of maternal toxicity, and fetuses were weighed, sexed, and evaluated for external, visceral, and skeletal anomalies. Exposure to 20,000mg/m(3) of BGVC produced slight reductions in maternal body weight/gain and decreased fetal body weight. G/MTBE exposure did not produce statistically significant maternal or developmental effects; however, two uncommon ventral wall closure defects occurred: gastroschisis (1 fetus at 10,000mg/m(3)) and ectopia cordis (1 fetus at 2000mg/m(3); 2 fetuses/1 litter at 10,000mg/m(3)). A second study (G/MTBE-2) evaluated similar exposure levels on GD 5-16 and an additional group exposed to 30,000mg/m(3) from GD 5-10. An increased incidence of cleft palate was observed at 30,000mg/m(3) G/MTBE. No ectopia cordis occurred in the replicate study, but a single observation of gastroschisis was observed at 30,000mg/m(3). The no observed adverse effect levels for maternal/developmental toxicity in the BGVC study were 10,000/2000mg/m(3), 20,000/20,000 for the G/MTBE study, and 10,000/20,000 for the G/MTBE-2 study. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Elemental properties of coal slag and measured airborne exposures at two coal slag processing facilities

PubMed Central

Mugford, Christopher; Boylstein, Randy; Gibbs, Jenna L

2017-01-01

In 1974, the National Institute for Occupational Safety and Health recommended a ban on the use of silica sand abrasives containing >1% silica due to the risk of silicosis. This gave rise to substitutes including coal slag. An Occupational Safety and Health Administration investigation in 2010 uncovered a case cluster of suspected pneumoconiosis in four former workers at a coal slag processing facility in Illinois, possibly attributable to occupational exposure to coal slag dust. This article presents the results from a National Institute for Occupational Safety and Health industrial hygiene survey at the same coal slag processing facility and a second facility. The industrial hygiene survey consisted of the collection of: a) bulk samples of unprocessed coal slag, finished granule product, and settled dust for metals and silica; b) full-shift area air samples for dust, metals, and crystalline silica; and c) full-shift personal air samples for dust, metals, and crystalline silica. Bulk samples consisted mainly of iron, manganese, titanium, and vanadium. Some samples had detectable levels of arsenic, beryllium, cadmium, and cobalt. Unprocessed coal slags from Illinois and Kentucky contained 0.43–0.48% (4,300–4,800 mg/kg) silica. Full-shift area air samples identified elevated total dust levels in the screen (2–38 mg/m3) and bag house (21 mg/m3) areas. Full-shift area air samples identified beryllium, chromium, cobalt, copper, iron, nickel, manganese, and vanadium. Overall, personal air samples for total and respirable dust (0.1–6.6 mg/m3 total; and 0.1–0.4 mg/m3 respirable) were lower than area air samples. All full-shift personal air samples for metals and silica were below published occupational exposure limits. All bulk samples of finished product granules contained less than 1% silica, supporting the claim coal slag may present less risk for silicosis than silica sand. We note that the results presented here are solely from two coal slag processing facilities, and more in-depth air monitoring is needed to better characterize occupational exposure to coal slag dust, metals, and silica at similar facilities. PMID:27808662

A modified micrometeorological gradient method for estimating O3 dry depositions over a forest canopy

NASA Astrophysics Data System (ADS)

Wu, Z. Y.; Zhang, L.; Wang, X. M.; Munger, J. W.

2015-07-01

Small pollutant concentration gradients between levels above a plant canopy result in large uncertainties in estimated air-surface exchange fluxes when using existing micrometeorological gradient methods, including the aerodynamic gradient method (AGM) and the modified Bowen ratio method (MBR). A modified micrometeorological gradient method (MGM) is proposed in this study for estimating O3 dry deposition fluxes over a forest canopy using concentration gradients between a level above and a level below the canopy top, taking advantage of relatively large gradients between these levels due to significant pollutant uptake in the top layers of the canopy. The new method is compared with the AGM and MBR methods and is also evaluated using eddy-covariance (EC) flux measurements collected at the Harvard Forest Environmental Measurement Site, Massachusetts, during 1993-2000. All three gradient methods (AGM, MBR, and MGM) produced similar diurnal cycles of O3 dry deposition velocity (Vd(O3)) to the EC measurements, with the MGM method being the closest in magnitude to the EC measurements. The multi-year average Vd(O3) differed significantly between these methods, with the AGM, MBR, and MGM method being 2.28, 1.45, and 1.18 times that of the EC, respectively. Sensitivity experiments identified several input parameters for the MGM method as first-order parameters that affect the estimated Vd(O3). A 10% uncertainty in the wind speed attenuation coefficient or canopy displacement height can cause about 10% uncertainty in the estimated Vd(O3). An unrealistic leaf area density vertical profile can cause an uncertainty of a factor of 2.0 in the estimated Vd(O3). Other input parameters or formulas for stability functions only caused an uncertainly of a few percent. The new method provides an alternative approach to monitoring/estimating long-term deposition fluxes of similar pollutants over tall canopies.

[Growth of wheat from seed-to-seed in space flight

NASA Technical Reports Server (NTRS)

Levinskikh, M. A.; Sychev, V. N.; Derendiaeva, T. A.; Signalova, O. B.; Podol'skii, I. G.; Padalka, G. I.; Avdeev, S. V.; Bingham, G. E.; Campbell, W. F. (Principal Investigator)

2000-01-01

In our earlier space experiment with super dwarf wheat we found the spikes developed in space to be barren. The cause of the full crop sterility was sensitivity of this wheat species to the ethylene concentration of 0.3-0.8 mg/m3 during the experiment. The follow-up ground experiments were made to identify species of dwarf wheat that could be raised in space greenhouse Svet and are distinguished by partial tolerance of their reproductive organs to elevated ethylene in air. The choice fell on the USU-Apogee cultivar specially developed for planting in growth chambers as an integral part of various bioregenerative life support systems, including the space ones. An experiment with wheat Apogee was performed in greenhouse Svet on board MIR. The period of the full crop vegetation cycle was not significantly altered under the spaceflight conditions. The experiment yielded 508 seeds from 12 plants, i.e. by 38% less than in laboratory experiments and by 69% more as compared with results of growing crops in ethylene-contaminated atmosphere (1 mg/m3). Mass of the space seeds was low if compared with the laboratory crops. This was the first time when the feasibility of gathering seeds from wheat that had passed the whole vegetation cycle in space flight was demonstrated. The experiment will give mightly impetus to the advancement of research on space biological LSS and gravitational biology.

Occupational exposure to styrene in the fibreglass reinforced plastic industry: comparison between two different manufacturing processes.

PubMed

Tranfo, Giovanna; Gherardi, Monica; Paci, E; Gatto, Mariapia; Gordiani, A; Caporossi, Lidia; Capanna, Silvia; Sisto, Renata; Papaleo, B; Fiumalbi, Carla; Garofani, Patrizia

2012-01-01

Styrene is used in manufacturing fiberglass reinforced plastics: and occupational exposure was related to neurotoxicology and genotoxicity. The sum of the metabolites mandelic and phenylglyoxylic acids is the ACGIH biomarker for occupational exposure with a BEI of 400 mg/g of creatinine in end shift urine corresponding to a airborne styrene concentration of 85 mg/m3. There are two main molding processes, open and closed, the last more effective at controlling worker's styrene exposure. To compare the open molding process to the compression of fiber reinforced resin foils, a kind of closed molding, monitoring the styrene exposure of workers in two production sites (A and B). Environmental Monitoring was carried out by Radiello samplers and Biological Monitoring by means of the determination of MA and PGA with HPLC/MS/MS in 10 workers at Site A and 14 at Site B. The median values for styrene exposure resulted 31.1 mg/m3 for Site A and 24.4 mg/m for Site B, while the medians for the sum of the two metabolites in the end shift urine were 86.7 e 33.8 mg/g creatinine respectively. There is a significant linear correlation between personal styrene exposure and the excretion of styrene metabolites (R = 0.74). As expected the exposure markers of the workers of the two production sites resulted higher in the open process. The analytical results of both environmental and biological monitoring were all below the occupational exposure limits, confirming the efficacy of the protective devices.

Effects of hydrodynamics processes on phosphorus fluxes from sediment in large, shallow Taihu Lake.

PubMed

You, Ben-Sheng; Zhong, Ji-Cheng; Fan, Cheng-Xin; Wang, Tong-Cheng; Zhang, Lu; Ding, Shi-Ming

2007-01-01

The turnover of phosphorus (P) in lake sediments, a major cause of eutrophication and subsequent deterioration of water quality, is in need of deep understanding. In this study, effects of resuspension on P release were studied in cylindrical microcosms with Y-shape apparatus. The results indicated that there was a positive correlation between flux of suspended substance across sediment-water interface (F(SS)) and the wind speed, and an increasing F(SS) during each wind process followed by a steady state. The maximal F(SS) under light, moderate, and strong wind conditions were 299.9 +/- 41.1, 573.4 +/- 61.7, and 2093.8 +/- 215.7 g/m2, respectively. However, flux of P across sediment-water interface (F(P)) did not follow a similar pattern as F(SS) responding to wind intensity, which increased and reached the maximum in initial 120 min for light wind, then decreased gradually, with maximal flux of 9.4 +/- 1.9 mg/m2. A rapid increase of F(P) at the first 30 min was observed under moderate wind, with maximal flux of 11.2 +/- 0.6 mg/m2. Surprisingly, strong wind caused less F(P) than under light and moderate wind conditions with maximal flux of 3.5 +/- 0.9 mg/m2. F(SS) in water column declined obviously during the sedimentation process after winds, but F(P) varied with wind regime. No obvious difference was detected on F(P) after 8 h sedimentation process, compared with the initial value, which means little redundant P left in the water column after winds.

[Dynamic monitoring and analysis of occupational hazards in working environment of foundry plant from 1987 to 2010].

PubMed

Lu, Yang; Zhang, Min; Chen, Wei-hong; Qi, Cheng

2013-08-01

To investigate the characteristics and changing trend of occupational hazards in the working environment of a foundry plant from 1987 to 2010. The foundry plant of a large-scale automobile company in Hubei Province, China was chosen as the study site. The data on occupational hazards in the working environment of the foundry plant in the past years were collected, and additional measurements were performed. The means and geometric means of the concentrations of occupational hazards were calculated. The characteristics and changing trend of occupational hazards from 1987 to 2010 were presented. There were dust, chemical, and physical occupational hazards in the working environment of the foundry plant, with silica dust, noise, and heat stress as the main ones. Dust, mainly silica dust, is found in all aspects of foundry. The mean concentration of silica dust was high (3.2∼8.2 mg/m(3)), exceeding the national occupational exposure limit (1 mg/m(3)). The mean concentrations of silica dust varied across different types of work, with higher levels in cast shakeout and finishing, overhead crane operation, and sand preparation. The mean concentration of respirable dust in the foundry plant was low (0.38 mg/m(3)), not exceeding the national occupational exposure limit (0.7 mg/m(3)). There were high concentrations of grinding wheel dust (10.6 mg/m(3)) and welding fume (5.7 mg/m(3)) in cast shakeout and finishing, exceeding the national occupational exposure limit (8 and 4 mg/m(3)). Coal dust was mainly found in melting as well as cast shakeout and finishing, with higher concentration in the former (4.7 mg/m(3). The main chemical occupational hazard in the environment of the foundry plant was formaldehyde (1.23 mg/m(3)), exceeding the national occupational exposure limit (0.5 mg/m(3)). The concentrations of ammonia, phenol, metal fume, sulfur dioxide, hydrogen sulfide, and phosphine in the foundry plant were low. The mean concentration of polycyclic aromatic hydrocarbons was 0.1405 µg/m(3), with a higher level in pouring. The main physical occupational hazards in the working environment of the foundry plant were noise and heat stress. Noise, mainly steady noise, was distributed in all workshops of the foundry plant, with a mean intensity of 85.1 db (A). Noise levels varied across different types of work, higher in cast shakeout and finishing (89.3 db (A)) and moulding (85.4 db (A)). Heat stress mainly existed in overhead crane operation (35.1°C), pouring (33.3°C), and melting (32.8°C). Dust, chemical, and physical occupational hazards co-existed in the working environment of the foundry plant. High concentration of dust was widely distributed in many workshops and across many types of work, but the dust concentration showed a downward trend. Chemical occupational hazards included ammonia, phenol, hydrogen sulfide, and metal fume, most at low concentrations. High-intensity noise was widely distributed in all working positions of foundry process and mainly from equipment operation, collision between parts, and gas injection. High-intensity heat stress mainly existed in overhead crane operation, pouring, and melting.

Toxicological assessment of green petroleum coke.

PubMed

McKee, Richard H; Herron, Deborah; Beatty, Patrick; Podhasky, Paula; Hoffman, Gary M; Swigert, James; Lee, Carol; Wong, Diana

2014-01-01

Green petroleum coke is primarily inorganic carbon with some entrained volatile hydrocarbon material. As part of the petroleum industry response to the high production volume challenge program, the potential for reproductive effects was assessed in a subchronic toxicity/reproductive toxicity screening test in rats (OECD 421). The repeated-dose portion of the study provided evidence for dust accumulation and inflammatory responses in rats exposed to 100 and 300 mg/m(3) but there were no effects at 30 mg/m(3). In the reproductive toxicity screen, the frequency of successful matings was reduced in the high exposure group (300 mg/m(3)) and was not significantly different from control values but was outside the historical experience of the laboratory. The postnatal observations (external macroscopic examination, body weight, and survival) did not indicate any treatment-related differences. Additional tests conducted to assess the potential hazards to aquatic (fish, invertebrates, and algae) and soil dwelling organisms (earthworms and vascular plants) showed few effects at the maximum loading rates of 1000 mg coke/L in aquatic studies and 1000 mg coke/kg soil in terrestrial studies. The only statistically significant finding was an inhibition of algal growth measured as either biomass or growth rate.

Exposure of bakery and pastry apprentices to airborne flour dust using PM2.5 and PM10 personal samplers

PubMed Central

Mounier-Geyssant, Estelle; Barthélemy, Jean-François; Mouchot, Lory; Paris, Christophe; Zmirou-Navier, Denis

2007-01-01

Background This study describes exposure levels of bakery and pastry apprentices to flour dust, a known risk factor of occupational asthma. Methods Questionnaires on work activity were completed by 286 students. Among them, 34 performed a series of two personal exposure measurements using a PM2.5 and PM10 personal sampler during a complete work shift, one during a cold ("winter") period, and the other during a hot ("summer") period. Results Bakery apprentices experience greater average PM2.5 and PM10 exposures than pastry apprentices (p < 0.006). Exposure values for both particulate fractions are greater in winter (average PM10 values among bakers = 1.10 mg.m-3 [standard deviation: 0.83]) than in summer (0.63 mg.m-3 [0.36]). While complying with current European occupational limit values, these exposures exceed the ACGIH recommendations set to prevent sensitization to flour dust (0.5 mg.m-3). Over half the facilities had no ventilation system. Conclusion Young bakery apprentices incur substantial exposure to known airways allergens, a situation that might elicit early induction of airways inflammation. PMID:17976230

Effect of the 2.0 mg/m3 coal mine dust standard on underground environmental dust levels.

PubMed

Parobeck

1975-08-01

The 1969 Federal Coal Mine Health and Safety Act established environmental dust standards for underground coal mines. The Act requires that the average concentration of respirable dust in the active workings of a mine be maintained at or below 3.0 mg/m3; and, that effective December 30, 1972, the 3.0 mg/m3 standard be reduced to 2.0 mg/m3. This paper discusses the current status of dust levels in our underground coal mines, the effect of the 2.0 mg/m3 standard on underground dust levels, and associates the current levels with specific operations and occupations. The comparison is made between current levels and those existing prior to December 30, 1972.

The More (Social Group Memberships), the Merrier: Is This the Case for Asians?

PubMed Central

Chang, Melissa X.-L.; Jetten, Jolanda; Cruwys, Tegan; Haslam, Catherine; Praharso, Nurul

2016-01-01

While previous studies have consistently shown that belonging to multiple groups enhances well-being, the current research proposes that for Asians, multiple group memberships (MGM) may confer fewer well-being benefits. We suggest that this is due, in part, to Asian norms about relationships and support seeking, making Asians more reluctant to enlist social support due to concerns about burdening others. Overall, MGM was associated with enhanced well-being in Westerners (Study 2), but not Asians (Studies 1–3). Study 2 showed that social support mediated the relationship between MGM and well-being for Westerners only. In Study 3, among Asians, MGM benefited the well-being of those who were least reluctant to enlist support. Finally, reviewing the MGM evidence-base to date, relative to Westerners, MGM was less beneficial for the well-being of Asians. The evidence underscores the importance of culture in influencing how likely individuals utilize their group memberships as psychological resources. PMID:27462281

Successful treatment of primary extramedullary leukemia (EML) of the uterus with radical surgery, chemotherapy, autologous bone marrow transplantation (BMT) and prophylactic local irradiation.

PubMed

Huter, O; Brezinka, C; Nachbaur, D; Schwaighofer, H; Lang, A; Niederwieser, D

1996-09-01

Extramedullary myeloid cell tumors are rare manifestations of acute nonlymphocytic leukemia (ANLL). While many advances in diagnosis have been made, dilemmas remain concerning the treatment of this disease. In primary extramedullary leukemia (EML) most reports agree upon a local therapy followed by systemic chemotherapy such as is used for ANLL. However, further prophylactic local or systemic therapy with stem cell support remains controversial. A 20-year-old patient was diagnosed as having granulocytic sarcoma (GS) of the uterus without evidence of ANLL in 1991. After resection of the tumor at the uterine cervix and chemotherapy with daunorubicin 50 mg/m2 (days 1-3) and cytosine-arabinoside 200 mg/m2 (days 1-7) in September 1991, complete remission was achieved. In October 1991 cytosine-arabinoside 1000 mg/m2 every 12 h from day 1 to day 6 and amsacrine 200 mg from day 5 to day 7 were given as consolidation. Two years later relapse occurred in the adnexae. After radical hysterectomy, the same induction and consolidation chemotherapy was administrated. Subsequently, cytoxane 60 mg/m2 and fractionated total body irradiation (6 x 200 cGy) were given as conditioning and the previously cryopreserved bone marrow was reinfused. Finally, after hematopoietic engraftment, prophylactic local irradiation (4500 cGy) to the pelvis was given resulting in a disease-free long-term survival of more than 36 months after relapse. Although this experience is confined to one patient, it may contribute to the design of prospective therapeutic studies in patients with primary EML.

NTP Toxicology and Carcinogenesis Studies of l-Epinephrine Hydrochloride (CAS No. 55-31-2) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

PubMed

1990-03-01

l-Epinephrine, an endogenous neurotransmitter hormone, is widely used for the treatment of allergic and respiratory disorders. NTP Toxicology and Carcinogenesis studies of epinephrine hydrochloride were conducted by exposing groups of F344/N rats and B6C3F1 mice of each sex to an aerosol containing epinephrine hydrochloride for 14 days, 13 weeks, 15 months, or 2 years. During the 14-day and 13-week studies, control animals were exposed to dilute aerosols of hydrochloric acid (pH 2.8), whereas during the 15-month and 2-year studies, controls were exposed to aerosols of water. Genetic toxicology studies of epinephrine were conducted in Salmonella typhimurium and Chinese hamster ovary (CHO) cells. Fourteen-Day Studies: Rats and mice were exposed to 0 or 12.5-200 mg/m3 epinephrine hydrochloride. Deaths occurred in male rats exposed to 12.5 mg/m3 or more and in females exposed to 25 mg/m3 or more. Deaths of mice occurred at concentrations of 50 mg/m3 or higher. Compound-related clinical signs included an increased respiratory rate in all groups of epinephrine-exposed rats and mice. At higher concentrations (100 and 200 mg/m3), excessive lacrimation and dyspnea in rats and exaggerated visual and auditory reflexes in mice were observed. Thirteen-Week Studies: Rats and mice were exposed to 0 or 2.5-40 mg/m3 epinephrine hydrochloride. Deaths in rats and mice were not concentration related. Final mean body weights of chemically exposed and hydrochloric acid aerosol control rats and mice were generally similar. Increased respiratory rates were noted in rats and mice exposed to 40 mg/m3. Heart and adrenal gland weights of rats and mice and liver weights of mice exposed to 40 mg/m3 were greater than those of aerosol controls. Squamous metaplasia occurred in the respiratory epithelium of the nasal mucosa of rats and mice exposed to 40 mg/m3. Degenerative lesions of the laryngeal muscle were seen in male and female rats exposed to 20 or 40 mg/m3. Inflammation in the glandular stomach was seen in male and female mice exposed to 10, 20, and 40 mg/m3, and uterine atrophy was seen in 7/10 female mice exposed to 40 mg/m3. Two-year studies were conducted by exposing groups of 60 rats or each sex to 0, 1.5, or 5 mg/m3 epinephrine hydrochloride, 5 days per week for 103 weeks. Groups of 60 mice of each sex were exposed to 0, 1.5, or 3 mg/m3 epinephrine hydrochloride, 5 days per week for 104 weeks. Use of these exposure concentrations represented a departure from the usual practice of utilizing doses equivalent to one-half the maximum tolerated dose (MTD) and the MTD for 2-year carcinogenicity studies. Thus, although the dose levels exceeded maximum human therapeutic use levels (normalized to body weight and surface area), they were less than one-half the MTD. Fifteen-Month Studies: Results of hematologic analyses did not show compound-related changes. Absolute liver weights for exposed mice (3 mg/m3) and rats (5 mg/m3) and relative liver weights for exposed rats (5 mg/m3) were significantly lower than those for controls. The absolute kidney weights for mice exposed to 3 mg/m3 and the kidney weight to body weight ratio for male mice exposed to 3 mg/m3 were significantly lower than those for controls. No compound-related lesions were seen in rats or mice. Body Weights and Survival in the Two-Year Studies: Mean body weights and survival of exposed and control rats and mice were similar (survival, rats--male: control, 33/50; 1.5 mg/m3, 27/50; 5 mg/m3, 32/50; female: 32/50; 29/50; 30/50; mice--male: control, 33/50; 1.5 mg/m3, 34/50; 3 mg/m3, 36/50; female: 32/50; 35/50; 34/50). Nonneoplastic and Neoplastic Effects in the Two-Year Studies: Suppurative inflammation of the nasal mucosa, dilatation of the nasal glands (Bowman's and septal), and hyperplasia of the respiratory epithelium were seen at increased incidences in male rats exposed to 5 mg/m3 and in female rats exposed to 1.5 or 5 mg/m3. Hyaline degeneration of the olfactory epithelium in male mice and suppurative inflammation of the nasal passage and hyaline degeneration of the respiratory epithelium in female mice were increased in the 1.5 and 3 mg/m3 groups compared with controls. No neoplasms seen in these studies were considered related to chemical exposure. Genetic Toxicology: Salmonella gene mutation tests with l-epinephrine yielded negative results in strain TA100 in the presence of exogenous metabolic activation (S9) and equivocal results in the absence of S9. No mutagenic activity was observed in strains TA98, TA1535, or TA1537 with or without S9. The responses observed in the CHO cell assay for induction of sister chromatid exchanges were considered to be negative and equivocal in the presence and absence of S9 activation, respectively. l-Epinephrine did not induce chromosomal aberrations in CHO cells with or without S9. Conclusions: Under the conditions of these 2-year studies, no carcinogenic effects were observed in male or female F344/N rats exposed to aerosols containing 1.5 or 5 mg/m3 l-epinephrine hydrochloride for 2 years or in B6C3F1 mice exposed to 1.5 or 3 mg/m3 l-epinephrine hydrochloride for 2 years. However, these studies were considered to be inadequate studies of carcinogenic activity because the concentrations used, which were chosen to represent multiples of therapeutic doses, were considered too low for the animals to have received an adequate systemic challenge from the compound. Synonyms: adrenaline hydrochloride; 4-(1-hydroxy-2-(methylamino)ethyl)-1,2-benzenediol; (-)3,4-dihydroxy-a-((methylamino)methyl)benzyl alcohol hydrochloride; methylaminoethanol catechol hydrochloride Trade names for epinephrine formulations: Primatene®. Mist; Sus-Phrine®.; Epipen®.; Supravenin Hydrochloride®.; Bronkaid®.

A phase I study of cabazitaxel in combination with platinum and 5-fluorouracil (PF) in locally advanced squamous cell carcinoma of head and neck (LA-SCCHN).

PubMed

Camille, Nadia; Rozehnal, John; Roy, Elizabeth; Uczkowski, Dariusz; Olson, Ashely; Genden, Eric; Teng, Marita; Bakst, Richard; Gupta, Vishal; Posner, Marshall; Misiukiewicz, Krzysztof

2017-08-01

There is a clinical need to improve outcomes for patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), especially in Human Papilloma Virus (HPV) negative and HPV positive subtypes with a significant history of tobacco use. In animal models bearing SCCHN, Cabazitaxel showed an excellent response rate compared to docetaxel and might prove useful in treatment of patients. The primary objective of this study was to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of cabazitaxel when combined with cisplatin and 5-fluorouracil (PF) in induction chemotherapy (IC) for patients with SCCHN. Cabazitaxel-PF IC administered in 3 cycles (each 21 days) followed by concurrent chemoradiation (CRT) or surgery has been evaluated to assess overall response rate (ORR) and progression-free survival (PFS) in this population. This phase I study employed a standard 3+3 design. DLT was defined as grade 4 or 5 toxicity or grade 3 toxicity lasting >7days. Out of 40 consented patients with stage IV, curable, previously untreated, LA-SCHHN and poor prognosis, 35 (32M, 3F) were enrolled and evaluated for toxicity: 19 oropharynx, 10 larynx, 2 oral cancer, 1 nasopharynx and 3 hypopharynx. Five dose levels of cabazitaxel (10, 12.5, 15, 17.5 and 20mg/m 2 ) were tested in combination with cisplatin 100mg/m 2 and 5-fluorouracil (5-FU) 800mg/m 2 /d×4days. Dose escalation for cabazitaxel was terminated upon the occurrences of 2 DLTs and the establishment of MTD. Cabazitaxel was then further escalated with cisplatin 75mg/m 2 and 5-FU 800mg/m 2 /d×4days in the subsequent 3 dose levels (17.5, 20 and 22.5mg/m 2 ). In the expansion cohort, 9 patients were enrolled at the 22.5mg/m 2 dose level. Following 3 cycles of IC, patients were evaluated for clinical, radiographic, and pathologic response to cabazitaxel-PF before beginning CRT or surgery. There were two DLTs (grade 4 hyperuricemia; neutropenic fever, sepsis, and grade 4 thrombocytopenia) among 2 patients in cohort 5 at the dose of 20mg/m 2 of cabazitaxel. There were no DLTs reported with cohorts using a lower dose of cisplatin, even in the expansion cohort. The study was stopped at the dose of 22.5mg/m 2 in accordance with the initial study design. With 33 evaluable patients for response, the Overall Response Rate (ORR) rate was 57.6%: 9.1% Complete Responses (CR) and 48.5% Partial Responses (PR) were noted. The recommended phase II dose for cabazitaxel in combination with cisplatin 75mg/m 2 and 5-FU 800mg/m 2 /d×4days is 22.5mg/m 2 and for cisplatin 100mg/m 2 and 5-FU 800mg/m 2 /d×4days is 17.5mg/m 2 . With a median follow-up of 39months, PFS for the entire non-metastatic population at 3years was approximately 58%. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Phase I Study of Triapine® in Combination with Doxorubicin in Patients with Advanced Solid Tumors

PubMed Central

Schelman, William R.; Morgan-Meadows, Sherry; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M.; Ivy, Percy; Wilding, George; Traynor, Anne M.

2011-01-01

Purpose To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine® administered in combination with doxorubicin. Study Design Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine® IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m2 and Triapine® 25 mg/m2. PK analysis was performed at various time-points before and after treatment. Results Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m2, Triapine® 45 mg/m2), 2 patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional 3 patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m2) with Triapine® 45 mg/m2. The 2 patients enrolled on this level had 2 DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine® were reduced to 45 mg/m2 and 25 mg/m2, respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Conclusions Pretreated patients with advanced malignancies can tolerate the combination of Triapine® and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m2 on day 1 and Triapine® 25 mg/m2 on days 1-4 of a 21 day cycle. PMID:19082825

Effects of Didecyldimethylammonium Chloride (DDAC) on Sprague-Dawley Rats after 13 Weeks of Inhalation Exposure.

PubMed

Kim, Yong-Soon; Lee, Sung-Bae; Lim, Cheol-Hong

2017-01-01

Didecyldimethylammonium chloride (DDAC) is used in many types of biocidal products including tableware, carpets, humidifiers, and swimming pools, etc. In spite of increased chances of DDAC exposure through inhalation, studies on the inhalation toxicity of DDAC are not common even though the toxicity of DDAC might be significantly higher if it were to be administered through routes other than the respiratory system. DDAC aerosols were exposed to Sprague-Dawley rats in whole body exposure chambers for a duration of 13 weeks. The Mass Median Aerodynamic Diameters of the DDAC aerosol were 0.63 μm, 0.81 μm, and 1.65 μm, and the geometric standard deviations were 1.62, 1.65, and 1.65 in the low (0.11 ± 0.06 mg/m 3 ), the middle (0.36 ± 0.20 mg/m 3 ) and the high (1.41 ± 0.71 mg/m 3 ) exposure groups, respectively. Body weight was confirmed to be clearly influenced by exposure to DDAC and mean body weight was approximately 35% lower in the high (1.41 ± 0.71 mg/m 3 ) male group and 15% lower in the high (1.41 ± 0.71 mg/m 3 ) female group compared to that of the control group. In the bronchoalveolar lavage fluid assay, the levels of albumin and lactate dehydrogenase had no effect on DDAC exposure. The lung weight increased for the middle (0.36 ± 0.20 mg/m 3 ) and the high (1.41 ± 0.71 mg/m 3 ) concentrations of the DDAC exposure group, and inflammatory cell infiltration and interstitial pneumonia were partially observed in the lungs of the middle (0.36 ± 0.20 mg/m 3 ) and the high (1.41 ± 0.71 mg/m 3 ) exposure groups. However, severe histopathological symptoms, including proteinosis and/or fibrosis, were not found. Based on the results of the changes in the body weight and lung weight, it is considered that the NOAEL (no-observed adverse effect) level for the 13-week exposure duration is 0.11 mg/m 3 .

[Domestication study about desulfuration microorganism from oxidation ditch by low concentration SO2].

PubMed

Huang, Bing; Shi, Zhe; Wang, Yan-Yan; Zhang, Shi-Ling

2010-06-01

An excellent desulfuration microorganism with a quick growth and propagation, high activation, high efficiency of removing SO2 is obtained from oxidation ditch of a city sewage treatment plant by inductive acclimatization over 6 d with low concentration SO2 gas (100-2 000 mg/m3). The desulfurition microorganism get their energy sources for growth from transforming SO2 (SO3(2-)) to SO4(2-). The predominant bacterium of the desulfuration microorganism has the same characteristic with Thiobacillus ferrooxidans (T. ferrooxidans), which showed that it was Gram negative, short rod bacteria with a single polar flagellum under a microscopic examination, and obtained its nourishment through the oxidation of inorganic compounds. The technology process condition of domestication and desulfuration of microorganism are particular studied, and the results showed that aerating time, SO2 flux and time to provide nutriment contained N, P, K to microorganism were very important. They have an ability with degradation rate of 160g/ (m3 x h) and degradation efficiency over 50% to transform sulfite to sulfate in liquid phase. The bacteria have a 98% of removing efficiency and over 80% of biodegradation efficiency for the 5 500 mg/m3 SO2 gas and the outlet concentration of SO2 is lower than 100 mg/m3, and also have a 95% of removing efficiency for 15 000 mg/m3 SO2 gas in the packed tower reactor with Raschig ring at 3s contact time.

Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Fludarabine and Cytarabine, in Pediatric Relapsed or Refractory Acute Leukemia.

PubMed

Alexander, Thomas B; Lacayo, Norman J; Choi, John K; Ribeiro, Raul C; Pui, Ching-Hon; Rubnitz, Jeffrey E

2016-12-01

Purpose To characterize the toxicity, pharmacokinetics, and pharmacodynamics of selinexor, a selective inhibitor of nuclear export, when combined with fludarabine and cytarabine, in children with relapsed or refractory leukemia. Patients and Methods Eighteen patients with relapsed or refractory acute leukemia were enrolled in the SELHEM (Selinexor With Fludarabine and Cytarabine for Treatment of Refractory or Relapsed Leukemia or Myelodysplastic Syndrome) clinical trial (NCT02212561). Selinexor, initially at 30 mg/m 2 per dose, was given orally on days 1, 3, 8, 10, 22, and 24 and was escalated according to a rolling-six design. Fludarabine 30 mg/m 2 and cytarabine 2 g/m 2 were administered on days 15 to 19. Pharmacokinetic and pharmacodynamic studies were performed on days 1 and 22. Response evaluations were performed on day 15 and at the completion of course 1. Results Among the 17 patients who were evaluable for toxicity, three were treated at 30 mg/m 2 , three at 40 mg/m 2 , six at 55 mg/m 2 , and five at 70 mg/m 2 . The most common grade 3 nonhematologic toxicity was asymptomatic hyponatremia. Two patients who were treated at 70 mg/m 2 experienced reversible cerebellar toxicity, thereby defining the dose-limiting toxicity. Pharmacokinetic parameters demonstrated that plasma exposure was dose proportional. Fifteen of 16 patients demonstrated at least a twofold increase of XPO1 mRNA, indicating inhibition of the XPO1 protein. In this group of heavily pretreated, relapsed, and refractory patients, seven of 15 evaluable patients (47%) achieved complete response or complete response with incomplete count recovery. Conclusion Selinexor, in combination with fludarabine and cytarabine, is tolerable at doses up to 55 mg/m 2 in pediatric patients with relapsed or refractory leukemia. All patients who received selinexor at ≥ 40 mg/m 2 demonstrated XPO1 target inhibition. Response rates are promising and will be further explored in a phase II trial.

Development of an Insect Repellent Spray for Textile Based on Permethrin-Loaded Lipid-Core Nanocapsules.

PubMed

Forgearini, Joana C; Michalowski, Cecília B; Assumpção, Evelise; Pohlmann, Adriana R; Guterres, Silvia S

2016-02-01

The aim of this study was to prepare and characterize permethrin-loaded lipid core nanocapsules (P-LNC) in order to produce a long last insect repellent spray formulation for clothes. P-LNC were prepared by self-assembling in aqueous solution showing a mean diameter of 201 +/- 4 nm with a monomodal distribution, a permethrin content of 4.6 +/- 0.1 mg/mL and zeta potential of--16.7 +/- 4 mV. P-LNC (0.46%), as well as the commercial product (0.46%) and the hydroalcoholic solution (0.50%) of permethrin were separately sprayed onto cotton or polyester, followed by successive washes of the fabric. The results showed that the fabrics treated with P-LNC are more resistant than other solutions in terms of remaining permethrin content. After twenty washes, the cotton treated with P-LNC, presented a concentration of 566 +/- 27 mg/M2 of impregnated permethrin, while for the treatment with the substance hydroalcoholic solution and with the commercial product the concentrations values were of 340 +/- 7 mg/M2 and 224 +/- 74 mg/M2, respectively. When the test was performed using polyester, this fiber was less adhesive than cotton, resulting in a final concentration of permethrin (after 20 washes) of 81 +/- 10 mg/m2 for P-LNC suspension, 94 +/- 8 mg/M2 for the substance hydroalcoolic solution and 22 +/- 3 mg/M2 for the commercial product. After impregnating cotton with the formulations and submitting to a temperature of 200 degrees C, the P-LNC also demonstrated higher adherence compared to the other formulations (407 +/- 67 mg/m2 for P-LNC, 236 +/- 72 mg/m2 for the substance hydroalcoholic solution and 158 +/- 62 mg/m2 for commercial product). These results showed that the repellent spray composed of P-LNC developed in this work is a promising and innovative product for the individual protection against insects, useful for impregnation onto cotton garments.

US Navy Submarine Sea Trial of NASA developed Multi-Gas Monitor

NASA Technical Reports Server (NTRS)

Mudgett, Paul D.; Manney, Joshua A.; Smith, Matthew J.; O'Connor, Sara Jane; Pilgrim, Jeffrey S.

2017-01-01

During a successful 2 year technology demonstration of the tunable diode laser spectroscopy (TDLS) based Multi-Gas Monitor (MGM) on the International Space Station (ISS), we began discussing with the US Navy the possibility of conducting a sea trial of an MGM on a submarine. The sea trial would also include a gas chromatography/differential mobility spectrometer based Air Quality Monitor (AQM), which is used operationally on ISS for volatile organic compound analysis. AQM preparation and results will be the subject of a separate paper. The Navy's interest in testing NASA equipment in general relates to their ongoing search for better air monitoring technology. NASA's goal is studying submarines as closed environment analogs to spacecraft. MGM's core technology was developed by Vista Photonics Inc. using Small Business Innovation Research (SBIR) grants and expanded for various applications using NASA program funding. The MGM measures oxygen, carbon dioxide, ammonia and water vapor in ambient air, displays concentrations with temperature and pressure, and stores 30 second moving averages. The sea trial involves collocating the instrument with the Central Atmosphere Monitoring System (CAMS Mk II) of the submarine, connecting it to rack power prior to departure, and letting it run during the entire 90 day patrol. All data is stored within MGM, with no connection to the vessel data bus. Crew intervention is limited to checking MGM periodically to see that it is working and power cycling if necessary. After the trial is over, the unit with its data will be retrieved. Post sea trial calibration check and data analysis are planned and results will be compared with both CAMS Mk II data and results from MGM's ISS technology demonstration. Since the sea trial itself has been delayed, this paper describes the preparation of MGM for the sea trial and also provides a summary of the latest data from the ISS MGM technology demonstration.

Assessing dust exposure in an integrated iron and steel manufacturing plant in South India.

PubMed

Ravichandran, B; Krishnamurthy, V; Ravibabu, K; Raghavan, S; Rajan, B K; Rajmohan, H R

2008-01-01

A study to monitor and estimate respirable particulate matter (RPM), toxic trace metal concentrations in the work environment was carried out in different sections of an integrated steel manufacturing industry. The average RPM concentration observed varied according to the section blast furnace was 2.41 mg/m;{3}; energy optimization furnace, 1.87 mg/m;{3}; sintering plant, 0.98 mg/m;{3}; continuous casting machine, 1.93 mg/m;{3}. The average trace metal concentration estimated from the RPM samples like iron, manganese, lead and chromium did not exceed ACGIH prescribed levels.

Use of positron emission tomography scan response to guide treatment change for locally advanced gastric cancer: the Memorial Sloan Kettering Cancer Center experience.

PubMed

Won, Elizabeth; Shah, Manish A; Schöder, Heiko; Strong, Vivian E; Coit, Daniel G; Brennan, Murray F; Kelsen, David P; Janjigian, Yelena Y; Tang, Laura H; Capanu, Marinela; Rizk, Nabil P; Allen, Peter J; Bains, Manjit S; Ilson, David H

2016-08-01

Early metabolic response on 18-fluorodeoxyglucose-positron emission tomography (FDG-PET) during neoadjuvant chemotherapy is PET non-responders have poor outcomes whether continuing chemotherapy or proceeding directly to surgery. Use of PET may identify early treatment failure, sparing patients from inactive therapy and allowing for crossover to alternative therapies. We examined the effectiveness of PET directed switching to salvage chemotherapy in the PET non-responders. Patients with locally advanced resectable FDG-avid gastric or gastroesophageal junction (GEJ) adenocarcinoma received bevacizumab 15 mg/kg, epirubicin 50 mg/m(2), cisplatin 60 mg/m(2) day 1, and capecitabine 625 mg/m(2) bid (ECX) every 21 days. PET scan was obtained at baseline and after cycle 1. PET responders, (i.e., ≥35% reduction in FDG uptake at the primary tumor) continued ECX + bev. Non-responders switched to docetaxel 30 mg/m(2), irinotecan 50 mg/mg(2) day 1 and 8 plus bevacizumab every 21 days for 2 cycles. Patients then underwent surgery. The primary objective was to improve the 2-year disease free survival (DFS) from 30% (historical control) to 53% in the non-responders. Twenty evaluable patients enrolled before the study closed for poor accrual. Eleven were PET responders and the 9 non-responders switched to the salvage regimen. With a median follow-up of 38.2 months, the 2-year DFS was 55% [95% confidence interval (CI), 30-85%] in responders compared with 56% in the non-responder group (95% CI, 20-80%, P=0.93). The results suggest that changing chemotherapy regimens in PET non-responding patients may improve outcomes. Results from this pilot trial are hypothesis generating and suggest that PET directed neoadjuvant therapy merits evaluation in a larger trial.

Plasma concentrations of polysorbate 80 measured in patients following administration of docetaxel or etoposide.

PubMed

Webster, L K; Linsenmeyer, M E; Rischin, D; Urch, M E; Woodcock, D M; Millward, M J

1997-01-01

Docetaxel (Taxotere, Rhone-Poulenc Rorer) and etoposide are water-insoluble drugs formulated with polysorbate 80 for intravenous administration. We have previously reported that surfactants, including polysorbate 80 and Cremophor EL, can reverse the multidrug resistance (MDR) phenotype in an experimental system and that plasma Cremophor EL concentrations measured following a 3-h infusion of paclitaxel were > or = 1 microliter/ml, sufficient to modulate MDR in vitro. The purpose of this study was to measure polysorbate 80 plasma concentrations in patients following intravenous administration of etoposide or docetaxel using a bioassay in which MDR-expressing cells are incubated with daunorubicin (DNR) plus 50/50 growth medium/plasma and equilibrium intracellular DNR fluorescence is measured by flow cytometry. In vitro experiments show maximal reversal of MDR at concentrations of 1.0-2.0 microliters/ml and 50% reversal at 0.2-0.3 microliter/ml. Patients received docetaxel at 75 mg/m2 (five patients) or 100 mg/m2 (four patients) (total dose 125-178 mg, containing 3.12-4.45 ml polysorbate 80) over 60 min. The median end-infusion polysorbate 80 concentration was 0.1 microliter/ml (range 0.07-0.41 microliter/ml). Only one patient had a level of > 0.2 microliter/ml. Five patients received intravenous etoposide at 120 mg/m2 over 45-120 min (total dose 180-250 mg, containing 0.67-0.93 ml polysorbate 80). In the end-infusion plasma sample, polysorbate 80 was not detectable (< 0.06 microliter/ml) in any patient. Plasma polysorbate 80 levels following an intravenous infusion of 120 mg/m2 etoposide or of docetaxel at doses used in Phase II trials, are insufficient to show modulation of MDR in vitro.

Treatment of malignant phaeochromocytoma with a combination of cyclophosphamide, vincristine and dacarbazine: own experience and overview of the contemporary literature.

PubMed

Deutschbein, Timo; Fassnacht, Martin; Weismann, Dirk; Reincke, Martin; Mann, Klaus; Petersenn, Stephan

2015-01-01

Malignant phaeochromocytomas are rare and highly aggressive tumours. This retrospective study evaluated the outcome of combined chemotherapy with cyclophosphamide, vincristine and dacarbazine (also known as CVD regimen). Patients with histologically and radiologically confirmed malignant phaeochromocytoma who were treated with the CVD regimen for progressive disease were retrospectively identified from chart review. Treatment cycles were usually repeated at 21-day intervals, with cyclophosphamide (750 mg/m(2) ), vincristine (1·4 mg/m(2) ) and dacarbazine (600 mg/m(2) ) on day 1, and dacarbazine only (600 mg/m(2) ) on day 2. The main outcome measures were best response during treatment and progression-free survival. Eight patients (4 males; median age 55·5 (range 31-77) years) with progressive disease underwent a median of 6 (range 3-11) cycles. Best treatment responses were as follows: partial response, n = 2 (25%); stable disease, n = 3 (38%); and progressive disease, n = 3 (38%). The median progression-free survival was 5·4 (range 2·5-26·8) months. After the initial administration of 6 cycles, two patients received a second course of chemotherapy with another 6 cycles after new progressive disease had been detected. Subsequently, these patients were progression-free for another 6·0 and 6·4 months. Mild gastrointestinal symptoms and fatigue were the most common adverse events. Although objective tumour response rates were lower than previously reported in small series, the CVD regimen allowed disease stabilization for a substantial period of time and may therefore be considered as a treatment option in advanced stages. To improve disease outcome, however, new therapeutic approaches and larger multicentre studies are needed. © 2014 John Wiley & Sons Ltd.

[Evaluation of long-term occupational exposure to dust and its effect on health during production of ceramic tiles].

PubMed

Gielec, L; Izycki, J; Woźniak, H

1992-01-01

A medical examination has been carried out of 500 workers (290 men and 210 women) of a ceramic plates plant. Also, the measurements of dust concentrations were made at some standard work places . In the materials used for manufacturing the plates crystalline phases and the content of free crystalline silica were determined using the X-ray diffraction method. In the animal experiments the fibrogenic activity of all materials used in the plant was examined and compared to the fibrogenic activity of standard quartz. As a result of the medical examination 64 cases of pneumoconiosis were diagnosed (13% of the subjects). The incidence rate of pneumoconiosis was similar for men and women. The radiological changes characteristic of pneumoconiosis took approximately 24 years of the workers tenure to develop. Type q changes were most frequent (69%), types p and r were observed in 14% of workers (mostly women). In 31% of workers tuberous changes of size B were observed. In 43.8% of the subjects restrictive disorders of ventilation were found. In 30% of workers chronic bronchitis was diagnosed. Dust concentrations at 11 work places were measured using the individual dosimetry method. Total dust concentrations ranged from 0.6 mg/m3 at the electricians posts to 60.1 mg/m3 at the workposts where the furnace truck restorers worked. Dust concentrations exceeded the MACs at 7 workposts. The respirable fraction concentrations ranged from 0.1 mg/m3 to 8.4 mg/m3. During the replacement of asbestos ropes and asbestos board used for insulating the furnace trucks mineral fibres (0.1-0.5 fibre/cm3) were found in the air. The following crystalline phases were determined in the materials: kaolinite, illite, quartz, orthoclase and microline.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of an inhalation system of high melting point metal fumes and its use for exposure of rats to chromium and nickel fumes.

PubMed

Serita, F; Homma, K; Fukuda, K; Sawatari, K; Suzuki, Y; Toya, T

1990-01-01

An experimental inhalation system was developed for fumes generated from powders of high melting point metals such as chromium, nickel, manganese and iron. The system consisted of a plasma flame metal sprayer as a fume generator, a granular bed type fume collector, a fluidized bed aerosol generator, an exposure and a control chamber of a horizontal-flow type and inhalant monitoring and controlling units. Performance of the chambers was ensured by a distribution test using flyash as a test aerosol. Using this system, rats were exposed to chromium fumes for one week or to nickel fumes for two months. The exposure concentrations of the chromium and nickel fumes were 1.85 +/- 0.55 mg/m3 and 0.51 +/- 0.15 mg/m3 (mean +/- SD), near the target levels of 2 mg/m3 and 0.5 mg/m3, respectively. The mass median aerodynamic diameter and the geometric standard deviation of the chromium fumes were 2.1 microns and 2.00, respectively. Those of the nickel fumes were 3.7 microns and 1.74, respectively. Species analysis of these fume particles revealed that 26.4% of the total chromium was hexavalent and the residue was trivalent and that 1-3% of the total nickel was nickel(III) and the residue was nickel(II). Inhaled-metal concentrations in the lungs showed steady increases with the exposure periods and were within the normal range of variation. On the basis of these results, it is concluded that this system is useful for long-term inhalation experiments using high melting point metal fumes.

Cisplatin plus gemcitabine versus a cisplatin-based triplet versus nonplatinum sequential doublets in advanced non-small-cell lung cancer: a Spanish Lung Cancer Group phase III randomized trial.

PubMed

Alberola, V; Camps, C; Provencio, M; Isla, D; Rosell, R; Vadell, C; Bover, I; Ruiz-Casado, A; Azagra, P; Jiménez, U; González-Larriba, J L; Diz, P; Cardenal, F; Artal, A; Carrato, A; Morales, S; Sanchez, J J; de las Peñas, R; Felip, E; López-Vivanco, G

2003-09-01

To compare the survival benefit obtained with cisplatin plus gemcitabine, a cisplatin-based triplet, and nonplatinum sequential doublets in advanced non-small-cell lung cancer (NSCLC). Stage IIIB to IV NSCLC patients were randomly assigned to receive cisplatin 100 mg/m2 day 1 plus gemcitabine 1,250 mg/m2 days 1 and 8, every 3 weeks for six cycles (CG); cisplatin 100 mg/m2 day 1 plus gemcitabine 1,000 mg/m2 and vinorelbine 25 mg/m2 days 1 and 8, every 3 weeks for six cycles (CGV); or gemcitabine 1,000 mg/m2 plus vinorelbine 30 mg/m2 days 1 and 8, every 3 weeks for three cycles, followed by vinorelbine 30 mg/m2 days 1 and 8 plus ifosfamide 3 g/m2 day 1, every 3 weeks for three cycles (GV-VI). Five hundred fifty-seven patients were assigned to treatment (182 CG, 188 CGV, 187 GV-VI). Response rates were significantly inferior for the nonplatinum sequential doublet (CG, 42%; CGV, 41%; GV-VI, 27%; CG v GV-VI, P =.003). No differences in median survival or time to progression were observed. Toxicity was higher for the triplet: grade 3 to 4 neutropenia (GC, 32%; CGV, 57%; GV-VI, 27%; P <.05); neutropenic fever (CG, 4%; CGV, 19%; GV-VI, 5%; P <.0001); grade 3 to 4 thrombocytopenia (CG, 19%; CGV, 23%; GV-VI, 3%; P =.0001); and grade 3 to 4 emesis (GC, 22%; GCV, 32%; GV-VI, 6%; P <.0001). On the basis of these results, CG remains a standard regimen for first-line treatment of advanced NSCLC.

Phase 1 study of ombrabulin in combination with cisplatin (CDDP) in Japanese patients with advanced solid tumors.

PubMed

Takahashi, Shunji; Nakano, Kenji; Yokota, Tomoya; Shitara, Kohei; Muro, Kei; Sunaga, Yoshinori; Ecstein-Fraisse, Evelyne; Ura, Takashi

2016-08-27

In clinical studies in Western countries, the recommended dose of combination ombrabulin a vascular disrupting agent, with cisplatin is 25 mg/m 2 ombrabulin with 75 mg/m 2 cisplatin every 3 weeks. Here, we report the first Phase 1 study of this treatment regimen in Japanese patients with advanced solid tumors. This was an open-label, multicenter, sequential cohort, dose-escalation Phase 1 study of ombrabulin with cisplatin administered once every 3 weeks. The study used a 3 + 3 design without intrapatient dose escalation. The investigated dose levels of ombrabulin were 15.5 and 25 mg/m 2 combined with cisplatin 75 mg/m 2 . The latter dose level was regarded as the maximum administered dose if more than one patient experienced dose-limiting toxicities. Ten patients were treated, but no dose-limiting toxicity was observed at both dose levels. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 was the maximum administered dose and regarded as the recommended dose in the combination regimen for Japanese patients with cancer. The most frequently reported drug-related adverse events were neutropenia, decreased appetite, constipation, nausea and fatigue. One partial response and five cases of stable disease were reported as the best overall responses. Pharmacokinetic parameters of ombrabulin and cisplatin were comparable with those in non-Japanese patients. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 once every 3 weeks was well tolerated and established as the recommended dose in Japanese patients with advanced solid tumors. The safety and pharmacokinetic profiles were comparable between Japanese and Caucasian patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Startup, Commissioning and Operation of Fenyi 100MW CFB Boiler

NASA Astrophysics Data System (ADS)

Wang, Zhiwei; Yu, Wugao; Bo, Shi

The first 100MW CFB boiler, designed by the Thermal Power Research Institute and manufactured by Harbin Boiler Company Limited, has been successfully running in Jiangxi Fenyi Power Plant since 2003. Local high ash content anthracite and lean coal that are very difficult to burn out are used in the 100 MW CFB boiler. The results of the 100MW CFB boiler shows that the CFB boiler can run in 30% MCR and startup with two under bed burners, and the boiler efficiency higher than 88% can be got after the combustion modification test. The CFB boiler can be operated with full load and reaches design parameters. The emissions of NO, N2O and CO are less than 7Omg/m3, 30mg/m3, and 125mg/m3, respectively, and SO2 less than 400mg/m3 after limestone injection. The bottom ash temperature from bed ash coolers is less than 120°C after its modification. Coal blockage at the coal storage silo is the main problem influencing the CFB boiler continuous operation. The running experiences for 5 years proved that the CFB boiler performance is successful, and the results were applied in 210 MW and 330 MW CFB Boiler design of Fenyi Power Plant.

Fugitive emission rates assessment of PM2.5 and PM10 from open storage piles in China

NASA Astrophysics Data System (ADS)

Cao, Yiqi; Liu, Tao; He, Jiao

2018-03-01

An assessment of the fugitive emission rates of PM2.5 and PM10 from an open static coal and mine storage piles. The experiment was conducted at a large union steel enterprises in the East China region to effectively control the fugitive particulate emissions pollution on daily work and extreme weather conditions. Wind tunnel experiments conducted on the surface of static storage piles, and it generated specific fugitive emission rates (SERs) at ground level of between ca.10-1 and ca.102 (mg/m2·s) for PM2.5 and between ca.101 and ca.103 (mg/m2·s) for PM10 under the u*(wind velocity) between ca.3.0 (m/s) and 10.0 (m/s). Research results show that SERs of different materials differ a lot. Material particulate that has lower surface moisture content generate higher SER and coal material generate higher SER than mine material. For material storage piles with good water infiltrating properties, aspersion is a very effective measure for control fugitive particulate emission.

Y-box-binding protein YB-1 identifies high-risk patients with primary breast cancer benefiting from rapidly cycled tandem high-dose adjuvant chemotherapy.

PubMed

Gluz, Oleg; Mengele, Karin; Schmitt, Manfred; Kates, Ronald; Diallo-Danebrock, Raihana; Neff, Frauke; Royer, Hans-Dieter; Eckstein, Niels; Mohrmann, Svjetlana; Ting, Evelyn; Kiechle, Marion; Poremba, Christopher; Nitz, Ulrike; Harbeck, Nadia

2009-12-20

To investigate the potential of Y-box-binding protein YB-1, a multifunctional protein linked to tumor aggressiveness and multidrug resistance, to identify patients with breast cancer likely to benefit from dose-intensified chemotherapy regimens. YB-1 was immunohistochemically determined in 211 primary tumors from the prospective, randomized West German Study Group WSG-AM-01 trial in high-risk (> or = 10 involved lymph-nodes) breast cancer (HRBC). Predictive impact of YB-1 was assessed by multivariate survival analysis, including time-varying factor-therapy interactions. At median follow-up of 61.7 months, patients receiving rapidly cycled tandem high-dose therapy (HD; two cycles [2x] epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2) every 14 days, followed by 2x epirubicin 90 mg/m(2), cyclophosphamide 3,000 mg/m(2), and thiotepa 400 mg/m(2) every 21 days) had better disease-free survival (DFS; hazard ratio [HR] = 0.62; 95% CI, 0.44 to 0.89) and overall survival (OS; HR = 0.59; 95% CI, 0.4 to 0.89) than those receiving conventional dose-dense chemotherapy (DD; 4x epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2), followed by 3x cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) every 14 days). High YB-1 was associated with aggressive tumor phenotype (negative steroid hormone receptor status, positive human epidermal growth factor receptor 2 and p53 status, high MIB-1, unfavorable tumor grade) and poor OS (median 78 v 97 months; P = .01). In patients with high YB-1, HD yielded a 63-month median DFS (P = .001) and a 46-month median OS advantage (P = .002) versus DD. In multivariate models, patients with high B-1 receiving HD (v DD) had one third the hazard rate after 20 months for DFS and one sixth after 40 months for OS. In a randomized prospective cancer therapy trial, for the first time, a strong predictive impact of YB-1 on survival has been demonstrated: enhanced benefit from HD (v DD) therapy occurs in HRBC with high YB-1. Future trials could therefore address optimal chemotherapeutic strategies,taking YB-1 into account.

A phase I dose escalation study of TTI-237 in patients with advanced malignant solid tumors.

PubMed

Wang-Gillam, Andrea; Arnold, Susanne M; Bukowski, Ronald M; Rothenberg, Mace L; Cooper, Wendy; Wang, Kenneth K; Gauthier, Eric; Lockhart, A Craig

2012-02-01

This study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of TTI-237, a novel anti-tubulin drug, administered weekly in patients with refractory solid tumors. Using an accelerated dose escalation design, patients with refractory solid tumors were enrolled in this study and treated with TTI-237 intravenously on days 1, 8 and 15 of a 28-day cycle. The starting dose was 4.5 mg/m(2). Pharmacokinetic studies were performed in patients at all dose levels. Twenty-eight patients were enrolled and treated with TTI-237 at dose of 4.5, 9, 15, 22.5 and 31.5 mg/m(2). One dose-limiting toxicity neutropenia fever was observed at 31.5 mg/m(2), and all seven patients developed grade 3 or 4 neutropenia at that dose level. TTI-237 dosage was de-escalated to 22.5 and 18 mg/m(2). Six patients were treated at the 18 mg/m(2) dose level without dose-limiting toxicity prior to trial termination. The mean terminal-phase elimination half-life (t(1/2)) for TTI-237 was 25-29 h, and the mean area under the concentration time curve at 31.5 mg/m(2) was 2,768 ng•h/mL. A protocol defined maximum tolerated dose was not determined because of early termination of the TTI-237 trial by the sponsor. 18 mg/m(2) may be a tolerable dose of TTI-237.

A phase I study of docetaxel as a radio-sensitizer for locally advanced squamous cell cervical cancer.

PubMed

Alvarez, Edwin A; Wolfson, Aaron H; Pearson, J Matt; Crisp, Meredith P; Mendez, Luis E; Lambrou, Nicholas C; Lucci, Joseph A

2009-05-01

This study was designed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of weekly docetaxel with concurrent radiotherapy (RT) for the primary treatment of locally advanced squamous cell carcinoma of the cervix. Eligible patients included those with locally advanced squamous cell cervical cancer without para-aortic lymph node involvement. Docetaxel dose levels were 20 mg/m(2), 30 mg/m(2) and 40 mg/m(2) given intravenously weekly for 6 cycles. Three patients were to be treated at each dose level and 6 to receive the MTD. Fifteen patients completed 4-6 cycles of chemotherapy. One of three patients experienced 2 delayed grade 3 severe adverse events (SAE) at the 20 mg/m(2) dose level consisting of colonic and ureteral obstruction. At the 30 mg/m(2) dose level, 1/4 patients had a probable treatment-related celiotomy due to obstipation and a necrotic tumor. Of the 8 patients treated at the 40 mg/m(2) dose level, 1 experienced grade 3 pneumonitis, likely treatment related. Overall, 10/15 (67%) experienced grade 1 or 2 diarrhea, 6 had grade 2 hematologic toxicity, and 2 had grade 2 hypersensitivity. 10 of 16 patients (67%) had no evidence of disease with follow-up ranging from 10-33 months (average 23 months). The recommended phase II dose of docetaxel administered weekly with concurrent radiotherapy for locally advanced squamous cell carcinoma of the cervix is 40 mg/m(2).

Synergistic insecticidal and repellent effects of combined pyrethroid and repellent-impregnated bed nets using a novel long-lasting polymer-coating multi-layer technique.

PubMed

Faulde, Michael K; Nehring, Oliver

2012-08-01

New and improved strategies for malaria control and prevention are urgently needed. As a contribution to an optimized personal protection strategy, a novel long-lasting insecticide and repellent-treated net (LLIRN) has been designed by binding combinations of permethrin plus N,N-diethyl-m-toluamide (DEET), or insect repellent 3535 (IR3535), and etofenprox plus DEET, onto fibres of bed net fabric employing a new multi-layer polymer-coating technique. Protective repellent efficacy, toxicological effectiveness and residual activity of 12 LLIRN types have been evaluated by laboratory testing against adult Aedes aegypti. The novel multi-layer LLIRN design allowed simultaneous embedding at concentrations up to 5,930 mg/m(2) for DEET, 3,408 mg/m(2) for IR3535, 2,296 mg/m(2) for permethrin and 2,349 mg/m(2) for etofenprox, respectively. IR3535 layers prevented co-binding of additional pyrethroid-containing polymer layers, thus making pyrethroids plus DEET LLIRNs an ideal combination. All LLIRNs revealed synergistic insecticidal effects which, when measured against concentration controls of the isolated compounds, were significant in all LLIRN types designed. DEET in DEET plus permethrin LLIRNs significantly (p < 0.0001) reduced the concentration-dependent permethrin 100 % knockdown (KD) time from 55 to 75 %, the corresponding 100 % kill time (p < 0.0001) from 55 to 64 %. DEET in DEET plus etofenprox LLIRNs reduced the dose-specific 100 % knockdown (KD) time of etofenprox from 42 to 50 % (p = 0.004), the 100 % kill time from 25 to 38 % (p < 0.0001). Permethrin or etofenprox did not influence spatial repellency of DEET or IR3535 on LLIRNs. Vice versa, DEET and IR3535 increased spatial and excitatory repellency and reduced landing and probing frequency on LLIRNs resulting in strongly enhanced biting protection, even at low concentrations. One hundred percent biting and probing protection of stored LLIRNs was preserved for 83 weeks with the 5,930 mg/m(2) DEET and 2,139 mg/m(2) etofenprox LLIRN, for 72 weeks with the 5,002 mg/m(2) DEET and 2,349 mg/m(2) etofenprox LLIRN, for 63 weeks with the 3,590 mg/m(2) DEET and 1,208 mg/m(2) permethrin LLRN, and for 61 weeks with the 4,711 mg/m(2) DEET and 702 mg/m(2) etofenprox LLIRN. Because 100 % bite protection with up to 75 % quicker contact toxicity of pyrethroids were documented, synergistic toxicological and repellent effects of multi-layer polymer-coating LLIRNs may overcome LLIN-triggered selection pressure for development of new kdr- and metabolic pyrethroid resistances while simultaneously increasing protective efficacy also against kdr- and metabolic pyrethroid-resistant mosquitoes substantially due to the repellent-induced effects of LLIRNs thus indicating that this approach is a promising new candidate for future bed net, curtain, and window screen impregnation aiming at optimized prevention from mosquito-borne diseases.

Gas and particle concentrations in horse stables with individual boxes as a function of the bedding material and the mucking regimen.

PubMed

Fleming, K; Hessel, E F; Van den Weghe, H F A

2009-11-01

The aim of this study was to compare different types of bedding and mucking regimens used in horse stables on the generation of airborne particulate matter <10 microm (PM10) and 3 biogenic gases (carbon dioxide, nitrous oxide, and especially ammonia). Three separate experiments were undertaken. The experiments were carried out in an enclosed stable (9.7 m long, 8.7 m wide, and 3.5 m high) that had 5 single boxes housing 4 horses. The measuring instruments were set up in the middle of one side of the stable. In Exp. 1, 3 types of bedding material (wheat straw, straw pellets, and wood shavings) used for horses were assessed according to their ammonia generation. Each type of bedding was used for 2 wk, with 3 repetitions. The mean ammonia concentrations within the stable were 3.07 +/- 0.23 mg/m(3) for wheat straw, 4.79 +/- 0.23 mg/m(3) for straw pellets, and 4.27 +/- 0.17 mg/m(3) for wood shavings. In Exp. 2, the effects of the mucking regimen on the generation of ammonia and PM10 from wheat straw (the bedding with the least ammonia generation in the previous experiment) were examined using 3 different daily regimens: 1) no mucking out, 2) complete mucking out, and 3) partial mucking out (removing only feces). The mean ammonia concentrations in the stable differed significantly among all 3 mucking regimens (P < 0.05). The greatest values were recorded when the stalls were mucked out completely every day [least squares means (LSM) = 2.25 +/- 0.1 mg/m(3)]. No mucking out resulted in an LSM of 1.92 +/- 0.1 mg of ammonia/m(3), whereas an LSM of 1.54 +/- 0.1 mg of ammonia/m(3) was found when the partial mucking out method was used. No mucking out also resulted in significantly less average PM10 (124.4 +/- 13.4 microg/m(3)) than in the other 2 regimens (P < 0.05). In Exp. 3, a 6-wk bedding regimen without mucking out was evaluated with regard to gas and airborne particle generation. The ammonia values were found not to increase constantly during the course of the 6-wk period. The average weekly values for PM10 also did not increase constantly but varied between approximately 90 and 140 microg/m. It can be concluded from the particle and gas generation patterns found in the results of all 3 experiments that wheat straw was the most suitable bedding of the 3 types investigated and that mucking out completely on a daily basis should not be undertaken in horse stables.

A phase I study of Triapine in combination with doxorubicin in patients with advanced solid tumors.

PubMed

Schelman, William R; Morgan-Meadows, Sherry; Marnocha, Rebecca; Lee, Fred; Eickhoff, Jens; Huang, Wei; Pomplun, Marcia; Jiang, Zhisheng; Alberti, Dona; Kolesar, Jill M; Ivy, Percy; Wilding, George; Traynor, Anne M

2009-05-01

To assess the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics and antitumor activity of Triapine administered in combination with doxorubicin. Patients were treated with doxorubicin intravenously (IV) on day 1 and Triapine IV on days 1-4 of a 21-day cycle. The starting dose (level 1) was doxorubicin 60 mg/m(2) and Triapine 25 mg/m(2). PK analysis was performed at various time-points before and after treatment. Twenty patients received a total of 49 courses of treatment on study. At dose level 2 (doxorubicin 60 mg/m(2), Triapine 45 mg/m(2)), two patients experienced DLTs (febrile neutropenia, grade 4 thrombocytopenia). An additional three patients were enrolled at dose level 1 without initial toxicity. Enrollment then resumed at dose level 2a with a decreased dose of doxorubicin (45 mg/m(2)) with Triapine 45 mg/m(2). The two patients enrolled on this level had two DLTs (diarrhea, CVA). Enrollment was planned to resume at dose level 1; however, the sixth patient enrolled to this cohort developed grade 5 heart failure (ejection fraction 20%, pretreatment EF 62%) after the second course. Thus, doxorubicin and Triapine were reduced to 45 and 25 mg/m(2), respectively (level 1a), prior to resuming enrollment at dose level 1, the MTD. The main drug-related toxicity was myelosuppression. Non-hematologic toxicities included mild-to-moderate fatigue, grade 3 diarrhea and grade 4 CVA. There was one treatment-related death due to heart failure. While no objective responses were observed, subjective evidence of clinical activity was observed in patients with refractory melanoma and prostate cancer. Pretreated patients with advanced malignancies can tolerate the combination of Triapine and doxorubicin at doses that achieve subjective clinical benefit with the main treatment-related toxicities being myelosuppression and fatigue. The MTD was determined to be doxorubicin 60 mg/m(2) on day 1 and Triapine 25 mg/m(2) on days 1-4 of a 21-day cycle.

Twenty-Eight-Day Repeated Inhalation Toxicity Study of Nano-Sized Neodymium Oxide in Male Sprague-Dawley Rats

PubMed Central

Kim, Yong-Soon; Lim, Cheol-Hong; Shin, Seo-Ho; Kim, Jong-Choon

2017-01-01

Neodymium is a future-oriented material due to its unique properties, and its use is increasing in various industrial fields worldwide. However, the toxicity caused by repeated exposure to this metal has not been studied in detail thus far. The present study was carried out to investigate the potential inhalation toxicity of nano-sized neodymium oxide (Nd2O3) following a 28-day repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed to nano-sized Nd2O3-containing aerosols via a nose-only inhalation system at doses of 0 mg/m3, 0.5 mg/m3, 2.5 mg/m3, and 10 mg/m3 for 6 hr/day, 5 days/week over a 28-day period, followed by a 28-day recovery period. During the experimental period, clinical signs, body weight, hematologic parameters, serum biochemical parameters, necropsy findings, organ weight, and histopathological findings were examined; neodymium distribution in the major organs and blood, bronchoalveolar lavage fluid (BALF), and oxidative stress in lung tissues were analyzed. Most of the neodymium was found to be deposited in lung tissues, showing a dose-dependent relationship. Infiltration of inflammatory cells and pulmonary alveolar proteinosis (PAP) were the main observations of lung histopathology. Infiltration of inflammatory cells was observed in the 2.5 mg/m3 and higher dose treatment groups. PAP was observed in all treatment groups accompanied by an increase in lung weight, but was observed to a lesser extent in the 0.5 mg/m3 treatment group. In BALF analysis, total cell counts, including macrophages and neutrophils, lactate dehydrogenase, albumin, interleukin-6, and tumor necrosis factor-alpha, increased significantly in all treatment groups. After a 4-week recovery period, these changes were generally reversed in the 0.5 mg/m3 group, but were exacerbated in the 10 mg/m3 group. The lowest-observed-adverse-effect concentration of nano-sized Nd2O3 was determined to be 0.5 mg/m3, and the target organ was determined to be the lung, under the present experimental conditions in male rats. PMID:28744356

OPEC/OJEC for stage 4 neuroblastoma in children over 1 year of age.

PubMed

Tweddle, D A; Pinkerton, C R; Lewis, I J; Ellershaw, C; Cole, M; Pearson, A D

2001-01-01

This paper reports the toxicity of OPEC/OJEC chemotherapy in stage 4 neuroblastoma patients over 1 year of age. Ninety-five patients with stage 4 neuroblastoma received alternating courses of OPEC/OJEC--vincristine 1.5 mg/m2 (O), cisplatin 80 mg/m2 (P), etoposide 200 mg/m2 (E), cyclophosphamide 600 mg/m2 (C), and carboplatin 500 mg/m2 (J), every 21 days if there was haematological recovery. Seventy out of ninety-five (74%) patients completed seven or more courses and were evaluable for toxicity. Of these 70 patients, 33% had more than three episodes of fever and sepsis, 35% required more than five blood or platelet transfusions, 36% had grade 2 or more gastrointestinal toxicity and 9% had neurotoxicity. There was a median reduction in GFR of 32 ml/min/1.73 m2 (-46 to 134) and there was one toxic death. OPEC/OJEC is a well-tolerated therapy for stage 4 neuroblastoma over 1 year of age.

The processing of the Viking Orbiter range data and its contribution to Mars gravity solutions

NASA Technical Reports Server (NTRS)

Lemoine, Frank G.; Rosborough, George W.; Smith, David E.

1992-01-01

The processing of Doppler data has been the primary method for deriving models of the Mars gravity field. Since the Mariner 9 and Viking spacecraft were placed in orbit about Mars, many models from degree and order 6 to degree and order 50 have been developed. However, during the Viking mission, some 26,000 range measurements to the two Viking Orbiters were also obtained. These data have not previously been used in the derivation of Mars gravity models. A portion of these range data have been processed simultaneously with the Doppler data. Normal equations were generated for both sets of data and were used to create two solutions complete to degree and order 30: a nominal solution including both the range and the Doppler data (MGM-R100), and another solution including only the Doppler data (MGM-R101). Tests with the covariances of these solutions, as well as with orbit overlap tests indicate that the interplanetary range data can be used to improve the modeling of the Mars gravity field.

Using Space for a Better Foundation on Earth: Mechanics of Granular Materials. Educational Brief. Grades 9-12.

ERIC Educational Resources Information Center

Alshibli, Khalid

This publication presents a science activity and instructional information on the mechanics of granular materials, interparticle friction and geometric interlocking between particles which is a fundamental concept in many fields like in the study of earthquakes. This document describes the Mechanics of Granular Materials (MGM) experiments which…

Experimental exposure of healthy subjects with emissions from a gas metal arc welding process--part II: biomonitoring of chromium and nickel.

PubMed

Gube, Monika; Brand, Peter; Schettgen, Thomas; Bertram, Jens; Gerards, Kerstin; Reisgen, Uwe; Kraus, Thomas

2013-01-01

The objective of this study was to investigate whether there is a relationship between the external exposure dose of chromium and nickel caused by a metal active gas welding process with a solid high-alloyed steel welding wire and inner exposure of subjects. In order to perform welding fume exposure under controlled and standardized conditions, the investigations were conducted in the "Aachen Workplace Simulation Laboratory". To perform biological monitoring of chromium and nickel, blood and urine samples of 12 healthy male non-smokers who never worked as welders were collected before and after a 6-h exposure to ambient air (0 mg/m(3)) and to welding fumes of a metal active gas welding process once with a concentration of the welding fume of 1 mg/m(3) and once with a concentration of 2.5 mg/m(3). Although the internal exposure to chromium and nickel in this study was comparatively low, the subjects showed significantly increased concentrations of these metals in urine after exposure to welding fume compared to the values at baseline. Moreover, the observed increase was significantly dose dependent for both of the substances. For the biological monitoring of chromium and nickel in urine of subjects exposed to welding fumes, a dependency on exposure dose was seen under standardized conditions after a single exposure over a period of 6 h. Thus, this study contributes to a better understanding of the relationship between ambient and biological exposures from welding fumes and provides a good basis for evaluating future biological threshold values for these metals in welding occupation.

[Volatile organic compounds concentrations and sources inside new air-conditioned bus].

PubMed

You, Ke-Wei; Ge, Yun-Shan; Qian, Yi-Xin; Liu, Wei; Feng, Bo; Zhang, Yan-Ni; Ning, Zhan-Wu; Hu, Bin; Zhao, Shou-Tang

2008-05-01

The distributing profile and concentration level inside new air-conditioned buses with 53 seats have been determined using the method of thermal desorption-capillary GC/MS under vehicle static conditions. Compounds were identified from their mass spectral data by using US National Institute of Standards and Technology (NIST02). The total numbers of identified components were 33 inside buses, including alkenes (15,45.4%), aromatic compounds (9,27.3%), alcohols (4,12.1%), ketones (3,9.1%) and esters (2,6.1%), especially in the range of C6-C10. The top 5 compounds measured inside buses were decane (8.01 mg/m3), 3-methylhexane (7.10 mg/m3), heptane (5.10 mg/m3), isoheptane (4.20 mg/m3) and 1-Methyl-3-ethylbenzene (3.56 mg/m3), and total volatile organic compounds (TVOC) > 52.5 mg/m3. The main sources of in-vehicle hydrocarbons and aromatic compounds comes from cabin components and interior trim materials (e.g., sealants, carpets, adhesives, paints, leather, plastics, PU foam and PE foam) that may retain certain VOCs during manufacturing, and/or emit these compounds over an extended period of time from off-gassing, aging-related breakdown products, heating/cooling and so on.

Dust and gas exposure in tunnel construction work.

PubMed

Bakke, B; Stewart, P; Ulvestad, B; Eduard, W

2001-01-01

Personal exposures to dust and gases were measured among 189 underground construction workers who were divided into seven occupational groups performing similar tasks in similar working conditions: drill and blast crew; shaft-drilling crew; tunnel-boring machine crew; shotcreting operators; support workers; concrete workers; and electricians. Outdoor tunnel workers were included as a low-exposed reference group. The highest geometric mean (GM) exposures to total dust (6-7 mg/m3) and respirable dust (2-3 mg/m3) were found for the shotcreters, shaft drillers, and tunnel-boring machine workers. Shaft drillers and tunnel-boring machine workers also had the highest GM exposures to respirable alpha-quartz (0.3-0.4 mg/m3), which exceeded the Norwegian occupational exposure limit (OEL) of 0.1 mg/m3. Shaft drillers had the highest exposure to oil mists (GM=1.4 mg/m3), which was generated mainly from pneumatic drilling. For other groups, exposure to oil mist from diesel exhaust and spraying of oil onto concrete forms resulted in exposures of 0.1-0.5 mg/m3. Exposure to nitrogen dioxide was similar across all groups (GM=0.4-0.9 ppm), except for shaft drillers and tunnel-boring machine workers, who had lower exposures. High short-term exposures (>10 ppm), however, occurred when workers were passing through the blasting cloud.

Phase II trial of irinotecan plus cisplatin in patients with recurrent or metastatic squamous carcinoma of the head and neck.

PubMed

Gilbert, Jill; Cmelak, Anthony; Shyr, Yu; Netterville, James; Burkey, Brian B; Sinard, Robert J; Yarbrough, Wendall G; Chung, Christine H; Aulino, Joseph M; Murphy, Barbara A

2008-07-01

Patients with recurrent or metastatic HNC have a poor response and survival with currently available chemotherapy agents. Thus, new agents are needed. The authors report the results of a phase II trial of irinotecan and cisplatin in patients with metastatic or recurrent HNC. Patients were treated with irinotecan 65 mg/m2 IV over 90 minutes and cisplatin 30 mg/m2 were administered intravenously weekly for four weeks, followed by a two week rest. However, after 17 patients were treated with weekly irinotecan at a dose of 65 mg/m2, toxicity analysis demonstrated the poor tolerance of that dose in this patient population. Thus, the protocol was amended, and irinotecan was dose reduced to a starting dose of 50 mg/m2. Twenty-three additional patients were treated with this dose. Forty patients were enrolled on study between February 2002 and April 2006, 17 patients at the first dose level and 23 patients at the amended dose level. Overall, 12 of 17 patients (71%) treated with irinotecan 65 mg/m2 experienced clinically significant grade 3 or 4 toxicity. Twelve patients required dose reductions. Toxicity was reduced but 17% of patients still experienced grade 3 or 4 toxicity on the lower irinotecan dose. The response rate was 35% for patients treated at irinotecan 65 mg/m2 and 22% for patients treated at 50 mg/m2. No complete responses were noted. The combination of irinotecan and cisplatin is efficacious in a poor prognosis group of patients but toxicity is substantial. (Copyright) 2008 American Cancer Society.

Phase I Study of Oxaliplatin and Irinotecan in Pediatric Patients with Refractory Solid Tumors: A Children’s Oncology Group Study

PubMed Central

McGregor, Lisa M.; Spunt, Sheri L.; Furman, Wayne L.; Stewart, Clinton F.; Schaiquevich, Paula; Krailo, Mark D.; Speights, RoseAnne; Ivy, Percy; Adamson, Peter C.; Blaney, Susan M.

2010-01-01

Background This study estimates the maximum tolerated dose (MTD) and describes the toxicities of oxaliplatin combined with irinotecan in children with refractory solid tumors. Methods Oxaliplatin was administered on days 1 and 8 in combination with irinotecan on days 1–5 and 8–12 of a 21-day cycle. An oral cephalosporin was administered daily to ameliorate irinotecan-associated diarrhea. Pharmacokinetic studies of oxaliplatin and UGT1A1 genotyping were performed. Results Thirteen patients were enrolled. Dose-limiting diarrhea (n = 3), serum lipase elevation (n = 3), serum amylase elevation (n = 2), colitis, abdominal pain, and headache (n = 1 each) occurred at the first dose level (60 mg/m2/dose oxaliplatin; 20 mg/m2/dose irinotecan). Only 1 of 7 patients treated with reduced doses of both agents (40 mg/m2/dose oxaliplatin; 15 mg/m2/dose irinotecan) experienced a DLT, diarrhea. When the oxaliplatin dose was re-escalated (60 mg/m2) with irinotecan 15 mg/m2, 2 of 3 patients had DLT (1 diarrhea, 1 hypokalemia). Myelosuppression was minimal. One patient had a complete response and another had stable disease for 6 cycles of therapy. The median oxaliplatin area under the concentration versus time curve (AUC0→∞) was 5.9 µ g·h/mL (range 1.8–7.6 µg·h/mL). The frequency of 6/6, 6/7, and 7/7 UGT1A1 promoter genotypes were 5/10, 4/10, and 1/10, respectively. Conclusion The oxaliplatin MTD was 40 mg/m2/dose on days 1 and 8 in combination with irinotecan 15 mg/m2/dose (days 1–5 and 8–12). There was some evidence of anti-tumor activity; however, severe toxicity, expected (diarrhea) and unexpected (elevation in pancreatic enzymes), was observed. PMID:19170226

Pharmacokinetic/pharmacodynamic modeling and simulation of neutropenia during phase I development of liposome-entrapped paclitaxel.

PubMed

Fetterly, Gerald J; Grasela, Thaddeus H; Sherman, Jeffrey W; Dul, Jeanne L; Grahn, Amy; Lecomte, Diane; Fiedler-Kelly, Jill; Damjanov, Nevena; Fishman, Mayer; Kane, Michael P; Rubin, Eric H; Tan, Antoinette R

2008-09-15

To evaluate the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of liposome-entrapped paclitaxel easy-to-use (LEP-ETU) and to characterize the relationship between LEP-ETU concentrations and the time course of neutropenia in cancer patients. LEP-ETU was administered to 88 patients and 63 were evaluable for pharmacokinetic/pharmacodynamic (PK/PD) analysis following 1.5- and 3-h infusions every 3 weeks (q3w; dose range, 135-375 mg/m(2)). MTD was identified using a 3 + 3, up-and-down dose-finding algorithm. PK/PD modeling was done to describe the temporal relationship between paclitaxel concentrations and neutrophil count. Simulations assessed the influence of dose and schedule on neutropenia severity to help guide dose selection. The MTD of LEP-ETU was identified as 325 mg/m(2). DLTs occurring at 375 mg/m(2) consisted of febrile neutropenia and neuropathy. The C(max) and area under the plasma concentration-time curve of LEP-ETU were less than proportional with increasing dose. The PK/PD model showed that LEP-ETU inhibition of neutrophil proliferation was 9.1% per 10 mug/mL of total paclitaxel concentration. The incidence of grade 4 neutropenia increased from 33% to 42% across the dose range of 275 to 325 mg/m(2) q3w. For a dose of 110 mg/m(2) given weekly, grade 4 neutropenia was estimated to be 16% compared with 42% for the same total dose administered q3w. LEP-ETU can be administered safely at higher doses than Taxol. Modeling and simulation studies predict that 325 mg/m(2) LEP-ETU q3w provides acceptable neutropenic events relative to those observed at 175 mg/m(2) Taxol q3w. A 275 mg/m(2) dose may offer an improved therapeutic index.

Prospective, open, multicentre Phase I/II trial to assess safety and efficacy of neoadjuvant radiochemotherapy with docetaxel and cisplatin for esophageal carcinoma.

PubMed

Ma, Hong-Bing; Di, Zheng-Li; Wen, Jiao; Ke, Yue; Sun, Xiaodong; Ren, Juan

2015-02-01

Esophageal squamous cell carcinoma is increasingly treated with trimodality therapy. The objective of this Phase I/II clinical study is to assess the efficacy and safety of neoadjuvant radiochemotherapy with docetaxel and cisplatin and radiotherapy in patients with esophagectomy for locally advanced squamous cell carcinoma of the esophagus with neoadjuvant chemoradiotherapy. Patients with esophageal squamous cell carcinoma received radiochemotherapy (50 Gy/25 fractions during Weeks 1-5) using a three-dimensional conformal radiation therapy or intensity-modulated radiation therapy technique together with weekly docetaxel (20 mg/m(2) at dose levels 1 and 2, 25 mg/m(2) at dose level 3 on Weeks 1-5) and cisplatin (30 mg/m(2) at dose level 1, 40 mg/m(2) at dose levels 2 and 3 on Weeks 1-5) from January 2009 to December 2011. The dose-limiting toxicities and maximum tolerated dose were the primary endpoints and overall response rate and progression-free survival were the secondary endpoints. Over this timeframe, a total of 49 patients completed trimodality therapy. Thirteen patients were treated at dose level 1, 21 patients at dose level 2 and 15 patients at dose level 3.The maximum tolerated dose for docetaxel was 20 mg/m(2) and cisplatin 40 mg/m(2). The complete response or partial response was observed in 26.5% (13/49) of patients. Thirty-four patients (69.4%) were treated with neoadjuvant radiochemotherapy followed by surgical resection. The median progression-free survival and median overall survival for all patients (n = 49) were 8 and 17.2 months, respectively. The median overall survival was 27.5 months for patients treated at dose level 2. Neoadjuvant radiochemotherapy with docetaxel 20 mg/m(2) and cisplatin 40 mg/m(2) was effective and tolerable induction regimen in patients with esophageal tumors. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Amorphous silica. Types, health effects of exposure, NDS].

PubMed

Woźniak, H; Wiecek, E

1995-01-01

Maximum allowable concentration (MAC) values for amorphous silica dust have not been identified in the Polish legal regulations up-to-date. In this work the authors review values of allowable (recommended) amorphous silica dust concentrations in other countries. Data on other types of amorphous silica (natural and synthetic) used in industry as well as data on health effects of exposure to these types of dust are presented. The work encompasses 42 entries in the references and one Table which includes the following proposed MAC values: Non-calcinate diatomaceous earth (diatomite) and synthetic silica: Total dust--10 mg/m3 Respirable dust--2 mg/m3 Calcinate diatomaceous earth (diatomite) and fused silica (vitreous silica): Total dust--2 mg/m3 Respirable dust--1 mg/m3.

[Investigation of the H₂S contamination in cabin causing fishermen's eye burns].

PubMed

Qian, Ding-Guo; Wang, Jian-Yue; Wang, Yun-Ming; Ma, Yin-Xiang; Huang, Yu-Geng; Zhou, Chang-Bo; Tang, Zhi-Bo

2010-12-01

To investigate the H(2)S pollution in cabins which caused the fishermen's eye burns. Fifty-six fishing boats' H(2)S concentration was surveyed and 56 fishermen's eyes were inspected. The air samples were collected from 21 fishing boats' cabins, where the eye burns took place and the monitoring conditions met the inspection requirement, in order to confirm the concentration of H(2)S when eye burns and the systemic poisoning happened. Thirty fishing boats were divided into two groups: one was using air ventilating and spraying, the other was using naturally ventilation to find out the effective method of dispersing H(2)S. Five fishing boats were surveyed in which the fishermen had slight symptom of bulbar conjunctiva hyperemia and cough to find out the minimum concentration of H(2)S which caused the eye burns and respiratory mucosa. Among 56 fishermen who were surveyed, 46 fishermen's eyes (92 eyes) burnt and they were from 21 vessels, 10 of them (20 eyes) were moderate, 36 of them (72 eyes) were light. The concentration of H(2)S in the 21 fishing boats' cabins which caused eye burns was (99 ± 38) mg/m(3). The first measuring of the concentration of H(2)S in the 30 fishing boats in which fish were not discharged yet was (219 ± 31) mg/m(3). Air ventilating and spraying group's concentration of H(2)S was (213 ± 24) mg/m(3), while that of naturally ventilation group's was (225 ± 36) mg/m(3). Dispersing after 1 hour, the concentration of H(2)S of air ventilating and spraying group was (21 ± 3) mg/m(3), the decreased concentration was (192 ± 21) mg/m(3), fell 90%; the concentration of naturally ventilation group was (184 ± 36) mg/m(3), the decreased concentration was (41 ± 8) mg/m(3), fell 18%. The difference between the two groups' decreased concentration was significant (t = 25.627, P < 0.05). The threshold value of H(2)S concentration that could cause the eye burns was 38 mg/m(3)(exposure time 120 min). In 7 vessels, the concentration of H(2)S in the cabins was (123 ± 9) mg/m(3) where 10 fishermen's moderate eye burns happened. In other 7 vessels, the concentration of H(2)S in the cabins was (54 ± 7) mg/m(3) where 19 fishermen's light eye burns happened. The difference of H(2)S concentration between the two groups was significant (t = 14.236, P < 0.05). High H(2)S concentration and long exposure time in cabin can cause serious eye burns. The bilge air ventilation and inner cabin spraying are the effective method to clear the H(2)S in cabin within short time.

Evolution of Welding-Fume Aerosols with Time and Distance from the Source: A study was conducted on the spatiotemporal variability in welding-fume concentrations for the characterization of first- and second-hand exposure to welding fumes.

PubMed

Cena, L G; Chen, B T; Keane, M J

2016-08-01

Gas metal arc welding fumes were generated from mild-steel plates and measured near the arc (30 cm), representing first-hand exposure of the welder, and farther away from the source (200 cm), representing second-hand exposure of adjacent workers. Measurements were taken during 1-min welding runs and at subsequent 5-min intervals after the welding process was stopped. Number size distributions were measured in real time. Particle mass distributions were measured using a micro-orifice uniform deposition impactor, and total mass concentrations were measured with polytetrafluorothylene filters. Membrane filters were used for collecting morphology samples for electron microscopy. Average mass concentrations measured near the arc were 45 mg/m 3 and 9 mg/m 3 at the farther distance. The discrepancy in concentrations at the two distances was attributed to the presence of spatter particles, which were observed only in the morphology samples near the source. As fumes aged over time, mass concentrations at the farther distance decreased by 31% (6.2 mg/m 3 ) after 5 min and an additional 13% (5.4 mg/m 3 ) after 10 min. Particle number and mass distributions during active welding were similar at both distances, indicating similar exposure patterns for welders and adjacent workers. Exceptions were recorded for particles smaller than 50 nm and larger than 3 μm, where concentrations were higher near the arc, indicating higher exposures of welders. These results were confirmed by microscopy analysis. As residence time increased, number concentrations decreased dramatically. In terms of particle number concentrations, second-hand exposures to welding fumes during active welding may be as high as first-hand exposures.

Pre-operative combined 5-FU, low dose leucovorin, and sequential radiation therapy for unresectable rectal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minsky, B.D.; Cohen, A.M.; Kemeny, N.

1993-04-02

The authors performed a Phase 1 trial to determine the maximum tolerated dose of combined pre-operative radiation (5040 cGy) and 2 cycles (bolus daily [times] 5) of 5-FU and low dose LV (20 mg/m2), followed by surgery and 10 cycles of post-operative LV/5-FU in patients with unresectable primary or recurrent rectal cancer. Twelve patients were entered. The initial dose of 5-FU was 325 mg/m2. 5-FU was to be escalated while the LV remained constant at 20 mg/m2. Chemotherapy began on day 1 and radiation on day 8. The post-operative chemotherapy was not dose escalated; 5-FU: 425 mg/m2 and LV: 20more » mg/m2. The median follow-up was 14 months (7--16 months). Following pre-operative therapy, the resectability rate with negative margins was 91% and the pathologic complete response rate was 9%. For the combined modality segment (preoperative) the incidence of any grade 3+ toxicity was diarrhea: 17%, dysuria: 8%, mucositis: 8%, and erythema: 8%. The median nadir counts were WBC: 3.1, HGB: 8.8, and PLT: 153000. The maximum tolerated dose of 5-FU for pre-operative combined LV/5-FU/RT was 325 mg/m2 with no escalation possible. Therefore, the recommended dose was less than 325 mg/m2. Since adequate doses of 5-FU to treat systemic disease could not be delivered until at least 3 months (cycle 3) following the start of therapy, the authors do not recommend that this 5-FU, low dose LV, and sequential radiation therapy regimen be used as presently designed. However, given the 91% resectability rate they remain encouraged with this approach. 31 refs., 1 fig., 2 tabs.« less

Radiation concurrent with gemcitabine for locally advanced head and neck cancer: a phase I trial and intracellular drug incorporation study.

PubMed

Eisbruch, A; Shewach, D S; Bradford, C R; Littles, J F; Teknos, T N; Chepeha, D B; Marentette, L J; Terrell, J E; Hogikyan, N D; Dawson, L A; Urba, S; Wolf, G T; Lawrence, T S

2001-02-01

To examine the feasibility and dose-limiting toxicity (DLT) of once-weekly gemcitabine at doses predicted in preclinical studies to produce radiosensitization, concurrent with a standard course of radiation for locally advanced head and neck cancer. Tumor incorporation of gemcitabine triphosphate (dFdCTP) was measured to assess whether adequate concentrations were achieved at each dose level. Twenty-nine patients with unresectable head and neck cancer received a course of radiation (70 Gy over 7 weeks, 5 days weekly) concurrent with weekly infusions of low-dose gemcitabine. Tumor biopsies were performed after the first gemcitabine infusion (before radiation started), and the intracellular concentrations of dFdCTP were measured. Severe acute and late mucosal and pharyngeal-related DLT required de-escalation of gemcitabine dose in successive patient cohorts receiving dose levels of 300 mg/m(2)/wk, 150 mg/m(2)/wk, and 50 mg/m(2)/wk. No DLT was observed at 10 mg/m(2)/wk. The rate of endoscopy- and biopsy-assessed complete tumor response was 66% to 87% in the various cohorts. Tumor dFdCTP levels were similar in patients receiving 50 to 300 mg/m(2) (on average, 1.55 pmol/mg, SD 1.15) but were barely or not detectable at 10 mg/m(2). A high rate of acute and late mucosa-related DLT and a high rate of complete tumor response were observed in this regimen at the dose levels of 50 to 300 mg/m(2), which also resulted in similar, subcytotoxic intracellular dFdCTP concentrations. These results demonstrate significant tumor and normal tissue radiosensitization by low-dose gemcitabine. Different regimens of combined radiation and gemcitabine should be evaluated, based on newer preclinical data promising an improved therapeutic ratio.

Comparison between the Amount of Environmental Change and the Amount of Transcriptome Change

PubMed Central

Ogata, Norichika; Kozaki, Toshinori; Yokoyama, Takeshi; Hata, Tamako; Iwabuchi, Kikuo

2015-01-01

Cells must coordinate adjustments in genome expression to accommodate changes in their environment. We hypothesized that the amount of transcriptome change is proportional to the amount of environmental change. To capture the effects of environmental changes on the transcriptome, we compared transcriptome diversities (defined as the Shannon entropy of frequency distribution) of silkworm fat-body tissues cultured with several concentrations of phenobarbital. Although there was no proportional relationship, we did identify a drug concentration “tipping point” between 0.25 and 1.0 mM. Cells cultured in media containing lower drug concentrations than the tipping point showed uniformly high transcriptome diversities, while those cultured at higher drug concentrations than the tipping point showed uniformly low transcriptome diversities. The plasticity of transcriptome diversity was corroborated by cultivations of fat bodies in MGM-450 insect medium without phenobarbital and in 0.25 mM phenobarbital-supplemented MGM-450 insect medium after previous cultivation (cultivation for 80 hours in MGM-450 insect medium without phenobarbital, followed by cultivation for 10 hours in 1.0 mM phenobarbital-supplemented MGM-450 insect medium). Interestingly, the transcriptome diversities of cells cultured in media containing 0.25 mM phenobarbital after previous cultivation (cultivation for 80 hours in MGM-450 insect medium without phenobarbital, followed by cultivation for 10 hours in 1.0 mM phenobarbital-supplemented MGM-450 insect medium) were different from cells cultured in media containing 0.25 mM phenobarbital after previous cultivation (cultivation for 80 hours in MGM-450 insect medium without phenobarbital). This hysteretic phenomenon of transcriptome diversities indicates multi-stability of the genome expression system. Cellular memories were recorded in genome expression networks as in DNA/histone modifications. PMID:26657512

A phase I and pharmacologic trial of two schedules of the proteasome inhibitor, PS-341 (bortezomib, velcade), in patients with advanced cancer.

PubMed

Dy, Grace K; Thomas, James P; Wilding, George; Bruzek, Laura; Mandrekar, Sumithra; Erlichman, Charles; Alberti, Dona; Binger, Kim; Pitot, Henry C; Alberts, Steven R; Hanson, Lorelei J; Marnocha, Rebecca; Tutsch, Kendra; Kaufmann, Scott H; Adjei, Alex A

2005-05-01

To define the toxicities, pharmacodynamics, and clinical activity of the proteasome inhibitor, PS-341 (bortezomib), in patients with advanced malignancies. Twenty-eight patients (14 male and 14 female) received PS-341 twice weekly for 4 of 6 weeks (schedule I). Because toxicity necessitated dose omissions on this schedule, 16 additional patients (12 male and 4 female) received PS-341 twice weekly for 2 of every 3 weeks (schedule II). A total of 73 courses of treatment was given (median, 2; range, 1-4). Inhibition of 20S proteasome activity in peripheral blood mononuclear cells (PBMC) and accumulation of proteasome-targeted polypeptides in tumor tissue were evaluated as pharmacodynamic markers of PS-341 activity. The most common toxicity was thrombocytopenia, which was dose limiting at 1.7 mg/m2 (schedule I) and 1.6 mg/m2 (schedule II), respectively. Sensory neuropathy was dose-limiting in a patient in schedule I. Grade > or =3 toxicities for schedule I were constipation, fatigue, myalgia, and sensory neuropathy. Grade > or =3 toxicities for schedule II were dehydration resulting from diarrhea, nausea and vomiting, fatigue, hypoglycemia, and hypotension. The maximum tolerated dose was 1.5 mg/m2 for both schedules. Reversible dose-dependent decreases in 20S proteasome activity in PBMCs were observed, with 36% inhibition at 0.5 mg/m2, 52% at 0.9 mg/m2, and 75% at 1.25 mg/m2. Accumulation of proteasome-targeted polypeptides was detected in tumor samples after treatment with PS-341. A patient with multiple myeloma had a partial response. PS-341 given 1.5 mg/m2 twice weekly for 2 of every 3 weeks is well tolerated and should be further studied.

[Exposure to VOCs in furniture factories in two populations in northern Colombia].

PubMed

Vargas-Ramos, Yadiris E; Marrugo-Negrete, José L

2014-01-01

Assess the exposure to volatile organic compounds (VOCs)in furniture handicraft factories workers in two populations of Sucre (Sincelejo and Sampués), North of Colombia.Identify possible signs and/or symptoms related to exposure to these contaminants. This was an analytical cross sectional study (2011), using a questionnaire. Study population consisted of 66 individuals, 41 exposed and 25 controls. Personal samples were collected for concentration quantifying of benzene, toluene, ethylbenzene and xylenes (both groups) and contrasting them with health effects possible attributed to these contaminants. The concentrations of benzene, toluene and m/p-xylene were higher in the exposed group (9.5 mg/m(3), 8.1 mg/m(3) and 12.1 mg/m(3))compared with the control group (0.2 mg/m(3), 0.3 mg/m(3) and 0.03 mg/m(3)). Muscular pain 82.9 % (PR=3.8; CI95%:1.2-11.8) and somnolence 65.9 % (PR=4.9; CI95%:1.7-14.7)were associated with a higher exposure.Factor such as mixtures of solvents (thinner) in the work and vehicles' traffic can contribute to these results. Several sources contribute to increases personal exposure of VOCs in furniture handicraft factories workers North of Colombia. Additionally, excessive use of these compounds may be generating adverse effects on the health of workers.

Two-week aerosol inhalation study on polyethylene glycol (PEG) 3350 in F-344 rats.

PubMed

Klonne, D R; Dodd, D E; Losco, P E; Troup, C M; Tyler, T R

1989-03-01

PEGs in the 3000 to 4000 MW range are used in many pharmaceutical and cosmetic applications; they produce little ocular or dermal irritation and have extremely low acute and subchronic toxicity by oral and dermal routes of administration. However, little information exists on the potential of aerosols of these materials to produce adverse health effects. F-344 rats were exposed to aerosols of PEG 3350 (20% w:w in water) at 0, 109, 567, or 1008 (highest attainable) mg/m3 for 6 hr/d, 5 d/wk for 2 wk. No exposure-related toxicity was found with regard to clinical signs, ophthalmology, serum chemistry, urinalysis, or gross pathology. Exposure-related effects included: a 50% increase in the neutrophil count (males only) at 1008 mg/m3; decreased body weight gain (16%) for both the 567 and 1008 mg/m3 groups (males only); absolute lung weights of both sexes were increased 10 and 18% for the 567 and 1008 mg/m3 groups, respectively. A slight increase in the number of macrophages in the alveoli was the only change observed histologically in all PEG 3350-exposed groups. Therefore, inhalation of aerosols of PEG 3350 at concentrations up to 1008 mg/m3 produced relatively little toxicity in rats, the lung was the target organ, and the no-observable-effect-level was between 109 to 567 mg/m3.

An analysis of employee exposure to organic dust at large-scale composting facilities

NASA Astrophysics Data System (ADS)

Sykes, P.; Allen, J. A.; Wildsmith, J. D.; Jones, K. P.

2009-02-01

The occupational health implications from exposure to dust, endotoxin and 1-3 β Glucan at commercial composting sites are uncertain. This study aims to establish employee exposure levels to inhalable and respirable dust, endotoxin and 1-3 β Glucan during various operational practices in the composting process. Personal samples were collected and the inhalable and respirable dust fractions were determined by gravimetric analysis. Endotoxin concentrations were determined using a Limulus Amebocyte Lysate assay (LAL). 1-3 β Glucan levels were estimated using a specific blocking agent to establish the contribution that these compounds gave to the original endotoxin assay. Employees' exposure to dust was found to be generally lower than the levels stipulated in the Control of Substances Hazardous to Health Regulations (COSHH) 2002 (as amended), (median inhalable fraction 1.08 mg/m3, min 0.25 mg/m3 max 10.80 mg/m3, median respirable fraction 0.05 mg/m3, min 0.02 mg/m3, max 1.49 mg/m3). Determination of the biological component of the dust showed that employees' exposures to endotoxin were elevated (median 31.5 EU/m3, min 2.00 EU/m3, max 1741.78 EU/m3), particularly when waste was agitated (median 175.0 EU/m3, min 2.03 EU/m3, max 1741.78 EU/m3). Eight out of 32 (25%) of the personal exposure data for endotoxin exceeded the 200 EU/m3 temporary legal limit adopted in the Netherlands and thirteen out of 32 (40.6%) exceeded the suggested 50 EU/m3 guidance level suggested to protect workers from respiratory health effects. A significant correlation was observed between employee inhalable dust exposure and personal endotoxin concentration (r = 0.728, p<0.05) and also personal endotoxin exposure and 1-3 β Glucan concentration (r = 0.817, p<0.05). Further work is needed to explore the possibility of using inhalable dust concentration as a predictor for personal endotoxin exposure. The general dust levels stipulated in the COSHH Regulations 2002 (as amended) are inadequate for managing the potential health risks associated with endotoxin exposure at composting sites. Employee exposure levels and dose-response disease mechanisms are not well understood at this present time. Consequently, in light of this uncertainty, it is recommended that a precautionary approach be adopted in managing the potential health risks associated with inhalation of organic dusts at composting sites.

[Comparative studies on toxicity of various dielectrics, petroleum derivatives, used in electroerosion technology. IV. Morphological and cytoenzymatic changes in the lungs and acid-base imbalance in rats chronically exposed to petroleum hydrocarbons].

PubMed

Starek, A; Kamiński, M

1981-01-01

In rats exposed to odourless kerosene of 75 and 300 mg/m3 concentration, for 14 weeks, morphologic and cytoenzymatic examinations of lungs have been carried out and acid-base equilibrium indices in blood have been determined. Passive congestion of lung parenchyma, subpleural blood extravasation, atelectasis foci, thickened interalveolar septa with infiltrates from neutrophils, lymphocytes, eosinophils and macrophages have been found. In addition a decrease in succinic dehydrogenase activity, NADPH -- tetrazolium reductase, and Mg++-ATP-ase and increase in acid phosphatase activity have been revealed. Those have been focal changes, involving, apart from bronchial tree (low exposure -- 75 mg/m3), the remaining lung parenchyma segments (high exposure -- 300 mg/m3). In addition, disturbances in acid-base equilibrium in form of compensated metabolic alkalosis (75 mg/m3) and compensated metabolic acidosis (300 mg/m3) have occurred. The obtained results demonstrate toxic effects of kerosene hydrocarbons on the function and structure of lungs.

Persistent DNA damage measured by comet assay of Sprague Dawley rat lung cells after five days of inhalation exposure and 1 month post-exposure to dispersed multi-wall carbon nanotubes (MWCNTs) generated by new MWCNT aerosol generation system.

PubMed

Kim, Jin Sik; Sung, Jae Huyck; Song, Kyung Seuk; Lee, Ji Hyun; Kim, Sun Man; Lee, Gun Ho; Ahn, Kang Ho; Lee, Jong Seong; Shin, Jae Hoon; Park, Jung Duck; Yu, Il Je

2012-08-01

Carbon nanotubes (CNTs) have specific physico-chemical properties that are useful for the electronics, automotive, and construction industries. Yet, despite their many advantages, there is a current lack of available information on the human health and environmental hazards of CNTs. For this reason, the current study investigated the inhalation toxicity potential of multiwall CNTs (MWCNTs). Eight-week-old rats were divided into four groups (10 rats in each group), the fresh-air control (0mg/m(3)), low-concentration group (0.16mg/m(3)), middle-concentration group (0.34mg/m(3)), and high-concentration group (0.94mg/m(3)), and the whole body was exposed to MWCNTs for 5 days (6h/day). Lung cells were then isolated from five rats in each group on day 0 and 1 month after the 5-day exposure, respectively. The MWCNTs were generated by a newly designed generation system, and the MWCNT concentrations in the exposure chambers monitored in accordance with National Institute for Occupational Safety and Health (NIOSH) 0500 using a membrane filter. The MWCNTs were also sampled for an elemental carbon concentration analysis using a glass filter. The animals exhibited no significant body weight changes, abnormal clinical signs, or mortality during the experiment. A single-cell gel electrophoresis assay (Comet assay) was conducted to determine the DNA damage in lung cells obtained from the right lung. As a result, the Olive tail moments were 23.00±1.76, 30.39±1.96, 22.96±1.26, and 33.98±2.21 for the control, low-, middle-, and high-concentration groups, respectively, on day 0 postexposure. Meanwhile, 1 month postexposure, the Olive tail moments were 25.00±2.71, 28.39±3.55, 22.56±1.36, and 31.97±3.16 for the control, low-, middle-, and high-concentration groups, respectively. Thus, the MWCNTs caused a statistically significant increase in lung DNA damage at high concentration (0.94mg/m(3)) when compared with the negative control group on day 0 and 1 month postexposure.

Anatomy of the auditory thalamocortical system in the Mongolian gerbil: nuclear origins and cortical field-, layer-, and frequency-specificities.

PubMed

Saldeitis, Katja; Happel, Max F K; Ohl, Frank W; Scheich, Henning; Budinger, Eike

2014-07-01

Knowledge of the anatomical organization of the auditory thalamocortical (TC) system is fundamental for the understanding of auditory information processing in the brain. In the Mongolian gerbil (Meriones unguiculatus), a valuable model species in auditory research, the detailed anatomy of this system has not yet been worked out in detail. Here, we investigated the projections from the three subnuclei of the medial geniculate body (MGB), namely, its ventral (MGv), dorsal (MGd), and medial (MGm) divisions, as well as from several of their subdivisions (MGv: pars lateralis [LV], pars ovoidea [OV], rostral pole [RP]; MGd: deep dorsal nucleus [DD]), to the auditory cortex (AC) by stereotaxic pressure injections and electrophysiologically guided iontophoretic injections of the anterograde tract tracer biocytin. Our data reveal highly specific features of the TC connections regarding their nuclear origin in the subdivisions of the MGB and their termination patterns in the auditory cortical fields and layers. In addition to tonotopically organized projections, primarily of the LV, OV, and DD to the AC, a large number of axons diverge across the tonotopic gradient. These originate mainly from the RP, MGd (proper), and MGm. In particular, neurons of the MGm project in a columnar fashion to several auditory fields, forming small- and medium-sized boutons, and also hitherto unknown giant terminals. The distinctive layer-specific distribution of axonal endings within the AC indicates that each of the TC connectivity systems has a specific function in auditory cortical processing. Copyright © 2014 Wiley Periodicals, Inc.

Personal exposure to dust and endotoxin in Robusta and Arabica coffee processing factories in Tanzania.

PubMed

Sakwari, Gloria; Mamuya, Simon H D; Bråtveit, Magne; Larsson, Lennart; Pehrson, Christina; Moen, Bente E

2013-03-01

Endotoxin exposure associated with organic dust exposure has been studied in several industries. Coffee cherries that are dried directly after harvest may differ in dust and endotoxin emissions to those that are peeled and washed before drying. The aim of this study was to measure personal total dust and endotoxin levels and to evaluate their determinants of exposure in coffee processing factories. Using Sidekick Casella pumps at a flow rate of 2l/min, total dust levels were measured in the workers' breathing zone throughout the shift. Endotoxin was analyzed using the kinetic chromogenic Limulus amebocyte lysate assay. Separate linear mixed-effects models were used to evaluate exposure determinants for dust and endotoxin. Total dust and endotoxin exposure were significantly higher in Robusta than in Arabica coffee factories (geometric mean 3.41 mg/m(3) and 10 800 EU/m(3) versus 2.10 mg/m(3) and 1400 EU/m(3), respectively). Dry pre-processed coffee and differences in work tasks explained 30% of the total variance for total dust and 71% of the variance for endotoxin exposure. High exposure in Robusta processing is associated with the dry pre-processing method used after harvest. Dust and endotoxin exposure is high, in particular when processing dry pre-processed coffee. Minimization of dust emissions and use of efficient dust exhaust systems are important to prevent the development of respiratory system impairment in workers.

Dissecting Stop Transfer versus Conservative Sorting Pathways for Mitochondrial Inner Membrane Proteins in Vivo*

PubMed Central

Park, Kwangjin; Botelho, Salomé Calado; Hong, Joonki; Österberg, Marie; Kim, Hyun

2013-01-01

Mitochondrial inner membrane proteins that carry an N-terminal presequence are sorted by one of two pathways: stop transfer or conservative sorting. However, the sorting pathway is known for only a small number of proteins, in part due to the lack of robust experimental tools with which to study. Here we present an approach that facilitates determination of inner membrane protein sorting pathways in vivo by fusing a mitochondrial inner membrane protein to the C-terminal part of Mgm1p containing the rhomboid cleavage region. We validated the Mgm1 fusion approach using a set of proteins for which the sorting pathway is known, and determined sorting pathways of inner membrane proteins for which the sorting mode was previously uncharacterized. For Sdh4p, a multispanning membrane protein, our results suggest that both conservative sorting and stop transfer mechanisms are required for insertion. Furthermore, the sorting process of Mgm1 fusion proteins was analyzed under different growth conditions and yeast mutant strains that were defective in the import motor or the m-AAA protease function. Our results show that the sorting of mitochondrial proteins carrying moderately hydrophobic transmembrane segments is sensitive to cellular conditions, implying that mitochondrial import and membrane sorting in the physiological environment may be dynamically tuned. PMID:23184936

Draft Environmental Assessment for the Combat Support Training Complex, Tyndall Air Force Base, Florida.

DTIC Science & Technology

1989-07-25

nwdas Green Seaturtle PK E E 1,19 FISH Acipenser oxyrhynchus &esotoi Gulf Sturgeon SR SSC UR2 17,19 Mustela vison lutensis Florida Mink P - UR2 13...immediately dangerous to life and health (IDLH) with respect to respiratory irritation. This represents the maximum concentration from which one could...Threshold 0.004 mg/m3 ACGIH’ Median effective concentration 1-5 mg/m3 ACGIH Respiratory irritation Permissible exposure limit (PEL) 0.4 mg/m3

Paclitaxel and carboplatin in early phase studies: Roswell Park Cancer Institute experience in the subset of patients with lung cancer.

PubMed

Creaven, P J; Raghavan, D; Pendyala, L; Loewen, G; Kindler, H L; Berghorn, E J

1997-08-01

The combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given by 3-hour infusion followed by carboplatin infused over 30 minutes has been evaluated in a series of phase I studies and is currently being explored in a phase II study in patients with limited- and extensive-stage small cell lung cancer. Pharmacokinetic measurements were performed at all dose levels in the phase I studies, in which the use of granulocyte colony-stimulating factor in previously treated patients enabled more than twice the dose of paclitaxel to be given with low to moderate doses of carboplatin (dosed to a target area under the concentration-time curve of 4.0 mg x min x mL[-1]). Treatment-naive patients tolerated high paclitaxel doses (270 mg/m2) with carboplatin (dosed to a target area under the curve of 4.5 mg x min x mL[-1]) without granulocyte colony-stimulating factor support. Twenty-three patients (including previously treated and untreated) with non-small cell lung cancer were entered at a variety of paclitaxel doses in the phase I studies. At 100 to 205 mg/m2 paclitaxel, none of nine treated patients responded; at 230 to 290 mg/m2, four (29%) of 14 responded. In the phase II study of paclitaxel 250 mg/m2 in previously untreated patients with small cell lung cancer, two of five evaluable patients with extensive-stage disease have shown a partial response. In a preliminary analysis of the pharmacodynamics of paclitaxel in relation to neurotoxicity (dose limiting in two of three phase I studies), neurotoxicity correlated with the total dose of paclitaxel, the area under the curve, and the peak paclitaxel concentration, but not with the length of time plasma paclitaxel levels remained above 0.05 micromol/L. These correlations were not strong, however, and analysis of these data is ongoing.

Worker exposure to volatile organic compounds in the vehicle repair industry.

PubMed

Wilson, Michael P; Hammond, S Katharine; Nicas, Mark; Hubbard, Alan E

2007-05-01

This study evaluated exposures among vehicle repair technicians to hexane, acetone, toluene, and total volatile organic compounds (VOCs). On randomly selected workdays, we observed a characteristic pattern of solvent use among 36 technicians employed in 10 repair shops, each of which used an aerosol solvent product. We obtained quantitative exposure measurements from a subset of nine technicians (employed in three of these shops) who used an aerosol product containing hexane (25-35%), acetone (45-55%), and toluene (5-10%). The time-weighted average (TWA) exposure concentration for task-length breathing zone (BZ) samples (n = 23) was 36 mg/m(3) for hexane, 50 mg/m(3) for acetone, and 10 mg/m(3) for toluene. The TWA area concentrations (n = 49) obtained contemporaneously with BZ samples ranged from 25% to 35% of the BZ concentrations. The solvent emission rate (grams emitted/task time) was correlated with the total VOC exposure concentration (R(2) = 0.45). The proportions of VOCs in the BZ samples were highly correlated (r = 0.89 to 0.95) and were similar to those of the bulk product. Continuous exposure measurements for total VOCs (n = 1238) during 26 tasks produced a mean BZ VOC "pulse" of 394 mg/m(3) within 1 min following initiation of solvent spraying. The geometric mean air speed was 5.2 meters/min in the work areas (n = 870) and was associated with 0.8 air changes per minute in the BZ. The findings suggest that vehicle repair technicians who use aerosol solvent products experience episodic, inhalation exposures to the VOCs contained in these products, and the proportions of VOCs in the breathing zone are similar to those of the bulk product. Because acetone appears to amplify the severity and duration of the neurotoxic effects of n-hexane, products formulated with both hexane and acetone should be avoided. Further evaluation of exposures to VOCs is needed in this industry, along with information on effective alternatives to aerosol solvent products.

An Evaluation of an Aftermarket Local Exhaust Ventilation Device for Suppressing Respirable Dust and Respirable Crystalline Silica Dust from Powered Saws

PubMed Central

Garcia, Alberto; Jones, Erica; Echt, Alan S.; Hall, Ronald M.

2015-01-01

The objective of this study was to quantify the respirable dust and respirable silica exposures of roofing workers using an electric powered circular saw with an aftermarket local exhaust ventilation attachment to cut concrete roofing tiles. The study was conducted to determine whether the local exhaust ventilation attachment was able to control respirable dust and respirable silica exposure below occupational exposure limits. Time-integrated filter samples and direct reading respirable dust concentrations were evaluated. The local exhaust ventilation consisted of a shroud attached to the cutting plane of the saw; the shroud was then connected to a small electric axial fan, which is intended to collect dust at the point of generation. All sampling was conducted with the control in use. Roofers are defined as those individuals who solely lay tiles. Cutters/roofers are defined as those workers who operate the powered saw to cut tiles and also lay tiles. Respirable dust from this evaluation ranged from 0.13 to 6.59 milligrams per cubic meter (mg/m3) with a geometric mean of 0.38 mg/m3 for roofers and from 0.45 to 3.82 mg/m3 with a geometric mean of 1.84 mg/m3 for cutters/roofers. Cutters/roofers usually handle areas close to crevices, edges, or tips of the roof whereas roofers handle areas where complete tiles can be placed. The respirable dust exposures for all cutters/roofers indicated concentrations exceeding the Occupational Safety and Health Administration’s (OSHA) permissible exposure limit (PEL) for respirable dust containing silica; it was also exceeded for some of the roofers. The respirable silica concentrations ranged from 0.04 to 0.15 mg/m3 with an average of 0.09 mg/m3 for roofers, and from 0.13 to 1.21 mg/m3 with an average of 0.48 mg/m3 for cutters/roofers. As with respirable dust, the respirable silica exposures to cutters/roofers were higher than the exposures for roofers. PMID:25148513

An evaluation of an aftermarket local exhaust ventilation device for suppressing respirable dust and respirable crystalline silica dust from powered saws.

PubMed

Garcia, Alberto; Jones, Erica; Echt, Alan S; Hall, Ronald M

2014-01-01

The objective of this study was to quantify the respirable dust and respirable silica exposures of roofing workers using an electric-powered circular saw with an aftermarket local exhaust ventilation attachment to cut concrete roofing tiles. The study was conducted to determine whether the local exhaust ventilation attachment was able to control respirable dust and respirable silica exposure below occupational exposure limits (OELs). Time-integrated filter samples and direct reading respirable dust concentrations were evaluated. The local exhaust ventilation consisted of a shroud attached to the cutting plane of the saw; the shroud was then connected to a small electric axial fan, which is intended to collect dust at the point of generation. All sampling was conducted with the control in use. Roofers are defined as those individuals who only lay tiles. Cutters/roofers are defined as those workers who operate the powered saw to cut tiles and also lay tiles. Respirable dust from this evaluation ranged from 0.13 to 6.59 milligrams per cubic meter (mg/m(3)) with a geometric mean of 0.38 mg/m(3) for roofers and from 0.45 to 3.82 mg/m(3) with a geometric mean of 1.84 mg/m(3) for cutters/roofers. Cutters/roofers usually handle areas close to crevices, edges, or tips of the roof whereas roofers handle areas where complete tiles can be placed. The respirable dust exposures for all cutters/roofers indicated concentrations exceeding the Occupational Safety and Health Administration's (OSHA) permissible exposure limit (PEL) for respirable dust containing silica; it was also exceeded for some of the roofers. The respirable silica concentrations ranged from 0.04 to 0.15 mg/m(3) with a geometric mean of 0.09 mg/m(3) for roofers, and from 0.13 to 1.21 mg/m(3) with a geometric mean of 0.48 mg/m(3) for cutters/roofers. As with respirable dust, the respirable silica exposures for cutters/roofers were higher than the exposures for roofers.

Local Geomorphology as a Determinant of Macrofaunal Production in a Mountain Stream.

PubMed

Huryn, Alexander D; Wallace, J Bruce

1987-12-01

By comparing distributions of functional group production among different habitats in an Appalachian mountain stream, the influence of site-specific geomorphology upon the overall functional group composition of the animal community was demonstrated. By replicated monthly sampling, substrate particle size distributions, current velocity, standing crops of benthic organic matter, and production of macrofauna were measured in each of three principal habitats: bedrock-outcrop, riffle, and pool. Samples were taken at randomly assigned locations and the relative number of samples taken from each habitat was assumed to be proportional to the area of the habitat within the stream. These proportions were used to weight production measured in each habitat and the resulting values were summed to obtain production per unit area of average stream bed. The bedrock-outcrop habitat was characterized by high material entertainment and export as indicated by significantly higher current velocities and lower standing crops of detritus compared to the riffle and pool habitats. Pools were sites of low entertainment and high retention of organic matter as demonstrated by significantly lower current velocities and higher accumulations of detritus than other habitats. The riffle habitat was intermediate to the bedrock-outcrop and pool habitats in all parameters measured. Annual production of collector-filterers was highest in the bedrock-outcrop (ash-free dry mass 1920 mg/m 2 ), followed by riffle (278 mg/m 2 ) and pool (32 mg/m 2 ). Although constituting only 19% of the stream area, the bedrock-outcrop habitat contributed 68% of the habitat-weighted collector-filterer production. Annual production of shredders was highest in pools (2616 mg/m 2 ), followed by riffles (1657 mg/m 2 ) and bedrock-outcrop (579 mg/m 2 ). The pool habitat, constituting 23% of stream area, contributed 36% of shredder production. Annual production of scrapers was highest in the riffle habitat (905 mg/m 2 ), followed by bedrock-outcrop (517-mg/m 2 ) and pool (238 mg/m 2 ). Riffles constituted 58% of total stream area and were the source of 77% of the habitat-weighted scraper production. Annual production of engulfing predators was greatest in the pool habitat (2313 mg/m 2 ), followed by riffles (1765 mg/m 2 ) and bedrock-outcrop (687 mg/m 2 ). The relatively lower production of engulfing predators in the bedrock-outcrop habitat reflects a functional shift in mode of resource acquisition by predators, with predaceous collector-filterers (Arcto-psychinae: Trichoptera) predominating in the bedrock-outcrop. Collector-gatherer production was more evenly distributed, with the bedrock-outcrop, riffle, and pool habitats each contributing 14, 54, and 33% to the habitat-weighted production, respectively. Unlike all other functional groups, this distribution was not significantly different from the distribution of stream area among habitats and reflected lack of dependence on specific physical attributes of the local environment for access to food by members of this functional group. Local geomorphology determined the diversity and spatial distribution of bedrock-outcrops, riffles, and pools in the study stream. In turn, the functional structure of the macrofauna, when viewed holistically, was the result of the integration of the relative contributions of each habitat type of total stream area. Total habitat-weighted annual production in the study stream was estimated at 5093 and 1921 mg/m 2 for primary and secondary consumers, respectively. The distribution of habitat-weighted production among functional groups was: collector-gatherers (39%), followed by shredders (225), engulfing predators (22%), scrapers (13%), and collector-filterers (8%). This functional structure agrees favorably with current conceptual models of head water streams draining forested catchments. © 1987 by the Ecological Society of America.

Respirable concrete dust--silicosis hazard in the construction industry.

PubMed

Linch, Kenneth D

2002-03-01

Concrete is an extremely important part of the infrastructure of modern life and must be replaced as it ages. Many of the methods of removing, repairing, or altering existing concrete structures have the potential for producing vast quantities of respirable dust. Since crystalline silica in the form of quartz is a major component of concrete, airborne respirable quartz dust may be produced during construction work involving the disturbance of concrete, thereby producing a silicosis hazard for exposed workers. Silicosis is a debilitating and sometimes fatal lung disease resulting from breathing microscopic particles of crystalline silica. Between 1992 and 1998, the National Institute for Occupational Safety and Health (NIOSH) made visits to construction projects where concrete was being mechanically disturbed in order to obtain data concerning respirable crystalline silica dust exposures. The construction activities studied included: abrasive blasting, concrete pavement sawing and drilling, and asphalt/concrete milling. Air samples of respirable dust were obtained using 10-mm nylon cyclone pre-separators, 37-mm polyvinyl chloride (PVC) filters, and constant-flow pumps calibrated at 1.7 L/min. In addition, high-volume respirable dust samples were obtained on 37-mm PVC filters using 1/2" metal cyclones (Sensidyne model 18) and constant-flow pumps calibrated at 9.0 L/min. Air sample analysis included total weight gain by gravimetric analysis according to NIOSH Analytical Method 600 and respirable crystalline silica (quartz and cristobalite) using x-ray diffraction, as per NIOSH Analytical Method 7500. For abrasive blasting of concrete structures, the respirable crystalline silica (quartz) concentration ranged up to 14.0 mg/m3 for a 96-minute sample resulting in an eight-hour time-weighted average (TWA) of 2.8 mg/m3. For drilling concrete highway pavement the respirable quartz concentrations ranged up to 4.4 mg/m3 for a 358-minute sample, resulting in an eight-hour TWA of 3.3 mg/m3. For concrete wall grinding during new building construction the respirable quartz measurements ranged up to 0.66 mg/m3 for a 191-minute sample, resulting in an eight-hour TWA of 0.26 mg/m3. The air sampling results for concrete sawing ranged up to 14.0 mg/m3 for a 350-minute sample resulting in an eight-hour TWA of 10.0 mg/m3. During the milling of asphalt from concrete highway pavement, the sampling indicated a respirable quartz concentration ranging up to 0.34 mg/m3 for a 504-minute sample, resulting in an eight-hour TWA of 0.36 mg/m3. The results of this work indicate the potential for respirable quartz concentrations involving disturbance of concrete to range up to 280 times the NIOSH Recommended Exposure Limit (REL) of 0.05 mg/m3 assuming exposure for an eight- to ten-hour workday. Considering the aging of the concrete infrastructure in the United States, these results pose a challenge to all who have an interest in preventing silica exposures and the associated disease silicosis.

Analysis of Relative Concentration of Ethanol and Other Odorous Compounds (OCs) Emitted from the Working Surface at a Landfill in China

PubMed Central

Li, Dong; Lu, Wenjing; Liu, Yanjun; Guo, Hanwen; Xu, Sai; Ming, Zhongyuan; Wang, Hongtao

2015-01-01

Estimating odor emissions from landfill sites is a complicated task because of the various chemical and biological species that exist in landfill gases. In this study, the relative concentration of ethanol and other odorous compounds emitted from the working surface at a landfill in China was analyzed. Gas sampling was conducted at the landfill on a number of selected days from March 2012 to March 2014, which represented different periods throughout the two years. A total of 41, 59, 66, 54, 63, 54, 41, and 42 species of odorous compounds were identified and quantified in eight sampling activities, respectively; a number of 86 species of odorous compounds were identified and quantified all together in the study. The measured odorous compounds were classified into six different categories (Oxygenated compounds, Halogenated compounds, Terpenes, Sulfur compounds, Aromatics, and Hydrocarbons). The total average concentrations of the oxygenated compounds, sulfur compounds, aromatics, halogenated compounds, hydrocarbons, and terpenes were 2.450 mg/m3, 0.246 mg/m3, 0.203 mg/m3, 0.319 mg/m3, 0.530 mg/m3, and 0.217 mg/m3, respectively. The relative concentrations of 59 odorous compounds with respect to the concentration of ethyl alcohol (1000 ppm) were determined. The dominant contaminants that cause odor pollution around the landfill are ethyl sulfide, methyl mercaptan, acetaldehyde, and hydrogen sulfide; dimethyl disulfide and dimethyl sulfide also contribute to the pollution to a certain degree. PMID:25769100

PM10 emissions and PAHs: The importance of biomass type and combustion conditions.

PubMed

Zosima, Angela T; Tzimou-Tsitouridou, Roxani D; Nikolaki, Spyridoula; Zikopoulos, Dimitrios; Ochsenkühn-Petropoulou, Maria Th

2016-01-01

The aim of the present work was to investigate the impact of biomass combustion with respect to conditions and fuel types on particle emissions (PM10) and their PAHs content. Special concern was on sampling, quantification and characterization of PM using different appliances, fuels and operating procedures. For this purpose different lab-scale burning conditions, two pellets stoves (8.5 and 10 kW) and one open fireplace were tested by using eight fuel types of biomass. An analytical method is described for the quantitative determination of 16 PAHs using liquid-liquid extraction and subsequent measurement by gas chromatography coupled to a mass spectrometer (GC-MS). Average PM10 emissions ranged from about 65 to 170 mg/m(3) at lab-scale combustions with flow oxygen at 13% in the exhaust gas, 85-220 mg/m(3) at 20% O2, 47-83 mg/m(3) at pellet stove of 10 kW, 34-69 mg/m(3) at pellet stove of 8.5 kW and 106-194 mg/m(3) at the open fireplace. The maximum permitted particle emission limit is 150 mg/m(3). Pellets originated from olive trees and from nonmixture trees were found to emit the lowest particulate matter in relation to the others, so they are considered healthiest and suitable for domestic heating reasons. In general, the results show that biomass open burning is an important PM10 and PAHs emission source.

A Phase II Study of Cetuximab (Erbitux®) plus FOLFIRI for Irinotecan and Oxaliplatin-refractory Metastatic Colorectal Cancer

PubMed Central

Koo, Dong Hoe; Lee, Jae-Lyun; Kim, Tae Won; Chang, Heung Moon; Ryu, Min-Hee; Lee, Sung Sook; Kim, Min Kyoung; Sym, Sun Jin; Lee, Jung Shin

2007-01-01

We have evaluated the efficacy and safety of cetuximab plus FOLFIRI for irinotecan and oxaliplatin-refractory colorectal cancers. From September 2004 to February 2006, 31 patients with metastatic colorectal cancer were treated with cetuximab (400 mg/m2 intravenously [IV] over 2 hr on day 1 followed by weekly 1-hr infusions of 250 mg/m2) plus bi-weekly FOLFIRI (irinotecan 150 mg/m2 IV over 90 min, and leucovorin 100 mg/m2 IV over 2 hr, followed by 5-FU 400 mg/m2 IV bolus on day 1, and followed by 5-FU 2,400 mg/m2 by continuous IV over 46 hrs). Patients received a median of four cycles (range: 1-23). Eight (25.8%) patients had confirmed partial responses and 10 (32.2%) had stable disease. After a median follow-up of 13.2 months for surviving patients, the median time to progression was 2.9 months, the median duration of response was 5.4 months, and the median overall survival was 10.9 months. Skin toxicity was observed in 25 patients (80.4%) including grade 3 in 6 patients (19.4%). Other common non-hematologic toxicities of all grades were mucositis (32.3%), asthenia (22.6%), diarrhea (12.9%), and paronychial cracking (12.9%). The combination of cetuximab with FOLFIRI was effective and tolerable in colorectal cancer patients heavily pretreated with a number of chemotherapy regimens. PMID:17923763

Health assessment of gasoline and fuel oxygenate vapors: developmental toxicity in rats.

PubMed

Roberts, Linda G; Gray, Thomas M; Trimmer, Gary W; Parker, Robert M; Murray, F Jay; Schreiner, Ceinwen A; Clark, Charles R

2014-11-01

Gasoline-vapor condensate (BGVC) or condensed vapors from gasoline blended with methyl t-butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME) diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA) were evaluated for developmental toxicity in Sprague-Dawley rats exposed via inhalation on gestation days (GD) 5-20 for 6h/day at levels of 0 (control filtered air), 2000, 10,000, and 20,000mg/m(3). These exposure durations and levels substantially exceed typical consumer exposure during refueling (<1-7mg/m(3), 5min). Dose responsive maternal effects were reduced maternal body weight and/or weight change, and/or reduced food consumption. No significant malformations were seen in any study. Developmental effects occurred at 20,000mg/m(3) of G/TAME (reduced fetal body weight, increased incidence of stunted fetuses), G/TBA (reduced fetal body weight, increased skeletal variants) and G/DIPE (reduced fetal weight) resulting in developmental NOAEL of 10,000mg/m(3) for these materials. Developmental NOAELs for other materials were 20,000mg/m(3) as no developmental toxicity was induced in those studies. Developmental NOAELs were equal to or greater than the concurrent maternal NOAELs which ranged from 2000 to 20,000mg/m(3). There were no clear cut differences in developmental toxicity between vapors of gasoline and gasoline blended with the ether or alcohol oxygenates. Copyright © 2014 Elsevier Inc. All rights reserved.

A phase I human trial of mitoguazone and gemcitabine sequential bi-weekly treatment of cancer patients.

PubMed

Ishmael, D Richard; Chen, Wei R; Hamilton, Steven A; Liu, Hong; Nordquist, Robert E

2003-01-01

Our previous studies have demonstrated the existence of synergism in a combination therapy using mitoguazone and gemcitabine when the mitoguazone is administered 24 hours before gemcitabine. Based on the cell culture and animal experimental results, a phase I clinical trial was performed in order to determine the toxicity of the combined treatment. Mitoguazone and gemcitabine were administered sequentially: mitoguazone on day 1 and gemcitabine on day 2. This cycle was repeated every 2 weeks. The dosages of these two drugs were varied between patients. Ten patients were enrolled in the study. Six patients began treatment at dose level 1 (mitoguazone 500 mg/m2, gemcitabine 1500 mg/m2), three at dose level 2 (mitoguazone 500 mg/m2, gemcitabine 2000 mg/m2), and one at dose level 3 (mitoguazone 600 mg/m2, gemcitabine 2000 mg/m2). Dose-limiting toxicity (DLT) was only observed in two patients treated at dose level 1 and one patient treated at dose level 3, while all the other patients only experienced nonhematologic toxicity, such as asthenia and mucositis. Two melanoma patients showed responses (one partial and one minor) to the treatment. One lymphoma patient also showed a brief partial response. This phase I trial indicated that the combination of mitoguazone and gemcitabine had limited but noticeable activity for treatment of cancer patients. Further study on the toxicity and on the effect of the scheduled mitoguazone-gemcitabine combination is needed.

Material Science

NASA Image and Video Library

2002-08-06

Twila Schneider of Infinity Technology in Huntsville, AL, uses a small sand displacement box to explain the principles of the Mechanics of Granular Materials (MGM-III) experiment to two young Virginia students. The activity was part of the Space Research and You education event held by NASA's Office of Biological and Physical Research on June 25, 2002, in Arlington, VA, to highlight the research that will be conducted on STS-107.

Metal-Coated <100>-Cut GaAs Coupled to Tapered Parallel-Plate Waveguide for Cherenkov-Phase-Matched Terahertz Detection: Influence of Crystal Thickness

NASA Astrophysics Data System (ADS)

delos Santos, Ramon; Mag-usara, Valynn; Tuico, Anthony; Copa, Vernalyn; Salvador, Arnel; Yamamoto, Kohji; Somintac, Armando; Kurihara, Kazuyoshi; Kitahara, Hideaki; Tani, Masahiko; Estacio, Elmer

2018-04-01

The influence of crystal thickness of metal-coated <100>-cut GaAs (M-G-M) on Cherenkov-phase-matched terahertz (THz) pulse detection was studied. The M-G-M detectors were utilized in conjunction with a metallic tapered parallel-plate waveguide (TPPWG). Polarization-sensitive measurements were carried out to exemplify the efficacy of GaAs in detecting transverse magnetic (TM)- and transverse electric (TE)-polarized THz waves. The reduction of GaAs' thickness increased the THz amplitude spectra of the detected TM-polarized THz electro-optic (EO) signal due to enhanced electric field associated with a more tightly-focused and well-concentrated THz radiation on the thinner M-G-M. The higher-fluence THz beam coupled to the thinner M-G-M improved the integrated intensity of the detected THz amplitude spectrum. This trend was not observed for TE-polarized THz waves, wherein the integrated intensities were almost comparable. Nevertheless, good agreement of spectral line shapes of the superposed TM- and TE-polarized THz-EO signals with that of elliptically polarized THz-EO signal demonstrates excellent polarization-resolved detection capabilities of M-G-M via Cherenkov-phase-matched EO sampling technique.

Prophylactic G-CSF and antibiotics enable a significant dose-escalation of triplet-chemotherapy in non-small cell lung cancer.

PubMed

Timmer-Bonte, J N H; Punt, C J A; vd Heijden, H F M; van Die, C E; Bussink, J; Beijnen, J H; Huitema, A D R; Tjan-Heijnen, V C G

2008-05-01

In advanced non-small cell lung cancer (NSCLC) the clinical benefit of a platinum-based doublet is only modest, therefore, attenuated dosed three-drug combinations are investigated. We hypothesized that with adequate support a full dosed chemotherapy triplet is feasible. The study was designed as a dose finding study of paclitaxel in chemotherapy-naive patients. Paclitaxel was given as a 3-h infusion on day 1, followed by fixed doses of teniposide (or etoposide) 100mg/m(2) days 1, 3, 5 and cisplatin 80 mg/m(2) day 1 every 3 weeks. As myelotoxicity was expected to be the dose-limiting toxicity, prophylactic G-CSF and antibiotic support was evaluated. Indeed, paclitaxel 120 mg/m(2) resulted in dose-limiting neutropenia, despite G-CSF support. Teniposide/etoposide day 1, 3, 5 was less myelotoxic compared to day 1, 2, 3. G-CSF support allowed paclitaxel dose-escalation to 250 mg/m(2). The addition of prophylactic antibiotics enabled dose-escalation to 275 mg/m(2) without reaching MTD. In conclusion, G-CSF and antibiotics prophylaxis enables the delivery of a full dosed chemotherapy triplet in previously untreated NSCLC patients.

Concentrations and size distribution of inhalable and respirable dust among sugar industry workers: a pilot study in Khon Kaen, Thailand.

PubMed

Sakunkoo, Pornpun; Chaiear, Naesinee; Chaikittiporn, Chalermchai; Sadhra, Steven

2011-11-01

There has been very limited information regarding bagasse exposure among workers in sugar industries as well as on health outcomes. The authors determined the occupational exposure of sugar industry workers in Khon Kaen to airborne bagasse dust. The size of the bagasse dust ranged from 0.08 to 9 µm with the highest size concentration of 2.1 to 4.7 µm. The most common size had a geometric mean diameter of 5.2 µm, with a mass concentration of 6.89 mg/m(3)/log µm. The highest mean values of inhalable and respirable dust were found to be 9.29 mg/m(3) from February to April in bagasse storage, 5.12 mg/m(3) from May to September, and 4.12 mg/m(3) from October to January. Inhalable dust concentrations were 0.33, 0.47, and 0.41 mg/m(3), respectively. Workers are likely to be exposed to high concentrations of bagasse dust and are at risk of respiratory diseases. Preventive measures, both in the form of engineering designs and personal protective devices, should be implemented.

Metal-Coated <100>-Cut GaAs Coupled to Tapered Parallel-Plate Waveguide for Cherenkov-Phase-Matched Terahertz Detection: Influence of Crystal Thickness

NASA Astrophysics Data System (ADS)

delos Santos, Ramon; Mag-usara, Valynn; Tuico, Anthony; Copa, Vernalyn; Salvador, Arnel; Yamamoto, Kohji; Somintac, Armando; Kurihara, Kazuyoshi; Kitahara, Hideaki; Tani, Masahiko; Estacio, Elmer

2018-06-01

The influence of crystal thickness of metal-coated <100>-cut GaAs (M-G-M) on Cherenkov-phase-matched terahertz (THz) pulse detection was studied. The M-G-M detectors were utilized in conjunction with a metallic tapered parallel-plate waveguide (TPPWG). Polarization-sensitive measurements were carried out to exemplify the efficacy of GaAs in detecting transverse magnetic (TM)- and transverse electric (TE)-polarized THz waves. The reduction of GaAs' thickness increased the THz amplitude spectra of the detected TM-polarized THz electro-optic (EO) signal due to enhanced electric field associated with a more tightly-focused and well-concentrated THz radiation on the thinner M-G-M. The higher-fluence THz beam coupled to the thinner M-G-M improved the integrated intensity of the detected THz amplitude spectrum. This trend was not observed for TE-polarized THz waves, wherein the integrated intensities were almost comparable. Nevertheless, good agreement of spectral line shapes of the superposed TM- and TE-polarized THz-EO signals with that of elliptically polarized THz-EO signal demonstrates excellent polarization-resolved detection capabilities of M-G-M via Cherenkov-phase-matched EO sampling technique.

[Distribution features of chlorophyll a and primary productivity in high frequency area of red tide in East China Sea during spring].

PubMed

Zhou, Weihua; Huo, Wenyi; Yuan, Xiangcheng; Yin, Kedong

2003-07-01

The distributions of chlorophyll a and primary productivity were determined during April to May 2002 in the East China Sea. The results showed that the average concentration of chlorophyll a was 1.086 mg.m-3 at surface layer, and that nano- and pico-phytoplankton (< 20 microns) dominated the phytoplankton biomass in this sea region during Spring (up to 64% of total chlorophyll a content). Ultra-phytoplankton (< 5 microns) consisted 27% of total phytoplankton biomass. Nutrients and feeding pressure of zooplankton affected the distribution of chlorophyll a and its size-fractionation. The average primary productivity was 10.091 mg.m-3.h-1, while that of red tide tracking stations R-03, RL-01 and RG-01 was 399.984 mg.m-3.h-1. Light and nutrients were the main factors affecting the distributions of chlorophyll a and primary productivity. The station DC-11 had a high concentration of phytoplankton biomass. The surface layer concentration of chlorophyll a and primary productivity were up to 9,082 mg.m-3 and 128,79 mg.m-3.h-1, respectively, but the color of the seawater was normal.

Respiratory effects of borax dust.

PubMed Central

Garabrant, D H; Bernstein, L; Peters, J M; Smith, T J; Wright, W E

1985-01-01

The relation of respiratory symptoms, pulmonary function, and abnormalities of chest radiographs to estimated exposures of borax dust has been investigated in a cross sectional study of 629 actively employed borax workers. Ninety three per cent of the eligible workers participated in the study and exposures ranged from 1.1 mg/m3 to 14.6 mg/m3. Symptoms of acute respiratory irritation such as dryness of the mouth, nose, or throat, dry cough, nose bleeds, sore throat, productive cough, shortness of breath, and chest tightness were related to exposures of 4.0 mg/m3 or more, and were infrequent at exposures of 1.1 mg/m3. Symptoms of persistent respiratory irritation meeting the definition of chronic simple bronchitis were related to exposure among non-smokers. Decrements in the FEV1 as a percentage of predicted were seen among smokers who had heavy cumulative borax exposures (greater than or equal to 80 mg/m3 years) but were not seen among less exposed smokers or among non-smokers. Radiographic abnormalities were uncommon and were not related to dust exposure. Borax dust appears to act as a simple respiratory irritant and perhaps causes small changes in the FEV1 among smokers who are heavily exposed. PMID:3878156

Effects of sources of protein and enzyme supplementation on protein digestibility and chyme characteristics in broilers.

PubMed

Yu, B; Lee, T T T; Chiou, P W S

2002-07-01

1. The purpose of this study was to evaluate the effects of protein source and enzyme supplementation on protein digestibility and chyme characteristics in broilers. 2. One hundred and twenty growing (13 d old) and 60 finishing (34 d old) Arbor Acre strain commercial male broilers were selected and placed into individual metabolic cages. 3. The experiment was a 5 x 2 factorial arrangement with 5 different sources of protein: casein, fish meal, soybean meal (SBM), soy protein concentrate (SPC), maize gluten meal (MGM) and two levels of protease (bromelain), 0 and 65 CDU/kg diets. 4. The diets were iso-nitrogenous and semi-purified, with Cr2O3 as an indicator for determination of ileal digestibility and chyme characteristics. 5. Apparent ileal protein digestibility (AIPD) in both growing and finishing chickens was highest on the casein diet, followed by fish meal, SBM, SPC and MGM. 6. Enzyme inclusion did not improve protein digestibility, but significantly decreased the digesta pH value in the gizzard and increased pH in the ileum in the 3-week-old broilers. 7. The digesta pH values in the gizzard and duodenum were significantly lower in the SBM and fish meal groups compared with the other protein groups. The molecular weight distribution pattern of the soluble protein in the chyme of the gastrointestinal (GI) segments showed a similar trend, regardless of the enzyme inclusion or the stage of growth. 8. The molecular weight profile of soluble protein changed dynamically in the casein fed broilers from the gizzard to ileum and the low molecular weight proteins, < 7 kDa, reached maximum levels at the ileum. The molecular weight profile of the soluble protein in the SBM and SPC changed between the jejunum and the ileum and in the intermediate molecular soluble protein weight (7 to 10 kDa) was significantly decreased. This indicated that the hydrolysis process began from the middle to the posterior end of the small intestine. 9. Similar profiles were also shown with fish meal protein. The pattern of distribution, however, did not show any prominent change in the GI segments of the MGM group. 10. The pepsin, trypsin and chymotrypsin protease activity in the gizzard and duodenum were highest in the casein group and lowest in the MGM group as compared with the other protein groups. 11. The rate change in the patterns of molecular weight distribution in soluble protein and the digestive enzyme activity provide indications of the partial digestibility of different protein sources. The exogenous enzyme, bromelain, did not show any beneficial effect on protein digestion.

Replacing groundnut cake with gluten meals of rice and maize in diets for growing Sahiwal cattle

PubMed Central

Malik, Tariq A.; Thakur, S. S.; Mahesh, M. S.; Yogi, R. K.

2017-01-01

Objective This experiment investigated the effect of isonitrogenous replacement of groundnut cake (GNC) by rice gluten meal (RGM) and maize gluten meal (MGM) at 75% level on nutrient intake, apparent digestibility, growth performance and related blood constituents in growing Sahiwal cattle. Methods Eighteen Sahiwal calves were divided into three groups, based on average body weight (87.24 kg) and age (6 to 12 mo), and treatments were assigned to the different groups randomly. The first group (GP-I) was kept as control and received GNC-based concentrate mixture. In second (GP-II) and third (GP-III) groups, 750 g/kg nitrogen (N) of GNC was substituted by RGM and MGM respectively, with similar forage:concentrate ratio (56:44). Results The 90 days of experimental feeding revealed that intake of dry matter, crude protein and digestibility coefficients for all nutrients did not differ among groups. Furthermore, although N balance was greater (p≤0.05) for GP-III than GP-I and GP-II, average daily gain was similar between GP-I and GP-II but greater (p≤0.05) for GP-III. In addition, feed efficiency and related haematological variables did not differ due to treatments. Conclusion Nutritional worth of GNC and RGM was highly comparable in terms of intake, digestibility and growth in growing calves. However, MGM was found to be more efficacious in improving growth rate than RGM at 75% replacement level of GNC protein. PMID:28423873

Hyperprogressive Disease in the Irradiation Field after a Single Dose of Nivolumab for Gastric Cancer: A Case Report

PubMed Central

Ogata, Takatsugu; Satake, Hironaga; Ogata, Misato; Hatachi, Yukimasa; Yasui, Hisateru

2018-01-01

Following the ATTRACTION-2 study, nivolumab was approved for advanced gastric cancer in Japan. However, pseudoprogression and hyperprogressive disease have been reported in patients treated with immune checkpoint inhibitors. We report a patient with gastric cancer who received nivolumab after radiotherapy only to experience rapid progression within the irradiation field after the first immunotherapy session. A 66-year-old man with dysphagia visited our hospital and was diagnosed with stage IV gastroesophageal cancer (human epidermal growth factor receptor-2 score = 0). He commenced a G-SOX regimen (S-1 80 mg/m2 on days 1–14 and oxaliplatin 100 mg/m2 on day 1, repeated every 3 weeks) in June 2017. The dysphagia worsened despite 3 cycles of G-SOX, and computed tomography (CT) revealed constriction of the gastroesophageal junction. To ameliorate the dysphagia, palliative chemoradiotherapy (S-1 and 50.4 Gy in 28 fractions) was performed starting in August 2017. The patient's dysphagia had not resolved after completing radiotherapy, and pain on swallowing worsened. Nivolumab (3 mg/m2 every 2 weeks) was administered 7 days after the completion of radiotherapy. The patient experienced malaise and worsening dysphagia before the second cycle. CT 15 days after the first nivolumab administration revealed rapid progression in the irradiation field. His general condition rapidly deteriorated, and he died 24 days after the first administration. This episode suggests that administration of nivolumab after radiotherapy may be a risk factor for hyperprogressive disease. PMID:29681813

Effects of experimental exposure to triethylamine on vision and the eye

PubMed Central

Jarvinen, P.; Engstrom, K.; Riihimaki, V.; Ruusuvaara, P.; Setala, K.

1999-01-01

OBJECTIVES: To determine the effect of triethylamine (TEA) on the cornea and to evaluate the cause of blurred vision. To find the lowest observed effect concentration of exposure to TEA. METHODS: Four people were exposed to TEA for 4 hours at concentrations of 40.6, 6.5, and 3.0 mg/m3. Before and after every exposure, symptoms and ocular microscopy findings were recorded. Binocular visual acuity and contrast sensitivity at 2.5% contrast were also measured. Also, before and after the 40.6 mg/m3 exposure, corneal thickness was measured and ocular dimensions were recorded by ultrasonography, endothelial cells of the cornea were analysed, and serum and lacrimal specimens were collected for the analysis of TEA. RESULTS: After exposure to 40.6 mg/m3 TEA there was a marked oedema in the corneal epithelium and subepithelial microcysts. However, corneal thickness increased only minimally because of the epithelial oedema. The lacrimal concentrations of TEA were, on average (range) 41 (18-83) times higher than the serum TEA concentrations. The vision was blurred in all subjects and visual acuity and contrast sensitivity had decreased in three of the four subjects. After exposure to TEA at 6.5 mg/m3 two subjects experienced symptoms, and contrast sensitivity had decreased in three of the four subjects. There were no symptoms or decreases in contrast sensitivity after exposure to a TEA concentration of 3.0 mg/m3. CONCLUSIONS: TEA caused a marked oedema and microcysts in corneal epithelium but only minor increases in corneal thickness. The effects may be mediated by the lacrimal fluid owing to its high TEA concentration. Four hour exposure to a TEA concentration of 3.0 mg/m3 seemed to cause no effects, whereas exposure to 6.5 mg/m3 for the same period caused blurred vision and a decrease in contrast sensitivity.   PMID:10341738

A controlled clinical trial testing two potentially non-cross-resistant chemotherapeutic regimens in small-cell carcinoma of the lung.

PubMed

Broder, L E; Selawry, O S; Charyulu, K N; Ng, A; Bagwell, S

1981-03-01

With the objectives of improving response rate, duration of response, and survival in small-cell carcinoma of the lung, 39 patients were randomized to remission-induction with either one of two potentially non-cross-resistant drug combinations: APE (consisting of adriamycin, 35 mg/m2 IV, D1 Q 3 weeks; procarbazine, 60 mg/m2 PO, D1-10 Q 3 weeks; and the epipodophyllotoxin (VP16-213), 130 mg/m2 IV, D8, 15 Q 3 weeks) or MOCC (composed of methotrexate, 15 mg/m2 IV (with [vincristine] Oncovin) or PO twice weekly D8-21 Q 3 weeks; Oncovin, 1.5 mg/m2 IV, D8, 15 Q 3 weeks; cyclophosphamide, 600 mg/m2 IV, D1 Q 3 weeks, and CCNU, 60 mg/m2 PO Q 6 weeks). A fixed crossover to the alternate regimen occurred at three months. Radiotherapy was delivered to the primary tumor (locoregional disease only) by a split course technique (1,750 rads for five days with a three-week split, followed by 3,400 rads over 17 days). The median survival including both arms was 11 months for regional and nine months for extensive disease. The chemotherapeutic activity of both regimens was comparable, with 15/17 (88 percent) of the patients responding to APE (including six complete) and 14/17 (82 percent) responding to MOCC (including five complete). The median survival for the complete responders was 11.7 months, while the partial responders survived for a median of 9.7 months. There were 2/9 (22 percent) responders to the alternate regimen at progressive disease. The overall incidence of CNS progression was 17 percent. The toxicity of the regimens was moderate, except for one instance of granulocytopenic death. This study establishes two equipotent drug combinations for the treatment of small-cell carcinoma of the lung.

Spatial variability of litter gaseous flux within a commercial broiler house: ammonia, nitrous oxide, carbon dioxide, and methane.

PubMed

Miles, D M; Owens, P R; Rowe, D E

2006-02-01

Twenty-eight flocks were grown on litter in a tunnel-ventilated, curtain-sided commercial broiler house prior to this summer flock. Grid measurements were made using a photo-acoustic multigas analyzer to assess the spatial variability of litter gases (NH3, N2O, CO2, and CH4) on d 1 and 21. The pooled results for the brood and non-brood areas of the house were 1) NH3 flux was greatest in the brood area at d 1, averaging 497 mg/(m2 x h), and had a mean of 370 mg/(m2 x h) in the vacant end of the house; 2) at d 21, the non-brood area had the greater average NH3 flux, 310 mg/(m2 x h), and flux in the brood area was 136 mg/(m2 x h); 3) N2O and CH4 fluxes were <60 mg/(m2 x h); and 4) on d 1, brood CO2 flux was 6,190 mg/(m2 x h) compared with 5,490 mg/ (m2 x h) at the opposite end of the house. On d 21, these values increased to 6,540 and 9,684 mg/(m2 x h) for the brood and non-brood areas. Ammonia flux seemed most affected by litter temperature. Carbon dioxide and CH4 increased from placement to mid growout, corresponding to increased moisture, especially near the fans. Contour plots were developed using geostatistical software to visually assess the spatial disparity among the measurements. This research provides a unique view of gas flux variation within the house. Collinear factors such as house management, bird size and age, and amount of deposition are significant factors for litter gas flux and should be considered in comprehensive models for emission estimates.

Phase I study of intravenous (IV) docetaxel and intraperitoneal (IP) oxaliplatin in recurrent ovarian and fallopian tube cancer.

PubMed

Taylor, Sarah E; Li, Ruosha; Petschauer, Jennifer S; Donovan, Heidi; O'Neal, Sara; Keeler, Amanda W; Zamboni, William C; Edwards, Robert P; Zorn, Kristin K

2015-09-01

The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IV docetaxel and IP oxaliplatin in women with recurrent ovarian (OV), fallopian tube (FT) or peritoneal (PP) cancer. Secondary objectives included response rate, time to progression, pharmacokinetics (PK) and quality of life (QoL). Patients received docetaxel 75mg/m(2) IV day (d) 1 and oxaliplatin escalating from 50mg/m(2) IP d2 every 3weeks using a 3+3 design. Treatment continued until disease progression, remission, or intolerable toxicity. Plasma and IP samples were taken to determine drug concentrations. MD Anderson Symptom Inventory and symptom interference scale were completed weekly. Thirteen patients were included. Median number of cycles was 6 (range 1-10). Ten patients had measureable disease. Best response was partial response (PR-2), stable disease (SD-7), and progressive disease (PD-1). Twenty-one Grades 3-4 toxicities were noted, commonly hematologic. Two patients had DLTs: prolonged neutropenia (1) and abdominal pain (1). MTD was d1 docetaxel 75mg/m(2) IV and d2 oxaliplatin 50mg/m(2) IP. Symptom burden peaked week one and returned to baseline by week two of each cycle on dose level 1. Dose level 2 had persistently high symptom burden and interference. At IP oxaliplatin doses of 50mg/m(2), total unbound drug exposure (AUC) averaged 8 times larger and Cmax reached concentrations 50-fold greater in IP fluid compared to plasma. Docetaxel 75mg/m(2) IV d1 and oxaliplatin 50mg/m(2) IP d2 is the MTD. Most patients had PR or SD. Patient-reported outcomes demonstrate temporary but tolerable decrements in QoL. IP oxaliplatin provides PK advantages over IV administration. Copyright © 2015 Elsevier Inc. All rights reserved.

Pediatric Phase I Trial and Pharmacokinetic Study of Vorinostat: A Children's Oncology Group Phase I Consortium Report

PubMed Central

Fouladi, Maryam; Park, Julie R.; Stewart, Clinton F.; Gilbertson, Richard J.; Schaiquevich, Paula; Sun, Junfeng; Reid, Joel M.; Ames, Matthew M.; Speights, Roseanne; Ingle, Ashish M.; Zwiebel, James; Blaney, Susan M.; Adamson, Peter C.

2010-01-01

Purpose The purpose of this study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), and pharmacokinetics of vorinostat administered as a single agent and in combination 13-cis retinoic acid (13cRA) in children with refractory solid tumors; to evaluate the tolerability of the solid tumor MTD in children with refractory leukemias; and to characterize the pharmacokinetics of a vorinostat suspension in children. Patients and Methods Vorinostat was administered orally daily starting at 180 mg/m2/d with escalations planned in 30% increments. Pharmacokinetic studies were performed with the initial dose. Acetyl-histone (H3) accumulation was assessed by Western blotting of peripheral blood mononuclear cells (PBMC). Results Sixty-four patients were enrolled on this multipart trial. In patients with solid tumors, the MTD was 230 mg/m2/d with dose-limiting neutropenia, thrombocytopenia, and hypokalemia at 300 mg/m2/d. DLTs observed with the combination of 13cRA and vorinostat included thrombocytopenia, neutropenia, anorexia, and hypertriglyceridemia, resulting in a MTD of vorinostat 180 mg/m2/d 4 times per week and 13cRA 80 mg/m2/dose twice per day, days 1 through 14 every 28 days. Wide interpatient variability was noted in vorinostat disposition, with area under the concentration-time curves at 230 mg/m2/d for the capsule (range, 1,415 to 9,291 ng/mL × hr) and oral suspension (range, 1,186 to 4,780 ng/mL × hr). Significant accumulation of acetylated H3 histone in PBMC was observed after administration of vorinostat, particularly at higher doses. One patient with neuroblastoma experienced a complete response to the combination. Conclusion In children with recurrent solid tumors, vorinostat is well-tolerated at 230 mg/m2/d, with a modest dose reduction being required when combining vorinostat with 13cRA. Drug disposition is similar to that observed in adults. PMID:20606092

Phase 1 multicenter study of vincristine sulfate liposomes injection and dexamethasone in adults with relapsed or refractory acute lymphoblastic leukemia.

PubMed

Thomas, Deborah A; Kantarjian, Hagop M; Stock, Wendy; Heffner, Leonard T; Faderl, Stefan; Garcia-Manero, Guillermo; Ferrajoli, Alessandra; Wierda, William; Pierce, Sherry; Lu, Biao; Deitcher, Steven R; O'Brien, Susan

2009-12-01

Dose intensification of chemotherapy has improved outcome for younger adults with de novo acute lymphoblastic leukemia (ALL). Novel formulations of standard chemotherapy agents may further reduce the incidence of disease recurrence after frontline chemotherapy. Vincristine (VCR) sulfate liposomes injection (VSLI) is a sphingomyelin/cholesterol nanoparticle encapsulated VCR formulation that improves the pharmacokinetic profile of VCR without augmenting neurotoxicity. A phase 1 trial of weekly, intravenous VSLI at 1.5 mg/m(2), 1.825 mg/m(2), 2.0 mg/m(2), 2.25 mg/m(2), or 2.4 mg/m(2) was conducted to determine the maximum tolerated dose (MTD) using a standard, 3 + 3 dose-escalation design. Dexamethasone (40 mg) was given on Days 1 through 4 and on Days 11 through 14 of each 4-week cycle. Thirty-six adults with relapsed/refractory ALL, all previously treated with conventional VCR, received at least 1 dose of VSLI. The MTD of VSLI was 2.25 mg/m(2) based on dose-limiting toxicities of grade 3 motor neuropathy, grade 4 seizure, and grade 4 hepatotoxicity in 1 patient each at the 2.4 mg/m(2) dose level. The most common toxicities attributed to VSLI included peripheral neuropathy (55%) and constipation (53%). A complete response (CR) was achieved in 7 of 36 patients (19%) based on an intent-to-treat analysis; the CR rate was 29% for the 14 patients who underwent therapy as their first salvage attempt. Four of 7 patients who achieved a CR underwent subsequent allogeneic stem cell transplantation in remission. In this study, VSLI plus dexamethasone appeared to be an effective salvage therapy option for relapsed/refractory ALL. A phase 2, international, multicenter clinical trial assessing the efficacy of single-agent VSLI as second salvage therapy for patients with previously treated ALL is underway. (c) 2009 American Cancer Society.

United States Preparedness to Respond to a Mumbai-Style Attack within the Homeland

DTIC Science & Technology

2010-02-17

IAD Dulles International Airport, monitoring in/out processing of Austrian, Canadian, Dutch, German, and Japanese Air Marshals as they transit U.S...Metro Cinema – a famous Metro-Goldwyn-Mayer (MGM) theater 7 Navy Department Library, “Riverine Warfare: The U.S. Navy‟s Operations on Inland

Estimating modal abundances from the spectra of natural and laboratory pyroxene mixtures using the modified Gaussian model

NASA Technical Reports Server (NTRS)

Sunshine, Jessica M.; Pieters, Carle M.

1993-01-01

The modified Gaussian model (MGM) is used to explore spectra of samples containing multiple pyroxene components as a function of modal abundance. The MGM allows spectra to be analyzed directly, without the use of actual or assumed end-member spectra and therefore holds great promise for remote applications. A series of mass fraction mixtures created from several different particle size fractions are analyzed with the MGM to quantify the properties of pyroxene mixtures as a function of both modal abundance and grain size. Band centers, band widths, and relative band strengths of absorptions from individual pyroxenes in mixture spectra are found to be largely independent of particle size. Spectral properties of both zoned and exsolved pyroxene components are resolved in exsolved samples using the MGM, and modal abundances are accurately estimated to within 5-10 percent without predetermined knowledge of the end-member spectra.

Inhalation of diethylamine--acute nasal effects and subjective response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lundqvist, G.R.; Yamagiwa, M.; Pedersen, O.F.

1992-03-01

Adult volunteers were exposed to 25 ppm (75 mg/m3) diethylamine in a climate chamber for 15 min in order to study the acute nasal reactions to an exposure equivalent to the present threshold limit value-short-term exposure limit. Changes in nasal volume and nasal resistance were measured by acoustic rhinometry and by rhinomanometry. Acute change in nasal volume, usually seen as acute nasal mucosa response to thermal stimuli, was not observed, nor was an acute change in nasal airway resistance. In a subsequent experiment, the aim was to measure acute sensory effects. Exposure to a concentration increasing from 0 to 12more » ppm took place for 60 min, equal to an average concentration of 10 ppm (30 mg/m3). A moderate to strong olfactory response and distinct nasal and eye irritation were observed. In spite of considerable individual variation, the results were in agreement with sensory effect estimates obtained from animal studies.« less

Spectrophotometric Determination of Nitrogen Oxides in the Air with 2-N-Ethyl-5-Naphthol-7-Sulfonic Acid

NASA Astrophysics Data System (ADS)

Huang, Y.; Shi, W.; Zhang, C.; Wen, H.

2017-09-01

For the determination of nitrogen oxides in the air, the structure of diazo and coupling compounds was studied and tested by experiments. The conditions and methods of diazo and coupling reactions were investigated. Furthermore, a spectrophotometric method using sulfanilamide as a diazo compound and 2-N-ethyl-5-naphthol-7-sulfonic acid (N-ethyl J acid) as a coupling compound was proposed. The maximum absorption wavelength of sulfanilamide-Nethyl J acid azo compound was at 478 nm. The molar absorptivity was 4.31 × 104 L/(mol × cm) with a recovery of 98.7-100.9% and RSD of 1.85%. For nitrogen oxides, the determinate limit of this measurement was 0.015 mg/m3 and the determinate range 0.024-2.0 mg/m3. Moreover, a high degree of correlation was observed between the results obtained by the proposed method and the standard methods. The proposed method can be easily applied to determine nitrogen oxides in the air.

Summary Report of Mission Acceleration Measurements for STS-89: Launched January 22, 1998

NASA Technical Reports Server (NTRS)

Hrovat, Kenneth; McPherson, Kevin

1999-01-01

Support of microgravity research on the 89th flight of the Space Transportation System (STS-89) and a continued effort to characterize the acceleration environment of the Space Shuttle Orbiter and the Mir Space Station form the basis for this report. For the STS-89 mission, the Space Shuttle Endeavour was equipped with a Space Acceleration Measurement System (SAMS) unit, which collected more than a week's worth of data. During docked operations with Mir, a second SAMS unit collected approximately a day's worth of data yielding the only set of acceleration measurements recorded simultaneously on the two spacecraft. Based on the data acquired by these SAMS units, this report serves to characterize a number of acceleration events and quantify their impact on the local nature of the accelerations experienced at the Mechanics of Granular Materials (MGM) experiment location. Crew activity was shown to nearly double the median root-mean-square (RMS) acceleration level calculated below 10 Hz, while the Enhanced Orbiter Refrigerator/Freezer operating at about 22 Hz was a strong acceleration source in the vicinity of the MGM location. The MGM science requirement that the acceleration not exceed q I mg was violated numerous times during their experiment runs; however, no correlation with sample instability has been found to this point. Synchronization between the SAMS data from Endeavour and from Mir was shown to be close much of the time, but caution with respect to exact timing should be exercised when comparing these data. When orbiting as a separate vehicle prior to docking, Endeavour had prominent structural modes above 3 Hz, while Mir exhibited a cluster of modes around 1 Hz. When mated, a transition to common modes was apparent in the two SAMS data sets. This report is not a comprehensive analysis of the acceleration data, so those interested in further details should contact the Principal Investigator Microgravity Services team at the National Aeronautics and Space Administration's John H. Glenn Research Center.

Cumulative or delayed nephrotoxicity after cisplatin (DDP) treatment.

PubMed

Pinnarò, P; Ruggeri, E M; Carlini, P; Giovannelli, M; Cognetti, F

1986-04-30

The present retrospective study reports data regarding renal toxicity in 115 patients (63 males, 52 females; median age, 56 years) who received cumulative doses of cisplatin (DDP) greater than or equal to 200 mg/m2. DDP was administered alone or in combination at a dose of 50-70 mg/m2 in 91 patients, and at a dose of 100 mg/m2 in 22 patients. Two patients after progression of ovarian carcinoma treated with conventional doses of DDP received 4 and 2 courses, respectively, of high-dose DDP (40 mg/m2 for 5 days) in hypertonic saline. The median number of DDP courses was 6 (range 2-14), and the median cumulative dose was 350 mg/m2 (range, 200-1200). Serum creatinine and urea nitrogen were determined before initiating the treatment and again 13-16 days after each administration. The incidence of azotemia (creatinina levels that exceeded 1.5 mg/dl) was similar before (7.8%) and after (6.1%) DDP doses of 200 mg/m2. Azotemia appears to be related to the association of DDP with other potentially nephrotoxic antineoplastic drugs (methotrexate) more than to the dose per course of DDP. Of 59 patients followed for 2 months or more after discontinuing the DDP treatment, 3 (5.1%) presented creatinine values higher than 1.5 mg/dl. The data deny that the incidence of nephrotoxicity is higher in patients receiving higher cumulative doses of DDP and confirm that increases in serum creatinine levels may occur some time after discontinuation of the drug.

Risk of silicosis in a Colorado mining community.

PubMed

Kreiss, K; Zhen, B

1996-11-01

We investigated exposure-response relations for silicosis among 134 men over age 40 who had been identified in a previous community-based random sample study in a mining town. Thirty-two percent of the 100 dust-exposed subjects had radiologic profusions of small opacities of I/O or greater at a mean time since first silica exposure of 36.1 years. Of miners with cumulative silica exposures of 2 mg/m3-years or less, 20% had silicosis; of miners accumulating > 2 mg/m3 years, 63% had silicosis. Average silica exposure was also strongly associated with silicosis prevalence rates, with 13% silicotics among those with average exposure of 0.025-0.05 mg/m3, 34% among those with exposures of > 0.05-0.1 mg/m3, and 75% among those with average exposures > 0.1 mg/m3. Logistic regression models demonstrated that time since last silica exposure and either cumulative silica exposure or a combination of average silica exposure and duration of exposure predicted silicosis risk. Exposure-response relations were substantially higher using measured silica exposures than using estimated silica exposures based on measured dust exposures assuming a constant silica proportion of dust, consistent with less exposure misclassification. The risk of silicosis found in this study is higher than has been found in workforce studies having no follow-up of those leaving the mining industry and in studies without job title-specific silica measurements, but comparable to several recent studies of dust exposure-response relationships which suggest that a permissible exposure limit of 0.1 mg/m3 for silica does not protect against radiologic silicosis.

Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

PubMed

Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

2007-07-01

Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

Histological Study of the Toxic Effects of Solder Fumes on Spermatogenesis in Rats

PubMed Central

Arab, Mohammad Reza; Heidari, Mohammad Hossein; Mashhadi, Rezvaneh; Mirzaei, Ramazan; Jahantigh, Mehdi

2011-01-01

Objective: Toxic fumes generated during the soldering process contain various contaminants released at sufficient rates to cause both short- and long-term health problems. Studies have shown that these fumes change the quality and quantity of semen fluid in exposed workers. The aim of the present study was to determine the potentially toxic effects of solder fumes on spermatogenesis in seminiferous tubules of rats as an experimental model, with conditioned media in an exposed chamber. Materials and Methods: A total number of 48 male Sprague Dawley adult rats were randomly divided into experimental (n=30) and control (n=18) groups. Based on exposure time, each group was further subdivided into two, four and six subgroups. Rats in the experimental groups were exposed to solder fumes in an exposure chamber for one hour/ day. The concentrations of fumes [formaldehyde, stanum (Sn) and lead (Pb)] were measured by a standard method via atomic absorption and spectrophotometry. According to a timetable, under deep anesthesia, the rats of both experimental and control subgroups were killed. After fixation of testes, specimens were weighed and routinely processed. Paraffin sections were stained by hematoxylin and eosin. Spermiogenesis index was calculated and data analyzed by Mann Whitney NPAR test. Results: Analysis of air samples in the exposure chamber showed the following fume concentrations: 0.193 mg/m3 for formaldehyde, 0.35 mg/m3 for Sn and 3 mg/m3 for Pb. Although there was no significant difference in testes weight between control and experimental subgroups, there was only a significant difference in spermiogenesis index between the six week experimental and control subgroups (p<0.02). Conclusion: The results of this study showed that solder fumes can change the spermiogenesis index in experimental groups in a time dependent manner. PMID:23671821

Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial.

PubMed

Ellis, Paul; Barrett-Lee, Peter; Johnson, Lindsay; Cameron, David; Wardley, Andrew; O'Reilly, Susan; Verrill, Mark; Smith, Ian; Yarnold, John; Coleman, Robert; Earl, Helena; Canney, Peter; Twelves, Chris; Poole, Christopher; Bloomfield, David; Hopwood, Penelope; Johnston, Stephen; Dowsett, Mitchell; Bartlett, John M S; Ellis, Ian; Peckitt, Clare; Hall, Emma; Bliss, Judith M

2009-05-16

Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration. In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2), cyclophosphamide 600 mg/m(2) at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m(2) at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m(2) at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493. All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0.95, 95% CI 0.85-1.08; p=0.44). 75.6% (95% CI 73.7-77.5) of patients in the experimental group and 74.3% (72.3-76.2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0.0001); the most frequent events were neutropenia (937 events vs 797 events), leucopenia (507 vs 362), and lethargy (456 vs 272). This study did not show any overall gain from the addition of docetaxel to standard anthracycline chemotherapy. Exploration of predictive biomarker-defined subgroups might have the potential to better target the use of taxane-based therapy. Cancer Research UK (CRUK 01/001), Sanofi-Aventis, Pfizer, and Roche.

Personal Exposure to Dust and Endotoxin in Robusta and Arabica Coffee Processing Factories in Tanzania

PubMed Central

Sakwari, Gloria

2013-01-01

Introduction: Endotoxin exposure associated with organic dust exposure has been studied in several industries. Coffee cherries that are dried directly after harvest may differ in dust and endotoxin emissions to those that are peeled and washed before drying. The aim of this study was to measure personal total dust and endotoxin levels and to evaluate their determinants of exposure in coffee processing factories. Methods: Using Sidekick Casella pumps at a flow rate of 2l/min, total dust levels were measured in the workers’ breathing zone throughout the shift. Endotoxin was analyzed using the kinetic chromogenic Limulus amebocyte lysate assay. Separate linear mixed-effects models were used to evaluate exposure determinants for dust and endotoxin. Results: Total dust and endotoxin exposure were significantly higher in Robusta than in Arabica coffee factories (geometric mean 3.41mg/m3 and 10 800 EU/m3 versus 2.10mg/m3 and 1400 EU/m3, respectively). Dry pre-processed coffee and differences in work tasks explained 30% of the total variance for total dust and 71% of the variance for endotoxin exposure. High exposure in Robusta processing is associated with the dry pre-processing method used after harvest. Conclusions: Dust and endotoxin exposure is high, in particular when processing dry pre-processed coffee. Minimization of dust emissions and use of efficient dust exhaust systems are important to prevent the development of respiratory system impairment in workers. PMID:23028014

Control technology for crystalline silica exposures in construction: wet abrasive blasting.

PubMed

Golla, Vijay; Heitbrink, William

2004-03-01

This study was designed to document the effect that wet abrasive blasting has on reducing worker exposure to crystalline silica, which has been associated with silicosis and premature death. In this study, worker exposure to respirable crystalline silica was monitored during wet abrasive blasting on the exterior walls of a parking garage to remove surface concrete and expose the underlying aggregate. In this process a wet sand mix comprised of 80% dry sand and 20% water was used. Sampling and analysis revealed that the geometric mean respirable quartz concentration was 0.2 mg/m(3) for workers conducting abrasive blasting and 0.06 mg/m(3) for helpers. When abrasive blasting was conducted in areas that apparently had reduced natural ventilation, dust exposures appeared to increase. When compared with other published data, this case study suggests that wet abrasive blasting causes less exposure to crystalline silica than dry abrasive blasting.

Improvement of Energy Efficiency and Environmental Safety of Thermal Energy Through the Implementation of Contact Energy Exchange Processes

NASA Astrophysics Data System (ADS)

Varlamov, Gennadii Borysovich; Romanova, Kateryna Alexandrovna; Nazarova, Iryna; Daschenko, Olga; Kapustiansky, Andry

2017-12-01

Energy efficiency improvement and ecological safety of heat power plants are urgent problems, which require scientifically grounded approaches and solutions. These problems can be solved partly within the presented heat-and-power cycles by including contact energy exchange equipment in the circuits of existing installations. A significant positive effect is obtained in the contact energy exchange installations, such as gas-steam installation `Aquarius' and the contact hydrogen heat generator that also can use hydrogen as a fuel. In these plants, the efficiency increases approximately by 10-12% in comparison with traditional installations, and the concentration of toxic substances, such as nitrogen oxides and carbon monoxide in flue gas can be reduced to 30 mg/m3 and to 5 mg/m3, respectively. Moreover, the plants additionally `generate' the clean water, which can be used for technical purposes.

Child Interacts with a Shear Strength Demonstrator

NASA Technical Reports Server (NTRS)

2002-01-01

Twila Schneider of Infinity Technology in Huntsville, AL, uses a small sand displacement box to explain the principles of the Mechanics of Granular Materials (MGM-III) experiment to two young Virginia students. The activity was part of the Space Research and You education event held by NASA's Office of Biological and Physical Research on June 25, 2002, in Arlington, VA, to highlight the research that will be conducted on STS-107.

NTP Toxicology and Carcinogenesis Studies of Cobalt Sulfate Heptahydrate (CAS No. 10026-24-1) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

PubMed

1998-08-01

Cobalt sulfate is used in the electroplating and electro chemical industries. It is also used as a coloring agent for ceramics and as a drying agent in inks, paints, varnishes, and linoleum. Cobalt sulfate may be added to animal feed as a mineral supplement and has been used as a top dressing on pasture lands. Cobalt sulfate was nominated by the National Cancer Institute for study based on a lack of information on the toxicity of soluble salts. Male and female F344/N rats and B6C3F1 mice were exposed to cobalt sulfate heptahydrate (approximately 99% pure) by inhalation for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium. The results of prechronic inhalation toxicity studies were reported previously (Bucher et al., 1990; NTP, 1991). 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate heptahydrate 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights Survival of exposed males and females was similar to that of the chamber controls. Mean body weights of exposed male and female rats were similar to those of the chamber controls throughout the study. Pathology Findings The incidences and severities of proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were markedly greater in all exposed groups of male and female rats than in the chamber controls. The incidences of alveolar epithelial hyperplasia in all groups of exposed males and in females exposed to 3.0 mg/m3 were significantly greater than those in the chamber control groups, as were the incidences of squamous metaplasia in 1.0 mg/m3 females and atypical alveolar epithelial hyperplasia in 3.0 mg/m3 females. In 3.0 mg/m3 males, the combined incidence of alveolar/ bronchiolar neoplasms (adenoma and/or carcinoma) was significantly greater than in the chamber controls. In female rats exposed to 1.0 or 3.0 mg/m3, the incidences of alveolar/bronchiolar neoplasms were significantly greater than those in the chamber control group and exceeded the NTP historical control ranges. A squamous cell carcinoma was observed in one 1.0 mg/m3 and one 3.0 mg/m3 female. The incidences of benign, complex, or malignant pheochromocytoma (combined) in 1.0 mg/m3 males and in 3.0 mg/m3 females were significantly greater than those in the chamber controls and exceeded the historical control ranges. Hyperplasia of the lateral wall of the nose, atrophy of the olfactory epithelium, and squamous metaplasia of the epiglottis were observed in all exposed groups of males and females, and the severities of these lesions increased with increasing exposure concentration. The incidences of squamous metaplasia of the lateral wall of the nose and metaplasia of the olfactory epithelium were increased in 3.0 mg/m3 males and females. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate heptahydrate 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights Survival of exposed males and females was similar to that of the chamber controls. Mean body weights of 3.0 mg/m3 male mice were less than those of the chamber controls from week 96 until the end of the study. The mean body weights of all exposed groups of female mice were generally greater than those of the chamber controls from week 20 until the end of the study. Pathology Findings The incidences of diffuse histiocytic cell infiltration in 3.0 mg/m3 males and of focal histiocytic cell infil tration in 3.0 mg/m3 females were significantly greater than those in the chamber controls. The incidences of alveolar/bronchiolar neoplasms in 3.0 mg/m3 males and females were significantly greater than those in the chamber control groups. The combined incidences of alveolar/bronchiolar adenoma or carcinoma and the incidences of alveolar/bronchiolar carcinoma in 3.0 mg/m3 males and females and the incidence of alveolar/bronchiolar adenoma in 3.0 mg/m3 females exceeded the NTP historical crical control ranges for inhalation studies. The incidences of atrophy of the olfactory epithelium in 1.0 and 3.0 mg/m3 males and females and hyper plasia of the olfactory epithelium in 3.0 mg/m3 males and females were significantly greater than in the chamber controls. Squamous metaplasia of the larynx was observed in all exposed groups of males and females. Male mice had a pattern of nonneoplastic liver lesions along with silver-staining helical organisms within the liver, characteristic of an infection with Helico bacter hepaticus. In NTP studies with H. hepaticus- associated hepatitis, increased incidences of hemangiosarcoma were seen in the liver of male mice. In this study of cobalt sulfate heptahydrate, incidences of hemangiosarcoma were increased in exposed groups of male mice. Because of the above association, interpretation of the increased incidences of hemangiosarcoma in the livers of male mice was confounded. Incidences of lesions at other sites in this study of cobalt sulfate heptahydrate were not considered to have been significantly impacted by the infection with H. hepaticus or its associated hepatitis. GENETIC TOXICOLOGY: Cobalt sulfate heptahydrate was mutagenic in S. typhimurium strain TA100 with and without liver S9 metabolic activation enzymes; no mutagenic activity was detected in strain TA98 or TA1535, with or without S9. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was some evidence of carcinogenic activity of cobalt sulfate heptahydrate in male F344/N rats based on increased incidences of alveolar/bronchiolar neoplasms. Marginal increases in incidences of pheochromocytomas of the adrenal medulla may have been related to exposure to cobalt sulfate heptahydrate. There was clear evidence of carcinogenic activity in female F344/N rats based on increased incidences of alveolar/bronchiolar neo-plasms and pheochromocytomas of the adrenal medulla in groups exposed to cobalt sulfate heptahydrate. There was clear evidence of carcinogenic activity of cobalt sulfate heptahydrate in male and female B6C3F1 mice based on increased incidences of alveolar/bronchiolar neoplasms. Exposure to cobalt sulfate heptahydrate caused a spectrum of inflammatory, fibrotic, and proliferative lesions in the respiratory tract of male and female rats and mice. Synonyms: Bieberite; cobalt(II) sulfate (1:1) heptahydrate; cobalt monosulfate heptahydrate; cobalt(II) sulphate heptahydrate; sulfuric acid, cobalt(2+) salt (1:1) heptahydrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gencoglu, Maria F.; Spurri, Amanda; Franko, Mitchell

We report that soft-templated mesoporous carbon is morphologically a non-nano type of carbon. It is a relatively newer variety of biomaterial, which has already demonstrated its successful role in drug delivery applications. To investigate the toxicity and biocompatibility, we introduced three types of mesoporous carbons with varying synthesis conditions and pore textural properties. We compared the Brunauer–Emmett–Teller (BET) surface area and pore width and performed cytotoxicity experiments with HeLa cells, cell viability studies with fibroblast cells and hemocomapatibility studies. Cytotoxicity tests reveal that two of the carbons are not cytotoxic, with cell survival over 90%. The mesoporous carbon with themore » highest surface area showed slight toxicity (~70% cell survival) at the highest carbon concentration of 500 μg/mL. Fibroblast cell viability assays suggested high and constant viability of over 98% after 3 days with no apparent relation with materials property and good visible cell-carbon compatibility. No hemolysis (<1%) was confirmed for all the carbon materials. Protein adsorption experiments with bovine serum albumin (BSA) and fibrinogen revealed a lower protein binding capacity of 0.2–0.6 mg/m 2 and 2–4 mg/m 2 for BSA and fibrinogen, respectively, with lower binding associated with an increase in surface area. The results of this study confirm the biocompatibility of soft-templated mesoporous carbons.« less

Mechanics of Granular Materials (MGM)

NASA Technical Reports Server (NTRS)

Alshibli, Khalid A.; Costes, Nicholas C.; Porter, Ronald F.

1996-01-01

The constitutive behavior of uncemented granular materials such as strength, stiffness, and localization of deformations are to a large extend derived from interparticle friction transmitted between solid particles and particle groups. Interparticle forces are highly dependent on gravitational body forces. At very low effective confining pressures, the true nature of the Mohr envelope, which defines the Mohr-Coulomb failure criterion for soils, as well as the relative contribution of each of non-frictional components to soil's shear strength cannot be evaluated in terrestrial laboratories. Because of the impossibility of eliminating gravitational body forces on earth, the weight of soil grains develops interparticle compressive stresses which mask true soil constitutive behavior even in the smallest samples of models. Therefore the microgravity environment induced by near-earth orbits of spacecraft provides unique experimental opportunities for testing theories related to the mechanical behavior of terrestrial granular materials. Such materials may include cohesionless soils, industrial powders, crushed coal, etc. This paper will describe the microgravity experiment, 'Mechanics of Granular Materials (MGM)', scheduled to be flown on Space Shuttle-MIR missions. The paper will describe the experiment's hardware, instrumentation, specimen preparation procedures, testing procedures in flight, as well as a brief summary of the post-mission analysis. It is expected that the experimental results will significantly improve the understanding of the behavior of granular materials under very low effective stress levels.

Productivity and Diversity of Phytoplankton in Relation to Copper Levels in San Diego Bay.

DTIC Science & Technology

1980-03-01

phytoplankton assemblages taken from the PIER (P), INLET (1), and NAVY (N) sites from July 1978 through June 1979... 15 Figure 7. Chlorophyll A levels (mg/m 3...PIER (P) and INLET (1) assemblages as a function of added copper (ppb)... 23 Figure 17. Trends in chlorophyll A levels (mg/m 3 ) of the PIER (P) and...E 10 P 5- J A S O N 0 J F M A M J 1978 1979Date Figure 7. Chlorophyll A levels (mg/m 3) of the phytoplank- ton assemblages taken from the PIER (P

Silicosis among gold miners: exposure--response analyses and risk assessment.

PubMed

Steenland, K; Brown, D

1995-10-01

This study sought to estimate the risk of silicosis by cumulative exposure-years in a cohort of miners exposed to silica, as well as the lifetime risk of silicosis under the current Occupational Safety and Health Administration (OSHA) standard (0.09 mg/m3). In a cohort study of 3330 gold miners who worked at least 1 year underground from 1940 to 1965 (average 9 years) and were exposed to a median silica level of 0.05 mg/m3 (0.15 mg/m3 for those hired before 1930), 170 cases of silicosis were determined from either death certificates or two cross-sectional radiographic surveys. The risk of silicosis was less than 1% with a cumulative exposure under 0.5 mg/m3-years, increasing to 68% to 84% for the highest cumulative exposure category of more than 4 mg/m3-years. Cumulative exposure was the best predictor of disease, followed by duration of exposure and average exposure. After adjustment for competing risks of death, a 45-year exposure under the current OSHA standard would lead to a lifetime risk of silicosis of 35% to 47%. Almost 2 million US workers are currently exposed to silica. Our results add to a small but increasing body of literature that suggests that the current OSHA silica exposure level is unacceptably high.

Effect of static magnetic field on trichloroethylene removal in a biotrickling filter.

PubMed

Quan, Yue; Wu, Hao; Yin, Zhenhao; Fang, Yingyu; Yin, Chengri

2017-09-01

A laboratory-scale biotrickling filter combined with a magnetic field (MF-BTF) and a single BTF (S-BTF) were set up to treat trichloroethylene (TCE) gas. The influences of phenol alone and NaAc-phenol as co-substrates and different MF intensities were investigated. At low MF intensity, MF-BTF displayed better performance with 0.20g/L of phenol, 53.6-337.1mg/m 3 of TCE, and empty bed residence times of 202.5s. The performances followed the order MF-BTF (60.0mT)>MF-BTF (30.0mT)>S-BTF (0mT)>MF-BTF (130.0mT), and the removal efficiencies (REs) and maximum elimination capacities (ECs) corresponded to: 92.2%-45.5%, 2656.8mg/m 3 h; 89.8%-37.2%, 2169.1mg/m 3 h; 89.8%-29.8%, 1967.7mg/m 3 h; 76.0%-20.8%, 1697.1mg/m 3 h, respectively. High-throughput sequencing indicated that the bacterial diversity was lower, whereas the relative abundances of Acinetobacter, Chryseobacterium, and Acidovorax were higher in MF-BTF. Results confirmed that a proper MF could improve TCE removal performance in BTF. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Detection rate analysis on neurological sign of workers exposed to different concentrations of carbon disulfide].

PubMed

Li, Kuirong; Zhou, Wenhui; Gu, Guizhen; Zhou, Shiyi; Zheng, Yuxin; Yu, Shanfa

2014-10-01

To study the effects of exposed to different concentrations of carbon disulfide on neurological signs of workers. Collection the information of concentration of carbon disulfide in the workplace or workers individuals exposed of a chemical fiber industry from 2004 to 2011, a total of 3 537 workers exposed to carbon disulfide were detected muscle strength and muscle tone, knee reflex, Achilles tendon reflex, trembling limbs, sensory function, and three chatter. Chi-square test was used for statistical analysis on abnormal neurological signs of workers. Eight hours time-weighted average concentration range of workers exposed to carbon disulfide in this chemical fiber industry was 0.2-41.0 mg/m(3), geometric mean was 2.38 mg/m(3). Concentration of carbon disulfide exposure of 1 771 workers was from 0.2 to 2.5 mg/m3( ≤ 2.5 mg/m(3)), 642 workers was 2.6-4.8 mg/m(3) (< 5.0 mg/m(3)), other 1 051 workers was from 5.1 to 41.0 mg/m(3) ( > 5.0 mg/m(3)) in all subjects. The different detection rates of knee reflex were 3.0% (31/1 045), 3.7% (21/574), 4.8% (16/331), 3.3% (10/305), 5.9% (11/187), 6.7% (68/1 022), the different detection rates of Achilles tendon reflex were 2.2% (23/1 045), 3.7% (21/574), 2.7% (9/331), 2.3% (7/305), 2.1% (4/187), 5.6% (57/1 022), the different detection rates of sensory dysfunction were 0.4% (4/1 045), 0.5% (3/574), 0.6% (2/331), 0.0% (0/305), 2.1% (4/187), 1.7% (17/1 022) in different cumulative amount of contact groups ( ≤ 10.0, 10.1-20.0, 20.1-30.0, 30.1-40.0, 40.1-50.0, >50.0 mg/m(3) per year), and the differences were statistically significant (χ(2) = 19.53, 21.27 and 15.89, all P values were <0.01) . Stratified according to age and gender, in addition to the ≤ 25 years group the difference of detection rate analysis on Achilles tendon reflex was statistically significant in the different concentration group (the ratio of on Achilles tendon reflex in the different groups of concentration of carbon disulfide exposure of 2.5, 2.6-5.0, ≥ 5.0 mg/m(3) were 0.4% (2/511), 1.0% (1/98), 2.1% (7/327), χ(2) = 5.59, P = 0.045) , the difference of detection rate analysis on neurological sign was not statistically significant in the different concentration group on the rest of the age and gender groups (P > 0.05). Within the concentration range of the object of study contact actual, different concentrations of carbon disulfide in addition to individual neurological signs of individual ages influential, it has no significant effect on the various signs of nervous system of workers of most age and gender groups, expect the age below the 25 years old group.

Cross-ecosystem fluxes: Export of polyunsaturated fatty acids from aquatic to terrestrial ecosystems via emerging insects.

PubMed

Martin-Creuzburg, Dominik; Kowarik, Carmen; Straile, Dietmar

2017-01-15

Cross-ecosystem fluxes can crucially influence the productivity of adjacent habitats. Emerging aquatic insects represent one important pathway through which freshwater-derived organic matter can enter terrestrial food webs. Aquatic insects may be of superior food quality for terrestrial consumers because they contain high concentrations of essential polyunsaturated fatty acids (PUFA). We quantified the export of PUFA via emerging insects from a midsize, mesotrophic lake. Insects were collected using emergence traps installed above different water depths and subjected to fatty acid analyses. Insect emergence from different depth zones and seasonal mean fatty acid concentrations in different insect groups were used to estimate PUFA fluxes. In total, 80.5mg PUFA m -2 yr -1 were exported, of which 32.8mgm -2 yr -1 were eicosapentaenoic acid (EPA), 7.8mgm -2 yr -1 were arachidonic acid (ARA), and 2.6mgm -2 yr -1 were docosahexaenoic acid (DHA). While Chironomidae contributed most to insect biomass and total PUFA export, Chaoborus flavicans contributed most to the export of EPA, ARA, and especially DHA. The export of total insect biomass from one square meter declined with depth and the timing at which 50% of total insect biomass emerged was correlated with the water depths over which the traps were installed, suggesting that insect-mediated PUFA fluxes are strongly affected by lake morphometry. Applying a conceptual model developed to assess insect deposition rates on land to our insect-mediated PUFA export data revealed an average total PUFA deposition rate of 150mgm -2 yr -1 within 100m inland from the shore. We propose that PUFA export can be reliably estimated using taxon-specific information on emergent insect biomass and seasonal mean body PUFA concentrations of adult insects provided here. Our data indicate that insect-mediated PUFA fluxes from lakes are substantial, implying that freshwater-derived PUFA can crucially influence food web processes in adjacent terrestrial habitats. Copyright © 2016 Elsevier B.V. All rights reserved.

An evaluation of analytical methods, air sampling techniques, and airborne occupational exposure of metalworking fluids.

PubMed

Verma, Dave K; Shaw, Don S; Shaw, M Lorraine; Julian, Jim A; McCollin, Shari-Ann; des Tombe, Karen

2006-02-01

This article summarizes an assessment of air sampling and analytical methods for both oil and water-based metalworking fluids (MWFs). Three hundred and seventy-four long-term area and personal airborne samples were collected at four plants using total (closed-face) aerosol samplers and thoracic samplers. A direct-reading device (DustTrak) was also used. The processes sampled include steel tube making, automotive component manufacturing, and small part manufacturing in a machine shop. The American Society for Testing and Materials (ASTM) Method PS42-97 of analysis was evaluated in the laboratory. This evaluation included sample recovery, determination of detection limits, and stability of samples during storage. Results of the laboratory validation showed (a) the sample recovery to be about 87%, (b) the detection limit to be 35 microg, and (c) sample stability during storage at room temperature to decline rapidly within a few days. To minimize sample loss, the samples should be stored in a freezer and analyzed within a week. The ASTM method should be the preferred method for assessing metalworking fluids (MWFs). The ratio of thoracic aerosol to total aerosol ranged from 0.6 to 0.7. A similar relationship was found between the thoracic extractable aerosol and total extractable aerosol. The DustTrak, with 10-microm sampling head, was useful in pinpointing the areas of potential exposure. MWF exposure at the four plants ranged from 0.04 to 3.84 mg/m3 with the geometric mean ranging between 0.22 to 0.59 mg/m3. Based on this data and the assumption of log normality, MWF exposures are expected to exceed the National Institute for Occupational Safety and Health recommended exposure limit of 0.5 mg/m3 as total mass and 0.4 mg/m3 as thoracic mass about 38% of the time. In addition to controlling airborne MWF exposure, full protection of workers would require the institution of programs for fluid management and dermal exposure prevention.

Cohort mortality study of roofing granule mine and mill workers. Part I: Estimation of historical crystalline silica exposures.

PubMed

Hewett, Paul; Morey, Sandy Z; Holen, Brian M; Logan, Perry W; Olsen, Geary W

2012-01-01

A study was conducted to construct a job exposure matrix for the roofing granule mine and mill workers at four U.S. plants. Each plant mined different minerals and had unique departments and jobs. The goal of the study was to generate accurate estimates of the mean exposure to respirable crystalline silica for each cell of the job exposure matrix, that is, every combination of plant, department, job, and year represented in the job histories of the study participants. The objectives of this study were to locate, identify, and collect information on all exposure measurements ever collected at each plant, statistically analyze the data to identify deficiencies in the database, identify and resolve questionable measurements, identify all important process and control changes for each plant-department-job combination, construct a time line for each plant-department combination indicating periods where the equipment and conditions were unchanged, and finally, construct a job exposure matrix. After evaluation, 1871 respirable crystalline silica measurements and estimates remained. The primary statistic of interest was the mean exposure for each job exposure matrix cell. The average exposure for each of the four plants was 0.042 mg/m(3) (Belle Mead, N.J.), 0.106 mg/m(3) (Corona, Calif.), 0.051 mg/m(3) (Little Rock, Ark.), and 0.152 mg/m(3) (Wausau, Wis.), suggesting that there may be substantial differences in the employee cumulative exposures. Using the database and the available plant information, the study team assigned an exposure category and mean exposure for every plant-department-job and time interval combination. Despite a fairly large database, the mean exposure for > 95% of the job exposure matrix cells, or specific plant-department-job-year combinations, were estimated by analogy to similar jobs in the plant for which sufficient data were available. This approach preserved plant specificity, hopefully improving the usefulness of the job exposure matrix.

Bitumen workers handling mastic versus rolled asphalt in a tunnel: assessment of exposure and biomarkers of irritation and genotoxicity.

PubMed

Raulf-Heimsoth, Monika; Marczynski, Boleslaw; Spickenheuer, Anne; Pesch, Beate; Welge, Peter; Rühl, Reinhold; Bramer, Rainer; Kendzia, Benjamin; Heinze, Evelyn; Angerer, Jürgen; Brüning, Thomas

2011-06-01

Emission levels of vapours and aerosols of bitumen are different when processing rolled asphalt compared to mastic asphalt, with working temperatures up to 180 and 250°C, respectively. During the Human Bitumen Study, we examined six workers handling rolled asphalt and mastic asphalt in two consecutive weeks at the same construction site in a tunnel. In addition to the determination of exposure to bitumen and polycyclic aromatic hydrocarbons (PAH) during shift, we examined urinary PAH metabolites, irritative and genotoxic effects before and after shift. Median personal shift concentration of vapours and aerosols of bitumen was 1.8 (range 0.9-2.4) mg/m(3) during the application of rolled asphalt and 7.9 (range 4.9-11.9) mg/m(3) when mastic asphalt was applied. Area measurement of vapours and aerosols of bitumen revealed higher concentrations than the personal measurements for mastic asphalt (mastic asphalt: 34.9 mg/m(3); rolled asphalt: 1.8 mg/m(3)). Processing mastic asphalt was associated also with higher PAH concentrations. Urinary 1-hydroxypyrene and the sum of 1-, 2+ 9-, 3- and 4-hydroxyphenanthrene increased slightly during shift without clear difference between mastic and rolled asphalt application. However, the post-shift urinary PAH-metabolite concentrations did not reflect the different PAH exposure during mastic and rolled asphalt application. Individual workers could be identified by their spirometry results indicating that these data reflect more chronic than acute effects. In most cases, an increase of 8-oxodGuo adducts was observed during shift that was independent of the asphalt application. 8-oxodGuo and (+)-anti-BPDE-DNA adducts were higher than in exposed workers of the Human Bitumen Study independent of the asphalt application. The DNA-strand breaks were considerably higher pre-shift and decreased during shift. In this study, mastic asphalt application led to significantly higher exposure to vapours and aerosols of bitumen, as well as to airborne PAH, compared to rolled asphalt application. Nevertheless, no differences in the excretion of urinary PAH metabolites, lung function impairment and genotoxic markers were detected. However, higher levels of genotoxicity markers on both examination days compared with the results of the Human Bitumen Study may indicate a possible influence of the specific tunnel setting.

Refractory acute leukaemia in adults treated with sequential colaspase and high-dose methotrexate.

PubMed

Yap, B S; McCredie, K B; Benjamin, R S; Bodey, G P; Freireich, E J

1978-09-16

Thirty-nine adults with acute leukaemia who had relapsed when receiving extensive chemotherapy were treated with a combination of methotrexate and colaspase (L-asparaginase) given sequentially. Patients initially received 50-80 mg/m(2) methotrexate, followed three hours later by intravenous colaspase, 40 000 IU/m(2). Seven days later intravenous methotrexate, 120 mg/m(2) was given. Each dose of methotrexate was followed 24 hours later by colaspase, and the two-day course of treatment was repeated every 7-14 days. The methotrexate dose was increased to tolerance by increments of 40 mg/m(2) with each course, while the colaspase dose remained constant unless abnormal liver function developed, when it was reduced by half.Overall, 18 out of 39 patients achieved complete remission (46%). Of these, 13 out of 21 (62%) had acute lymphoblastic leukaemia, three out of seven (43%) acute undifferentiated leukaemia, and two out of 11 (18%) acute myeloblastic leukaemia. The median duration of complete remission was 20 weeks and the median duration of survival in complete responders was 45 weeks. The median number of courses needed to achieve complete remission was three. The maximum tolerated dose of methotrexate was 400 mg/m(2) (median 200 mg/m(2)). Major side effects were due to colaspase. Methotrexate in doses of up to 400 mg/m(2) caused minimal myelosuppression and stomatitis, which suggested that colaspase given sequentially provides relative protection from methotrexate toxicity without the need for folinic acid (citrovorum factor) rescue.The combination of sequential colaspase and methotrexate is highly effective in reinducing remission in patients with acute lymphoblastic leukaemia or acute undifferentiated leukaemia. The regimen is easy to administer and relatively non-toxic, so it is suitable for use in outpatients, either alone or combined with other agents.

Combined carboplatin plus ifosfamide and cisplatin in patients with advanced ovarian carcinoma. A phase I-II study. GOCS (Gynecological Oncology Cooperative Study).

PubMed

Lorusso, V; Leone, B; Di Vagno, G; Manzione, L; Palmeri, S; Vallejo, C; Machiavelli, M; Nacci, G; Bilancia, D; Leonardi, V; Catino, A; Gargano, G; Loverro, G; Selvaggi, L; De Lena, M

1998-02-01

Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I-II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose escalation was allowed in the same patient. Grade 3-4 leukopenia and thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m2 and therefore the dose recommended for the phase II study was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients with a 21% pathological CR. With a minimum follow-up of 32 months (median 40 months), median progression-free survival and overall survival were 21 and 39 months, respectively. In conclusion, the combination of CDDP, PPL, and IFO provides an effective regimen for ovarian cancer with an acceptable toxicity profile.

Frontline rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib (VR-CAP) or vincristine (R-CHOP) for non-GCB DLBCL.

PubMed

Offner, Fritz; Samoilova, Olga; Osmanov, Evgenii; Eom, Hyeon-Seok; Topp, Max S; Raposo, João; Pavlov, Viacheslav; Ricci, Deborah; Chaturvedi, Shalini; Zhu, Eugene; van de Velde, Helgi; Enny, Christopher; Rizo, Aleksandra; Ferhanoglu, Burhan

2015-10-15

This phase 2 study evaluated whether substituting bortezomib for vincristine in frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy could improve efficacy in non-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB DLBCL), centrally confirmed by immunohistochemistry (Hans method). In total, 164 patients were randomized 1:1 to receive six 21-day cycles of rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), and doxorubicin 50 mg/m(2), all IV day 1, prednisone 100 mg/m(2) orally days 1-5, plus either bortezomib 1.3 mg/m(2) IV days 1, 4, 8, 11 (rituximab, cyclophosphamide, doxorubicin, and prednisone with bortezomib [VR-CAP]; n = 84) or vincristine 1.4 mg/m(2) (maximum 2 mg) IV day 1 (R-CHOP; n = 80). There were no significant differences between VR-CAP and R-CHOP in complete response rate (64.5%, 66.2%; odds ratio [OR], 0.91; P = .80), overall response rate (93.4%, 98.6%; OR, 0.21; P = .11), progression-free survival (hazard ratio [HR], 1.12; P = .76), or overall survival (HR, 0.89; P = .75). Rates of grade ≥3 adverse events (AEs; 88%, 89%), serious AEs (38%, 34%), discontinuations due to AEs (7%, 3%), and deaths due to AEs (2%, 5%) were similar with VR-CAP and R-CHOP. Grade ≥3 peripheral neuropathy rates were 6% and 3%, respectively. VR-CAP did not improve efficacy vs R-CHOP in non-GCB DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT01040871. © 2015 by The American Society of Hematology.

Phase 1 trial of irinotecan plus BCNU in patients with progressive or recurrent malignant glioma1

PubMed Central

Quinn, Jennifer A.; Reardon, David A.; Friedman, Allan H.; Rich, Jeremy N.; Sampson, John H.; Vredenburgh, James; Gururangan, Sridharan; Provenzale, James M.; Walker, Amy; Schweitzer, Holly; Bigner, Darell D.; Tourt-Uhlig, Sandra; Herndon, James E.; Affronti, Mary Lou; Jackson, Susanne; Allen, Deborah; Ziegler, Karen; Bohlin, Cindy; Lentz, Christy; Friedman, Henry S.

2004-01-01

Irinotecan is a topoisomerase I inhibitor previously shown to be active in the treatment of malignant glioma. We now report the results of a phase 1 trial of irinotecan plus BCNU, or 1,3-bis(2-chloroethyl)-1-nitrosourea, for patients with recurrent or progressive MG. Irinotecan dose escalation occurred independently within 2 strata: patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and patients not receiving EIAEDs. BCNU was administered at a dose of 100 mg/m2 over 1 h every 6 weeks on the same day as the first irinotecan dose was administered. Irinotecan was administered intravenously over 90 min once weekly. Treatment cycles consisted of 4 weekly administrations of irinotecan followed by a 2-week rest with dose escalation in cohorts of 3 to 6 patients. Seventy-three patients were treated, including 49 patients who were on EIAEDs and 24 who were not on EIAEDs. The maximum tolerated dose for patients not on EIAEDs was 125 mg/m2. The maximum tolerated dose for patients on EIAEDs was 225 mg/m2. Dose-limiting toxicity was evenly distributed among the following organ systems: pulmonary, gastrointestinal, cardiovascular, neurologic, infectious, and hematologic, without a clear predominance of toxicity involving any one organ system. There was no evidence of increasing incidence of toxicity involving one organ system as irinotecan dose was escalated. On the basis of these results, we conclude that the recommended doses of irinotecan for a phase 2 clinical trial when given in combination with BCNU (100 mg/m2) are 225 mg/m2 for patients on EIAEDs and 125 mg/m2 for patients not on EIAEDs. PMID:15134629

Intra-Arterial Chemotherapy with Osmotic Blood-Brain Barrier Disruption for Aggressive Oligodendroglial tumors: Results of a Phase I Study

PubMed Central

Guillaume, Daniel J.; Doolittle, Nancy D.; Gahramanov, Seymur; Hedrick, Nancy A.; Delashaw, Johnny B.; Neuwelt, Edward A.

2009-01-01

Objective Refractory anaplastic oligodendroglioma (AO) and oligoastrocytoma (OA) tumors are challenging to treat. This trial primarily evaluated toxicity and estimated the maximum tolerated dose (MTD) of intra-arterial (IA) melphalan, IA carboplatin and intravenous (IV) etoposide phosphate in conjunction with blood-brain barrier disruption (BBBD) in these tumors. The secondary measure was efficacy. Methods Thirteen subjects with temozolomide (TMZ) - refractory AO (11) or OA (2) underwent BBBD with carboplatin (IA, 200 mg/m2/day), etoposide phosphate (IV, 200 mg/m2/day), and melphalan (IA, dose escalation) every 4 weeks, for up to 1 year. Subjects underwent melphalan dose escalation (4, 8, 12, 16, and 20 mg/m2/day) until the MTD (one level below that producing grade 4 toxicity) was determined. Toxicity and efficacy were assessed. Results Two of four subjects receiving IA melphalan at 8 mg/m2/day developed grade 4 thrombocytopenia, thus the melphalan MTD was 4 mg/m2/day. Adverse events included asymptomatic subintimal tear (1 subject) and grade 4 thrombocytopenia (3 subjects). Two subjects demonstrated complete response, 3 had partial responses, 5 demonstrated stable disease and 3 progressed. Median overall PFS was 11 months. Subjects with complete or partial response demonstrated deletion of chromosomes 1p and 19q. In the 5 subjects with stable disease, 2 demonstrated 1p and 19q deletion and 3 demonstrated 19q deletion only. Conclusion In these patients with AO or OA tumors who failed TMZ, osmotic BBBD with IA carboplatin, IV etoposide phosphate, and IA melphalan (4mg/m2/day for 2 days) shows acceptable toxicity and encouraging efficacy, especially in subjects demonstrating 1p and/or 19q deletion. PMID:20023537

A phase I study of imexon plus gemcitabine as first-line therapy for advanced pancreatic cancer.

PubMed

Cohen, Steven J; Zalupski, Mark M; Modiano, Manuel R; Conkling, Paul; Patt, Yehuda Z; Davis, Peg; Dorr, Robert T; Boytim, Michelle L; Hersh, Evan M

2010-07-01

Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer. Patients with untreated locally advanced or metastatic pancreatic adenocarcinoma received therapy in sequential cohorts on regimen A (n = 19; imexon 200 or 280 mg/m(2) intravenously (IV) over 30 min days 1-5, 15-19 and gemcitabine 800 or 1,000 mg/m(2) IV over 30 min on days 1,8,15 every 28 days) or regimen B (n = 86; imexon 280-1,300 mg/m(2) IV over 30-60 min days 1, 8, and 15 and gemcitabine 1,000 mg/m(2) IV over 30 min on days 1, 8, and 15 every 28 days). One hundred five patients received 340 treatment cycles (median 2, range 1-16). median age 63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and pain, often with transient, acute diarrhea. Best response was confirmed partial response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There was a dose proportional increase in imexon AUC across the doses tested with terminal half life 69 min at the MTD and no alteration of gemcitabine pharmacokinetics. The recommended phase II dose of imexon is 875 mg/m(2) with gemcitabine 1,000 mg/m(2). DLT was acute abdominal pain and cramping. Encouraging antitumor responses support further evaluation of this combination in advanced pancreatic cancer.

Phase II randomized study of trabectedin given as two different every 3 weeks dose schedules (1.5 mg/m2 24 h or 1.3 mg/m2 3 h) to patients with relapsed, platinum-sensitive, advanced ovarian cancer.

PubMed

Del Campo, J M; Roszak, A; Bidzinski, M; Ciuleanu, T E; Hogberg, T; Wojtukiewicz, M Z; Poveda, A; Boman, K; Westermann, A M; Lebedinsky, C

2009-11-01

This randomized, open-label, phase II clinical trial evaluated the optimal regimen of trabectedin administered every 3 weeks in patients with platinum-sensitive, relapsed, advanced ovarian cancer (AOC). Patients previously treated with less than two or two previous chemotherapy lines were randomized to receive trabectedin 1.5 mg/m(2) 24 h (arm A, n = 54) or 1.3 mg/m(2) 3 h (arm B, n = 53). Objective response rate (ORR) per RECIST was the primary efficacy end point. Toxic effects were graded according to the National Cancer Institute-Common Toxicity Criteria v. 2.0. ORR was 38.9% [95% confidence interval (CI) 25.9% to 53.1%; arm A] and 35.8% (95% CI 23.1% to 50.2%; arm B) (intention-to-treat primary analysis). Median time to progression was 6.2 months (95% CI 5.3-8.6 months; arm A) and 6.8 months (95% CI 4.6-7.4 months; arm B). Frequent severe adverse events were nausea/vomiting (24%, arm A; 15%, arm B) and fatigue (15%, arm A; 10%, arm B). Common severe laboratory abnormalities were transient, noncumulative neutropenia (55%, arm A; 37%, arm B) and transaminase increases (alanine aminotransferase, 55%, arm A; 59%, arm B). Both every-3-weeks trabectedin regimes, 1.5 mg/m(2) 24 h and 1.3 mg/m(2) 3 h, were active and reasonably well tolerated in AOC platinum-sensitive patients. Trabectedin every-3-weeks has promising activity and deserves to be further evaluated in relapsed AOC.

A properly configured ring structure is critical for the function of the mitochondrial DNA recombination protein, Mgm101.

PubMed

Nardozzi, Jonathan D; Wang, Xiaowen; Mbantenkhu, MacMillan; Wilkens, Stephan; Chen, Xin Jie

2012-10-26

Mgm101 is a Rad52-type recombination protein of bacteriophage origin required for the repair and maintenance of mitochondrial DNA (mtDNA). It forms large oligomeric rings of ∼14-fold symmetry that catalyze the annealing of single-stranded DNAs in vitro. In this study, we investigated the structural elements that contribute to this distinctive higher order structural organization and examined its functional implications. A pair of vicinal cysteines, Cys-216 and Cys-217, was found to be essential for mtDNA maintenance. Mutations to the polar serine, the negatively charged aspartic and glutamic acids, and the hydrophobic amino acid alanine all destabilize mtDNA in vivo. The alanine mutants have an increased propensity of forming macroscopic filaments. In contrast, mutations to aspartic acid drastically destabilize the protein and result in unstructured aggregates with severely reduced DNA binding activity. Interestingly, the serine mutants partially disassemble the Mgm101 rings into smaller oligomers. In the case of the C216S mutant, a moderate increase in DNA binding activity was observed. By using small angle x-ray scattering analysis, we found that Mgm101 forms rings of ∼200 Å diameter in solution, consistent with the structure previously established by transmission electron microscopy. We also found that the C216A/C217A double mutant tends to form broken rings, which likely provide free ends for seeding the growth of the super-stable but functionally defective filaments. Taken together, our data underscore the importance of a delicately maintained ring structure critical for Mgm101 activity. We discuss a potential role of Cys-216 and Cys-217 in regulating Mgm101 function and the repair of damaged mtDNA under stress conditions.

Pharmacokinetics and tolerability of human mouse chimeric anti-CD22 monoclonal antibody in Chinese patients with CD22-positive non-Hodgkin lymphoma.

PubMed

Li, Su; Zhang, Dongsheng; Sun, Jian; Li, Zhinming; Deng, Liting; Zou, Benyan; Zhan, Jing; Jiang, Wenqi

2012-01-01

The safety and pharmacokinetics assessment of antibodies targeting CD22 (e.g., epratuzumab) have been established in western Caucasian populations, but there are no reports of the effects in Chinese populations. This dose-escalation study examines the safety, pharmacokinetics and biologic effects of multiple doses of anti-CD22 human-murine chimeric monoclonal antibody SM03 in 21 Chinese patients with CD22-positive non-Hodgkin lymphoma. Most of drug-related adverse events (AEs) were mild and reversible. Two patients experienced serious AEs (hemorrhage); one patient had grade 4 neutropenia; one patient had asymptomatic grade III prolongation of activated partial thromboplastin time (APTT). Major AEs included fever (71%), prolongation of APTT (42.8%), leukocytopenia (44.4%), alanine transaminase elevation (28.6%), elevated serum creatinine (23.8%) and injection site skin redness (14.3%). Circulating B cells transiently decreased without significant effects on T cells or immunoglobulin levels. Pharmacokinetic data revealed that mean maximum observed SM03 concentration and mean AUC from time zero to infinity increased in a dose-dependent manner up to 360 mg/m (2) SM03. Mean clearance was similar at doses ≤ 360 mg/m (2) and decreased significantly at dose 480 mg/m (2), supporting saturation of B-cell binding at 360 mg/m (2). Across all dose levels and histologies, one patient achieved partial response at 480 mg/m (2) dose; 14 patients had stable disease as best response and four patients progressed. Overall, SM03 was tolerated at doses ranging from 60-480 mg/m (2) and had potential efficacy in Chinese patients with follicular lymphoma.

A Phase I Study of Zoledronic Acid and Low Dose Cyclophosphamide in Recurrent/Refractory Neuroblastoma: A New Approaches to Neuroblastoma Therapy (NANT) Study

PubMed Central

Russell, Heidi V.; Groshen, Susan G.; Ara, Tasnim; DeClerck, Yves A.; Hawkins, Randy; Jackson, Hollie A.; Daldrup-Link, Heike E.; Marachelian, Araz; Skerjanec, Andrej; Park, Julie R.; Katzenstein, Howard; Matthay, Katherine K.; Blaney, Susan M.; Villablanca, Judith G.

2010-01-01

Background Zoledronic acid, a bisphosphonate, delays progression of bone metastases in adult malignancies. Bone is a common metastatic site of advanced neuroblastoma. We previously reported efficacy of zoledronic acid in a murine model of neuroblastoma bone invasion prompting this Phase I trial of zoledronic acid with cyclophosphamide in children with neuroblastoma and bone metastases. The primary objective was to determine recommended dosing of zoledronic acid for future trials. Procedure Escalating doses of intravenous zoledronic acid were given every 28 days with oral metronomic cyclophosphamide (25 mg/m2/day). Toxicity, response, zoledronic acid pharmacokinetics, bone turnover markers, serum IL-6, and sIL-6R were evaluated. Results Twenty-one patients, median age 7.5 (range 0.8 - 25.6) years were treated with 2 mg/m2 (n=4), 3 mg/m2 (n=3), or 4 mg/m2 (n=14) zoledronic acid. Fourteen patients were evaluable for dose escalation. A median of one (range 1-18) courses was given. Two dose limiting toxicities (Grade 3 hypophosphatemia) occurred at 4 mg/m2 zoledronic acid. Other Grade 3-4 toxicities included hypocalcemia (n=2), elevated transaminases (n=1), neutropenia (n=2), anemia (n=1), lymphopenia (n=1), and hypokalemia (n=1). Osteosclerosis contributed to fractures in one patient after 18 courses. Responses in evaluable patients included 1 partial response, 9 stable disease (median 4.5 courses, range 3-18), and 10 progressions. Zoledronic acid pharmacokinetics were similar to adults. Markers of osteoclast activity and serum IL-6 levels decreased with therapy. Conclusions Zoledronic acid with metronomic cyclophosphamide is well tolerated with clinical and biologic responses in recurrent/refractory neuroblastoma. The recommended dose of zoledronic acid is 4 mg/m2 every 28 days. PMID:21671363

Highly effective reduced toxicity dose-intensive pilot protocol for non-metastatic limb osteogenic sarcoma (SCOS 89).

PubMed

Shkalim-Zemer, Vered; Ash, Shifra; Toledano, Helen; Kollender, Yehuda; Issakov, Josephine; Yaniv, Isaac; Cohen, Ian J

2015-11-01

Aggressive chemotherapy protocols for non-metastatic limb osteosarcoma have improved histological response without affecting prognosis. This study evaluated the toxicity and outcome of a dose-intensive, high-dose 3- to 5-drug pilot protocol, SCOS 89. The cohort included 26 patients (14 male; ages 6.5-22 years) with non-metastatic limb osteosarcoma treated at a tertiary pediatric medical center between 1989 and 2013. Preoperatively, patients received two courses of once-weekly pulses of high-dose methotrexate (12-30 g/m(2)) for 2 weeks; doxorubicin (90 mg/m(2)) with dexrazoxane, combined with cisplatin (200 mg/m(2)), was added in week 3. Following methotrexate, 760 mg/m(2) of folinic acid was administered. Postoperative chemotherapy was continued to a total of 14 courses of methotrexate, doxorubicin (up to a total dose of 360 mg/m(2)), and cisplatin (up to a total dose of 560 mg/m(2)). If toxicity occurred or <90 % tumor necrosis, ifosfamide (12 g/m(2)) plus etoposide (500 mg/m(2)) was substituted for doxorubicin, cisplatin, or methotrexate. Toxicity and death rates were calculated. All patients underwent definitive limb salvage surgery. Six patients died of infection, recurrent disease, or secondary malignancy. Median follow-up was 100 months (range 2-290). Event-free and overall survival rates, respectively, were 88 and 96 % at 2 years, 80 and 87.6 % at 5 years, 80 and 78 % at 10 years. Eleven patients required ifosfamide/etoposide substitution. One patient had a transient decreased left ventricular ejection fraction. Two patients developed acute nephrotoxicity during therapy, but no neurotoxicity. Seven patients had hearing impairment. The SCOS 89 yields a high event-free survival rate with reduced nephro-/neuro-/cardiotoxicity in patients with non-metastatic limb osteosarcoma.

Pulmonary response to inhaled Kevlar aramid synthetic fibers in rats.

PubMed

Lee, K P; Kelly, D P; Kennedy, G L

1983-11-01

Groups of male rats were exposed to specially prepared ultrafine Kevlar pulp fibers (du Pont's registered trademark for certain aramid fibers) at atmospheric concentrations of either 0.1, 0.5, 3.0, or 18 mg/m3 for 2 weeks. Rats were killed at 0 and 2 weeks and 3 and 6 months postexposure (PE) except the rats exposed to 18 mg/m3, which were killed 0, 4, and 14 days and 1, 3, and 6 months PE. Another group of male rats was exposed to 18 mg/m3 (respirable dust approximately 2.5 mg/m3) of commercial Kevlar fibers for 2 weeks and were killed at 0 and 2 weeks and 3 and 6 months PE. Inhaled ultrafine Kevlar fibers were mostly phagocytized by alveolar macrophages (dust cells) in the alveolar ducts and adjoining alveoli after exposure to either 0.1 or 0.5 micrograms/m3. Most dust cells had disappeared and lungs showed a normal appearance throughout 6 months PE. The pulmonary response almost satisfied the biological criteria for a nuisance dust. Rats exposed to 3 mg/m3 ultrafine Kevlar fibers revealed occasional patchy thickening of alveolar ducts with dust cells and inflammatory cells but with no collagen fibers deposited throughout 6 months PE. After exposure to 18 mg/m3 ultrafine Kevlar, the respiratory bronchioles, alveolar ducts, and adjoining alveoli showed granulomatous lesions with dust cells by 2 weeks PE. The granulomatous lesions converted to patchy fibrotic thickening with dust cells after 1 month PE. The fibrotic lesions were markedly reduced in cellularity, size, and numbers from 3 to 6 months PE but revealed networks of reticulum fibers with slight collagen fiber deposition.

Tracheal cancer treated with a short course of external and endoluminal radio-chemotherapy combined with cetuximab – a case report

PubMed Central

Papadopoulou, Aikaterini; Froudarakis, Marios; Abatzoglou, Ioannis

2011-01-01

Primary tumors of the trachea are rare. Such cases are presented with acute respiratory distress demanding immediate therapeutic intervention. Herein, we present a case of an unresectable second primary tracheal cancer treated with intraluminal brachytherapy (8 Gy at 1 cm from catheter) followed by a short course of external beam hypofractionated radiotherapy (4.5 Gy × 4 fractions) and a final brachytherapy fraction (8 Gy), delivering a biological dose higher than 57.5 Gy (for α/β = 4 Gy) to the tumor within 4 weeks. Concurrent chemotherapy consisted of: fluoruracil (1000 mg/m2), leucovorin (100 mg/m2), oxaliplatin (80 mg/m2) and cetuximab (500 mg/m2), administered every two weeks for two consecutive cycles. Complete response was evident during the second brachytherapy fraction and the patient is alive with no evidence of disease, two years after therapy, without any late radiation sequel. PMID:27853478

[Cryotherapy is useful and safe in the prevention of oral mucositis after high-dose melphalan (L-PAM)].

PubMed

Inagaki, Noriko; Ohue, Yukiko; Shigeta, Hiroe; Tasaka, Taizo

2006-11-01

We prospectively assessed the effectiveness of cryotherapy after high-dose L-PAM to prevent oral mucositis. Cryotherapy with ice tips was commenced 15 minutes before L-PAM administration, and continued until the end of administration. Twenty-six patients were enrolled in this study. Thirteen patients with myeloma were treated with 200 mg/m2 L-PAM followed by autologous peripheral blood stem cell transplantation, and 13 patients (4 AML, 4 MDS, 2 ALL, 2 lymphoma and 1 CML) were treated with 140 mg/m2 L-PAM followed by allogeneic stem cell transplantation. Grade 1 mucositis occurred in four of 13 patients (31%) with 200 mg/m2 L-PAM, and 2 of 13 patients (16%) with 140 mg/m2 L-PAM. Only one patient had grade 2 mucositis, and no grade 3 mucositis were observed. The procedure was well tolerated in all patients. These data suggest that cryotherapy is effective to minimize L-PAM-induced oral mucositis.

Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study.

PubMed

von Minckwitz, Gunter; Rezai, Mahdi; Loibl, Sibylle; Fasching, Peter A; Huober, Jens; Tesch, Hans; Bauerfeind, Ingo; Hilfrich, Jörn; Eidtmann, Holger; Gerber, Bernd; Hanusch, Claus; Kühn, Thorsten; du Bois, Andreas; Blohmer, Jens-Uwe; Thomssen, Christoph; Dan Costa, Serban; Jackisch, Christian; Kaufmann, Manfred; Mehta, Keyur; Untch, Michael

2010-04-20

PURPOSE Capecitabine can be integrated either concomitantly or sequentially to anthracycline-plus-taxane-based regimens. PATIENTS AND METHODS Patients with large operable or locally advanced tumors, with hormone receptor-negative tumors, or with receptor-positive tumors but also clinically node-positive disease were recruited to receive preoperatively four cycles of epirubicin plus cyclophosphamide (EC; epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2)). Patients were then randomly assigned to four cycles of docetaxel (100 mg/m(2)), four cycles of docetaxel + capecitabine (TX; docetaxel 75 mg/m(2) plus capecitabine 1,800 mg/m(2)), or four cycles of docetaxel (75 mg/m(2)) followed by four cycles of capecitabine (1,800 mg/m(2); T-X). Patients with human epidermal growth factor receptor 2 (HER-2) -positive tumors received trastuzumab concomitantly with all cycles. Primary objectives were to assess the effect of docetaxel by comparing EC plus docetaxel versus EC plus TX and to assess the effect of duration by comparing EC plus TX versus EC plus T-X on pathologic complete response (pCR, without invasive/noninvasive breast tumor, regardless of nodal status) at surgery, irrespective of trastuzumab treatment. Results Of 1,509 patients starting EC, 1,421 were randomly assigned to docetaxel (n = 471), TX (n = 471), or T-X (n = 479). At surgery, pCR rates were 22.3%, 19.5%, and 22.3%, respectively; the difference for docetaxel (EC plus docetaxel v EC plus TX) was 2.8% (95% CI, -2.4% to 8.0%; P = .298).The difference for duration was -2.8% (95% CI, -8.0% to 2.4%; P = .298). Breast conservation rates were 70.1%, 68.4%, and 65.3%, respectively (P = .781 for docetaxel; P = .270 for duration). Concomitant but not sequential treatment with docetaxel was associated with more diarrhea; nail changes, and hand-foot-syndrome, but it was associated with less edema. CONCLUSION Adding capecitabine to or prolonging duration of neoadjuvant EC plus docetaxel does not result in higher efficacy at surgery.

Blood and bronchoalveolar lavage fluid acetylcholinesterase levels following microinstillation inhalation exposure to sarin in Guinea pigs.

PubMed

Che, Magnus M; Conti, Michele; Boylan, Megan; Sciuto, Alfred M; Gordon, Richard K; Nambiar, Madhusoodana P

2008-07-01

We determined acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition in the bronchoalveolar lavage fluid (BALF) following inhalation exposure to chemical threat nerve agent (CTNA) sarin. Age- and weight-matched male guinea pigs were exposed to five different doses of sarin (169.3, 338.7, 508, 677.4, and 846.5 mg/m(3)) using a microinstillation inhalation exposure technique for 4 min. The technique involves aerosolization of the agent in the trachea using a microcatheter with a center hole that delivers the agent and multiple peripheral holes that pumps air to aerosolize the agent at the tip. Animals exposed to higher doses of sarin occasionally developed seizures and succumbed to death within 15 min after exposure. The LCt(50) for sarin using the microinstillation technique was determined to be close to 677.4 mg/m(3). Ear blood AChE activity showed a dose-dependent inhibition at 15 min postexposure. The inhibition of blood AChE remained constant over 35 and 55 min after sarin exposure indicating that there was no lung depot effect. Cardiac blood AChE and butyrylcholinesterase (BChE) activity in surviving animals euthanized at 24 h postexposure showed a dose-dependent inhibition with an inhibition of 60% at 677.4 and 846.5 mg/m(3) sarin exposure. AChE and BChE activity in bronchoalveolar lavage fluid (BALF) showed a slight increase at 338.7 to 677.4 mg/m(3) sarin exposure but a marginal inhibition at 169.3 mg/m(3). In contrast, the AChE protein levels determined by immunoblotting showed an increase at 169.3 mg/m(3) in the BALF. The BALF protein level, a biomarker of lung injury, was increased maximally at 338.7 mg/m(3) and that increase was dropped with an increase in the dose of sarin. The BALF protein levels correlated with the AChE and BChE activity. These data suggest that sarin microinstillation inhalation exposure results in respiratory toxicity and lung injury characterized by changes in lavage AChE, BChE, and protein levels.

Effects of Didecyldimethylammonium Chloride on Sprague-Dawley Rats after Two Weeks of Inhalation Exposure

PubMed Central

Chung, Yong-Hyun

2014-01-01

Didecyldimethylammonium chloride (DDAC) is used for various purposes, such as a fungicide for coolants, an antiseptic for wood, and disinfectant for cleaning. Despite the increasing likelihood of DDAC inhalation, available data on its toxicity from inhalation are scarce. Therefore, this study was aimed at confirming the toxicity of DDAC after inhalation exposure for 2 wk. Male Sprague-Dawley rats were exposed to approximately 0.15 mg/m3, 0.6 mg/m3, and 3.6 mg/m3 DDAC aerosols in whole-body exposure chambers. After DDAC exposure for 2 wk, effects of DDAC on body weight, blood, bronchoalveolar lavage (BAL), and the lungs were verified. The mass median aerodynamic diameter of DDAC aerosols was 1.86 μm and the geometric standard deviation was 2.75. The concentrations of DDAC aerosols for the low, medium, and high groups were 0.15 ± 0.15 mg/m3, 0.58 ± 0.40 mg/m3, and 3.63 ± 1.56 mg/m3, respectively. Body weight gain was significantly influenced by DDAC exposure. In the high group, a body weight decrease of 2.6 g was observed, whereas a 25.8 g increase was observed in the normal control group after the first 3 days. The low and medium groups showed 23.3 g and 20.4 g increases, respectively, after the first 3 days. Decreases in body weight were recovered during the next 4 days. In contrast, no changes were noted in hematological and blood biochemistry parameters after DDAC exposure. Furthermore, only mild effects were observed on bronchoalveolar cell differentiation counts and cell damage parameters in the BAL fluids of the medium and high groups. Although inflammatory cell infiltration and interstitial pneumonia were partially observed, fibrosis was not found in the lungs of the medium and high groups. In conclusion, body weight gain and the lungs were mainly affected by DDAC exposure. The noobserved-adverse-effect level (NOAEL) for DDAC was determined as 0.15 mg/m3. PMID:25343015

Results of Upfront Therapy for Marginal Zone Lymphoma.

PubMed

Ortega, José L; Cabanillas, Fernando; Rivera, Noridza; Tirado-Gomez, Maribel; Hallman, Deana; Pardo, Wandaly I; Bruno, Margarita

2017-12-01

Marginal zone lymphomas (MZLs) are indolent disorders composed of 3 subtypes: extranodal marginal zone lymphoma (MALT), splenic marginal zone lymphoma (SMZL), and nodal marginal zone lymphoma (NMZL). Early-stage MALT is treated with radiotherapy or antibiotics, and advanced MALT and NMZL are managed with either watch and wait or chemotherapy. SMZLs are treated with splenectomy or rituximab. However, because these approaches have failed to cure patients with SMZL and NMZL, we have systematically used upfront chemotherapy for them, as well as for advanced MALT. We report the outcomes of this approach. A total of 44 patients with MZL were identified from our database and divided into 2 groups. Group 1 (22 with early-stage MALT) patients received either radiotherapy (n = 17) or antibiotics with or without surgery (n = 5). Group 2 included 9 patients with advanced MALT, 9 with SMZL, and 4 with NMZL. Group 2 was treated with FND-R (fludarabine 25 mg/m 2 on days 1 to 3, mitoxantrone 10 mg/m 2 on day 1, dexamethasone 20 mg on days 1 to 5, and rituximab 375 mg/m 2 on day 1; n = 14) or CHOP-R (cyclophosphamide 750 mg/m 2 on day 1, doxorubicin 50 mg/m 2 on day 1, vincristine 2 mg intravenous push on day 1, prednisone 100 mg/m 2 orally on days 1 to 5, rituximab 375 mg/m 2 on day 1; n = 8), followed by maintenance rituximab for 70%. All patients achieved complete remission, and only 2 patients in group 1 had developed a relapse at 70 and 75 months. Both relapses were stage I MALT that had initially been treated with radiotherapy. Both were salvaged with FND-R and remained free of disease at 27 and 39 months after the relapse. At 10 years, the failure-free survival for the 44 patients was 80% and the overall survival was 100%. None of the patients in group 2 developed a relapse. The long-term toxicities have been acceptable. The excellent responses using upfront chemotherapy for MZL suggests that this disorder is curable. Our results should be confirmed in a prospective trial. Copyright © 2017 Elsevier Inc. All rights reserved.

Biweekly XELOX (capecitabine and oxaliplatin) as first-line treatment in elderly patients with metastatic colorectal cancer.

PubMed

Grande, Carlos; Quintero, Guillermo; Candamio, Sonia; París Bouzas, Lorena; Villanueva, María José; Campos, Begoña; Gallardo, Elena; Alvarez, Elena; Casal, Joaquín; Mel, José Ramón

2013-04-01

The combination of oxaliplatin and oral capecitabine (XELOX) has shown to be an active regimen in metastatic colorectal cancer (MCRC). However, the experience with XELOX in elderly patients is limited. This study aimed to evaluate the efficacy and safety of XELOX as first-line treatment in elderly patients with MCRC. Patients aged ≥70years with previously untreated MCRC received oxaliplatin 85mg/m(2) on day 1, every 2weeks plus capecitabine 1000mg/m(2) (or capecitabine 750mg/m(2) if creatinine clearance was 30-50mL/min) twice daily on days 1-7, every 2weeks. Treatment was continued until progression, intolerable toxicity, or for a maximum of 12cycles. Thirty-five patients were enrolled. Median age was 78years (range, 70-83). Patients received a median of 11cycles of treatment. The objective response rate (ORR) was 49% and the tumor control rate was 86%. Median time to progression and overall survival were 8.6 (95% CI: 5.5-11.7) and 15.5 (95% CI: 9.6-21.3) months, respectively. Toxicities were generally mild to moderate. Major grade 1-2 toxicities were asthenia (40%), nausea (43%), and diarrhea (40%). No grade 4 toxicity was detected and grade 3 toxicities were reported in 17% of patients. There was no treatment-related death. Our findings show that the biweekly XELOX regimen represents an effective and tolerable first-line treatment option for elderly patients with MCRC. Copyright © 2013 Elsevier Inc. All rights reserved.

Silicosis among gold miners: exposure--response analyses and risk assessment.

PubMed Central

Steenland, K; Brown, D

1995-01-01

OBJECTIVES. This study sought to estimate the risk of silicosis by cumulative exposure-years in a cohort of miners exposed to silica, as well as the lifetime risk of silicosis under the current Occupational Safety and Health Administration (OSHA) standard (0.09 mg/m3). METHODS. In a cohort study of 3330 gold miners who worked at least 1 year underground from 1940 to 1965 (average 9 years) and were exposed to a median silica level of 0.05 mg/m3 (0.15 mg/m3 for those hired before 1930), 170 cases of silicosis were determined from either death certificates or two cross-sectional radiographic surveys. RESULTS. The risk of silicosis was less than 1% with a cumulative exposure under 0.5 mg/m3-years, increasing to 68% to 84% for the highest cumulative exposure category of more than 4 mg/m3-years. Cumulative exposure was the best predictor of disease, followed by duration of exposure and average exposure. After adjustment for competing risks of death, a 45-year exposure under the current OSHA standard would lead to a lifetime risk of silicosis of 35% to 47%. CONCLUSIONS. Almost 2 million US workers are currently exposed to silica. Our results add to a small but increasing body of literature that suggests that the current OSHA silica exposure level is unacceptably high. PMID:7573620

Acute nose-only exposure of rats to phosgene. Part II. Concentration x time dependence of changes in bronchoalveolar lavage during a follow-up period of 3 months.

PubMed

Pauluhn, Jürgen

2006-08-01

Groups of young adult male Wistar rats were acutely exposed to phosgene gas for either 30 or 240 min using a directed-flow nose-only mode of exposure. In 30-min exposed rats the concentrations were 0.94, 2.02, 3.89, 7.35, and 15.36 mg/m3, which relate to C x t products of 28.2, 60.6, 116.7, 220.5, and 460.8 mg/m3 x min. In 240-min exposed rats the concentrations were 0.96, 0.387, 0.786, 1.567, and 4.2 mg/m3, which relate C x t products of 47.0, 92.9, 188.6, 376, and 1008 mg/m3 x min. Six rats/group were sacrificed on postexposure days 1, 3, 7, 14, and 84, while the rats of the 1008 mg/m3 x min group where sacrificed on postexposure days 1, 7, 14, and 28. The focus of measurements was directed toward indicators of inflammatory response and increased transmucosal permeability in bronchoalveolar lavage (BAL), including lung weights. Lungs from rats sacrificed at the end of the postexposure period were additionally examined by histopathology. Mortality did not occur at any C x t product. The most pronounced changes were related to C x t-dependent increases in the following markers in BAL: protein, soluble collagen, polymorphonuclear leukocytes (PMN) counts, and alveolar macrophages with foamy appearance. These indicators were maximal on the first postexposure day, while total cell counts and alveolar macrophages containing increased phospholipids reached their climax around post-exposure day 3. At 1008 mg/m3 x min the most sensitive indicators in BAL, that is, protein, PMN, and collagen, resolved within 2 wk, whereas at lower C x t products they reached the level of the control by postexposure day 7. At 1008 mg/m3 x min (day 28), histopathology revealed a minimal to slight hypercellularity in terminal bronchioles with focal peribronchiolar inflammatory infiltrates and focal septal thickening. At lower C x t products (day 84) the rats from all groups were indistinguishable and Sirius red-stained lungs did not provide evidence of late-onset sequelae, such as fibrotic changes or collagen deposition. At similar C x t products the changes in BAL were slightly less pronounced using 30-min exposure periods when compared to 240-min exposure periods. In summary, the phosgene-induced transmucosal permeability caused a C x t-dependent increase of several BAL indicators, of which those of protein, PMN, and soluble collagen were most pronounced. Exposure intensities up to 116.7 mg/m3 x min did not cause changes different from those observed in controls, while at 188.6 mg/m3 x min distinct differences to the control existed. Despite the extensively increased airway permeability, histopathology did not provide evidence of lung tissue remodeling or irreversible sequelae.

Combination of romidepsin with cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated patients with peripheral T-cell lymphoma: a non-randomised, phase 1b/2 study.

PubMed

Dupuis, Jehan; Morschhauser, Franck; Ghesquières, Hervé; Tilly, Hervé; Casasnovas, Olivier; Thieblemont, Catherine; Ribrag, Vincent; Bossard, Céline; Le Bras, Fabien; Bachy, Emmanuel; Hivert, Bénédicte; Nicolas-Virelizier, Emmanuelle; Jardin, Fabrice; Bastie, Jean-Noel; Amorim, Sandy; Lazarovici, Julien; Martin, Antoine; Coiffier, Bertrand

2015-04-01

Romidepsin is a histone deacetylase inhibitor approved in the USA for patients with recurrent or refractory peripheral T-cell lymphoma and has shown activity in this setting with mainly haematological and gastrointestinal toxicity. Although it has limited efficacy, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used for treatment of de-novo peripheral T-cell lymphoma. We aimed to assess the safety, tolerability, and activity of romidepsin combined with CHOP in patients with previously untreated disease. We enrolled patients aged 18-80 years with histologically proven, previously untreated, peripheral T-cell lymphoma (Eastern Cooperative Oncology Group performance status ≤2) into a dose-escalation (phase 1b) and expansion (phase 2) study at nine Lymphoma Study Association centres in France. In the dose-escalation phase, we allocated consecutive blocks of three participants to receive eight 3 week cycles of CHOP (intravenous cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and vincristine 1.4 mg/m(2) [maximum 2 mg] on day 1 and oral prednisone 40 mg/m(2) on days 1-5) in association with varying doses of romidepsin. The starting dose was 10 mg/m(2) intravenously on days 1 and 8 of each cycle, and we used a 3 + 3 design. We assessed dose-limiting toxicities only during the first two cycles. The primary endpoint was to determine the recommended dose for the combination. For the phase 2 study, we aimed to increase the cohort of patients receiving the recommended dose to a total of 25 patients. Patients were assessed for safety outcomes at least twice per cycle according to the Common Terminology Criteria for Adverse Events, version 4.0. Safety analyses included all patients who received at least one dose of romidepsin and CHOP. This trial is registered at the European Clinical Trials Database (EudraCT), number 2010-020962-91 and ClinicalTrials.gov, number NCT01280526. Between Jan 13, 2011, and May 21, 2013, we enrolled 37 patients (18 treated in phase 1b and 19 patients in phase 2). Three of six patients initially treated at 10 mg/m(2) had a dose-limiting toxicity. The dose-escalation committee decided to modify the study protocol to redefine dose-limiting toxicities with regard to haematological toxicity. Three patients were treated with 8 mg/m(2) of romidepsin, an additional three at 10 mg/m(2) (one dose-limiting toxicity), and six patients at 12 mg/m(2) (three dose-limiting toxicities). We chose romidepsin 12 mg/m(2) as the recommended dose for phase 2. Of the 37 patients treated, three had early cardiac events (two myocardial infarctions and one acute cardiac failure). No deaths were attributable to toxicity. 25 (68%) of 37 patients had at least one serious adverse event. Overall, the most frequent serious adverse events were febrile neutropenia (five [14%] of 37 patients), physical health deterioration (five [14%]), lung infection (four [11%]), and vomiting (three [8%]). 33 (89%) of patients had grade 3-4 neutropenia, and 29 (78%) had grade 3-4 thrombocytopenia. Romidepsin can be combined with CHOP but this combination should now be tested in comparison to CHOP alone in a randomised trial. Celgene. Copyright © 2015 Elsevier Ltd. All rights reserved.

Physicochemical Characteristics of Dust Particles in HVOF Spraying and Occupational Hazards: Case Study in a Chinese Company

NASA Astrophysics Data System (ADS)

Huang, Haihong; Li, Haijun; Li, Xinyu

2016-06-01

Dust particles generated in thermal spray process can cause serious health problems to the workers. Dust particles generated in high velocity oxy-fuel (HVOF) spraying WC-Co coatings were characterized in terms of mass concentrations, particle size distribution, micro morphologies, and composition. Results show that the highest instantaneous exposure concentration of dust particles in the investigated thermal spray workshop is 140 mg/m3 and the time-weighted average concentration is 34.2 mg/m3, which are approximately 8 and 4 times higher than the occupational exposure limits in China, respectively. The large dust particles above 10 μm in size present a unique morphology of polygonal or irregular block of crushed powder, and smaller dust particles mainly exist in the form of irregular or flocculent agglomerates. Some heavy metals, such as chromium, cobalt, and nickel, are also found in the air of the workshop and their concentrations are higher than the limits. Potential occupational hazards of the dust particles in the thermal spray process are further analyzed based on their characteristics and the workers' exposure to the nanoparticles is assessed using a control banding tool.

Assessment of historical exposures in a nickel refinery in Norway.

PubMed

Grimsrud, T K; Berge, S R; Resmann, F; Norseth, T; Andersen, A

2000-08-01

The aim of the study was, on the basis of new information on nickel species and exposure levels, to generate a specific exposure matrix for epidemiologic analyses in a cohort of Norwegian nickel-refinery workers with a known excess of respiratory cancer. A department-time-exposure matrix was constructed with average exposure to total nickel estimated as the arithmetic mean of personal measurements for periods between 1973 and 1994. From 1972 back to the start of production in 1910, exposure concentrations were estimated through retrograde calculation with multiplication factors developed on the basis of reported changes in the metallurgical process and work environment. The relative distribution of water-soluble nickel salts (sulfates and chlorides), metallic nickel, and particulates with limited solubility (sulfides and oxides) was mainly derived from speciation analyses conducted in the 1990s. The average concentration of nickel in the breathing zone was < or = 0.7 mg/m3 for all workers after 1978. Exposure levels for smelter and roaster day workers were 2-6 mg/m3 before 1970, while workers in nickel electrolysis and electrolyte purification were exposed to concentrations in the range of 0.15-1.2 mg/m3. The level of water-soluble nickel was of the same order for workers in the smelting and roasting departments as in some of the electrolyte purification departments. Compared with earlier estimates, the present matrix probably offers a more reliable description of past exposures at the plant.

[Airborne particles in a multi-wall carbon nanotube production plant: observation of particle emission and personal exposure 1: Measurement in the packing process].

PubMed

Takaya, Mitsutoshi; Serita, Fumio; Ono-Ogasawara, Mariko; Shinohara, Yasushi; Saito, Hiroyuki; Koda, Shigeki

2010-01-01

In order to assess the exposure risks of multiwall carbon nanotubes (MWCNT) for packing workers, we carried out real-time monitoring in the two types of packing facilities of MWCNT, and exposure measurements for the packing workers. In the real-time monitoring, a scanning mobility particle sizer (SMPS) and an optical particle counter (OPC) were used to measure nanoscale particles and sub-micron/micron scale particles, respectively. A personal sampler with PM 4.0 was used to measure the personal exposures in the packing facilities. One of the packing facilities is manually operated and the other is automated. The concentrations of airborne dust in both facilities were almost the same as each other at 0.24 mg/m(3) (total dust). However, the results of personal exposure measurements were quite different between the two facilities. The exposure concentrations of workers in the manually and automated operations were 2.39/0.39 (total/respirable) mg/m(3) and 0.29/0.08 (total/respirable) mg/m(3), respectively. From the time series study, submicron scale particles were released into the workplace air when the CNT products were put into temporary container bags from a hopper and manually packed into shipping bags. However, the task-related nanoscale particle release was not observed. The manual packing operation is one of the "hot spots" in MWCNT production facilities, and automation brings much improvement to reduce MWCNT exposure.

Pulmonary risk of intraoral surface conditioning using crystalline silica.

PubMed

Mayer, Beate; Raithel, Hans; Weltle, Dieter; Niedermeier, Wilhelm

2003-01-01

This study evaluated the pulmonary risk caused by possible respirable dust of Al2O3 and SiO(x) resulting from chairside tribochemical sandblasting procedures in a dental office. Dust was collected using a trap near the working field, and quantitative morphologic determination and identification were performed with SEM and EDAX. Forty blasting processes (total time 20 minutes) were aimed at a dummy to obtain maximum pollution of the workplace. Respirable dust fraction was measured using personal air samplers with an 8-microm cellulose-nitrate filter and a volume flow rate of 2 L/min. Mass of the respirable dust fraction was determined, and respirable free crystalline silica was identified with the help of infrared spectroscopy. Blasting of metal or ceramic surfaces with tribochemical agents produces respirable and potentially harmful SiO(x) and Al2O3 particles with a diameter of less than 5 microm, showing a total concentration in the air of less than 0.3 mg/m3. With and without dental suction, the concentration of the respirable free crystalline silica was smaller than 0.02 mg/m3. Concern regarding the risk of chairside tribochemical methods and possible impairment of health of patients and dental staff is unfounded, even under extreme conditions or without protective measures, since the concentrations of SiO(x) found in the air of the workplace were far below the current threshold value of 0.15 mg/m3.

Rituximab-dose-dense chemotherapy with or without high-dose chemotherapy plus autologous stem-cell transplantation in high-risk diffuse large B-cell lymphoma (DLCL04): final results of a multicentre, open-label, randomised, controlled, phase 3 study.

PubMed

Chiappella, Annalisa; Martelli, Maurizio; Angelucci, Emanuele; Brusamolino, Ercole; Evangelista, Andrea; Carella, Angelo Michele; Stelitano, Caterina; Rossi, Giuseppe; Balzarotti, Monica; Merli, Francesco; Gaidano, Gianluca; Pavone, Vincenzo; Rigacci, Luigi; Zaja, Francesco; D'Arco, Alfonso; Cascavilla, Nicola; Russo, Eleonora; Castellino, Alessia; Gotti, Manuel; Congiu, Angela Giovanna; Cabras, Maria Giuseppina; Tucci, Alessandra; Agostinelli, Claudio; Ciccone, Giovannino; Pileri, Stefano A; Vitolo, Umberto

2017-08-01

The prognosis of young patients with diffuse large B-cell lymphoma at high risk (age-adjusted International Prognostic Index [aa-IPI] score 2 or 3) treated with R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisone) is poor. The aim of this study was to investigate the possible benefit of intensification with high-dose chemotherapy and autologous stem-cell transplantation as part of first-line treatment in these patients. We did a multicentre, open-label, randomised, controlled, phase 3 trial with a 2 × 2 factorial design to compare, at two different R-CHOP dose levels, a full course of rituximab-dose-dense chemotherapy (no transplantation group) versus an abbreviated course of rituximab-dose-dense chemotherapy followed by consolidation with R-MAD (rituximab plus high-dose cytarabine plus mitoxantrone plus dexamethasone) and high-dose BEAM chemotherapy (carmustine, etoposide, cytarabine, and melphalan) plus autologous stem-cell transplantation (transplantation group) in young patients (18-65 years) with untreated high-risk diffuse large B-cell lymphoma (aa-IPI score 2-3). At enrolment, patients were stratified according to aa-IPI score and randomly assigned (1:1:1:1) to receive R-CHOP (intravenous rituximab 375 mg/m 2 , cyclophosphamide 750 mg/m 2 , doxorubicin 50 mg/m 2 , and vincristine 1·4 mg/m 2 on day 1, plus oral prednisone 100 mg on days 1-5) delivered in a 14-day cycle (R-CHOP-14) for eight cycles; high-dose R-CHOP-14 (R-MegaCHOP-14; R-CHOP-14 except for cyclophosphamide 1200 mg/m 2 and doxorubicin 70 mg/m 2 ) for six cycles; R-CHOP-14 for four cycles followed by R-MAD (intravenous rituximab 375 mg/m 2 on day 1 or 4 plus intravenous cytarabine 2000 mg/m 2 and dexamethasone 4 mg/m 2 every 12 h on days 1-3 plus intravenous mitoxantrone 8 mg/m 2 on days 1-3) plus BEAM (intravenous carmustine 300 mg/m 2 on day -7, intravenous cytarabine 200 mg/m 2 twice a day on days -6 to -3, intravenous etoposide 100 mg/m 2 twice a day on days -6 to -3, plus intravenous melphalan 140 mg/m 2 on day -2) and autologous stem-cell transplantation (day 0); or R-MegaCHOP-14 for four cycles followed by R-MAD plus BEAM and autologous stem-cell transplantation. The primary endpoint was failure-free survival at 2 years in the intention-to-treat population. This study is registered with EudraCT (2005-002181-14; 2007-000275-42) and with ClinicalTrials.gov, number NCT00499018. Between Jan 10, 2006, and Sept 8, 2010, 399 patients were randomly assigned to receive transplantation (n=199) or no transplantation (n=200); 203 patients were assigned to receive R-CHOP-14 and 196 were assigned to receive R-MegaCHOP-14. With a median follow-up of 72 months (IQR 57-88), 2-year failure-free survival was 71% (95% CI 64-77) in the transplantation group versus 62% (95% CI 55-68) in the no transplantation group (hazard ratio [HR] 0·65 [95% CI 0·47-0·91]; stratified log-rank test p=0·012). No difference in 5-year overall survival was observed between these groups (78% [95% CI 71-83] versus 77% [71-83]; HR 0·98 [0·65-1·48]; stratified log-rank test p=0·91). Grade 3 or worse haematological adverse events were reported in 183 (92%) of 199 patients in the transplantation group versus 135 (68%) of 200 patients in the no transplantation group. Grade 3 or worse non-haematological adverse events were reported in 90 (45%) versus 31 (16%); the most common grade 3 or worse non-haematological adverse event was gastrointestinal (49 [25%] vs 19 [10%]). Treatment-related deaths occurred in 13 (3%) patients; eight in the transplantation group and five in the no transplantation group. Abbreviated rituximab-dose-dense chemotherapy plus R-MAD plus BEAM and autologous stem-cell transplantation reduced the risk of treatment failure compared with full course rituximab-dose-dense chemotherapy in young patients with diffuse large B-cell lymphoma at high risk. However, these results might not be clinically meaningful, since this improvement did not reflect an improvement in overall survival. These results do not support further consideration of the use of intensification of R-CHOP as an upfront strategy in patients with diffuse large B-cell lymphoma with poor prognosis. Fondazione Italiana Linfomi. Copyright © 2017 Elsevier Ltd. All rights reserved.

2011 AFMS Medical Research Symposium Held in National Harbor, Maryland on August 2-4, 2011. Volume 3: Force Health Protection Track

DTIC Science & Technology

2011-08-01

Exposure 311 -+- Control R=9 JP8 200 mg/m1+ Noise 85dB n= lO JP8 750 mg/m1+ Nohe 85dB n=9 JP815D~ mg!m3+Nohe 85dB n=9...Force Health Protection 24 Results- Study 4: DPOAE DPOAE 1 0 Day Post Exposure Males Control tt=5 • JP8 1000 mglm3 n=S Ml +- Noi5 e lO !db 15...min/h x 6h n=5 B -::.::.~:::r·= lO . . .. ~.·:~· .· . ~>. • .. -~~ .. . ~ ~ . . n ..~ !"-. IL~ ~+,-------,------,,-------~,.-----~~----~ Fnquency

Gas-geochemical condition and ecological functions of urban soils in areas with gas generating grounds

NASA Astrophysics Data System (ADS)

Mozharova, Nadezhda; Lebed-Sharlevich, Iana; Kulachkova, Svetlana

2014-05-01

Rapid urbanization and expansion of city borders lead to development of new areas, often following with relief changes, covering of gully-ravine systems and river beds with technogenic grounds containing construction and municipal waste. Decomposition of organic matter in these grounds is a source of methane and carbon dioxide. Intensive generation and accumulation of CO2 and CH4 into grounds may cause a fire and explosion risk for constructed objects. Gases emission to the atmosphere changes the global balance of GHGs and negatively influences on human health. The aim of this investigation is to study gas-geochemical condition and ecological functions of urban soils in areas with gas generating grounds. Studied areas are the gully-ravine systems or river beds, covered with technogenic grounds during land development. Stratigraphic columns of these grounds are 5-17 meters of man-made loamy material with inclusion of construction waste. Gas generating layer with increased content of organic matter, reductive conditions and high methanogenic activity (up to 1.0 ng*g-1*h-1) is situated at the certain depth. Maximum CH4 and CO2 concentrations in this layer reach dangerous values (2-10% and 11%, respectively) in the current standards. In case of disturbance of ground layer (e.g. well-drilling) methane is rapidly transferred by convective flux to atmosphere. The rate of CH4 emission reaches 100 mg*m-2*h-1 resulting in its atmospheric concentration growth by an order of magnitude compared with background. In normal occurrence of grounds methane gradually diffuses into the upper layers by pore space, consuming on different processes (e.g. formation of organic matter, nitrogen compounds or specific particles of magnetite), and emits to atmosphere. CH4 emission rate varies from 1 to 40 mg*m-2*h-1 increasing with depth of grounds. Carbon dioxide emission is about 100 mg*m-2*h-1. During soil formation on gas generating grounds bacterial oxidation of methane, one of the most important ecological functions of such soils, is initiated. Due to high rate of this process (25-30 ng*g-1*h-1) accumulation of methane in the profile does not observed, its content in soil averages 2-5 ppm. Methane emission from soils is low (0.01-0.03 mg*m-2*h-1) or there is a weak consumption of atmospheric CH4, whereby its concentration in the air corresponds to the average content of this gas. Active methane oxidation and decomposition of organic matter under aerobic conditions result to intensive formation of carbon dioxide and, thus, increase its emission (600 mg*m-2*h-1), concentration in soils (0.2-0.9%) and in atmosphere (up to 0.5%). Fixed concentration of CO2 in the air is dangerous for human health. Thus, presence of gas generating grounds with high content of organic matter leads to methane formation, causing its intensive emission to atmosphere. At upper layers of soils and grounds bacterial oxidation of methane occurs and results in complete CH4 utilization. During this process significant amounts of carbon dioxide are released and accumulated in the atmosphere up to concentration dangerous for people. Carbon dioxide emission increases current level of this gas in the urban atmosphere.

Effect of dietary protein concentration on ammonia and greenhouse gas emitting potential of dairy manure.

PubMed

Lee, C; Hristov, A N; Dell, C J; Feyereisen, G W; Kaye, J; Beegle, D

2012-04-01

Two experiments were conducted to investigate the effect of dietary crude protein concentration on ammonia (NH(3)) and greenhouse gas (GHG; nitrous oxide, methane, and carbon dioxide) emissions from fresh dairy cow manure incubated in a controlled environment (experiment 1) and from manure-amended soil (experiment 2). Manure was prepared from feces and urine collected from lactating Holstein cows fed diets with 16.7% (DM basis; HCP) or 14.8% CP (LCP). High-CP manure had higher N content and proportion of NH(3)- and urea-N in total manure N than LCP manure (DM basis: 4.4 vs. 2.8% and 51.4 vs. 30.5%, respectively). In experiment 1, NH(3) emitting potential (EP) was greater for HCP compared with LCP manure (9.20 vs. 4.88 mg/m(2) per min, respectively). The 122-h cumulative NH(3) emission tended to be decreased 47% (P=0.09) using LCP compared with HCP manure. The EP and cumulative emissions of GHG were not different between HCP and LCP manure. In experiment 2, urine and feces from cows fed LCP or HCP diets were mixed and immediately applied to lysimeters (61×61×61 cm; Hagerstown silt loam; fine, mixed, mesic Typic Hapludalf) at 277 kg of N/ha application rate. The average NH(3) EP (1.53 vs. 1.03 mg/m(2) per min, respectively) and the area under the EP curve were greater for lysimeters amended with HCP than with LCP manure. The largest difference in the NH(3) EP occurred approximately 24 h after manure application (approximately 3.5 times greater for HCP than LCP manure). The 100-h cumulative NH(3) emission was 98% greater for HCP compared with LCP manure (7,415 vs. 3,745 mg/m(2), respectively). The EP of methane was increased and that of carbon dioxide tended to be increased by LCP compared with HCP manure. The cumulative methane emission was not different between treatments, whereas the cumulative carbon dioxide emission was increased with manure from the LCP diet. Nitrous oxide emissions were low in this experiment and did not differ between treatments. In the conditions of these experiments, fresh manure from dairy cows fed a LCP diet had substantially lower NH(3) EP, compared with manure from cows fed a HCP diet. The LCP manure increased soil methane EP due to a larger mass of manure added to meet plant N requirements compared with HCP manure. These results represent effects of dietary protein on NH(3) and GHG EP of manure in controlled laboratory conditions and do not account for environmental factors affecting gaseous emissions from manure on the farm. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Marine Habitats. Man and the Gulf of Mexico Series.

ERIC Educational Resources Information Center

Irby, Bobby N.; And Others

"Man and the Gulf of Mexico (MGM)" is a marine science curriculum developed to meet the marine science needs of tenth through twelfth grade students in Mississippi and Alabama schools. This MGM unit, which focuses on marine habitats, contains an introduction (with unit objectives and brief introductory comments) followed by five…

FOI and Fire at the MGM Grand.

ERIC Educational Resources Information Center

Thompson, William N.; Marie, Janice

The fire at the MGM Grand Hotel in Las Vegas, Nevada, brought to light a lack of compliance with the freedom of information philosophy and its supporting statutes. Freedom of information means circulation of important information. However, at the Grand Hotel, the hotel staff had not been properly trained in disaster procedures, the escape…

Phase II trial of cytarabine, cisplatin and vindesine for advanced non-small cell lung cancer.

PubMed

Bianco, A; Perez, J E; Machiavelli, M; Leone, B A; Romero, A; Rabinovich, M G; Vallejo, C T; Rodriguez, R; Cuevas, M A; Alvarez, L A

1990-02-28

Thirty-two patients with advanced non-small cell lung cancer (NSCLC) were entered in this study to evaluate the efficacy and toxicity of a chemotherapy schedule including cisplatin (C) 40 mg/m2 intravenously (i.v.) on days 1-3; vindesine (V) 3 mg/m2 i.v. on day 1, and cytarabine (ara-C) 15 mg/m2 subcutaneously every 12 hours on days 1-3 (total dose: 90 mg/m2). Cisplatin was administered simultaneously with one dose of ara-C. Cycles were repeated every 28 days. Five patients out of 28 (18%) fully evaluable for response presented partial remissions. No complete response was observed. Median survival was 8 months and median duration of response was 4 months. Hematologic toxicity was severe in 3 patients. There were no toxicity-related deaths. Other adverse reactions included nausea and vomiting, alopecia and peripheral neuropathy. We conclude that this chemotherapy combination is marginally effective against NSCLC showing in this group of patients a low number of responses of short duration without a significant impact on survival.

Phase II study of neoadjuvant gemcitabine, pegylated liposomal doxorubicin, and docetaxel in locally advanced breast cancer.

PubMed

Artioli, Grazia; Grazia, Artioli; Mocellin, Simone; Simone, Mocellin; Borgato, Lucia; Lucia, Borgato; Cappetta, Alessandro; Alessandro, Cappetta; Bozza, Fernando; Fernando, Bozza; Zavagno, Giorgio; Giorgio, Zavagno; Zovato, Stefania; Stefania, Zovato; Marchet, Alberto; Alberto, Marchet; Pastorelli, Davide; Davide, Pastorelli

2010-09-01

This was a phase II study to assess the activity of a novel neoadjuvant regimen in locally-advanced breast cancer. Fifty patients with histological confirmation of locally advanced breast cancer received treatment with gemcitabine 1000 mg/m(2) (day 1) followed by gemcitabine 800 mg/m(2) plus docetaxel 75 mg/m(2) plus pegylated liposomal doxorubicin (PLD) 30 mg/m(2) (day 8) every 3 weeks for at least 4 cycles, plus a final 2 additional cycles. Tumour size was T1 (n=2), T2 (n=32), T3 (n=14), T4 (n=2). All 50 patients underwent surgery. Clinical complete, partial and no response were observed in 13 (26%), 24 (48%) and 11 (22%) patients, respectively (overall response rate: 74%). The number of chemotherapy cycles was found to be an independent predictor of a pathologic complete response. The combination of gemcitabine-docetaxel-PLD can yield high tumour response rates in patients with locally-advanced breast cancer who undergo a full treatment of 6 cycles.

Long-term study on workers occupationally exposed to ethylbenzene.

PubMed

Bardodĕj, Z; Círek, A

1988-01-01

Ethylbenzene is synthesized from benzene; subject to catalytic dehydrogenation it yields styrene, a raw material for the production of synthetic rubber and plastics. Long-term biomonitoring of occupational ethylbenzene exposures, carried out in the past 20 years in some 200 ethylbenzene-production workers, revealed this substance to pose little hazard to human health. As it turned out, mandelic acid concentrations in these workers' urine never exceeded 3.25 mmol.l-1 and none of the exposed showed damage to hematopoiesis and/or liver tissue. Over the last 10 years no case of malignancy has been recorded in this industrial facility belonging to a larger chemical complex where the overall incidence of cancer is about 3 times the national average. Today's low-level ethylbenzene exposures would make it fully justifiable if the present-day MAC limits, both whole-shift (200 mg.m-3) and peak (1,000 mg.m-3), were to be halved, i.e. to be lowered to 100 mg.m3 and 500 mg.m3 respectively. These newly recommended limit values are no more exceeded nowadays.

Treatment of advanced Hodgkin's disease with B-CAVE following MOPP failure.

PubMed

Porzig, K J; Portlock, C S; Robertson, A; Rosenberg, S A

1978-05-01

Between March 1973, and December 1976, 22 patients who developed disease progression during or after MOPP therapy were treated with a new combination, B-CAVe (Bleomycin 5 mg/m2 iv days 1, 28, 35; CCNU 100 mg/m2 po day 1; adriamycin 60 mg/m2 iv day 1; and vinblastine 5 mg/m2 iv day 1). Objective responses were achieved in 17 of 22 patients (77%) and 11 of 22 responses were complete (50%). The actuarial survival for all patients is 16.4 months. For complete responders the median is 24 months with 2 complete responders dead without evidence of Hodgkin's Disease. Median relapse free survival for complete responders has not been reached at 35+ months while that for partial responders is 14 months. Significant adriamycin cardiotoxicity was encountered in two patients. There were no life threatening bacterial infections during B-CAVe. Two patients died of Pneumocystis carinii several months after cessation of therapy. B-CAVe is effective in the therapy of advanced Hodgkin's disease after MOPP failure, and this regimen is comparable to other previously reported MOPP salvage combinations.

The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.

PubMed

Burnett, Alan K; Milligan, Donald; Goldstone, Anthony; Prentice, Archibald; McMullin, Mary-Frances; Dennis, Michael; Sellwood, Elizabeth; Pallis, Monica; Russell, Nigel; Hills, Robert K; Wheatley, Keith

2009-05-01

The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress.

Gemcitabine and vinorelbine (GV) versus cisplatin, gemcitabine and vinorelbine (CGV) as first-line treatment in advanced non small cell lung cancer: results of a prospective randomized phase II study.

PubMed

Esteban, Emilio; Fra, Joaquin; Fernández, Yolanda; Corral, Norberto; Vieitez, José M; Palacio, Isabel; de Sande, José L; Fernández, José L; Muñiz, Isabel; Villanueva, Noemi; Estrada, Enrique; Mareque, Beatriz; Uña, Esther; Buesa, José M; Lacave, Angel J

2006-05-01

The objective of this study was to assess whether adding cisplatin to gemcitabine/vinorelbine combination improves the clinical outcome in patients with non-small-cell lung cancer (NSCLC). Chemotherapy-naïve patients with advanced NSCLC; age < or = 75 years: Karnofsky performance status > or = 60%, and with adequate hematological, renal and hepatic function, were randomized into 2 treatment groups to receive Gemcitabine 1250 mg/m2 + vinorelbine 30 mg/m2 (GV group), or cisplatin 50 mg/m2 + gemcitabine 1000 mg/m2 + vinorelbine 25 mg/m2 (CGV group). All drugs were administered on days 1 and 8 every three weeks: From September 1999 to March 2003, 114 patients were enrolled. No statistically significant difference was observed in GV vs CGV group in objective response (37 versus 47%, respectively; P = 0.5), median time to progression (5 versus 5.8 months; P = 0.6), overall survival (9 versus 10 months; P = 0.9) and 1-year survival (26 versus 28%; P = 0.9). Conversely, toxicities were significantly higher for CGV, including grade 3-4 neutropenia (24 versus 45%); neutropenic fever (4 versus 14%, including one toxic death); grade 3-4 thrombocytopenia (2 versus 14%); and grade 3-4 emesis (2 versus 14%). Our results suggest that the combination of gemcitabine and vinorelbine is less toxic than three-drug combination with cisplatin while showing similar efficacy.

Initial paclitaxel improves outcome compared with CMFP combination chemotherapy as front-line therapy in untreated metastatic breast cancer.

PubMed

Bishop, J F; Dewar, J; Toner, G C; Smith, J; Tattersall, M H; Olver, I N; Ackland, S; Kennedy, I; Goldstein, D; Gurney, H; Walpole, E; Levi, J; Stephenson, J; Canetta, R

1999-08-01

To determine the place of single-agent paclitaxel compared with nonanthracycline combination chemotherapy as front-line therapy in metastatic breast cancer. Patients with previously untreated metastatic breast cancer were randomized to receive either paclitaxel 200 mg/m(2) intravenously (IV) over 3 hours for eight cycles (24 weeks) or standard cyclophosphamide 100 mg/m(2)/d orally on days 1 to 14, methotrexate 40 mg/m(2) IV on days 1 and 8, fluorouracil 600 mg/m(2) IV on days 1 and 8, and prednisone 40 mg/m(2)/d orally on days 1 to 14 (CMFP) for six cycles (24 weeks) with epirubicin recommended as second-line therapy. A total of 209 eligible patients were randomized with a median survival duration of 17.3 months for paclitaxel and 13.9 months for CMFP. Multivariate analysis showed that patients who received paclitaxel survived significantly longer than those who received CMFP (P =.025). Paclitaxel produced significantly less severe leukopenia, thrombocytopenia, mucositis, documented infections (all P <.001), nausea or vomiting (P =.003), and fever without documented infection (P =.007), and less hospitalization for febrile neutropenia than did CMFP (P =.001). Alopecia, peripheral neuropathy, and myalgia or arthralgia were more severe with paclitaxel (all P <.0001). Overall, quality of life was similar for both treatments (P > = .07). Initial paclitaxel was associated with significantly less myelosuppression and fewer infections, with longer survival and similar quality of life and control of metastatic breast cancer compared with CMFP.

Cytotoxicity and genotoxicity in human lung epithelial A549 cells caused by airborne volatile organic compounds emitted from pine wood and oriented strand boards.

PubMed

Gminski, Richard; Tang, Tao; Mersch-Sundermann, Volker

2010-06-16

Due to the massive reduction of air-change rates in modern, energy-saving houses and dwellings, the contribution of volatile organic compound (VOCs) emissions from wood-based materials to indoor air quality has become increasingly important. To evaluate toxicity of VOC mixtures typically emitted from pine wood and oriented strand boards (OSB) and their main constituents (selected terpenes and aldehydes), cytotoxicity and genotoxicity were investigated in human A549 lung cells. To facilitate exposure directly via gas phase, a 250 L emission chamber was combined with a Vitrocell exposure system. VOC exposure concentrations were measured by GC/MSD. Biological effects were determined after an exposure time of 1h by measuring cytotoxicity (erythrosine B staining) and genotoxicity (comet assay). Neither cytotoxic nor genotoxic effects were observed for VOC mixtures emitted from pine wood or OSB at loading factors of approximately 13 m(2)/m(3) (worst case conditions) of the panels (with maximum VOC levels of about 80 mg/m(3)) in comparison to clean air. While alpha-pinene and Delta(3)-carene did not induce toxic effects even at exposure concentrations of up to 1800 mg/m(3) and 600 mg/m(3), respectively, hexanal showed a cytotoxic effect at 2000 mg/m(3). The alpha,beta-unsaturated aldehydes 2-heptenal and 2-octenal caused genotoxic effects in concentrations exceeding 100mg/m(3) and 40 mg/m(3), respectively. In conclusion, high concentrations of VOCs and VOC mixtures emitted from pine wood and OSB did not lead to adverse effects in A549 human lung cells even at concentrations 10(2) to 10(5)-fold higher than those found in normal indoor air. Attention must be paid to mutagenic and possibly carcinogenic alpha,beta-unsaturated aldehydes. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Exposure assessment of workplace manufacturing titanium dioxide particles

NASA Astrophysics Data System (ADS)

Xu, Huadong; Zhao, Lin; Chen, Zhangjian; Zhou, Jingwen; Tang, Shichuan; Kong, Fanling; Li, Xinwei; Yan, Ling; Zhang, Ji; Jia, Guang

2016-10-01

With the widespread use of titanium dioxide (TiO2) human exposure is inevitable, but the exposure data on TiO2 are still limited. This study adopted off-line filter-based sampling combined with real-time activity-based monitoring to measure the concentrations in a workplace manufacturing TiO2 (primary diameter: 194 ± 108 nm). Mass concentrations (MCs) of aerosol particles in the packaging workshop (total dust: 3.17 mg/m3, nano dust: 1.22 mg/m3) were much higher than those in the milling workshop (total dust: 0.79 mg/m3, nano dust: 0.31 mg/m3) and executive office (total dust: 0.44 mg/m3, nano dust: 0.19 mg/m3). However, the MCs of TiO2 were at a relatively low level in the packaging workshop (total TiO2: 46.4 μg/m3, nano TiO2: 16.7 μg/m3) and milling workshop (total TiO2: 39.4 μg/m3, nano TiO2: 19.4 μg/m3) by ICP-MS. The number concentration (NC), surface area concentration (SAC) of aerosol particles potentially deposited in alveolar (SACA), and tracheobronchial (SACTB) regions of lungs in the packaging workshop were (1.04 ± 0.89) × 105 particles/cm3, 414.49 ± 395.07, and 86.01 ± 83.18 μm2/cm3, respectively, which were all significantly higher than those of the milling workshop [(0.12 ± 0.40) × 105 particles/cm3, 75.38 ± 45.23, and 17.60 ± 9.22 μm2/cm3, respectively] as well as executive office and outdoor background ( p < 0.05). Activity-related characteristics were found in both workshops, and the time-variant characteristics showed very similar trends for 3 days in the packaging workshop. Our study provides important data of TiO2 particles exposure in the workplace.

Study on OELs for enzyme-containing detergent in China.

PubMed

Zhang, X D; Liang, Y X; Lee, C S; Jin, T Y

2004-01-01

This study is aimed at setting occupational exposure levels for total detergent dust and enzymes in detergent industries. The study population consisted of 795 workers from four enzyme-containing detergent manufacturing plants (A1, A2, B1 and B2), and 156 control workers from an electronic assembly factory. Work environment monitoring was conducted using high volume of air sampler fro measuring the concentration of total dust (mg/m3), and analyzing the level of enzyme (ng/m3) by ELISA method. A standard questionnaires, pulmonary function test, and skin prick test are used to assess health effects. The levels of detergent total dust varied from 0.2 mg/m3 to 12.54 mg/m3. For enzyme levels, in A1, B1 and B2, the concentration ranged from non-detectable to 9.92 ng/m3 and in A2, the concentration was analyzed by enzyme activity methods and was expressed as Gu/m3 (1 Gu/m3 = 16 ng/m3). The concentration is between 0.16-31.36 ng/m3. Non-specific irritation rates in exposed workers were significantly higher than that in controls. Based on the data collected from A1, B1 and control plants, 95% benchmark dose lower bound were calculated as 1.17 mg/m3. The difference of pulmonary function between exposed workers and controls is not significant. The results of SPT showed that neither Savinase- nor Alcalase-induced sensitization was found in controls. The prevalence rates of sensitization for Savinase and Alcalase were ranged between 3.2% and 31% in all enzyme-containing detergent manufacturers investigated. No case of occupational asthma was observed. For total dust, 1 mg/m3 is suggested as permissible concentration-time weighted average (PC-TWA), and 2 mg/m3 as permissible concentration-short term exposure limit (PC-STEL). For the enzyme Subtilisins, 15 ng/m3 is suggested as PC-TWA, and 30 ng/m3 as PC-STEL.

Subchronic inhalation of coal dust particulate matter 10 induces bronchoalveolar hyperplasia and decreases MUC5AC expression in male Wistar rats.

PubMed

Kania, Nia; Setiawan, Bambang; Widjadjanto, Edi; Nurdiana, Nurdiana; Widodo, M Aris; Kusuma, H M S Chandra

2014-10-01

Coal dust is a pollutant found in coal mines that are capable of inducing oxidative stress and inflammation, but the effects on lung metaplasia as an early step of carcinogenesis remain unknown. The purpose of the present study was to evaluate the effects of PM10 coal dust on lung histology, MUC5AC expression, epidermal growth factor (EGF) expression, and epidermal growth factor receptor (EGFR) expression. An experimental study was done on male Wistar rats, which were divided into the following groups: control groups exposed to coal dust for 14 days (at doses of 6.25 mg/m(3), 12.5 mg/m(3), and 25 mg/m(3)), and the groups exposed to coal dust for 28 days (at doses of 6.25 mg/m(3), 12.5 mg/m(3), and 25 mg/m(3)). EGF expressions in rat lungs were measured by ELISA. EGFR and MUC5AC were measured by a confocal laser scanning microscope. The bronchoalveolar epithelial image of the group exposed to coal dust for 14 and 28 days showed a epithelial rearrangement, hyperplastic (metaplastic) goblet cells, and scattered massive inflammatory cells. The pulmonary parenchymal image of the group of exposed to coal dust for 14 and 28 days showed scattered inflammatory cells filling up the pulmonary alveolar networks, leading to an appearance of thickened parenchymal alveoli until emphysema-like structure. There was no significant difference in MUC5AC, EGF, and EGFR expressions for 14-d exposure (p>0.05). There was no significant difference in EGF and EGFR expressions for 28-d exposure (p>0.05), but there was a significant difference in MUC5AC expression (p<0.05). We concluded that subchronic inhalation of coal dust particulate matter 10 induces bronchoalveolar reactive hyperplasia and rearrangement of epithelial cells which accompanied by decrease expression MUC5AC in male rats. Copyright © 2014 Elsevier GmbH. All rights reserved.

Dose-finding study of intensive weekly alternating schedule of docetaxel, 5-fluorouracil, and oxaliplatin, FD/FOx regimen, in metastatic gastric cancer.

PubMed

Bruera, Gemma; Massacese, Silvia; Galvano, Antonio; Mas, Antonella Dal; Guadagni, Stefano; Calvisi, Giuseppe; Ciacco, Eugenio; Russo, Antonio; Ricevuto, Enrico

2018-04-17

Proper administration timing, dose-intensity, efficacy/toxicity ratio of triplet docetaxel (DTX), 5-fluorouracil (5-FU), and oxaliplatin (OXP) should be improved to safely perform three-drugs intensive first line in advanced gastric cancer (GC). This dose-finding study investigated recommended 5-FU and OXP doses, safety of triplet regimen and preliminary activity. Schedule: 12h-timed-flat-infusion 5-FU 700-1000 mg/m 2 /d 1-2, 8-9, 15-16, 22-23, with 100 mg/m 2 /d increase for dose level; DTX 50 mg/m 2 d 1, 15 fixed dose, OXP at three increasing dose-levels 60-70-80 mg/m 2 d 8, 22, every 4 weeks. Intra- and inter-patients dose-escalation was planned. Ten fit <75 years patients were enrolled: median age 59; young-elderly 4 (40%). From first to fifth dose level, 5 patients (1 per cohort) were enrolled according to intra-patient dose escalation, no dose-limiting toxicity (DLT) were reported. At sixth level, 1 DLT, G2 diarrhea, was reported, thus other 2 patients were enrolled, DLT 1/3 patients (33%). Maximum tolerated dose (MTD) was not reached. 5-FU and OXP recommended doses (RD) were 1000 mg/m 2 /d and 80 mg/m 2 , respectively. To confirm RD, other 3 patients were enrolled, without DLT. Cumulative G3-4 toxicities were: neutropenia 50%, leucopenia 20%, hypoalbuminemia 10%, mucositis 10%, asthenia 20%. Limiting toxicity syndromes were 30%, 25% in young-elderly, all multiple site. Objective response rate intent-to-treat 60%, disease control rate 90%. After 15 months follow-up, progression-free and overall survival, 6 and 17 months, respectively. First line intensive FD/FOx regimen adding DXT/5-FU/OXP can be safely administered at recommended doses in advanced GC, with promising high activity and efficacy.

A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer.

PubMed

Masters, G A; Mauer, A M; Hoffman, P C; Wyka, D; Samuels, B L; Krauss, S A; Watson, S; Golomb, H; Vokes, E E

1998-06-01

We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.

Occupational exposure to organic solvents during paint stripping and painting operations in the aeronautical industry.

PubMed

Vincent, R; Poirot, P; Subra, I; Rieger, B; Cicolella, A

1994-01-01

The exposure of workers to methylene chloride and phenol in an aeronautical workshop was measured during stripping of paint from a Boeing B 747. Methylene chloride exposure was measured during two work days by personal air sampling, while area sampling was used for phenol. During paint stripping operations, methylene chloride air concentrations ranged from 299.2 mg/m3 (83.1 ppm) to 1888.9 mg/m3 (524.7 ppm). The exposures to methylene chloride calculated for an 8-h work day ranged from 86 mg/m3 (23.9 ppm) to 1239.5 mg/m3 (344.3 ppm). In another aeronautical workshop, exposure to organic solvents, especially ethylene glycol monoethylether acetate (EGEEA), was controlled during the painting of an Airbus A 320. The external exposure to solvents and EGEEA was measured by means of individual air sampling. The estimation of internal exposure to EGEEA was made by measuring its urinary metabolite, ethoxyacetic acid (EAA). Both measurements were made during the course of 3 days. The biological samples were taken pre- and post-shift. During painting operations, methyl ethyl ketone, ethyl acetate, n-butyl alcohol, methyl isobutyl ketone, toluene, n-butyl acetate, ethylbenzene, xylenes and EGEEA were detected in working atmospheres. For these solvents, air concentrations ranged from 0.1 ppm to 69.1 ppm. EGEEA concentrations ranged from 29.2 mg/m3 (5.4 ppm) to 150.1 mg/m3 (27.8 ppm). For biological samples, the average concentrations of EAA were 108.4 mg/g creatinine in pre-shift and 139.4 mg/g creatinine in post-shift samples. Despite the fact that workers wore protective respiratory equipment during paint spraying operations, EEA urinary concentrations are high and suggest that percutaneous uptake is the main route of exposure for EGEEA.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain magnetic resonance imaging and manganese concentrations in red blood cells of smelting workers: Search for biomarkers of manganese exposure

PubMed Central

Jiang, Yueming; Zheng, Wei; Long, Liling; Zhao, Weijia; Li, Xiangrong; Mo, Xuean; Lu, Jipei; Fu, Xue; Li, Wenmei; Liu, Shouting; Long, Quanyong; Huang, Jinli; Pira, Enrico

2014-01-01

The MRI technique has been used in diagnosis of manganism in humans and non-human primates. This cross-sectional study was designed to explore whether the pallidal signal intensity in T1-weighted MRI correlated with Mn levels in the blood compartment among Mn-exposed workers and to understand to what extent the MRI signal could reflect Mn exposure. A group of 18 randomly selected male Mn-exposed workers of which 13 were smelting workers with high exposure (mean of airborne Mn in work place: 1.26 mg/m3; range: 0.31–2.93 mg/m3), and 5 power distribution control workers with low exposure (0.66 mg/m3 and 0.23–0.77 mg/m3) from a ferroalloy factory, and another group of 9 male subjects as controls from a non-smelting factory who were office or cafeteria workers (0.01 mg/m3 and 0–0.03 mg/m3) were recruited for neurological tests, MRI examination, and analysis of Mn in whole blood (MnB), plasma (MnP) or red blood cells (MnRBC). No clinical symptoms and signs of manganism were observed among these workers. MRI data showed average increases of 7.4% (p < 0.05) and 16.1% (p < 0.01) in pallidal index (PI) among low- and high-exposed workers, respectively, as compared to controls. Fourteen out of 18 Mn-exposed workers (78%) had intensified PI values, while this proportion was even higher (85%) among the high Mn-exposed workers. Among exposed workers, the PI values were significantly associated with MnRBC (r = 0.55, p = 0.02). Our data suggest that the workers exposed to airborne Mn, but without clinical symptoms, display an exposure-related, intensified MRI signal. The MRI, as well as MnRBC, may be useful in early diagnosis of Mn exposure. PMID:16978697

Brain magnetic resonance imaging and manganese concentrations in red blood cells of smelting workers: search for biomarkers of manganese exposure.

PubMed

Jiang, Yueming; Zheng, Wei; Long, Liling; Zhao, Weijia; Li, Xiangrong; Mo, Xuean; Lu, Jipei; Fu, Xue; Li, Wenmei; Liu, Shouting; Long, Quanyong; Huang, Jinli; Pira, Enrico

2007-01-01

The MRI technique has been used in diagnosis of manganism in humans and non-human primates. This cross-sectional study was designed to explore whether the pallidal signal intensity in T1-weighted MRI correlated with Mn levels in the blood compartment among Mn-exposed workers and to understand to what extent the MRI signal could reflect Mn exposure. A group of 18 randomly selected male Mn-exposed workers of which 13 were smelting workers with high exposure (mean of airborne Mn in work place: 1.26 mg/m3; range: 0.31-2.93 mg/m3), and 5 power distribution control workers with low exposure (0.66 mg/m3 and 0.23-0.77 mg/m3) from a ferroalloy factory, and another group of 9 male subjects as controls from a non-smelting factory who were office or cafeteria workers (0.01 mg/m3 and 0-0.03 mg/m3) were recruited for neurological tests, MRI examination, and analysis of Mn in whole blood (MnB), plasma (MnP) or red blood cells (MnRBC). No clinical symptoms and signs of manganism were observed among these workers. MRI data showed average increases of 7.4% (p<0.05) and 16.1% (p<0.01) in pallidal index (PI) among low- and high-exposed workers, respectively, as compared to controls. Fourteen out of 18 Mn-exposed workers (78%) had intensified PI values, while this proportion was even higher (85%) among the high Mn-exposed workers. Among exposed workers, the PI values were significantly associated with MnRBC (r=0.55, p=0.02). Our data suggest that the workers exposed to airborne Mn, but without clinical symptoms, display an exposure-related, intensified MRI signal. The MRI, as well as MnRBC, may be useful in early diagnosis of Mn exposure.

A Phase I Dose-Escalation Study of Danusertib (PHA-739358) Administered as a 24-hour Infusion With and Without G-CSF in a 14-day Cycle in Patients with Advanced Solid Tumors

PubMed Central

Cohen, Roger B.; Jones, Suzanne F.; Aggarwal, Charu; von Mehren, Margaret; Cheng, Jonathan; Spigel, David R.; Greco, F. Anthony; Mariani, Mariangela; Rocchetti, Maurizio; Ceruti, Roberta; Comis, Silvia; Laffranchi, Bernard; Moll, Jurgen; Burris, Howard A.

2009-01-01

Purpose This study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of the intravenous pan-aurora kinase inhibitor PHA-739358, danusertib, in patients with advanced solid tumors. Experimental Design In Part 1, patients received escalating doses of danusertib (24-h infusion every 14 days) without filgrastim (G-CSF). Febrile neutropenia was the dose-limiting toxicity without G-CSF. Further dose escalation was performed in part 2 with G-CSF. Blood samples were collected for danusertib pharmacokinetics and pharmacodynamics. Skin biopsies were collected to assess histone H3 phosphorylation (pH3). Results Fifty-six patients were treated, 40 in part 1 and 16 in part 2. Febrile neutropenia was the dose limiting toxicity in Part 1 without G-CSF. Most other adverse events were grade 1–2, occurring at doses ≥360 mg/m2 with similar incidence in parts 1 and 2. The MTD without G-CSF is 500 mg/m2. The recommended phase 2 dose (RP2D) in Part 2 with G-CSF is 750 mg/m2. Danusertib demonstrated dose-proportional pharmacokinetics in parts 1 and 2 with a median half-life of 18–26 hours. pH3 modulation in skin biopsies was observed at ≥500 mg/m2. One patient with refractory small cell lung cancer (1000 mg/m2 with G-CSF) had an objective response lasting 23 weeks. One patient with refractory ovarian cancer had 27% tumor regression and 30% CA125 decline. Conclusions Danusertib was well tolerated with target inhibition in skin at ≥500 mg/m2. Preliminary evidence of anti-tumor activity, including a PR and several occurrences of prolonged stable disease (SD), was seen across a variety of advanced refractory cancers. Phase II studies are ongoing. PMID:19825950

Phase 1B/2 study of the HSP90 inhibitor AUY922 plus trastuzumab in metastatic HER2-positive breast cancer patients who have progressed on trastuzumab-based regimen.

PubMed

Kong, Anthony; Rea, Daniel; Ahmed, Samreen; Beck, J Thaddeus; López López, Rafael; Biganzoli, Laura; Armstrong, Anne C; Aglietta, Massimo; Alba, Emilio; Campone, Mario; Hsu Schmitz, Shu-Fang; Lefebvre, Caroline; Akimov, Mikhail; Lee, Soo-Chin

2016-06-21

This open-label, multicenter, phase 1B/2 trial assessed AUY922 plus trastuzumab in patients with locally advanced or metastatic HER2-positive breast cancer previously treated with chemotherapy and anti-HER2 therapy. This study was composed of a dose-escalation part with AUY922 administered weekly at escalating doses with trastuzumab 2 mg/kg/week (phase 1B), followed by a phase 2 part using the same regimen at recommended phase 2 dose (RP2D). The primary objectives were to determine the maximum tolerated dose (MTD) and/or RP2D (phase 1B), and to evaluate preliminary antitumor activity (phase 2) of AUY922 plus trastuzumab at MTD/RP2D. Forty-five patients were treated with AUY922 plus trastuzumab (4 in phase 1B with AUY922 at 55 mg/m2 and 41 in phase 1B/2 with AUY922 at 70 mg/m2 [7 in phase 1B and 34 in phase 2]). One patient in phase 1B (70 mg/m2) experienced a dose-limiting toxicity (grade 3 diarrhea); the RP2D was weekly AUY922 70 mg/m2 plus trastuzumab. Of the 41 patients in the 70 mg/m2 cohort, the overall response rate (complete or partial responses) was 22.0% and 48.8% patients had stable disease. Study treatment-related adverse events occurred in 97.8% of patients; of these, 31.1% were grade 3 or 4. Forty-one patients (91.1%) reported ocular events (82.3% had grade 1 or 2 events). Two patients (4.4%) had ocular events leading to the permanent discontinuation of study treatment. AUY922 at 70 mg/m2 plus trastuzumab standard therapy is well tolerated and active in patients with HER2-positive metastatic breast cancer who progressed on trastuzumab-based therapy.

Dust exposure in workers from grain storage facilities in Costa Rica.

PubMed

Rodríguez-Zamora, María G; Medina-Escobar, Lourdes; Mora, Glend; Zock, Jan-Paul; van Wendel de Joode, Berna; Mora, Ana M

2017-08-01

About 12 million workers are involved in the production of basic grains in Central America. However, few studies in the region have examined the occupational factors associated with inhalable dust exposure. (i) To assess the exposure to inhalable dust in workers from rice, maize, and wheat storage facilities in Costa Rica; (ii) to examine the occupational factors associated with this exposure; and (iii) to measure concentrations of respirable and thoracic particles in different areas of the storage facilities. We measured inhalable (<100μm) dust concentrations in 176 personal samples collected from 136 workers of eight grain storage facilities in Costa Rica. We also measured respirable (<4μm) and thoracic (<10μm) dust particles in several areas of the storage facilities. Geometric mean (GM) and geometric standard deviation (GSD) inhalable dust concentrations were 2.0mg/m 3 and 7.8 (range=<0.2-275.4mg/m 3 ). Personal inhalable dust concentrations were associated with job category [GM for category/GM for administrative staff and other workers (95% CI)=4.4 (2.6, 7.2) for packing; 20.4 (12.3, 34.7) for dehulling; 109.6 (50.1, 234.4) for unloading in flat bed sheds; 24.0 (14.5, 39.8) for unloading in pits; and 31.6 (18.6, 52.5) for drying], and cleaning task [15.8 (95% CI: 10.0, 26.3) in workers who cleaned in addition to their regular tasks]. Higher area concentrations of thoracic dust particles were found in wheat (GM and GSD=4.3mg/m 3 and 4.5) and maize (3.0mg/m 3 and 3.9) storage facilities, and in grain drying (2.3mg/m 3 and 3.1) and unloading (1.5mg/m 3 and 4.8) areas. Operators of grain storage facilities showed elevated inhalable dust concentrations, mostly above international exposure limits. Better engineering and administrative controls are needed. Copyright © 2017 Elsevier GmbH. All rights reserved.

A phase I study of WR-2721 in combination with total body irradiation (TBI) in patients with refractory lymphoid malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coia, L.; Krigel, R.; Hanks, G.

This Phase I study was designed to establish the maximum tolerated dose (MTD) of WR-2721 when given twice weekly with total body irradiation (TBI) in the treatment of patients with advanced refractory lymphoid malignancies and to define the toxicities of this combination and schedule. Patients eligible for this study had advanced recurrent indolent non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL). Patients had symptomatic or progressive disease, a performance status of 0, 1, or 2, and adequate bone marrow, hepatic, and renal function. Only patients failing one or two regimens of prior chemotherapy were eligible. Patients who had received priormore » extended field irradiation were ineligible. Patients received TBI twice weekly (Tuesday and Friday) to a total of 10 doses at 15 cGy/fx. WR-2721 was given intravenously over 15 min beginning 30 min before irradiation. The escalation of WR-2721 was Level 1: 740 mg/m2 and Level 2: 910 mg/m2. The MTD of WR-2721 was that dose which produced predictable and reversible toxicity and would not interfere with patient well-being. Seven patients were entered onto the study, three at 740 mg/m2 and four at 910 mg/m2. Five patients had CLL and two patients small lymphocytic NHL. No patient had hypotension or nausea requiring reduction in dose level or even interruption of infusion of WR-2721. At 740 mg/m2 no grade 3 or 4 toxicities related to WR-2721 were observed, but two patients could not complete treatment because of TBI-induced prolonged thrombocytopenia following treatments 5 and 8. One patient completed all 10 treatments. At 910 mg/m2 of WR-2721, two patients requested removal from study because of malaise, one after 5 cycles and one after 7 cycles. One patient completed all 10 treatments.« less

Studies on the inhalation toxicology of two fiberglasses and amosite asbestos in the syrian golden hamster. Part I. Results of a subchronic study and dose selection for a chronic study.

PubMed

Hesterberg, T W; Axten, C; McConnell, E E; Hart, G A; Miiller, W; Chevalier, J; Everitt, J; Thevenaz, P; Oberdörster, G

1999-09-01

A multidose, subchronic inhalation study was used to estimate the maximum tolerated dose (MTD) of 901 fiberglass (MMVF10.1) for a chronic inhalation study using hamsters. Subchronic study results indicated that 30 mg/m(3) [250-300 WHO fibers (>5 microm long)/cm(3) and 100-130 fibers/cm(3) >20 microm long] meets or exceeds the estimated MTD, and chronic study results confirmed this. For the subchronic study, hamsters were exposed 6 h/day, 5 days/wk, for 13 wk to MMVF10.1 at 3, 16, 30, 45, and 60 mg/m(3) (36, 206, 316, 552, or 714 WHO fibers/cm(3)), then monitored for 10 wk. Results demonstrating MTD were: inflammatory response (all fiber exposures); elevated lung cell proliferation with @ges;16 mg/m(3); lung lavage neutrophil elevations with @ges;16 mg/m(3) and lactate dehydrogenase (LDH) and protein elevations with > or = 30 mg/m(3); and persistent abnormal macrophage/fiber clumps in lungs exposed to 45 and 60 mg/m(3), which suggest overloading of clearance mechanisms. For the chronic study, hamsters were exposed for 78 wk to MMVF10a (901 fiber glass) or MMVF33 (special-application 475 fiberglass) at approximately 300 WHO fibers/cm(3) ( approximately 100 fibers/cm(3) @gt;20 @mu;m long), or to amosite asbestos at an equivalent concentration and 2 lower concentrations. All fiber-exposed animals had pulmonary inflammation, elevated lung lavage cells, and increased lung cell proliferation. Between 52 and 78 wk of exposure, lung burdens of all fibers increased at an accelerated rate, suggesting impairment of clearance mechanisms. MMVF33 and amosite induced fibrosis and pleural mesothelioma. These findings substantiate that exposures in the chronic study adequately tested the toxic potential of fiberglass.

IMPACT OF SULPHUR DIOXIDE ON THE RESPIRATORY SYSTEM OF TBILISI POPULATION.

PubMed

Vepkhvadze, N; Kiladze, N; Khorbaladze, M; Kochoradze, T; Kugoti, I

2017-04-01

The possible relationship between levels of sulphur dioxide (SO2) in the air and the rate of respiratory diseases has been studied. Results of monitoring of main contaminants of outdoor air were analyzed and they are reflected in Environmental Report 2015. Information on morbidity by respiratory system diseases of Tbilisi population is has been taken from 2011-2015 reports of the National Center of Disease Control. Identified that there is no consistent correlation between sulphur dioxide concentration in the air and respiratory system disease rates in the population, including children. Obtained data demonstrated that during the study period maximum SO2 concentration was registered in 2015 - 0,14 mg/m3 (exceeding almost 3 times maximum permissible concentration - 0,5 mg/m3) and in the same year high morbidity rates are registered (incidence -18106,08), though the lowest rates are registered in 2011 (0,09 mg/m3), when incidence of respiratory system diseases in this period (13103.2) exceeds the rates registered in 2012, 2013 and 2014 (12736.4, 11336.3, 13009.0 accordingly). There is no direct correlation between the morbidity rates of 0-15 year old children and SO2 concentration. Maximum incidence rate is registered in 2015 (48487.0) and in the same year is also registered maximum concentration of SO2 (0,14 mg/m3), whereas the lowest rate is registered in 2013 (35538,70), when SO2 concentration in 2013 is lower only by 0.02 mg/m3 compared to the concentration in 2015. Direct correlation between morbidity with asthma in children and concentration of SO2 was not identified. Prevalence of asthma is minimal in 2014 (65,4), maximal in 2012 (207,1), whereas SO2 concentration in 2014 (0,13 mg/m3) exceeds the concentration in 2012 (0,12 mg/m3). It has to be considered, that besides SO2 there are many small intensity adverse factors, which are also risk factors for development of respiratory diseases. Isolated action of these factors with certain concentrations may not demonstrate any adverse effects on human health, but the combined effect of their action is stronger and obviously will affect general health and specifically - respiratory system. Implementation of urgent measures for further improvement of their ambient air quality has been recommended, which will be the basis for minimizing of many chronic diseases.

Phase I study of olaparib plus gemcitabine in patients with advanced solid tumours and comparison with gemcitabine alone in patients with locally advanced/metastatic pancreatic cancer.

PubMed

Bendell, J; O'Reilly, E M; Middleton, M R; Chau, I; Hochster, H; Fielding, A; Burke, W; Burris, H

2015-04-01

Olaparib (Lynparza) is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor that induces synthetic lethality in cancers with homologous recombination defects. In this phase I, dose-escalation trial, patients with advanced solid tumours received olaparib (50-200 mg capsules b.i.d.) continuously or intermittently (days 1-14, per 28-day cycle) plus gemcitabine [i.v. 600-800 mg/m(2); days 1, 8, 15, and 22 (cycle 1), days 1, 8, and 15 (subsequent cycles)] to establish the maximum tolerated dose. A separate dose-escalation phase evaluated olaparib in tablet formulation (100 mg o.d./b.i.d.; days 1-14) plus gemcitabine (600 mg/m(2)). In an expansion phase, patients with genetically unselected locally advanced or metastatic pancreatic cancer were randomised 2 : 1 to the tolerated olaparib capsule combination dose or gemcitabine alone (1000 mg/m(2)). Sixty-six patients were treated [dose-escalation phase, n = 44 (tablet cohort, n = 12); dose-expansion phase, n = 22 (olaparib plus gemcitabine, n = 15; gemcitabine alone, n = 7)]. In the dose-escalation phase, four patients (6%) experienced dose-limiting toxicities (raised alanine aminotransferase, n = 2; neutropenia, n = 1; febrile neutropenia, n = 1). Grade ≥3 adverse events were reported in 38/47 patients (81%) treated with olaparib capsules plus gemcitabine; most common were haematological toxicities (55%). Tolerated combinations were olaparib 100 mg b.i.d. capsule (intermittently, days 1-14) plus gemcitabine 600 mg/m(2) and olaparib 100 mg o.d. tablet (intermittently, days 1-14) plus gemcitabine 600 mg/m(2). There were no differences in efficacy observed during the dose-expansion phase. Olaparib 100 mg b.i.d. (intermittent dosing; capsules) plus gemcitabine 600 mg/m(2) is tolerated in advanced solid tumour patients, with no unmanageable/unexpected toxicities. Continuous dosing of olaparib or combination with gemcitabine at doses >600 mg/m(2) was not considered to have an acceptable tolerability profile for further study. NCT00515866. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Estimation of respirable dust exposure among coal miners in South Africa.

PubMed

Naidoo, Rajen; Seixas, Noah; Robins, Thomas

2006-06-01

The use of retrospective occupational hygiene data for epidemiologic studies is useful in determining exposure-outcome relationships, but the potential for exposure misclassification is high. Although dust sampling in the South African coal industry has been a legal requirement for several decades, these historical data are not readily adequate for estimating past exposures. This study describes the respirable coal mine dust levels in three South African coal mines over time. Each of the participating mining operations had well-documented dust sampling information that was used to describe historical trends in dust exposure. Investigator-collected personal dust samples were taken using standardized techniques from the face, backbye (underground jobs not at the coal face), and surface from 50 miners at each mine, repeated over three sampling cycles. Job histories and exposure information was obtained from a sample of 684 current miners and 188 ex-miners. Linear models were developed to estimate the exposure levels associated with work in each mine, exposure zone, and over time using a combination of operator-collected historical data and investigator-collected samples. The estimated levels were then combined with work history information to calculate cumulative exposure metrics for the miner cohort. The mean historical and investigator-collected respirable dust levels were within international norms and South African standards. Silica content of the dust samples was also below the 5% regulatory action level. Mean respirable dust concentrations at the face, based on investigator-collected samples, were 0.9 mg/m(3), 1.3 mg/m(3), and 1.9 mg/m(3) at Mines 1, 2, and 3, respectively. The operator-collected samples showed considerable variability across exposure zones, mines, and time, with the annual means at the face ranging from 0.4 mg/m(3) to 2.9 mg/m(3). Statistically significant findings were found between operator- and investigator-collected dust samples. Model-based arithmetic mean dust estimates at the face were 1.2 mg/m(3), 2.0 mg/m(3), and 0.9 mg/m(3) for Mines 1, 2, and 3, respectively. Using these levels, the mean cumulative exposure for the cohort was 56.8 mg-years/m(3). Current miners had a mean cumulative exposure of 66.5 mg-years/m(3), compared with ex-miners of 26.8 mg-years/m(3). Improvements in dust management or the use of different sampling equipment could account for the significant differences seen between operator- and investigator-collected data. Regression modeling for estimating mean dust levels over time using combined historical and investigator-collected data seems a reasonable method and useful in constructing models to describe cumulative exposures in a cohort of current and ex-miners.

[Recommendations for the use of methotrexate in patients with juvenile idiopathic arthritis].

PubMed

Calvo, I; Antón, J; López Robledillo, J C; de Inocencio, J; Gamir, M L; Merino, R; Lacruz, L; Camacho, M; Rua, M J; Bustabad, S; Díaz Cordovés-Rego, G

2016-03-01

To develop a consensus document of recommendations for the use of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). A group of eleven experts proposed several clinical questions on the use of MTX in patients with JIA. A systematic review was conducted and the evidence and recommendations for each question were extracted. The results were discussed and validated by the experts in a work session to establish the final recommendations. MTX is recommended as the first drug for inducing remission in JIA, and its indication should be made according to the clinical category of the patient. Prior to treatment, it is recommended to perform a complete blood count, including white cells, levels of liver enzymes, serum creatinine, and other analytical parameters according to specific risk factors. Treatment should be initiated with a dose of 10-15 mg/m(2)/week. In cases of uveitis or polyarthritis, an initial dose of 15 mg/m(2)/week should be considered. For a better bioavailability and tolerability, it is preferable to administer MTX parenterally if the dose is ≥15 mg/m(2)/week. It is necessary to periodically perform an analytical monitoring of the patient and to assess possible alterations in liver enzymes to make changes if necessary. Combinations with biological agents may be necessary, as well as the concomitant addition of folic or folinic acid. This document describes the main recommendations for the appropriate use of MTX in JIA patients, according to scientific evidence and clinical experience. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Mechanistic perspective of mitochondrial fusion: tubulation vs. fragmentation.

PubMed

Escobar-Henriques, Mafalda; Anton, Fabian

2013-01-01

Mitochondrial fusion is a fundamental process driven by dynamin related GTPase proteins (DRPs), in contrast to the general SNARE-dependence of most cellular fusion events. The DRPs Mfn1/Mfn2/Fzo1 and OPA1/Mgm1 are the key effectors for fusion of the mitochondrial outer and inner membranes, respectively. In order to promote fusion, these two DRPs require post-translational modifications and proteolysis. OPA1/Mgm1 undergoes partial proteolytic processing, which results in a combination between short and long isoforms. In turn, ubiquitylation of mitofusins, after oligomerization and GTP hydrolysis, promotes and positively regulates mitochondrial fusion. In contrast, under conditions of mitochondrial dysfunction, negative regulation by proteolysis on these DRPs results in mitochondrial fragmentation. This occurs by complete processing of OPA1 and via ubiquitylation and degradation of mitofusins. Mitochondrial fragmentation contributes to the elimination of damaged mitochondria by mitophagy, and may play a protective role against Parkinson's disease. Moreover, a link of Mfn2 to Alzheimer's disease is emerging and mutations in Mfn2 or OPA1 cause Charcot-Marie-Tooth type 2A neuropathy or autosomal-dominant optic atrophy. Here, we summarize our current understanding on the molecular mechanisms promoting or inhibiting fusion of mitochondrial membranes, which is essential for cellular survival and disease control. This article is part of a Special Issue entitled: Mitochondrial dynamics and physiology. Copyright © 2012 Elsevier B.V. All rights reserved.

Marine and Estuarine Ecology. Man and the Gulf of Mexico.

ERIC Educational Resources Information Center

Irby, Bobby N.; And Others

"Man and the Gulf of Mexico (MGM)" is a marine science curriculum developed to meet the marine science needs of tenth through twelfth grade students in Mississippi and Alabama schools. This MGM unit, which focuses on marine and estuarine ecology, is divided into six sections. The first section contains unit objectives, discussions of the…

Diversity of Marine Animals. Man and the Gulf of Mexico Series.

ERIC Educational Resources Information Center

Irby, Bobby N., Comp.; And Others

"Man and the Gulf of Mexico" (MGM) is a marine science curriculum series developed to meet the needs of 10th through 12th grade students in Mississippi and Alabama schools. This MGM unit on the diversity of marine animals is divided into 16 sections. These sections focus on: marine protozoans; sponges; coelenterates; ctenophores;…

Suppression of plant growth by nitrogen dioxide.

PubMed

Taylor, O C; Eaton, F M

1966-01-01

Nicotiana glutinosa and pinto bean seedlings (Phaseolus vulgaris) were exposed for short periods (3 days or less) to high concentrations of NO(2) (4.11-20.53 mg/m(3) to compare the resulting leaf lesions with ozone damage produced at concentrations of 0.43 to 0.86 mg/m(3). Although the same physiological age leaf tissue was damaged by both toxicants, damage caused by NO(2) was unlike that caused by ozone. Pinto bean (Phaseolus vulgaris) and Pearson improved tomato (Lycopersicon esculentum) seedlings were continuously exposed for 10 to 22 days, to low concentrations of NO(2) (less than 1.03 mg/m(3)). These exposures caused significant growth suppression, increase in green color (total chlorophyll content), and distortion of leaves.

Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation.

PubMed

Fabi, Alessandra; Metro, Giulio; Russillo, Michelangelo; Vidiri, Antonello; Carapella, Carmine Maria; Maschio, Marta; Cognetti, Francesco; Jandolo, Bruno; Mirri, Maria Alessandra; Sperduti, Isabella; Telera, Stefano; Carosi, Mariantonia; Pace, Andrea

2009-03-31

In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m(2) weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting. 40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m(2) to 100 mg/m(2). Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients. Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine. Low-dose fotemustine at 65-75 mg/m(2) (induction phase) followed by 75-85 mg/m(2) (maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.

Pilot study of vincristine, oral irinotecan, and temozolomide (VOIT regimen) combined with bevacizumab in pediatric patients with recurrent solid tumors or brain tumors.

PubMed

Wagner, Lars; Turpin, Brian; Nagarajan, Rajaram; Weiss, Brian; Cripe, Timothy; Geller, James

2013-09-01

The combination of vincristine, oral irinotecan, and temozolomide (VOIT regimen) has shown antitumor activity in a pediatric Phase I trial. To further potentiate synergy, we assessed the safety and feasibility of adding bevacizumab to VOIT for children and young adults with recurrent tumors. Patients received vincristine (1.5 mg/m(2) on day 1), oral irinotecan (90 mg/m(2) on days 1-5), temozolomide (100-150 mg/m(2) on days 1-5), and bevacizumab (15 mg/kg on day 1) in 3-week cycles, which were repeated for up to six cycles. Cefixime prophylaxis was used to reduce irinotecan-associated diarrhea. Thirteen patients received 36 total cycles. Six of the first 10 patients required dose reductions due to toxicity during the first cycle (n = 3) or subsequent cycles (n = 3), and these grade 3 side effects included prolonged nausea, dehydration, anorexia, neuropathy, diarrhea, and abdominal pain, as well as prolonged grade 4 neutropenia. After reducing daily temozolomide to 100 mg/m(2) , three additional patients tolerated therapy well without the need for dose reductions. Toxicities attributed to bevacizumab were limited to grade 1 epistaxis (1) and grade 2 proteinuria (1). Tumor responses were seen in both patients with Ewing sarcoma. Reducing temozolomide from 150 to 100 mg/m(2) /day improved tolerability, and treatment with this lower temozolomide dose was feasible and convenient as outpatient therapy. Although responses were seen in Ewing sarcoma, the benefit of adding bevacizumab remains unclear. Copyright © 2013 Wiley Periodicals, Inc.

Cefixime allows greater dose escalation of oral irinotecan: a phase I study in pediatric patients with refractory solid tumors.

PubMed

Furman, Wayne L; Crews, Kristine R; Billups, Catherine; Wu, Jianrong; Gajjar, Amar J; Daw, Najat C; Patrick, Christian C; Rodriguez-Galindo, Carlos; Stewart, Clinton F; Dome, Jeffrey S; Panetta, John C; Houghton, Peter J; Santana, Victor M

2006-02-01

Irinotecan is active against a variety of malignancies; however, severe diarrhea limits its usefulness. In our phase I study, the intravenous formulation of irinotecan was administered orally daily for 5 days for 2 consecutive weeks (repeated every 21 days) to children with refractory solid tumors. Our objectives were to determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and pharmacokinetics of oral irinotecan and to evaluate whether coadministration of cefixime (8 mg/kg/d beginning 5 days before irinotecan and continuing throughout the course) ameliorates irinotecan-induced diarrhea. In separate cohorts, irinotecan doses were escalated from 15 to 45 mg/m2/d without cefixime and then from 45 to 60 and 75 mg/m2/d with cefixime. Without cefixime, diarrhea was dose limiting at irinotecan 45 mg/m2/d. Myelotoxicity was not significant at any dose. The MTD was 40 mg/m2/d without cefixime but 60 mg/m2/d with cefixime. Systemic exposure to SN-38 at the MTD was significantly higher with cefixime than without cefixime (mean SN-38 area under the curve: 19.5 ng x h/mL; standard deviation [SD], 6.8 ng x h/mL v 10.4 ng x h/mL; SD, 4.3 ng x h/mL, respectively; P = .030). Cefixime administered with oral irinotecan is well tolerated in children and allows greater dose escalation of irinotecan. Because diarrhea is a major adverse effect of both intravenous and oral irinotecan, further evaluation of the use of cefixime to ameliorate this adverse effect is warranted.

Childhood central adiposity at ages 5 and 9 shows consistent relationship with that of the maternal grandmother but not other grandparents.

PubMed

Somerville, R; Khalil, H; Segurado, R; Mehegan, J; Viljoen, K; Heinen, M; Murrin, C; Kelleher, C C

2018-05-09

The importance of a life course approach to childhood obesity has been emphasized; however, few studies can prospectively investigate relationships in three-generation families. To prospectively investigate the relationship between grandparental and grandchild waist circumference (WC) at ages 5 and 9 down maternal and paternal lines. At baseline in the Lifeways Cross-Generation Cohort, 1094 children were born to 1082 mothers; 585 were examined at age 5 and 298 at age 9. Of the total 589 children with measured WC, data were also available from 745 grandparents. Child WC was standardized for age and sex, and theory-based hierarchical linear regression was used. Maternal grandmother (MGM) WC was predictive of grandchild WC at both time points. At age 5, grandchild's standardized birth weight (B = 0.266, p = 0.001), mother's means tested eligibility for free medical care (B = 1.029, p = 0.001) and grandchild seeing maternal grandparents daily (B = 0.312, p = 0.048) were significant alongside MGM WC (B = 0.015, p = 0.019). At age 9, only MGM WC (B = 0.022, p = 0.033) and mother's WC (B = 0.032, p = 0.005) were significant. Mediation analysis with mother's WC showed significant direct relationship of MGM and grandchild WC. This prospective cross-generational cohort shows consistent patterns of association between MGM and grandchild WC, not seen in other grandparental lineages. © 2018 World Obesity Federation.

Assessment of respirable dust and its free silica contents in different Indian coalmines.

PubMed

Mukherjee, Ashit K; Bhattacharya, Sanat K; Saiyed, Habibullah N

2005-04-01

Assessment of respirable dust, personal exposures of miners and free silica contents in dust were undertaken to find out the associated risk of coal workers' pneumoconiosis in 9 coal mines of Eastern India during 1988-91. Mine Research Establishment (MRE), 113A Gravimetric Dust Sampler (GDS) and personal samplers (AFC 123), Cassella, London, approved by Director General of Mines Safety (DGMS) were used respectively for monitoring of mine air dust and personal exposures of miners. Fourier Transform Infra-red (FTIR) Spectroscopy determined free silica in respirable dusts. Thermal Conditions like Wet Bulb Globe Temperature (WBGT) index, humidity and wind velocity were also recorded during monitoring. The dust levels in the face return air of both, Board & Pillar (B&P) and Long Wall (LW) mining were found above the permissible level recommended by DGMS, Govt. of India. The drilling, blasting and loading are the major dusty operations in B&P method. Exposures of driller and loader were varied between, 0.81-9.48 mg/m3 and 0.05-9.84 mg/m3 respectively in B&P mining, whereas exposures of DOSCO loader, Shearer operator and Power Support Face Worker were varied between 2.65-9.11 mg/m3, 0.22-10.00 mg/m3 and 0.12-9.32 mg/m3 respectively in LW mining. In open cast mining, compressor and driller operators are the major exposed groups. The percentage silica in respirable dusts found below 5% in all most all the workers except among query loaders and drillers of open cast mines.

The sub-chronic toxicity of regular White Spirit in rats.

PubMed

Carrillo, Juan-Carlos; Adenuga, M David; Mckee, Richard H

2014-10-01

Hydrocarbon solvents are mostly complex substances (UVCB) with carbon numbers in the range of approximately C5-C20. One of the most common types is a C9-C14 aliphatic solvent containing approximately 20% aromatics and commonly known as White Spirit in Europe and mineral spirits in the US. In previous repeated inhalation toxicity studies, White Spirit was reported to cause minimal systemic effects in most animal species with few effects other than male rat-specific kidney changes at levels up to approximately 2000mg/m(3). In the present study male and female rats were exposed to White Spirit vapors, 6h/day, 5days/week for 13weeks at levels of approximately 2000, 4000, or 8000mg/m(3) to assess the potential for effects at higher exposure levels. All of the rats survived the treatment period. In life observations were largely restricted to acute central nervous system (CNS) effects in the high exposure group. Terminal body weights of high exposure groups animals were significantly below control values. Statistically significant differences in the clinical and hematological observations were small and within normal physiological limits. Weights of some organs including liver, spleen and kidneys were elevated, but microscopic examination indicated that the only pathological effects were changes in the kidneys of the male rats, consistent with an α2u-globulin-mediated process, which is gender and species-specific and not relevant to humans. The overall no observed adverse effect level (NOAEC) was 4000mg/m(3). Copyright © 2014 Elsevier Inc. All rights reserved.

Exposures to jet fuel and benzene during aircraft fuel tank repair in the U.S. Air Force.

PubMed

Carlton, G N; Smith, L B

2000-06-01

Jet fuel and benzene vapor exposures were measured during aircraft fuel tank entry and repair at twelve U.S. Air Force bases. Breathing zone samples were collected on the fuel workers who performed the repair. In addition, instantaneous samples were taken at various points during the procedures with SUMMA canisters and subsequent analysis by mass spectrometry. The highest eight-hour time-weighted average (TWA) fuel exposure found was 1304 mg/m3; the highest 15-minute short-term exposure was 10,295 mg/m3. The results indicate workers who repair fuel tanks containing explosion suppression foam have a significantly higher exposure to jet fuel as compared to workers who repair tanks without foam (p < 0.001). It is assumed these elevations result from the tendency for fuel, absorbed by the foam, to volatilize during the foam removal process. Fuel tanks that allow flow-through ventilation during repair resulted in lower exposures compared to those tanks that have only one access port and, as a result, cannot be ventilated efficiently. The instantaneous sampling results confirm that benzene exposures occur during fuel tank repair; levels up to 49.1 mg/m3 were found inside the tanks during the repairs. As with jet fuel, these elevated benzene concentrations were more likely to occur in foamed tanks. The high temperatures associated with fuel tank repair, along with the requirement to wear vapor-permeable cotton coveralls for fire reasons, could result in an increase in the benzene body burden of tank entrants.

Diversity of Marine Plants. Man and the Gulf of Mexico Series.

ERIC Educational Resources Information Center

Irby, Bobby N., Comp.; And Others

"Man and the Gulf of Mexico" (MGM) is a marine science curriculum series developed to meet the needs of 10th through 12th grade students in Mississippi and Alabama schools. This MGM unit on the diversity of marine plants is divided into 12 sections. The first section introduces the unit by providing objectives and activities on why…

Phase I trial of bortezomib and dacarbazine in melanoma and soft tissue sarcoma.

PubMed

Poklepovic, Andrew; Youssefian, Leena E; Youseffian, Leena; Winning, Mary; Birdsell, Christine A; Crosby, Nancy A; Ramakrishnan, Viswanathan; Ernstoff, Marc S; Roberts, John D

2013-08-01

Preclinical studies in human melanoma cell lines and murine xenograft tumor models suggest that the proteasome inhibitor bortezomib enhances the activity of the cytotoxic agent dacarbazine. We performed a phase I trial of bortezomib and dacarbazine in melanoma, soft tissue sarcoma, and amine precursor uptake and decarboxylation tumors. The primary objective was to identify recommended phase II doses for the combination. Bortezomib and dacarbazine were both administered intravenously once weekly. All patients received prophylactic antiemetics. Dose escalation proceeded using a standard 3 + 3 design. Response was assessed according to NCI RECIST v1.0. Twenty eight patients were enrolled to six dose levels. Bortezomib 1.6 mg/m(2) and dacarbazine 580 mg/m(2) are the recommended phase II weekly doses. The combination was generally well tolerated. Among 15 patients with melanoma there was one durable complete response in a patient with an exon-11 cKIT mutation, and one partial response. Among 12 patients with soft tissue sarcoma there was one partial response. Bortezomib 1.6 mg/m(2) and dacarbazine 580 mg/m(2) administered intravenously once weekly is well tolerated and has at least minimal activity in melanoma and soft tissue sarcoma.

Health-hazard evaluation report HETA 83-391-1683, Continental Coffee Products Company, Houston, Texas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arnold, S.J.; Markel, H.L.; Morawetz, J.S.

1986-04-01

The International Chemical Workers Union requested an evaluation be made of the health status of employees at the Continental Coffee Products Company, Houston, Texas with particular attention given to potential exposure to pesticide residues on imported coffee beans. Analysis of air samples revealed the following concentration ranges: 29 personal respirable-dust samples ranging from 0.03 to 2.03 milligrams/cubic meter (mg/m3); 27 of 28 personal total dust samples, 0.09 to 2.65 mg/m3; four area respirable-dust samples, 0.11 to 0.53 mg/m3; and four area total dust samples, 0.16 to 2.39 mg/m3. Pesticide exposures were significantly below acceptable daily intakes. The authors conclude thatmore » it would not be expected that employees would be exposed to pesticide levels posing an appreciable threat to health. Recommendations were made to increase the use of local exhaust ventilation; to improve work practices to reduce generation of dust and accumulation; increase ventilation in the basement re-mix operation; and train employees toward the understanding of potential hazards and their role in controlling dust.« less

Analytical techniques and method validation for the measurement of selected semivolatile and nonvolatile organofluorochemicals in air.

PubMed

Reagen, William K; Lindstrom, Kent R; Thompson, Kathy L; Flaherty, John M

2004-09-01

The widespread use of semi- and nonvolatile organofluorochemicals in industrial facilities, concern about their persistence, and relatively recent advancements in liquid chromatography/mass spectrometry (LC/MS) technology have led to the development of new analytical methods to assess potential worker exposure to airborne organofluorochemicals. Techniques were evaluated for the determination of 19 organofluorochemicals and for total fluorine in ambient air samples. Due to the potential biphasic nature of most of these fluorochemicals when airborne, Occupational Safety and Health Administration (OSHA) versatile sampler (OVS) tubes were used to simultaneously trap fluorochemical particulates and vapors from workplace air. Analytical methods were developed for OVS air samples to quantitatively analyze for total fluorine using oxygen bomb combustion/ion selective electrode and for 17 organofluorochemicals using LC/MS and gas chromatography/mass spectrometry (GC/MS). The experimental design for this validation was based on the National Institute of Occupational Safety and Health (NIOSH) Guidelines for Air Sampling and Analytical Method Development and Evaluation, with some revisions of the experimental design. The study design incorporated experiments to determine analytical recovery and stability, sampler capacity, the effect of some environmental parameters on recoveries, storage stability, limits of detection, precision, and accuracy. Fluorochemical mixtures were spiked onto each OVS tube over a range of 0.06-6 microg for each of 12 compounds analyzed by LC/MS and 0.3-30 microg for 5 compounds analyzed by GC/MS. These ranges allowed reliable quantitation at 0.001-0.1 mg/m3 in general for LC/MS analytes and 0.005-0.5 mg/m3 for GC/MS analytes when 60 L of air are sampled. The organofluorochemical exposure guideline (EG) is currently 0.1 mg/m3 for many analytes, with one exception being ammonium perfluorooctanoate (EG is 0.01 mg/m3). Total fluorine results may be used to determine if the individual compounds quantified provide a suitable mass balance of total airborne organofluorochemicals based on known fluorine content. Improvements in precision and/or recovery as well as some additional testing would be needed to meet all NIOSH validation criteria. This study provided valuable information about the accuracy of this method for organofluorochemical exposure assessment.

Emissions of fluorides from welding processes.

PubMed

Szewczyńska, Małgorzata; Pągowska, Emilia; Pyrzyńska, Krystyna

2015-11-01

The levels of fluoride airborne particulates emitted from welding processes were investigated. They were sampled with the patented IOM Sampler, developed by J. H. Vincent and D. Mark at the Institute of Occupational Medicine (IOM), personal inhalable sampler for simultaneous collection of the inhalable and respirable size fractions. Ion chromatography with conductometric detection was used for quantitative analysis. The efficiency of fluoride extraction from the cellulose filter of the IOM sampler was examined using the standard sample of urban air particle matter SRM-1648a. The best results for extraction were obtained when water and the anionic surfactant N-Cetyl-N-N-N-trimethylammonium bromide (CTAB) were used in an ultrasonic bath. The limits of detection and quantification for the whole procedure were 8μg/L and 24μg/L, respectively. The linear range of calibration was 0.01-10mg/L, which corresponds to 0.0001-0.1mg of fluorides per m(3) in collection of a 20L air sample. The concentration of fluorides in the respirable fraction of collected air samples was in the range of 0.20-1.82mg/m(3), while the inhalable fraction contained 0.23-1.96mg/m(3) of fluorides during an eight-hour working day in the welding room. Copyright © 2015. Published by Elsevier B.V.

[Expression of heat shock protein 70 and its mRNA in career exposure to manganese].

PubMed

Chen, Wenwen; Shao, Hua; Chi, Mingfeng; Zhang, Zhihu; Shan, Yongle; Zou, Wei

2015-10-01

To analyze the expression levels of heat shock protein70 (HSPs70) and HSPs70 mRNA in different exposure to manganese, and research the neuroprotective effect on the career exposure to manganese. From 2008 to 2009, with cross-sectional study design, and in a locomotive and rolling stock works, by stratified random sampling method, the exposed sample consisted of 180 welders from different welding shops and 100 unexposed in the last three years, non-welder controls with age-matched workers of similar socioeconomic status from the same industry. The control workers had not been exposed to neurotoxic chemicals. The mRNA expressions of four different metabolic enzyme were detected by SYBR Green I quantitative real-time polymerase chain reaction. The expression levels of the two enzymes mRNA in different exposure to manganese were analyzed. The expressions of HSPs70 were detected by Western blot. The concentration of air manganese was determined by GFAAS. The average concentration of 8 h time (8h-TWA) was used to express the level of individual exposure to manganese, according to the air manganese workplace occupational exposure limit (8h-TWA=0.15 mg/m3), the exposed group is divided into high exposed group (>0.15 mg/m3) and low exposure group (<0.15 mg/m3). The individuals exposed to manganese dose of exposed group ((0.25±0.31) mg/m3) was higher than the control group ((0.06±0.02) mg/m3) (t=6.15, P=0.001); individuals exposed to manganese dose of high exposure group for (0.42±0.34) mg/m3, which was higher than low exposure group (0.09±0.07) mg/m3 (t=9.80, P=0.001). HSPs70 mRNA and protein of exposure group (5.65±0.21, 3.26±0.15) were higher than the reference group (0.41±0.03, 1.32±0.12) (t=18.91, t=8.68, P=0.001). HSP70 mRNA and protein of high exposure group (6.48±0.37, 3.67±0.26) were higher than the low exposure group (5.15±0.23, 3.02±0.19) (t=3.24, t=2.01, P=0.003, P=0.043). The expression of peripheral blood lymphocytes HSPs70 level and HSPs70 mRNA workers exposed to manganese increased and protect nerve cells from related to Mn stimulation induced lipid peroxidation damag.

Toxic Hazards Research Unit

DTIC Science & Technology

1981-12-01

Carcinomas 2/373 4/357 4/357 14/363b DUODENUM ADENOMA 1/310 5/303 7 / 3 0 9 a 5/308 HEMANGIOMA 5/387 9/371 5/368 22/371b HEMANGIOSARCOMA 1/387 4/371...JP-5 Unexposed 150 mg/m 3 750 mg/m3 Controls Exposed Exposed Liver: Fatty Change 34 30 32 Necrosis 5 2 0 Adenoma 1 4 0 Hemangiosarcoma 1 0 0 Kidney

Ocular effects of exposure to triethylamine in the sand core cold box of a foundry.

PubMed Central

Reilly, M J; Rosenman, K D; Abrams, J H; Zhu, Z; Tseng, C; Hertzberg, V; Rice, C

1995-01-01

OBJECTIVES--To assess the acute and chronic ophthalmological effects of triethylamine exposure among foundry workers. METHODS--Ocular effects on people currently, previously, and never exposed to triethylamine in a foundry cold box were studied at two points in time. The initial phase included an ocular examination with a slit lamp to assess corneal health, a visual acuity test, and a questionnaire to assess vision symptoms. The follow up included measurements of corneal thickness with an ultrasonic pachymeter and the vision symptoms questionnaire before and after the shift and at the beginning and end of the week. Personal air measurements for triethylamine were also obtained during the follow up. RESULTS--The vision symptoms of blurriness, halos around lights, and blue hazy vision occurred more often in currently exposed workers than those previously or never exposed to triethylamine. Air concentrations of triethylamine ranged from < 0.33 mg/m3 to 20.3 mg/m3. Among currently exposed workers, symptoms were more common among those with exposure to > 10 mg/m3 of triethylamine (odds ratio (OR) = 3.0, 95% confidence interval (95% CI) 0.35-25.6). No differences in corneal thickness were found in currently or previously exposed workers and those never exposed. No increase in corneal thickness was found after v before the shift. CONCLUSION--Despite low concentrations of triethylamine and no corneal oedema, workers exposed to triethylamine reported vision symptoms. Possible explanations for these symptoms without corneal oedema are that triethylamine affects ciliary muscle function or that the corneal oedema was transient and not present when corneal thickness measurements were taken. No chronic effects were found in previously exposed workers. Further research is needed to elucidate the mechanism for the reported vision symptoms, which occurred below the current United States eight hour time weighted standard of 100 mg/m3 and the American Conference of Governmental Industrial Hygienists (ACGIH) recommended value at the time of our study of 40 mg/m3. We recommend that air concentrations be maintained to meet the current recommended ACGIH threshold of 4.1 mg/m3. PMID:7795757

A randomized phase II study of weekly nab-paclitaxel plus gemcitabine or simplified LV5FU2 as first-line therapy in patients with metastatic pancreatic cancer: the AFUGEM GERCOR trial.

PubMed

Bachet, Jean-Baptiste; Chibaudel, Benoist; Bonnetain, Franck; Validire, Pierre; Hammel, Pascal; André, Thierry; Louvet, Christophe

2015-10-06

Metastatic pancreatic adenocarcinoma (PAC) prognosis remains dismal and gemcitabine monotherapy has been the standard treatment over the last decade. Currently, two first-line regimens are used in this setting: FOLFIRINOX and nab-paclitaxel plus gemcitabine. Increasing translational data on the predictive value of hENT1 for determining gemcitabine efficacy suggest that a non-gemcitabine-based regimen is favored in about 60 % of patients with PAC due to high resistance of PAC to this cytotoxic drug. This study aims to evaluate the efficacy of weekly nab-paclitaxel combined with gemcitabine or a simplified (s) LV5FU2 regimen in patients with previously untreated metastatic PAC. AFUGEM is a two-stage, open-label, randomized, multicenter, phase II trial. Patients with PAC who meet the inclusion criteria and provide written informed consent will be randomized in a 1:2 ratio to either nab-paclitaxel (125 mg/m(2)) plus gemcitabine (1000 mg/m(2)) given on days 1, 8, and 15 every 28 days or nab-paclitaxel (125 mg/m(2)) plus sLV5FU2 (leucovorin 400 mg/m(2) followed by bolus 400 mg/m(2) 5-fluorouracil and by 5-fluorouracil 2400 mg/m(2) as an 46-h intravenous infusion) given on days 1 and 15 every 28 days. A total of 114 patients will be randomized to one of the treatment arms. The primary endpoint is progression-free survival at 4 months. Secondary outcomes are rate and duration of response, disease control, overall survival, safety, and quality of life. Potential biomarkers of gemcitabine (hENT1, dCK) and 5-fluorouracil (TS) efficacy will be assessed. The AFUGEM trial is designed to provide valuable information regarding efficacy and tolerability of nab-paclitaxel plus gemcitabine and nab-paclitaxel plus sLV5FU2 regimens. Identification of potential predictive biomarkers of gemcitabine and 5-fluorouracil is likely to drive therapeutic decisions in patients with metastatic PAC. AFUGEM is registered at Clinicaltrials.gov: NCT01964534 , October 15, 2013.

Weekly infusional high-dose fluorouracil (HD-FU), HD-FU plus folinic acid (HD-FU/FA), or HD-FU/FA plus biweekly cisplatin in advanced gastric cancer: randomized phase II trial 40953 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group and the Arbeitsgemeinschaft Internistische Onkologie.

PubMed

Lutz, Manfred P; Wilke, Hansjochen; Wagener, D J Theo; Vanhoefer, Udo; Jeziorski, Krzysztof; Hegewisch-Becker, Susanna; Balleisen, Leopold; Joossens, Eric; Jansen, Rob L; Debois, Muriel; Bethe, Ullrich; Praet, Michel; Wils, Jacques; Van Cutsem, Eric

2007-06-20

This multicentric, randomized, two-stage phase II trial evaluated three simplified weekly infusional regimens of fluorouracil (FU) or FU plus folinic acid (FA) and cisplatin (Cis) with the aim to select a regimen for future phase III trials. A total of 145 patients with advanced gastric cancer where randomly assigned to weekly FU 3,000 mg/m2/24 hours (HD-FU), FU 2,600 mg/m2/24 hours plus dl-FA 500 mg/m2 or l-FA 250 mg/m2 (HD-FU/FA), or FU 2000 mg/m2/24 hours plus FA plus biweekly Cis 50 mg/m2, each administered for 6 weeks with a 1-week rest. The primary end point was the response rate. Confirmed responses were observed in 6.1% (two of 33) of the eligible patients treated with HD-FU, in 25% (12 of 48, including one complete remission [CR]) with HD-FU/FA, and in 45.7% (21 of 46, including four CRs) with HD-FU/FA/Cis. The HD-FU arm was closed after stage 1 because the required minimum number of responses was not met. The median progression-free survival of all patients in the HD-FU, HD-FU/FA, and HD-FU/FA/Cis arm was 1.9, 4.0, and 6.1 months, respectively. The median overall survival was 7.1, 8.9, and 9.7 months, and the survival rate at 1 year was 24.3%, 30.3%, and 45.3%, respectively. Grade 4 toxicities were rare. The most relevant grade 3/4 toxicities were neutropenia in 1.9%, 5.4%, and 19.6%, and diarrhea in 2.7%, 1.9%, and 3.9% of the cycles in the HD-FU, HD-FU/FA, and HD-/FU/Cis arms, respectively. Weekly infusional FU/FA plus biweekly Cis is effective and safe in patients with gastric cancer.

Epirubicin plus paclitaxel regimen as second-line treatment of patients with small-cell lung cancer.

PubMed

Pasello, Giulia; Carli, Paolo; Canova, Fabio; Bonanno, Laura; Polo, Valentina; Zago, Giulia; Urso, Loredana; Conte, Pierfranco; Favaretto, Adolfo

2015-04-01

Most patients with small cell lung cancer (SCLC) experience relapse within one year after first-line treatment. The aim of this study was to describe activity and safety of second-line with epirubicin at 70 mg/m(2) followed by paclitaxel at 135 mg/m(2) on day 1 every three weeks for a maximum of six cycles. This is a retrospective review of all patients with SCLC evaluated for second-line treatment between 2003 and 2013 at our Institution. Sixty-eight patients received the study regimen of epirubicin with paclitaxel. We observed partial response in 19 (30%), stable disease in 22 (34%) and total early failure rate in 23 (36%) patients. Median progression free and overall survival were 21.8 and 26.5 weeks, respectively. Haematological toxicities were as follows: grade 3-4 leukopenia and neutropenia in 18 (31%) and 30 (22%) of patients, respectively; grade 3 anaemia and grade 4 thrombocytopenia were reported in 2 (3%) and 5 (9%) of patients, respectively. Epirubicin with paclitaxel is an active and tolerable second-line regimen in patients with SCLC. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Acute respiratory toxicity following inhalation exposure to soman in guinea pigs.

PubMed

Perkins, Michael W; Pierre, Zdenka; Rezk, Peter; Sabnekar, Praveena; Kabra, Kareem; Chanda, Soma; Oguntayo, Samuel; Sciuto, Alfred M; Doctor, Bhupendra P; Nambiar, Madhusoodana P

2010-06-01

Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m(3) concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m(3) soman survived, while animals exposed to 841, and 1121 mg/m(3) resulted in 38% and 13% survival, respectively. The microinstillation inhalation exposure LCt(50) for soman determined by probit analysis was 827.2mg/m(3). A majority of the animals that died at 1121 mg/m(3) developed seizures and died within 15-30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5-6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs. (c) 2010 Elsevier Inc. All rights reserved.

Phase I safety, pharmacokinetic and pharmacodynamic evaluation of the vascular disrupting agent ombrabulin (AVE8062) in patients with advanced solid tumors.

PubMed

Sessa, Cristiana; Lorusso, Patricia; Tolcher, Anthony; Farace, Françoise; Lassau, Nathalie; Delmonte, Angelo; Braghetti, Antonio; Bahleda, Rastislav; Cohen, Patrick; Hospitel, Marie; Veyrat-Follet, Christine; Soria, Jean-Charles

2013-09-01

The vascular disrupting agent ombrabulin rapidly reduces tumor blood flow and causes necrosis in vivo. A phase I dose-escalation study was designed to determine the recommended phase II dose (RP2D) of single-agent ombrabulin administered once every three weeks in patients with advanced solid malignancies. Ombrabulin (30-minute infusion) was escalated from 6 to 60 mg/m2, with RP2D cohort expansion. Safety, tumor response, pharmacokinetics, and pharmacodynamic biomarkers were evaluated. Eleven dose levels were evaluated in 105 patients. Two patients had dose-limiting toxicities in cycle 1 during escalation: grade 3 abdominal pain at 50 mg/m2, grade 3 tumor pain/grade 3 hypertension at 60 mg/m2, and the RP2D was 50 mg/m2 (39 patients). Common toxicities were headache, asthenia, abdominal pain, nausea, diarrhea, transient hypertension, anemia, and lymphopenia. No clinically significant QTc prolongations or left ventricular ejection fraction (LVEF) decreases occurred. Ombrabulin was rapidly converted to its active metabolite RPR258063 (half-life 17 minutes and 8.7 hours, respectively), both having dose-proportional exposure. Weak inhibition of CYP2C19-mediated metabolism occurred at the clinical doses used and there was no effect on CYP1A2 and CYP3A4. A patient with rectal cancer had a partial response and eight patients had stable disease lasting four months or more. Circulating endothelial cells (CEC), VEGF, and matrix metalloproteinase (MMP)-9 levels increased significantly six to 10 hours postinfusion in a subset of patients. The recommended schedule for single-agent ombrabulin is 50 mg/m2 every 3 weeks. CECs, VEGF, and MMP-9 are potential biomarkers of ombrabulin activity. ©2013 AACR.

The anthropometry of children and adolescents may be influenced by the prenatal smoking habits of their grandmothers: A longitudinal cohort study

PubMed Central

Golding, Jean; Northstone, Kate; Gregory, Steven; Miller, Laura L; Pembrey, Marcus

2014-01-01

Objectives Previously, in the Avon Longitudinal Study of Parents and Children (ALSPAC), we have shown different sex-specific birth anthropometric measurements contingent upon whether or not prenatal smoking was undertaken by paternal grandmother (PGM±), maternal grandmother (MGM±), and the study mother (M±). The findings raised the question as to whether there were long-term associations on the growth of the study children over time. Methods Measures of weight, height, body mass index, waist circumference, lean mass, and fat mass of children in the ALSPAC study from 7 to 17 years of age were used. We compared growth in four categories at each age: PGM+M− with PGM−M−; MGM+M− with MGM−M−; PGM+M+ with PGM−M+; MGM+M+ with MGM−M+; and adjusted for housing tenure, maternal education, parity, and paternal smoking at the start of the study pregnancy. Results We found that if the PGM had, but the study mother had not, smoked in pregnancy, the girls were taller and both genders had greater bone and lean mass. However, if the MGM had smoked prenatally but the mother had not (MGM+M−), the boys became heavier than expected with increasing age—an association that was particularly due to lean rather than fat mass, reflected in increased strength and fitness. When both the maternal grandmother and the mother had smoked (MGM+M+) girls had reduced height, weight, and fat/lean/bone mass when compared with girls born to smoking mothers whose own mothers had not smoked (MGM−M+). Conclusions This study indicates that smoking in humans can have sex-specific transgenerational effects. Am. J. Hum. Biol. 26:731–739, 2014. © 2014 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc. PMID:25130101

US Navy Submarine Sea Trial of NASA developed Multi-Gas Monitor

NASA Technical Reports Server (NTRS)

Mudgett, Paul D.; Manney, Joshua A.; Pilgrim, Jeffrey S.

2017-01-01

During a successful 2 year technology demonstration of the tunable diode laser spectroscopy (TDLS) based Multi-Gas Monitor (MGM) on the International Space Station (ISS), we began discussing with the US Navy the possibility of conducting a sea trial of an MGM on a submarine. The sea trial would also include a gas chromatography/differential mobility spectrometer based Air Quality Monitor (AQM), which is used operationally on ISS for select volatile organic compounds. AQM results will be the subject of a separate paper. The Navy’s interest in testing NASA equipment is in a planned update to the environmental monitoring equipment used aboard submarines. NASA’s goal is studying submarines as closed environment analogs to spacecraft. MGM’s core technology was developed by Vista Photonics Inc using Small Business Innovation Research (SBIR) grants and expanded for various applications using NASA program funding. The MGM measures oxygen, carbon dioxide, ammonia and water vapor in ambient air, displays concentrations with temperature and pressure, and stores 30 second moving averages. The sea trial involves colocating the instrument with the Central Air Monitor (CAM) and connecting it to rack power prior to departure, and letting it run during the entire sea trial of a few months duration. All data stored is inside MGM, with no connection to the vessel data bus. Crew intervention is limited to checking MGM periodically to see that it is working and power cycling if the display is OFF. After the trial is over, the unit with its data will be retrieved. Post sea trial calibration check and data analysis are planned and results will be compared with both CAM data and results from MGM’s ISS technology demonstration.

Phase I trial of capecitabine rapidly disintegrating tablets and concomitant radiation therapy in children with newly diagnosed brainstem gliomas and high-grade gliomas

PubMed Central

Kilburn, Lindsay B.; Kocak, Mehmet; Schaedeli Stark, Franziska; Meneses-Lorente, Georgina; Brownstein, Carrie; Hussain, Sazzad; Chintagumpala, Murali; Thompson, Patrick A.; Gururangan, Sri; Banerjee, Anuradha; Paulino, Arnold C.; Kun, Larry; Boyett, James M.; Blaney, Susan M.

2013-01-01

Background We conducted a phase I study to estimate the maximum tolerated dose and describe the dose-limiting toxicities and pharmacokinetics of oral capecitabine rapidly disintegrating tablets given concurrently with radiation therapy to children with newly diagnosed brainstem or high-grade gliomas. Methods Children 3–21 y with newly diagnosed intrinsic brainstem or high-grade gliomas were eligible for enrollment. The starting dose was 500 mg/m2, given twice daily, with subsequent cohorts enrolled at 650 mg/m2 and 850 mg/m2 using a 3 + 3 phase I design. Children received capecitabine at the assigned dose daily for 9 wks starting from the first day of radiation therapy (RT). Following a 2-wk break, patients received 3 courses of capecitabine 1250 mg/m2 twice daily for 14 days followed by a 7-day rest. Pharmacokinetic sampling was performed in consenting patients. Six additional patients with intrinsic brainstem gliomas were enrolled at the maximum tolerated dose to further characterize the pharmacokinetic and toxicity profiles. Results Twenty-four patients were enrolled. Twenty were fully assessable for toxicity. Dose-limiting toxicities were palmar plantar erythroderma (grades 2 and 3) and elevation of alanine aminotransferase (grades 2 and 3). Systemic exposure to capecitabine and metabolites was similar to or slightly lower than predicted based on adult data. Conclusions Capecitabine with concurrent RT was generally well tolerated. The recommended phase II capecitabine dose when given with concurrent RT is 650 mg/m2, administered twice daily. A phase II study to evaluate the efficacy of this regimen in children with intrinsic brainstem gliomas is in progress (PBTC-030). PMID:23592571

Pulmonary effects of inhaled zinc oxide in human subjects, guinea pigs, rats, and rabbits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gordon, T.; Chen, L.C.; Fine, J.M.

1992-08-01

Occupational exposure to freshly formed zinc oxide (ZnO) particles (less than 1.0 micron aerodynamic diameter) produces a well-characterized response known as metal fume fever. An 8-hr threshold limit value (TLV) of 5 mg/m3 has been established to prevent adverse health effects because of exposure to ZnO fumes. Because animal toxicity studies have demonstrated pulmonary effects near the current TLV, the present study examined the time course and dose-response of the pulmonary injury produced by inhaled ZnO in guinea pigs, rats, rabbits, and human volunteers. The test animals were exposed to 0, 2.5, or 5.0 mg/m3 ZnO for up to 3more » hr and their lungs lavaged. Both the lavage fluid and recovered cells were examined for evidence of inflammation or altered cell function. The lavage fluid from guinea pigs and rats exposed to 5 mg/m3 had significant increases in total cells, lactate dehydrogenase, beta-glucuronidase, and protein content. These changes were greatest 24 hr after exposure. Guinea pig alveolar macrophage function was depressed as evidenced by in vitro phagocytosis of opsonized latex beads. Significant changes in lavage fluid parameters were also observed in guinea pigs and rats exposed to 2.5 mg/m3 ZnO. In contrast, rabbits showed no increase in biochemical or cellular parameters following a 2-hr exposure to 5 mg/m3 ZnO. Differences in total lung burden of ZnO, as determined in additional animals by atomic absorption spectroscopy, appeared to account for the observed differences in species responses. Although the lungs of guinea pigs and rats retained approximately 20% and 12% of the inhaled dose, respectively, rabbits retained only 5%.« less

Forest soil CO2 fluxes as a function of understory removal and N-fixing species addition.

PubMed

Li, Haifang; Fu, Shenglei; Zhao, Hongting; Xia, Hanping

2011-01-01

We report on the effects of forest management practices of understory removal and N-fixing species (Cassia alata) addition on soil CO2 fluxes in an Eucalyptus urophylla plantation (EUp), Acacia crassicarpa plantation (ACp), 10-species-mixed plantation (Tp), and 30-species-mixed plantation (THp) using the static chamber method in southern China. Four forest management treatments, including (1) understory removal (UR); (2) C. alata addition (CA); (3) understory removal and replacement with C. alata (UR+CA); and (4) control without any disturbances (CK), were applied in the above four forest plantations with three replications for each treatment. The results showed that soil CO2 fluxes rates remained at a high level during the rainy season (from April to September), followed by a rapid decrease after October reaching a minimum in February. Soil CO2 fluxes were significantly higher (P < 0.01) in EUp (132.6 mg/(m2 x hr)) and ACp (139.8 mg/(m2 x hr)) than in Tp (94.0 mg/(m2 x hr)) and THp (102.9 mg/(m2 x hr)). Soil CO2 fluxes in UR and CA were significantly higher (P < 0.01) among the four treatments, with values of 105.7, 120.4, 133.6 and 112.2 mg/(m2 x hr) for UR+CA, UR, CA and CK, respectively. Soil CO2 fluxes were positively correlated with soil temperature (P < 0.01), soil moisture (P < 0.01), NO3(-)-N (P < 0.05), and litterfall (P < 0.01), indicating that all these factors might be important controlling variables for soil CO2 fluxes. This study sheds some light on our understanding of soil CO2 flux dynamics in forest plantations under various management practices.

Phase I and Pharmacokinetic Study of Cetuximab and Irinotecan in Children With Refractory Solid Tumors: A Study of the Pediatric Oncology Experimental Therapeutic Investigators' Consortium

PubMed Central

Trippett, Tanya M.; Herzog, Cynthia; Whitlock, James A.; Wolff, Johannes; Kuttesch, John; Bagatell, Rochelle; Hunger, Stephen P.; Boklan, Jessica; Smith, Amy A.; Arceci, Robert J.; Katzenstein, Howard M.; Harbison, Christopher; Zhou, Xiaofei; Lu, Haolan; Langer, Christiane; Weber, Martin; Gore, Lia

2009-01-01

Purpose To determine the dose of cetuximab that can be safely combined with irinotecan for treatment of pediatric and adolescent patients with refractory solid tumors. Patients and Methods This open-label, phase I study enrolled patients ages 1 to 18 years with advanced refractory solid tumors, including tumors of the CNS. Patient cohorts by age group (children, ages 1 to 12 years; adolescents, ages 13 to 18 years) received escalating weekly doses of cetuximab (75, 150, 250 mg/m2) in a 3 + 3 design, plus irinotecan (16 or 20 mg/m2/d) for 5 days for 2 consecutive weeks every 21 days. The primary end points were establishing the maximum-tolerated dose (MTD), recommended phase II dose (RPIID), and pharmacokinetics of the combination. Preliminary safety and efficacy data were also collected. Results Twenty-seven children and 19 adolescents received a median of 7.1 and 6.0 weeks of cetuximab therapy, respectively. Cetuximab 250 mg/m2 weekly plus irinotecan 16 mg/m2/d (pediatric) or 20 mg/m2/d (adolescent) have been established as the MTD/RPIID. Dose-limiting toxicities included diarrhea and neutropenia. Mild to moderate (grade 1 to 2) acneiform rash occurred in a majority of patients; no grade 3 to 4 rashes were observed. Cetuximab demonstrated dose-dependent clearance in both children and adolescents, similar to that in adults. There were two confirmed partial responses, both in patients with CNS tumors. Stable disease was achieved in 18 patients overall, including 10 patients with CNS tumors (38.5%). Conclusion The cetuximab/irinotecan combination can be given safely to children and adolescents with cancer. Promising activity, particularly in CNS tumors, warrants phase II evaluation of this regimen. PMID:19770383

Concomitant chemoradiotherapy versus induction docetaxel, cisplatin and 5 fluorouracil (TPF) followed by concomitant chemoradiotherapy in locally advanced head and neck cancer: a phase II randomized study.

PubMed

Paccagnella, A; Ghi, M G; Loreggian, L; Buffoli, A; Koussis, H; Mione, C A; Bonetti, A; Campostrini, F; Gardani, G; Ardizzoia, A; Dondi, D; Guaraldi, M; Cavallo, R; Tomio, L; Gava, A

2010-07-01

Concomitant chemoradiotherapy (CT/RT) is the standard treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). We evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5-fluorouracil (TPF) before CT/RT versus CT/RT alone. Patients with stage III-IVM0 SCCHN, Eastern Cooperative Oncology Group performance status of zero to one, were randomly assigned to receive CT/RT alone (arm A: two cycles of cisplatin 20 mg/m(2), days1-4, plus 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or three cycles of TPF (arm B: docetaxel 75 mg/m(2) and cisplatin 80 mg/m(2), day 1, and 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, every 3 weeks) followed by the same CT/RT. The primary end point was the rate of radiologic complete response (CR) at 6-8 weeks after the end of CT/RT. A total of 101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and 39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms. Induction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility.

Simultaneous production of bioethanol and value-added d-psicose from Jerusalem artichoke (Helianthus tuberosus L.) tubers.

PubMed

Song, Younho; Oh, Chihoon; Bae, Hyeun-Jong

2017-11-01

In this study, the production of bioethanol and value added d-psicose from Jerusalem artichoke (JA) was attempted by an enzymatic method. An enzyme mixture used for hydrolysis of 100mgmL -1 JA. The resulting concentrations of released d-fructose and d-glucose were measured at approximately 56mgmL -1 and 15mgmL -1 , respectively. The d-psicose was epimerized from the JA hydrolyzate, and the conversion rate was calculated to be 32.1%. The residual fructose was further converted into ethanol at 18.0gL -1 and the yield was approximately 72%. Bioethanol and d-psicose were separated by pervaporation. This is the first study to report simultaneous d-psicose production and bioethanol fermentation from JA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Orbital-angular-momentum mode-group multiplexed transmission over a graded-index ring-core fiber based on receive diversity and maximal ratio combining

NASA Astrophysics Data System (ADS)

Zhang, Junwei; Zhu, Guoxuan; Liu, Jie; Wu, Xiong; Zhu, Jiangbo; Du, Cheng; Luo, Wenyong; Chen, Yujie; Yu, Siyuan

2018-02-01

An orbital-angular-momentum (OAM) mode-group multiplexing (MGM) scheme based on a graded-index ring-core fiber (GIRCF) is proposed, in which a single-input two-output (or receive diversity) architecture is designed for each MG channel and simple digital signal processing (DSP) is utilized to adaptively resist the mode partition noise resulting from random intra-group mode crosstalk. There is no need of complex multiple-input multiple-output (MIMO) equalization in this scheme. Furthermore, the signal-to-noise ratio (SNR) of the received signals can be improved if a simple maximal ratio combining (MRC) technique is employed on the receiver side to efficiently take advantage of the diversity gain of receiver. Intensity-modulated direct-detection (IM-DD) systems transmitting three OAM mode groups with total 100-Gb/s discrete multi-tone (DMT) signals over a 1-km GIRCF and two OAM mode groups with total 40-Gb/s DMT signals over an 18-km GIRCF are experimentally demonstrated, respectively, to confirm the feasibility of our proposed OAM-MGM scheme.

[Evaluation of measurement uncertainty of welding fume in welding workplace of a shipyard].

PubMed

Ren, Jie; Wang, Yanrang

2015-12-01

To evaluate the measurement uncertainty of welding fume in the air of the welding workplace of a shipyard, and to provide quality assurance for measurement. According to GBZ/T 192.1-2007 "Determination of dust in the air of workplace-Part 1: Total dust concentration" and JJF 1059-1999 "Evaluation and expression of measurement uncertainty", the uncertainty for determination of welding fume was evaluated and the measurement results were completely described. The concentration of welding fume was 3.3 mg/m(3), and the expanded uncertainty was 0.24 mg/m(3). The repeatability for determination of dust concentration introduced an uncertainty of 1.9%, the measurement using electronic balance introduced a standard uncertainty of 0.3%, and the measurement of sample quality introduced a standard uncertainty of 3.2%. During the determination of welding fume, the standard uncertainty introduced by the measurement of sample quality is the dominant uncertainty. In the process of sampling and measurement, quality control should be focused on the collection efficiency of dust, air humidity, sample volume, and measuring instruments.

Response of removal rates to various organic carbon and ammonium loads in laboratory-scale constructed wetlands treating artificial wastewater.

PubMed

Wu, Shubiao; Kuschk, Peter; Wiessner, Arndt; Kästner, Matthias; Pang, Changle; Dong, Renjie

2013-01-01

High levels (92 and 91%) of organic carbon were successfully removed from artificial wastewater by a laboratory-scale constructed wetland under inflow loads of 670 mg/m2 x d (100 mg/d) and 1600 mg/m2d (240 mg/d), respectively. Acidification to pH 3.0 was observed at the low organic carbon load, which further inhibited the denitrification process. An increase in carbon load, however, was associated with a significant elevation of pH to 6.0. In general, sulfate and nitrate reduction were relatively high, with mean levels of 87 and 90%, respectively. However, inhibition of nitrification was initiated with an increase in carbon loads. This effect was probably a result of competition for oxygen by heterotrophic bacteria and an inhibitory effect of sulfide (S2) toxicity (concentration approximately 3 mg/L). In addition, numbers of healthy stalks of Juncus effusus (common rush) decreased from 14 000 to 10 000/m2 with an increase of sulfide concentration, indicating the negative effect of sulfide toxicity on the wetland plants.

Reducing risk of Anthracycline-related heart failure after childhood cancer | Division of Cancer Prevention

Cancer.gov

Childhood cancer survivors are at a 15-fold risk of developing heart failure (HF) compared to age-matched controls. There is a strong dose-dependent association between anthracyclines and risk of HF; the incidence approaches 20% at cumulative doses between 300-600 mg/m2, and exceeds 30% for doses >600 mg/m2. Outcome following HF is poor; 5-year survival rate is |

Feasibility and toxicity of docetaxel before or after fluorouracil, epirubicin and cyclophosphamide as adjuvant chemotherapy for early breast cancer.

PubMed

Abe, Hajime; Mori, Tsuyoshi; Kawai, Yuki; Cho, Hirotomi; Kubota, Yoshihiro; Umeda, Tomoko; Kurumi, Yoshimasa; Tani, Tohru

2013-06-01

The tolerance and safety associated with the administration order of the anthracycline and taxane drugs have not been evaluated. Breast cancer patients with node-positive or high-risk patients with node-negative were eligible. The feasibility and toxicity were evaluated in the following regimens--arm A, 3 courses of fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2) and cyclophosphamide 500 mg/m(2) (FEC) followed by 3 courses of docetaxel 100 mg/m(2) (DOC); arm B, 3 courses of DOC followed by 3 courses of FEC. Forty-two patients were registered. The relative dose intensity was 94.2 % for FEC and 97.8 % for DOC in arm A, and 98.9 % for DOC and 95.2 % for FEC in arm B. In arm A, grade 3 or higher hematological toxicity was observed in nine patients, and febrile neutropenia developed in three patients with FEC. In arm B, grade 3 or higher hematological toxicity was observed in seven patients, but febrile neutropenia was not noted in any patient. The regimens in both arms A and B were safe regarding adjuvant chemotherapy for early breast cancer. However, DOC followed by FEC might be more tolerable. Further studies will maximize the results obtained with DOC followed by FEC.

Allogeneic hematopoietic cell transplantation for consolidation of VGPR or CR for newly diagnosed multiple myeloma

PubMed Central

Nishihori, T; Ochoa-Bayona, JL; Kim, J; Pidala, J; Shain, K; Baz, R; Sullivan, D; Jim, HS; Anasetti, C; Alsina, M

2015-01-01

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative approach in patients with multiple myeloma, but its use for consolidation of first remission has not yet been fully explored. Twenty-two myeloma patients with very good partial response (VGPR) or CR received allogeneic peripheral blood grafts as consolidation from HLA-matched donors between 2007 and 2012. Conditioning regimens were fludarabine (30 mg/m2 i.v. if with bortezomib and 40 mg/m2 i.v. when without bortezomib, ×4 days) plus melphalan (70 mg/m2 intravenously ×2 days) with (n = 13) or without (n = 9) bortezomib (1.3 mg/m2). The cumulative incidence of grades 2–4 acute GVHD at day 100 was 45% (95% CI: 24–65%) and moderate-to-severe chronic GVHD at 2 years was 46% (95% CI: 19–69%). With a median follow-up of 18 (range, 2–61) months, the 2-year PFS estimate is 74.8% (95% CI: 45–90%), which compares favorably with the 52% (95% CI: 35–66%) after autologous HCT for similar patients (a median follow-up of 30 (range, 9–55) months). We are conducting a phase 2 study to assess the efficacy of allogeneic HCT as post-remission therapy. PMID:23542223

Effects of exposure to ethylene glycol ethers on shipyard painters: II. Male reproduction.

PubMed

Welch, L S; Schrader, S M; Turner, T W; Cullen, M R

1988-01-01

To determine whether 2-ethoxyethanol (2-EE) and 2-methoxyethanol (2-ME) affected the reproductive potential of exposed men, we examined the semen of 73 painters and 40 controls who work in a large shipyard. An industrial hygiene survey was performed to characterize the work environment. The men supplied information on demographic characteristics, medical conditions, personal habits, and reproductive history; underwent a physical examination; and provided a semen sample. Semen samples were analyzed for pH, volume, turbidity, liquidity, viability by stain exclusion and hypo-osmotic stress, sperm density and count per ejaculate, motility using a videotape technique, morphology, and morphometry. Serum was analyzed for testosterone, FSH, and LH. The industrial hygiene survey revealed that the painters were exposed to 2-EE at a time-weighted average (TWA) of 0-80.5 mg/m3 with a mean of 9.9 mg/m3, and to 2-ME at a TWA of 0-17.7 mg/m3 with a mean of 2.6 mg/m3. Painters had an increased prevalence of oligospermia and azoospermia and an increased odds ratio for a lower sperm count per ejaculate, while smoking was controlled. This finding is consistent with prior animal studies and with one human study. Potential biases and confounding of the data are discussed.

Level and distribution of employee exposures to total and respirable wood dust in two Canadian sawmills.

PubMed

Teschke, K; Hertzman, C; Morrison, B

1994-03-01

Personal respirable (N = 230) and total (N = 237) dust measurements were made in two coastal British Columbia sawmills using a sampling strategy that randomly selected workers from all jobs in the mills over two seasons. Information about job title, department, season, weather conditions, location of the job relative to wood-cutting machines, and control measures also was collected at the time of sampling. Only 16 respirable wood dust samples were above the detection limit of 0.08 mg/m3; all 16 had levels < or = 0.20 mg/m3. Total wood dust concentrations were also low (36% less than the detection limit), with a mean of 0.51 mg/m3, and ranging from < 0.08 to 52 mg/m3. Measurements of exposure taken close to chippers, planers, and multiple saws had the highest total wood dust levels. Sawmill department and booth enclosures also were associated with wood dust concentrations, while local exhaust ventilation and weather conditions were not. Wood dust levels in this study were generally lower than in other studies of this industry, but most sawmill investigations report mean wood dust concentrations lower than those measured in the furniture and cabinetmaking industries, where concerns about wood dust exposures initially were raised.

A phase I trial of Flavopiridol in relapsed multiple myeloma

PubMed Central

Hofmeister, Craig C.; Poi, Ming; Bowers, Mindy A.; Zhao, Weiqiang; Phelps, Mitch A.; Benson, Don M.; Kraut, Eric H.; Farag, Sherif; Efebera, Yvonne A.; Sexton, Jennifer; Lin, Thomas S.; Grever, Michael; Byrd, John C.

2014-01-01

Purpose Flavopiridol is primarily a cyclin-dependent kinase (CDK)-9 inhibitor and we performed a dose escalation trial to determine the maximum tolerated dose, safety, and generate a pharmacokinetic profile. Methods Patients with a diagnosis of relapsed myeloma after at least two prior treatments were included. Flavopiridol was administered as a bolus then continuous infusion weekly for 4 weeks in a 6 week cycle. Results Fifteen patients were treated at three dose levels (30 mg/m2 bolus, 30 mg/m2 CIV to 50 mg/m2 bolus, 50 mg/m2 CIV). Cytopenias were significant and elevated transaminases (grade 4 in 3 patients, grade 3 in 4 patients, and grade 2 in 3 patients) were noted but were transient. Diarrhea (grade 3 in 6 patients, grade 2 in 5 patients) did not lead to hospital admission. There were no confirmed partial responses although one patient with t(4;14) had a decrease in his monoclonal protein greater than 50% percent that did not persist. Pharmacokinetic properties were similar to prior publications and immunohistochemical staining for cyclin D1 and phospho-retinoblastoma did not predict response. Conclusions Flavopiridol as a single agent given by bolus then infusion caused significant diarrhea, cytopenias, and transaminase elevation but only achieved marginal responses in relapsed myeloma (ClinicalTrials.gov identifier NCT00112723). PMID:24241210

Tolerability of lomustine in combination with cyclophosphamide in dogs with lymphoma.

PubMed

Rassnick, Kenneth M; Bailey, Dennis B; Malone, Erin K; Flory, Andrea B; Kiselow, Michael A; Intile, Joanne L

2014-01-01

This retrospective study describes toxicity associated with a protocol of lomustine (CCNU) and cyclophosphamide (CTX) in dogs with lymphoma. CCNU was administered per os (PO) at a targeted dosage of 60 mg/m(2) body surface area on day 0, CTX was administered PO at a targeted dosage of 250 mg/m(2) divided over days 0 through 4, and all dogs received prophylactic antibiotics. Ninety treatments were given to the 57 dogs included in the study. Neutropenia was the principal toxic effect, and the overall frequency of grade 4 neutropenia after the first treatment of CCNU/CTX was 30% (95% confidence interval, 19-43%). The mean body weight of dogs with grade 4 neutropenia (19.7 kg ± 13.4 kg) was significantly less than the mean body weight of dogs that did not develop grade 4 neutropenia (31.7 kg ± 12.4 kg; P = .005). One dog (3%) developed hematologic changes suggestive of hepatotoxicity. No dogs had evidence of either renal toxicity or hemorrhagic cystitis. Adverse gastrointestinal effects were uncommon. On the basis of the findings reported herein, a dose of 60 mg/m(2) of CCNU combined with 250 mg/m(2) of CTX (divided over 5 days) q 4 wk is tolerable in tumor-bearing dogs.

Analysis of MSS (Marine Seismic System) and OBS (Ocean Bottom Seismograph) Data Collected during the NGENDEI Seismic Experiment

DTIC Science & Technology

1986-08-01

34Wave-wave interactions, microseisms, and infra - sonic ambient noise in the ocean," J. Acoust. Soc. Am. 78, 981-994, 1985. 8. R. G. Adair, J. A...properties were very con- sistent. Sonic velocities measured at 400 kliz with a Hamilton Frame Velocimeter varied only slightly from 1.5 kilometers/second...physical properties measurements. This sample gave a much higher sonic velocity of 3.8 kilometers/second and a wet bulk desity of 2.46 Mg/m*3. A thin

Brain region-specific activity patterns after recent or remote memory retrieval of auditory conditioned fear.

PubMed

Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

2012-09-19

Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or retrieval. To investigate this possibility, we systematically imaged the brain activity patterns in the lateral amygdala, MGm/PIN, and AuV/TeA using activity-dependent induction of immediate early gene zif268 after recent and remote memory retrieval of auditory conditioned fear. Consistent with the critical role of the amygdala in fear memory, the zif268 activity in the lateral amygdala was significantly increased after both recent and remote memory retrieval. Interesting, however, the density of zif268 (+) neurons in both MGm/PIN and AuV/TeA, particularly in layers IV and VI, was increased only after remote but not recent fear memory retrieval compared to control groups. Further analysis of zif268 signals in AuV/TeA revealed that conditioned tone induced stronger zif268 induction compared to familiar tone in each individual zif268 (+) neuron after recent memory retrieval. Taken together, our results support that the lateral amygdala is a key brain site for permanent fear memory storage and suggest that MGm/PIN and AuV/TeA might play a role for remote memory storage or retrieval of auditory conditioned fear, or, alternatively, that these auditory brain regions might have a different way of processing for familiar or conditioned tone information at recent and remote time phases.

Relation between various chromium compounds and some other elements in fumes from manual metal arc stainless steel welding.

PubMed

Matczak, W; Chmielnicka, J

1993-03-01

For the years 1987-1990 160 individual samples of manual metal arc stainless steel (MMA/SS) welding fumes from the breathing zone of welders in four industrial plants were collected. Concentrations of soluble and insoluble chromium (Cr) III and Cr VI compounds as well as of some other welding fume elements (Fe, Mn, Ni, F) were determined. Concentration of welding fumes in the breathing zone ranged from 0.2 to 23.4 mg/m3. Total Cr amounted to 0.005-0.991 mg/m3 (including 0.005-0.842 mg/m3 Cr VI). Total Cr content of fumes varied from 0.1 to 7.4%. The distribution of particular Cr compounds was: 52.6% soluble Cr (including 50.7% Cr VI), 65.5% total Cr VI, and 11.4% insoluble Cr VI. The results obtained indicate that MMA/SS welding is a process that could be highly hazardous to human health. Evaluation of occupational exposure has shown that MMA/SS welders may exceed the admissible concentrations of soluble and insoluble Cr VI forms as well as of Mn and Ni. In the plants investigated the sum of the ratios of concentrations of particular welding fumes in the breathing zone of welders exceeded corresponding maximum allowable concentration values by 24 times (including 17 times for total Cr VI). Due to the variety and changeability of particular parameters occurring in the working environment, the composition of MMA/SS welding fumes (in the welder's breathing zone) is so variable that it is not possible to assess the exposure by means of one universal exposure indicator (maximum additive hygienic limit value). The evaluation should be based on the results of measurements of concentrations of particular elements in welding fumes.

Relation between various chromium compounds and some other elements in fumes from manual metal arc stainless steel welding.

PubMed Central

Matczak, W; Chmielnicka, J

1993-01-01

For the years 1987-1990 160 individual samples of manual metal arc stainless steel (MMA/SS) welding fumes from the breathing zone of welders in four industrial plants were collected. Concentrations of soluble and insoluble chromium (Cr) III and Cr VI compounds as well as of some other welding fume elements (Fe, Mn, Ni, F) were determined. Concentration of welding fumes in the breathing zone ranged from 0.2 to 23.4 mg/m3. Total Cr amounted to 0.005-0.991 mg/m3 (including 0.005-0.842 mg/m3 Cr VI). Total Cr content of fumes varied from 0.1 to 7.4%. The distribution of particular Cr compounds was: 52.6% soluble Cr (including 50.7% Cr VI), 65.5% total Cr VI, and 11.4% insoluble Cr VI. The results obtained indicate that MMA/SS welding is a process that could be highly hazardous to human health. Evaluation of occupational exposure has shown that MMA/SS welders may exceed the admissible concentrations of soluble and insoluble Cr VI forms as well as of Mn and Ni. In the plants investigated the sum of the ratios of concentrations of particular welding fumes in the breathing zone of welders exceeded corresponding maximum allowable concentration values by 24 times (including 17 times for total Cr VI). Due to the variety and changeability of particular parameters occurring in the working environment, the composition of MMA/SS welding fumes (in the welder's breathing zone) is so variable that it is not possible to assess the exposure by means of one universal exposure indicator (maximum additive hygienic limit value). The evaluation should be based on the results of measurements of concentrations of particular elements in welding fumes. PMID:8457491

Contribution of biomass burning to particles matter smaller than ten microns in Mexico City during April 2013.

NASA Astrophysics Data System (ADS)

Mendoza Campos, Alejandra; Agustin Garcia Reynoso, Jóse; Castro Romero, Telma; Carbajal Perez, Jóse Noel; Gerardo Ruiz Suarez, Luis; Peralta Rosales, Oscar Augusto

2015-04-01

A forest fire is a natural combustion process in a specific geographic area, it's depends on meteorological variables, topography and vegetation type, The wildfires are potential sources of large amounts of pollutants. The main air pollutants emitted in a forest fire are the particles (PM10 and PM2.5) Carbon Monoxide (CO), Nitrogen Oxides (NOx), Volatile Organic Compounds (VOCs) and a negligible amount of Sulfur Dioxide (SO2) (Chow 1995), The study of the impact of air quality in Mexico City for a forest fire occurred on April 14 of 2013 was conducted a duration of 26 hours of grassland burning and consuming an extension of 150 ha, the WRF-Chem, WRF-fire and METv3 models were used to perform the study, for the study two modeling were made, one including emissions from forest fires and the other one no emission-fire, when interpolation is made between the two modeling and obtained the impact of air quality in Mexico City, performing calculating emissions and modeling, the impact on air quality for PM10particles were observed arriving at a concentration of 350 mg/m3 due to wildfire occurred, this issue exceeds the maximum permissible limit of PM10particles governed by NOM-025-SSA1-1993 that establishes a maximum of 120 mg/m3 on average for 24 hours, the modeling results with measured data is corroborated weather Stations the environmental monitoring network of the Mexico City, that alerts an environmental contingency for particles for the post-wildfire day. Until now is review the rule which establishes a maximum of 75 mg/m3 on average for 24 hours, implying greater involvement in air quality.

Evaluation of Respirable Crystalline Silica in High School Ceramics Classrooms

PubMed Central

Fechser, Matthew; Alaves, Victor; Larson, Rodney; Sleeth, Darrah

2014-01-01

Air concentrations of respirable crystalline silica were measured in eleven (11) high school ceramics classrooms located in Salt Lake County, UT, USA. Respirable dust was collected on PVC filters using precision flow pumps and cyclone samplers (n = 44). Filters were subsequently analyzed for respirable dust and percent crystalline silica content. The geometric mean of the silica concentrations was 0.009 mg/m3 near the teacher’s work station and 0.008 mg/m3 near the kilns. The number of students in the classroom was correlated to the silica concentration in the ceramics classroom, but no correlation was found between the silica concentrations and either the size of the classroom or the age of the building. Results from this study indicate that ceramics teachers may be at an increased risk of exposure to crystalline silica based on the ACGIH TLV of 0.025 mg/m3, with an exceedance of 21%. PMID:24464235

Evaluation of respirable crystalline silica in high school ceramics classrooms.

PubMed

Fechser, Matthew; Alaves, Victor; Larson, Rodney; Sleeth, Darrah

2014-01-23

Air concentrations of respirable crystalline silica were measured in eleven (11) high school ceramics classrooms located in Salt Lake County, UT, USA. Respirable dust was collected on PVC filters using precision flow pumps and cyclone samplers (n = 44). Filters were subsequently analyzed for respirable dust and percent crystalline silica content. The geometric mean of the silica concentrations was 0.009 mg/m3 near the teacher's work station and 0.008 mg/m3 near the kilns. The number of students in the classroom was correlated to the silica concentration in the ceramics classroom, but no correlation was found between the silica concentrations and either the size of the classroom or the age of the building. Results from this study indicate that ceramics teachers may be at an increased risk of exposure to crystalline silica based on the ACGIH TLV of 0.025 mg/m3, with an excess of 21%.

Immune evasion via PD-1/PD-L1 on NK cells and monocyte/macrophages is more prominent in Hodgkin lymphoma than DLBCL

PubMed Central

Vari, Frank; Arpon, David; Keane, Colm; Hertzberg, Mark S.; Talaulikar, Dipti; Jain, Sanjiv; Cui, Qingyan; Han, Erica; Tobin, Josh; Bird, Robert; Cross, Donna; Hernandez, Annette; Gould, Clare; Birch, Simone

2018-01-01

Much focus has been on the interaction of programmed cell death ligand 1 (PD-L1) on malignant B cells with programmed cell death 1 (PD-1) on effector T cells in inhibiting antilymphoma immunity. We sought to establish the contribution of natural killer (NK) cells and inhibitory CD163+ monocytes/macrophages in Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL). Levels of PD-1 on NK cells were elevated in cHL relative to DLBCL. Notably, CD3−CD56hiCD16-ve NK cells had substantially higher PD-1 expression relative to CD3−CD56dimCD16+ cells and were expanded in blood and tissue, more marked in patients with cHL than patients with DLBCL. There was also a raised population of PD-L1-expressing CD163+ monocytes that was more marked in patients with cHL compared with patients with DLBCL. The phenotype of NK cells and monocytes reverted back to normal once therapy (ABVD [doxorubicin 25 mg/m2, bleomycin 10 000 IU/m2, vinblastine 6 mg/m2, dacarbazine 375 mg/m2, all given days 1 and 15, repeated every 28 days] or R-CHOP [rituximab 375 mg/m2, cyclophosphamide 750 mg/m2 IV, doxorubicin 50 mg/m2 IV, vincristine 1.4 mg/m2 (2 mg maximum) IV, prednisone 100 mg/day by mouth days 1-5, pegfilgrastim 6 mg subcutaneously day 4, on a 14-day cycle]) had commenced. Tumor-associated macrophages (TAMs) expressed high levels of PD-L1/PD-L2 within diseased lymph nodes. Consistent with this, CD163/PD-L1/PD-L2 gene expression was also elevated in cHL relative to DLBCL tissues. An in vitro functional model of TAM-like monocytes suppressed activation of PD-1hi NK cells, which was reversed by PD-1 blockade. In line with these findings, depletion of circulating monocytes from the blood of pretherapy patients with cHL and patients with DLBCL enhanced CD3−CD56hiCD16-ve NK-cell activation. We describe a hitherto unrecognized immune evasion strategy mediated via skewing toward an exhausted PD-1-enriched CD3−CD56hiCD16-ve NK-cell phenotype. In addition to direct inhibition of NK cells by the malignant B cell, suppression of NK cells can occur indirectly by PD-L1/PD-L2-expressing TAMs. The mechanism is more prominent in cHL than DLBCL, which may contribute to the clinical sensitivity of cHL to PD-1 blockade. PMID:29449276

Sensitivity analyses of exposure estimates from a quantitative job-exposure matrix (SYN-JEM) for use in community-based studies.

PubMed

Peters, Susan; Kromhout, Hans; Portengen, Lützen; Olsson, Ann; Kendzia, Benjamin; Vincent, Raymond; Savary, Barbara; Lavoué, Jérôme; Cavallo, Domenico; Cattaneo, Andrea; Mirabelli, Dario; Plato, Nils; Fevotte, Joelle; Pesch, Beate; Brüning, Thomas; Straif, Kurt; Vermeulen, Roel

2013-01-01

We describe the elaboration and sensitivity analyses of a quantitative job-exposure matrix (SYN-JEM) for respirable crystalline silica (RCS). The aim was to gain insight into the robustness of the SYN-JEM RCS estimates based on critical decisions taken in the elaboration process. SYN-JEM for RCS exposure consists of three axes (job, region, and year) based on estimates derived from a previously developed statistical model. To elaborate SYN-JEM, several decisions were taken: i.e. the application of (i) a single time trend; (ii) region-specific adjustments in RCS exposure; and (iii) a prior job-specific exposure level (by the semi-quantitative DOM-JEM), with an override of 0 mg/m(3) for jobs a priori defined as non-exposed. Furthermore, we assumed that exposure levels reached a ceiling in 1960 and remained constant prior to this date. We applied SYN-JEM to the occupational histories of subjects from a large international pooled community-based case-control study. Cumulative exposure levels derived with SYN-JEM were compared with those from alternative models, described by Pearson correlation ((Rp)) and differences in unit of exposure (mg/m(3)-year). Alternative models concerned changes in application of job- and region-specific estimates and exposure ceiling, and omitting the a priori exposure ranking. Cumulative exposure levels for the study subjects ranged from 0.01 to 60 mg/m(3)-years, with a median of 1.76 mg/m(3)-years. Exposure levels derived from SYN-JEM and alternative models were overall highly correlated (R(p) > 0.90), although somewhat lower when omitting the region estimate ((Rp) = 0.80) or not taking into account the assigned semi-quantitative exposure level (R(p) = 0.65). Modification of the time trend (i.e. exposure ceiling at 1950 or 1970, or assuming a decline before 1960) caused the largest changes in absolute exposure levels (26-33% difference), but without changing the relative ranking ((Rp) = 0.99). Exposure estimates derived from SYN-JEM appeared to be plausible compared with (historical) levels described in the literature. Decisions taken in the development of SYN-JEM did not critically change the cumulative exposure levels. The influence of region-specific estimates needs to be explored in future risk analyses.

Eddy Mediated Nutrient Pattern in the North Eastern Arabian Sea

NASA Astrophysics Data System (ADS)

Thachaparambil, M.; Moolakkal Antony, R.; B R, S.; V N, S.; N, C.; M, S.

2016-02-01

A Cold Core Eddy (CCE) mediated nutrient pattern in the North Eastern Arabian Sea (NEAS) is explained based on in situ measurments during March 2013 onboard FORV Sagar Sampada which was not reported earlier in the area. Samples for physical, chemical and biological parameters were collected in 5 stations along the diameter of the eddy and following standard protocols. The core of the CCE is identified at 21°20.38'N; 66°30.68'E with a diameter of 120Km. Earlier studies explaining the process and the forcing mechanism of the particular eddy records that, the eddy is short term (1-3 months) and is regular during the season. Surface waters were well oxygenated (>4.8 ml L-1) in the core. Surface value of nutrients viz., Nitrate, Nitrite, Silicate and phosphate in the core regions was 0.9µM, 0.01 µM, 0.5 µM and 0.7 µM respectively indicating upwelling in the core. Spring intermonsoon (SIM) is generally termed as a transition period between the active winter and summer seasons and as per earlier studies, high biological production and the regularly occurring Noctilica bloom is supported by the nutrient loading due to convective mixing during winter as well as regenerated production. However, present observations shows that, nutrient pumping due to the upwelling associated with the CCE also contributes for sustaining high biological production and are evident in the Chl a and mesozooplankton biovolume which records values of 4.35mg/m3 and 1.09ml/m3 respectively in the core. An intense Noctiluca blooms observed in the western flank of the eddy (Chl a 13.25 mg/m3; cell density 5.8×106 cells/litre), where Nitrate concentration records 1.04µM explains the role of such mesoscale processes in the sustenance of the HAB events. While eastern flank of the CCE showed typical open ocean condition of the season showing Nitrate 0.08µM; Chl a 0.23mg/m3; and phytoplankton cell density as 421 cells/litre. Keywords: Cold core eddy, nutrients, NEAS, SIM, biological production

[Field investigation of occupational disease diagnosis in Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from 2009 to 2014: an analysis of 136 cases].

PubMed

Fan, C Y; Li, X D; Wen, W; Wang, Y Y; Zhang, Y; Lang, L

2016-04-20

To investigate the characteristics of 136 patients with occupational diseases, to summarize key techniques used in field investigation, and to provide a scientific basis for the development of standard operating procedures for field investigation of occupational disease diagnosis. Field investigation and routine data analysis were performed to analyze the cases diagnosed by Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from January 2009 to December 2014. A total of 136 cases of occupational diseases were diagnosed by Guangdong Provincial Hospital for Occupational Disease Prevention and Treatment from 2009 to 2014, and there were 66 cases of leukemia, 18 cases of suspected occupational benzene poisoning, 12 cases of suspected occupational handarm vibration disease, and 11 cases of suspected pneumoconiosis. Of all these patients, 41.91% were engaged in at least three types of work, 70.59% were exposed to at least three types of chemicals, 25.74% experienced changes in technical processes and chemicals, and 47.06% had disputes on the chemicals they were exposed to during verification by both parties. Occupational hazard factors were detected. Most samples (358)were used to measure benzene concentration in workplace air, among which 11.7% had a benzene concentration of >6.00 mg/m(3)(exceeding standard), 13.41% had a benzene concentration of 3.26~6.00 mg/m(3), 75.42% had a benzene concentration of<0.03 to <3.25 mg/m(3). The samples of suspected occupational hand-arm vibration disease, suspected pneumoconiosis, and suspected occupational noiseinduced hearing loss had high overstandard rates (100%, 93.8%, and 83.3%, respectively). Field investigation of occupational disease diagnosis reveals large numbers of cases of leukemia, suspected occupational benzene poisoning, suspected occupational hand-arm vibration disease, and suspected pneumoconiosis. The key aspects of field investigation include confirmation of the history of occupational exposure, identification of occupational hazard factors, confirmation of the changes in technical processes and chemicals, detection of occupational hazard factors, sampling and analysis of raw materials, and epidemiological investigation of workers with the same type of work.

Randomized Multicenter Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (DCF) Versus DCF Plus Growth Factor Support in Patients With Metastatic Gastric Adenocarcinoma: A Study of the US Gastric Cancer Consortium.

PubMed

Shah, Manish A; Janjigian, Yelena Y; Stoller, Ronald; Shibata, Stephen; Kemeny, Margaret; Krishnamurthi, Smitha; Su, Yungpo Bernard; Ocean, Allyson; Capanu, Marinela; Mehrotra, Bhoomi; Ritch, Paul; Henderson, Charles; Kelsen, David P

2015-11-20

Docetaxel, cisplatin, and fluorouracil (DCF) is a standard first-line three-drug chemotherapy regimen for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma and is associated with significant toxicity. We examined the safety and efficacy of a modified DCF (mDCF) regimen in a randomized multicenter phase II study. Previously untreated patients with metastatic gastric or GEJ adenocarcinoma were randomly assigned to receive either mDCF (fluorouracil 2,000 mg/m2 intravenously [IV] over 48 hours, docetaxel 40 mg/m2 IV on day 1, cisplatin 40 mg/m2 IV on day 3, every 2 weeks) or parent DCF (docetaxel 75 mg/m2, cisplatin 75 mg/m2, and fluorouracil 750 mg/m2 IV over 5 days with granulocyte colony-stimulating factor, every 3 weeks). The study had 90% power to differentiate between 6-month progression-free survival of 26% and 43%, with type I and II error rates of 10% each. An early stopping rule for toxicity was included, defined as grade 3 to 4 adverse event rate > 70% in the first 3 months. From November 2006 to June 2010, 85 evaluable patients were enrolled (male, n = 61; female, n = 24; median age, 58 years; Karnofsky performance status, 90%; GEJ, n = 28; gastric, 57). mDCF (n = 54) toxicity rates included 54% grade 3 to 4 toxicity (22% hospitalized) within the first 3 months and 76% grade 3 to 4 toxicity over the course of treatment. The DCF arm (n = 31) closed early because of toxicity, with rates of 71% grade 3 to 4 toxicity (52% hospitalized) within 3 months and 90% grade 3 to 4 toxicity over the course of treatment. Six-month PFS was 63% (95% CI, 48% to 75%) for mDCF and 53% (95% CI, 34% to 69%) for DCF. Median overall survival was improved for mDCF (18.8 v 12.6 months; P = .007). mDCF is less toxic than parent DCF, even when supported with growth factors, and is associated with improved efficacy. mDCF should be considered a standard first-line option for patients with metastatic gastric or GEJ adenocarcinoma.

Subchronic 13-week inhalation exposure of rats to multiwalled carbon nanotubes: toxic effects are determined by density of agglomerate structures, not fibrillar structures.

PubMed

Pauluhn, Jürgen

2010-01-01

Wistar rats were nose-only exposed to multiwalled carbon nanotubes (MWCNT, Baytubes) in a subchronic 13-week inhalation study. The focus of study was on respiratory tract and systemic toxicity, including analysis of MWCNT biokinetics in the lungs and lung-associated lymph nodes (LALNs). The time course and concentration dependence of pulmonary effects were examined by bronchoalveolar lavage (BAL) and histopathology up to 6 months postexposure. Particular emphasis was directed to the comparative characterization of MWCNT structures prior to and after micronization and dry powder dispersion into inhalation chambers. These determinations were complemented by additional analyses in digested BAL cells. Animals were exposed on 6 h/day, 5 days per week for 13 consecutive weeks to 0, 0.1, 0.4, 1.5, and 6 mg/m(3). The subchronic exposure to respirable solid aerosols of MWCNT was tolerated without effects suggestive of systemic toxicity. Kinetic analyses demonstrated a markedly delayed clearance of MWCNT from lungs at overload conditions. Translocation into LALNs occurred at 1.5 and 6 mg/m(3) and required at least 13 weeks of study to become detectable. At these exposure levels, the lung and LALN weights were significantly increased. Sustained elevations in BAL polymorphonuclear neutrophils and soluble collagen occurred at these concentrations with borderline effects at 0.4 mg/m(3). Histopathology revealed principal exposure-related lesions at 0.4 mg/m(3) and above in the upper respiratory tract (goblet cell hyper- and/or metaplasia, eosinophilic globules, and focal turbinate remodeling) and the lower respiratory tract (inflammatory changes in the bronchioloalveolar region and increased interstitial collagen staining). Granulomatous changes and a time-dependent increase of a bronchioloalveolar hyperplasia occurred at 6 mg/m(3). All end points examined were unremarkable at 0.1 mg/m(3) (no-observed-adverse-effect-level). In summary, this study demonstrates that the induced pathological changes are consistent with overload-related phenomena. Hence, the etiopathological sequence of inflammatory events caused by this type of MWCNT appears to be related to the high displacement volume of the low-density MWCNT assemblage structure rather than to any yet ill-defined intrinsic toxic property. Thus, the hypothesis of study is verified, namely, common denominators between carbon black and MWCNT do exist.

Cumulative alkylating agent exposure and semen parameters in adult survivors of childhood cancer: a report from the St Jude Lifetime Cohort Study.

PubMed

Green, Daniel M; Liu, Wei; Kutteh, William H; Ke, Raymond W; Shelton, Kyla C; Sklar, Charles A; Chemaitilly, Wassim; Pui, Ching-Hon; Klosky, James L; Spunt, Sheri L; Metzger, Monika L; Srivastava, DeoKumar; Ness, Kirsten K; Robison, Leslie L; Hudson, Melissa M

2014-10-01

Few data define the dose-specific relation between alkylating agent exposure and semen variables in adult survivors of childhood cancer. We undertook this study to test the hypothesis that increased exposure to alkylating agents would be associated with decreased sperm concentration in a cohort of adult male survivors of childhood cancer who were not exposed to radiation therapy for their childhood cancer. We did semen analysis on 214 adult male survivors of childhood cancer (median age 7·7 years [range 0·01-20·3] at diagnosis, 29·0 years [18·4-56·1] at assessment, and a median of 21·0 years [10·5-41·6] since diagnosis) who had received alkylating agent chemotherapy but no radiation therapy. Alkylating agent exposure was estimated using the cyclophosphamide equivalent dose (CED). Odds ratios (ORs) and 95% CIs for oligospermia (sperm concentration >0 and <15 million per mL) and azoospermia were calculated with logistic regression modelling. Azoospermia was noted in 53 (25%) of 214 participants, oligospermia in 59 (28%), and normospermia (sperm concentration ≥15 million per mL) in 102 (48%) participants. 31 (89%) of 35 participants who received CED less than 4000 mg/m(2) were normospermic. CED was negatively correlated with sperm concentration (correlation coefficient=-0·37, p<0·0001). Mean CED was 10 830 mg/m(2) (SD 7274) in patients with azoospermia, 8480 mg/m(2) (4264) in patients with oligospermia, and 6626 mg/m(2) (3576) in patients with normospermia. In multivariable analysis, CED was significantly associated with an increased risk per 1000 mg/m(2) CED for azoospermia (OR 1·22, 95% CI 1·11-1·34), and for oligospermia (1·14, 1·04-1·25), but age at diagnosis and age at assessment were not. Impaired spermatogenesis was unlikely when the CED was less than 4000 mg/m(2). Although sperm concentration decreases with increasing CED, there was substantial overlap of CED associated with normospermia, oligospermia, and azoospermia. These data can inform pretreatment patient counselling and use of fertility preservation services. US National Cancer Institute, American Lebanese Syrian Associated Charities. Copyright © 2014 Elsevier Ltd. All rights reserved.

Performance of Prototype High-Flow Inhalable Dust Sampler in a Livestock Production Facility

PubMed Central

Anthony, T. Renée; Cai, Changjie; Mehaffy, John; Sleeth, Darrah; Volckens, John

2017-01-01

A high-flow inhalable sampler, designed for operational flow rates up to 10 L/min using computer simulations and examined in wind tunnel experiments, was evaluated in the field. This prototype sampler was deployed in collocation with an IOM (the benchmark standard sampler) in a swine farrowing building to examine the sampling performance for assessing concentrations of inhalable particulate mass and endotoxin. Paired samplers were deployed for 24-hours on 19 days over a three-month period. On each sampling day, the paired samplers were deployed at three fixed locations and data were analyzed to identify agreement and to examine systematic biases between concentrations measured by these samplers. Thirty-six paired gravimetric samples were analyzed; insignificant, unsubstantial differences between concentrations were identified between the two samplers (p=0.16; mean difference 0.03 mg/m3). Forty-four paired samples were available for endotoxin analysis, and a significant (p=0.001) difference in endotoxin concentration was identified: the prototype sampler, on average, had 120 EU/m3 more endotoxin than did the IOM samples. Since the same gravimetric samples were analyzed for endotoxin content, the endotoxin difference is likely attributable to differences in endotoxin extraction. The prototype’s disposable thin-film polycarbonate capsule was included with the filter in the 1-hour extraction procedure while the internal plastic cassette of the IOM required a rinse procedure that is susceptible to dust losses. Endotoxin concentrations measured with standard plastic IOM inserts that follow this rinsing procedure may underestimate the true endotoxin exposure concentrations. The maximum concentrations in the study (1.55 mg/m3 gravimetric, 2328 EU/m3 endotoxin) were lower than other agricultural or industrial environments. Future work should explore the performance of the prototype sampler in dustier environments, where concentrations approach particulates not otherwise specified (PNOS) limits of 10 mg/m3, including using the prototype as a personal sampler. PMID:27792469

Performance of prototype high-flow inhalable dust sampler in a livestock production facility.

PubMed

Anthony, T Renée; Cai, Changjie; Mehaffy, John; Sleeth, Darrah; Volckens, John

2017-05-01

A high-flow inhalable sampler, designed for operational flow rates up to 10 L/min using computer simulations and examined in wind tunnel experiments, was evaluated in the field. This prototype sampler was deployed in collocation with an IOM (the benchmark standard sampler) in a swine farrowing building to examine the sampling performance for assessing concentrations of inhalable particulate mass and endotoxin. Paired samplers were deployed for 24 hr on 19 days over a 3-month period. On each sampling day, the paired samplers were deployed at three fixed locations and data were analyzed to identify agreement and to examine systematic biases between concentrations measured by these samplers. Thirty-six paired gravimetric samples were analyzed; insignificant, unsubstantial differences between concentrations were identified between the two samplers (p = 0.16; mean difference 0.03 mg/m 3 ). Forty-four paired samples were available for endotoxin analysis, and a significant (p = 0.001) difference in endotoxin concentration was identified: the prototype sampler, on average, had 120 EU/m 3 more endotoxin than did the IOM samples. Since the same gravimetric samples were analyzed for endotoxin content, the endotoxin difference is likely attributable to differences in endotoxin extraction. The prototype's disposable thin-film polycarbonate capsule was included with the filter in the 1-hr extraction procedure while the internal plastic cassette of the IOM required a rinse procedure that is susceptible to dust losses. Endotoxin concentrations measured with standard plastic IOM inserts that follow this rinsing procedure may underestimate the true endotoxin exposure concentrations. The maximum concentrations in the study (1.55 mg/m 3 gravimetric, 2328 EU/m 3 endotoxin) were lower than other agricultural or industrial environments. Future work should explore the performance of the prototype sampler in dustier environments, where concentrations approach particulates not otherwise specified (PNOS) limits of 10 mg/m 3 , including using the prototype as a personal sampler.

STS-107 Crew Interviews: Ilan Ramon, Mission Specialist

NASA Technical Reports Server (NTRS)

2002-01-01

STS-107 Mission Specialist Ilan Ramon is seen during this preflight interview, where he gives a quick overview of the mission before answering questions about his inspiration to become an astronaut and his career path. He outlines his role in the mission in general, and specifically in conducting on-board science experiments. He discusses the following instruments and sets of experiments in detail: CM2 (Combustion Module 2), FREESTAR (Fast Reaction Enabling Science Technology and Research), MEIDEX (Mediterranean Israeli Dust Experiment) and MGM (Mechanics of Granular Materials). Ramon also mentions on-board activities during launch and reentry, mission training and microgravity research. In addition, he touches on the dual work-shift nature of the mission, the use of crew members as research subjects including pre and postflight monitoring activities, the emphasis on crew safety during training and the value of international cooperation.

Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles.

PubMed

Cunningham, David; Hawkes, Eliza A; Jack, Andrew; Qian, Wendi; Smith, Paul; Mouncey, Paul; Pocock, Christopher; Ardeshna, Kirit M; Radford, John A; McMillan, Andrew; Davies, John; Turner, Deborah; Kruger, Anton; Johnson, Peter; Gambell, Joanna; Linch, David

2013-05-25

Dose intensification with a combination of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) every 2 weeks improves outcomes in patients older than 60 years with diffuse large B-cell lymphoma compared with CHOP every 3 weeks. We investigated whether this survival benefit from dose intensification persists in the presence of rituximab (R-CHOP) in all age groups. Patients (aged ≥18 years) with previously untreated bulky stage IA to stage IV diffuse large B-cell lymphoma in 119 centres in the UK were randomly assigned centrally in a one-to-one ratio, using minimisation, to receive six cycles of R-CHOP every 14 days plus two cycles of rituximab (R-CHOP-14) or eight cycles of R-CHOP every 21 days (R-CHOP-21). R-CHOP-21 was intravenous cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1·4 mg/m(2) (maximum dose 2 mg), and rituximab 375 mg/m(2) on day 1, and oral prednisolone 40 mg/m(2) on days 1-5, administered every 21 days for a total of eight cycles. R-CHOP-14 was intravenous cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), vincristine 2 mg, rituximab 375 mg/m(2) on day 1, and oral prednisolone 100 mg on days 1-5, administered every 14 days for six cycles, followed by two further infusions of rituximab 375 mg/m(2) on day 1 every 14 days. The trial was not masked. The primary outcome was overall survival (OS). This study is registered, number ISRCTN 16017947. 1080 patients were assigned to R-CHOP-21 (n=540) and R-CHOP-14 (n=540). With a median follow-up of 46 months (IQR 35-57), 2-year OS was 82·7% (79·5-85·9) in the R-CHOP-14 group and 80·8% (77·5-84·2) in the R-CHOP-21 (standard) group (hazard ratio 0·90, 95% CI 0·70-1·15; p=0·3763). No significant improvement was noted in 2-year progression-free survival (R-CHOP-14 75·4%, 71·8-79·1, and R-CHOP-21 74·8%, 71·0-78·4; 0·94, 0·76-1·17; p=0·5907). High international prognostic index, poor-prognosis molecular characteristics, and cell of origin were not predictive for benefit from either schedule. Grade 3 or 4 neutropenia was higher in the R-CHOP-21 group (318 [60%] of 534 vs 167 [31%] of 534), with no prophylactic use of recombinant human granulocyte-colony stimulating factor mandated in this group, whereas grade 3 or 4 thrombocytopenia was higher with R-CHOP-14 (50 [9%] vs 28 [5%]); other frequent grade 3 or 4 adverse events were febrile neutropenia (58 [11%] vs 28 [5%]) and infection (125 [23%] vs 96 [18%]). Frequencies of non-haematological adverse events were similar in the R-CHOP-21 and R-CHOP-14 groups. R-CHOP-14 is not superior to R-CHOP-21 chemotherapy for previously untreated diffuse large B-cell lymphoma; therefore, R-CHOP-21 remains the standard first-line treatment in patients with this haematological malignancy. No molecular or clinical subgroup benefited from dose intensification in this study. Chugai Pharmaceutical, Cancer Research UK, National Institute for Health Research Biomedical Research Centres scheme at both University College London and the Royal Marsden NHS Foundation Trust, and Institute of Cancer Research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of long-duration exposure on optical system components

NASA Technical Reports Server (NTRS)

Harvey, Gale A.

1991-01-01

The optical materials and UV detectors experiment (SOO50-1) was a set of 18 optical windows, filters, and ultraviolet detectors. The optical specimens were all retrieved in excellent condition. No delamination or blistering of the filters occurred. No discoloration of the optical window materials occurred, but the MgF2 window did experience roughing. The most notable degradation of the optics were the deposition of an organic film on the exposed surfaces. The film absorption was measured using a Fourier transform infrared spectrometer and a UV spectrometer. The 6 percent absorption at 3.4 microns corresponds to about 100 mgm/sq ft of organic film. The UV absorption was almost 100 percent at 200 nm and about 50 percent at 380 nm.

Carboplatin plus paclitaxel in the treatment of gynecologic malignancies: the Cleveland Clinic experience.

PubMed

Markman, M; Kennedy, A; Webster, K; Kulp, B; Peterson, G; Belinson, J

1997-10-01

To examine the toxicity profile and antineoplastic activity of carboplatin (area under the concentration-time curve of 4 to 7.5) plus 3-hour infusional paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (135 or 175 mg/m2) in women with advanced gynecologic malignancies, we retrospectively reviewed the experience of the Gynecologic Cancer Program at The Cleveland Clinic with this combination chemotherapy regimen. To date, 92 patients (median age, 67 years) have received a total of 460 courses (median number per patient, six) of this two-drug combination. The initial paclitaxel dose was 175 mg/m2 and the carboplatin area under the concentration-time curve was > or = 5 in 72% and 73% of patients, respectively. The major toxicity was neutropenia (grade 4 in 9% of patients), resulting in two febrile episodes and a single septic death. Grade 4 thrombocytopenia and grade 3 peripheral neuropathy were noted in one and two patients, respectively. Twelve patients (13%) experienced at least one episode of paclitaxel-associated hypersensitivity, but all were able to continue with the treatment program. Of the 62 patients with ovarian cancer or primary peritoneal carcinoma with carbohydrate antigen-125 levels > or = 60 U/mL before the initiation of chemotherapy, 74% exhibited a > or = 90% decline in the tumor marker following treatment. We conclude that the combination of carboplatin and 3-hour infusional paclitaxel can be administered in the outpatient setting with a highly acceptable toxicity profile and with major activity in patients with ovarian cancer and primary carcinoma of the peritoneum.

Comparison of histologic diagnosis between stereotactic core needle biopsy and open surgical biopsy.

PubMed

Bauer, R L; Sung, J; Eckhert, K H; Koul, A; Castillo, N B; Nemoto, T

1997-06-01

This study correlates the histologic findings of stereotactic core needle biopsy (SCNB) with open surgical biopsy (OSB) and identifies which lesions can be treated definitively based only on the SCNB histology. Women who underwent SCNB between July 1, 1993, and January 1, 1969, were identified by retrospective chart review. Mammographic (MGM) lesions found by SCNB to be ductal or lobular hyperplasia with atypia, or carcinoma underwent OSB. When the histologic findings by SCNB were inconsistent with the MGM findings, the lesion also underwent OSB. 799 women underwent SCNB with 96 (12%) of these going on to OSB. MGM findings in the 92 who presented without a palpable mass included microcalcifications (MCS) in 39, mass in 47, MCS and mass in 7, and tissue distortion in 3. One hundred one breast lesions biopsied first by SCNB, then by OSB were correlated histologically. Sensitivity of SCNB is 89%, with a specificity of 94%. Eight-four women (88%) were able to have definitive treatment at time of OSB because of prior SCNB, and 703/799 (88%) of women were spared OSB entirely. SCNB accurately identifies benign breast histology and invasive cancers in women with MGM abnormalities, a distinct advantage over fine needle aspiration cytology. SCNB does not reliably identify women with DCIS and invasion. All women with SCNB diagnosis of ductal or lobular atypia should also undergo OSB.

Exposure to benzene, toluene, xylenes and total hydrocarbons among snowmobile drivers in Sweden.

PubMed

Eriksson, Kåre; Tjärner, Dan; Marqvardsen, Inger; Järvholm, Bengt

2003-03-01

The exposure to benzene, toluene, xylenes and total hydrocarbons among 25 individuals exposed to exhaust from a snowmobile equipped with a two-stroke engine has been evaluated. Sampling was performed by pumped and diffusive sampling in parallel. There was a relatively bad agreement between the two air-sampling methods. The bad agreement can in part be explained by back diffusion of the substances from the samplers, a high face velocity, and deposition of droplets of unburned gasoline onto or in the vicinity of the samplers. The levels of benzene ranged from not detectable (< or =0.01 mgm(-3)) to 2.5 mgm(-3). For toluene, xylenes and total hydrocarbons the exposure was 0.10-12.0, < or =0.05-13.0 and 0.90-273 mgm(-3) respectively. The result from two measurements on individuals travelling on an open sleigh at the rear of the vehicle indicated higher levels of benzene, 0.7-0.8 mgm(-3). Children are often riding as a passenger on a sledge and may thus have a higher exposure than their parents. This study indicates that spare time driving a snowmobile may cause a considerable exposure to benzene. Using a four-stroke engine equipped with a catalyst could reduce the exposure. To reduce the exposure for the passenger on a sleigh an extension of the exhaust pipe may be effective.

Analysis of the efficacy and safety of a combined gemcitabine, oxaliplatin and pegaspargase regimen for NK/T-cell lymphoma

PubMed Central

Xia, Zhong-jun; Huang, Hui-qiang; Jiang, Wen-qi; Lu, Yue

2016-01-01

Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive neoplasm with a poor outcome. Novel L-asparaginase-based treatment regimens, such as GELOX (gemcitabine, oxaliplatin, and L-asparaginase) and P-gemox (gemcitabine, oxaliplatin, and pegaspargase), have shown promising results against stage IE/IIE ENKTL. To define the general applicability of P-gemox, in a retrospective analysis we examined the efficacy and safety of P-gemox in a cohort of 117 patients with newly diagnosed or relapsed/refractory ENKTL. Treatment included 2 to 8 cycles of P-gemox: intravenous gemcitabine (1250 mg/m2) and oxaliplatin (85 mg/m2) and intramuscular pegaspargase (2500 IU/m2) on day 1 and repeated every 2 weeks, or intravenous gemcitabine (1000 mg/m2) on days 1 and 8 and intravenous oxaliplatin (130 mg/m2) and intramuscular pegaspargase (2500 IU/m2) on day 1 and repeated every 3 weeks. Upon completion of treatment, the overall response rate was 88.8%, and responses were similar for newly diagnosed and relapsed/refractory patients. After a median follow-up of 17 months, the 3-year overall and progression-free survival rates were 72.7% and 57.8%, respectively. Multivariate analysis showed that CR after treatment was the most significant factor affecting survival. P-gemox thus appears to be an effective and well-tolerated treatment for patients with ENKTL. PMID:27072578

Home cage locomotor changes in non-human primates after prolonged welding-fume exposure.

PubMed

Kim, Choong Yong; Sung, Jae Hyuck; Chung, Yong Hyun; Park, Jung Duck; Han, Jeong Hee; Lee, Jong Seong; Heo, Jeong Doo; Yu, Il Je

2013-12-01

To define the relationship between the brain concentration of manganese and neurological signs, such as locomotion, after prolonged welding-fume exposure, cynomolgus monkeys were acclimated for 1 month and then divided into three concentration groups: unexposed, low concentration (31 mg/m(3) total suspended particulate (TSP), 0.9 mg/m(3) of Mn), and high concentration (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of TSP. The monkeys were exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h per day over 8 months in an inhalation chamber system equipped with an automatic fume generator. The home cage locomotor activity and patterns were determined using a camera system over 2-4 consecutive days. After 25 and 32 weeks of exposure, the home cage locomotor activity of the high-concentration primates was found to be 5-6 times higher than that of the unexposed primates, and this increased locomotor activity was maintained for 7 weeks after ceasing the welding-fume exposure, eventually subsiding to three times higher after 13 weeks of recovery. Therefore, the present results, along with our previous observations of a high magnetic resonance imaging (MRI) T1 signal in the globus pallidus and increased blood Mn concentration, indicate that prolonged welding-fume exposure can cause neurobehavioral changes in cynomolgus monkeys.

Open-label Bendamustine Monotherapy for Pediatric Patients With Relapsed or Refractory Acute Leukemia: Efficacy and Tolerability

PubMed Central

Brown, Patrick; Megason, Gail; Ahn, Hyo Seop; Cho, Bin; Kirov, Ivan; Frankel, Lawrence; Aplenc, Richard; Bensen-Kennedy, Debra; Munteanu, Mihaela; Weaver, Jennifer; Harker-Murray, Paul

2014-01-01

This open-label, single-arm, phase I/II, dose-escalation study was designed to determine the recommended phase II dose (RP2D), pharmacokinetics, tolerability, and efficacy of bendamustine in pediatric patients (age ranging from 1 to 20 y) with histologically proven relapsed/refractory acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Patients (27 with ALL, 16 with AML) received intravenous bendamustine on days 1 and 2 of each treatment cycle. Phase I involved planned dose escalation of bendamustine to establish the RP2D for phase II. Objectives included overall response rate, duration of response, and tolerability. Eleven patients were treated in phase I, and the RP2D was 120 mg/m2. In phase II, 32 patients received bendamustine 120 mg/m2. Two patients with ALL (bendamustine 90 mg/m2) experienced complete response (CR). Among patients who received bendamustine 120 mg/m2, 2 experienced partial response (PR); 7 had stable disease. The overall response rate (CR+CR without platelet recovery [CRp]) was 4.7% and biological activity rate (CR+CRp+PR) was 9.3%. No AML patients responded. The most common adverse events were anemia, neutropenia, thrombocytopenia, pyrexia, nausea, vomiting, and diarrhea. Bendamustine monotherapy has acceptable tolerability in heavily pretreated children with relapsed/refractory ALL or AML and appears to have some activity in ALL, warranting further studies in combination trials. PMID:24072240

Optimizing the induction chemotherapy regimen for patients with locoregionally advanced nasopharyngeal Carcinoma: A big-data intelligence platform-based analysis.

PubMed

Peng, Hao; Tang, Ling-Long; Chen, Bin-Bin; Chen, Lei; Li, Wen-Fei; Mao, Yan-Ping; Liu, Xu; Zhang, Yuan; Liu, Li-Zhi; Tian, Li; Guo, Ying; Sun, Ying; Ma, Jun

2018-04-01

This study aimed at identifying the optimal induction chemotherapy regimen for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy. We identified eligible patients with newly-diagnosed stage III-IVA NPC (excluding T3N0) between September 2009 and May 2015. Survival outcomes and grade 3-4 toxicities were compared between different IC regimen groups. In total, 3738 patients were eligible for this study, with 1572 (42.1%), 1085 (29.0%) and 1081 (28.9%) receiving TPF, PF and TP, respectively. In the whole population, multivariate analysis found that TPF seems to be better than PF and TP. Howerver, subgroup analysis revealed TPF and TP had same effectiveness in patients receiving a cumulative cisplatin dose (CCD) ≥200mg/m 2 in concurrent chemotherapy, while TPF shows relatively better survival benefit in patients receiving CCD<200mg/m 2 . Grade 3-4 toxicities were similar between TPF and TP groups, but were relatively higher than that in PF group. Our study concluded that induction TP regimen may be enough for patients receiving a CCD≥200mg/m 2 , while TPF may be superior to TP and PF for patients receiving a CCD<200mg/m 2 , although grade 3-4 toxic events were more common but tolerable. Further studies are needed to validate our findings. Copyright © 2018 Elsevier Ltd. All rights reserved.

Significant efficacy and well safety of apatinib in an advanced liver cancer patient: a case report and literature review

PubMed Central

Shao, Wenbo; Zhu, Hui; Zhang, Jingze; Wang, Haiyong; Kong, Li; Yu, Jinming

2017-01-01

Apatinib is a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. Previous studies have suggested that apatinib is safe and effective in some solid tumors. We report one case with advanced hepatocellular carcinoma (HCC), who received apatinib combined with transhepatic arterial chemotherapy and embolization (TACE), and chemotherapy respectively. TACE was administered three times once a month, using lipiodol 10ml, oxaliplatin 150mg, and tegafur 1g. The dose of apatinib was 500 mg/d from day 4 to 24. After TACE, the patient received chemotherapy of regimen FOLFOX4, oxaliplatin intravenously at 85 mg/m2 on day 1, calcium levofolinate 200 mg/m2 on day 1 and 2, 5-fluorouracil 400 mg/m2 intravenously and 5-fluorouracil 600 mg/m2 intravenously pumped for 22h on day 1 and 2, cycled every two weeks for seven cycles. He took concurrently apatinib with a dose of 500mg daily from 1 to 10 days per cycle. He was confirmed as partial response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST). The level of serum alpha-fetoprotein (AFP) decreased from 60500 ng/ml to 12.7 ng/ml, and the progression free survival (PFS) time was more than eight months. It indicated that apatinib may be a superior choice for HCC patients. PMID:28103584

Significant efficacy and well safety of apatinib in an advanced liver cancer patient: a case report and literature review.

PubMed

Kou, Peisi; Zhang, Yan; Shao, Wenbo; Zhu, Hui; Zhang, Jingze; Wang, Haiyong; Kong, Li; Yu, Jinming

2017-03-21

Apatinib is a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2. Previous studies have suggested that apatinib is safe and effective in some solid tumors. We report one case with advanced hepatocellular carcinoma (HCC), who received apatinib combined with transhepatic arterial chemotherapy and embolization (TACE), and chemotherapy respectively. TACE was administered three times once a month, using lipiodol 10ml, oxaliplatin 150mg, and tegafur 1g. The dose of apatinib was 500 mg/d from day 4 to 24. After TACE, the patient received chemotherapy of regimen FOLFOX4, oxaliplatin intravenously at 85 mg/m2 on day 1, calcium levofolinate 200 mg/m2 on day 1 and 2, 5-fluorouracil 400 mg/m2 intravenously and 5-fluorouracil 600 mg/m2 intravenously pumped for 22h on day 1 and 2, cycled every two weeks for seven cycles. He took concurrently apatinib with a dose of 500mg daily from 1 to 10 days per cycle. He was confirmed as partial response (PR) by the Response Evaluation Criteria in Solid Tumors (RECIST). The level of serum alpha-fetoprotein (AFP) decreased from 60500 ng/ml to 12.7 ng/ml, and the progression free survival (PFS) time was more than eight months. It indicated that apatinib may be a superior choice for HCC patients.

Pulmonary Evaluation of Permissible Exposure Limit of Syntroleum S-8 Synthetic Jet Fuel in Mice

PubMed Central

Wong, Simon S.; Thomas, Alana; Barbaris, Brian; Lantz, R. Clark; Witten, Mark L.

2009-01-01

No current studies have systematically examined pulmonary health effects associated with Syntroleum S-8 synthetic jet fuel (S-8). In order to gain an understanding about the threshold concentration in which lung injury is observed, C57BL/6 male mice were nose-only exposed to S-8 for 1 h/day for 7 days at average concentrations of 0 (control), 93, 352, and 616 mg/m3. Evaluation of pulmonary function, airway epithelial barrier integrity, and pathohistology was performed 24 h after the final exposures. Significant decreases were detected in expiratory lung resistance and total lung compliance of the 352 mg/m3 group, for which no clear concentration-dependent alterations could be determined. No significant changes in respiratory permeability were exhibited, indicating that there was no loss of epithelial barrier integrity following S-8 exposure. However, morphological examination and morphometric analysis of distal lung tissue, by using transmission electron microscopy, revealed cellular damage in alveolar type II epithelial cells, with significant increases in volume density of lamellar bodies/vacuoles at 352 and 616 S-8 mg/m3. Moreover, terminal bronchiolar Clara injury, as evidenced by apical membrane blebs, was observed at relatively low concentrations, suggesting if this synthetic jet fuel is utilized, the current permissible exposure limit of 350 mg/m3 for hydrocarbon fuels should cautiously be applied. PMID:19357071

Pulmonary evaluation of permissible exposure limit of syntroleum S-8 synthetic jet fuel in mice.

PubMed

Wong, Simon S; Thomas, Alana; Barbaris, Brian; Lantz, R Clark; Witten, Mark L

2009-06-01

No current studies have systematically examined pulmonary health effects associated with Syntroleum S-8 synthetic jet fuel (S-8). In order to gain an understanding about the threshold concentration in which lung injury is observed, C57BL/6 male mice were nose-only exposed to S-8 for 1 h/day for 7 days at average concentrations of 0 (control), 93, 352, and 616 mg/m(3). Evaluation of pulmonary function, airway epithelial barrier integrity, and pathohistology was performed 24 h after the final exposures. Significant decreases were detected in expiratory lung resistance and total lung compliance of the 352 mg/m(3) group, for which no clear concentration-dependent alterations could be determined. No significant changes in respiratory permeability were exhibited, indicating that there was no loss of epithelial barrier integrity following S-8 exposure. However, morphological examination and morphometric analysis of distal lung tissue, by using transmission electron microscopy, revealed cellular damage in alveolar type II epithelial cells, with significant increases in volume density of lamellar bodies/vacuoles at 352 and 616 S-8 mg/m(3). Moreover, terminal bronchiolar Clara injury, as evidenced by apical membrane blebs, was observed at relatively low concentrations, suggesting if this synthetic jet fuel is utilized, the current permissible exposure limit of 350 mg/m(3) for hydrocarbon fuels should cautiously be applied.

A phase I and pharmacokinetic study of lapatinib in combination with infusional 5-fluorouracil, leucovorin and irinotecan.

PubMed

Midgley, R S; Kerr, D J; Flaherty, K T; Stevenson, J P; Pratap, S E; Koch, K M; Smith, D A; Versola, M; Fleming, R A; Ward, C; O'Dwyer, P J; Middleton, M R

2007-12-01

This study determined the optimally tolerated regimen (OTR) of oral lapatinib administered in combination with infusional 5-fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) and assessed the safety, tolerability and pharmacokinetics of the combination. Twenty-five patients were enrolled; 12 patients were treated at three dose levels to determine OTR; then 13 patients were treated at OTR to evaluate the pharmacokinetics of the combination. The 2-weekly OTR comprised lapatinib 1250 mg/day with irinotecan 108 mg/m(2) (day 1) and leucovorin 200 mg/m(2), 5-FU bolus 240 mg/m(2) and 5-FU infusion 360 mg/m(2) (days 1 and 2); doses of 5-FU and irinotecan represent a 40% reduction in dose compared to conventional FOLFIRI. Dose-limiting toxicities were grade 3 diarrhoea and grade 4 neutropenia. Co-administration of lapatinib increased the area under the plasma concentration-time curve of SN-38, the active metabolite of irinotecan, by an average of 41%; no other pharmacokinetic interactions were observed. Of 19 patients evaluable for disease response assessment, four patients had partial response and nine patients had stable disease. The combination of lapatinib and FOLFIRI is safe and demonstrates clinical activity; the documented PK interaction can effectively be compensated by lowering the doses of 5-FU and irinotecan. This regime may be further tested in a phase II trial.

The indoor volatile organic compound (VOC) characteristics and source identification in a new university campus in Tianjin, China.

PubMed

Kang, Jian; Liu, Junjie; Pei, Jingjing

2017-06-01

This study investigates the volatile organic compounds (VOCs) constituents and concentration levels on a new university campus, where all of the buildings including classrooms and student dormitories were newly built and decorated within 1 year. Investigated indoor environments include dormitories, classrooms, and the library. About 30 dormitory buildings with different furniture loading ratios were measured. The characteristics of the indoor VOCs species are analyzed and possible sources are identified. The VOCs were analyzed with gas chromatography-mass spectroscopy (GC-MS). It was found that the average total VOC (TVOC) concentration can reach 2.44 mg/m 3 . Alkenes were the most abundant VOCs in dormitory rooms, contributing up to 86.5% of the total VOCs concentration. The concentration of α-pinene is the highest among the alkenes. Unlike the dormitory rooms, there is almost no room with TVOC concentration above 0.6 mg/m 3 in classroom and library buildings. Formaldehyde concentration in the dormitory rooms increased about 23.7% after the installation of furniture, and the highest level reached 0.068 mg/m 3 . Ammonia released from the building antifreeze material results in an average indoor concentration of 0.28 mg/m 3 , which is 100% over the threshold and should be seriously considered. Further experiments were conducted to analyze the source of the α-pinene and some alkanes in dormitory rooms. The results showed that the α-pinene mainly comes from the bed boards, while the wardrobes are the main sources of alkanes. The contribution of the pinewood bed boards to the α-pinene and TVOC concentration can reach up to above 90%. The same type rooms were sampled 1 year later and the decay rate of α-pinene is quite high, close to 100%, so that it almost cannot be detected in the sampled rooms. Analysis of indoor volatile organic compounds (VOCs) in newly built campus buildings in China identified the specific constituents of indoor VOCs contaminants exposed to Chinese college students. The main detected substances α-pinene, β-pinene, and 3-carene originated from solid wood bed boards and should be seriously considered. In addition, the contribution rates of building structure materials and furniture to specific VOCs constituents are quantitative calculated. Also, the decay rates of these specific constituents within 1 year are also quantitative calculated in this paper. This study can help us to better understand the sources and concentration levels of VOC contaminants in campus buildings, and to help select appropriate materials in buildings.

JP-8 jet fuel can promote auditory impairment resulting from subsequent noise exposure in rats.

PubMed

Fechter, Laurence D; Gearhart, Caroline; Fulton, Sherry; Campbell, Jerry; Fisher, Jeffrey; Na, Kwangsam; Cocker, David; Nelson-Miller, Alisa; Moon, Patrick; Pouyatos, Benoit

2007-08-01

We report on the transient and persistent effects of JP-8 jet fuel exposure on auditory function in rats. JP-8 has become the standard jet fuel utilized in the United States and North Atlantic Treaty Organization countries for military use and it is closely related to Jet A fuel, which is used in U.S. domestic aviation. Rats received JP-8 fuel (1000 mg/m(3)) by nose-only inhalation for 4 h and half of them were immediately subjected to an octave band of noise ranging between 97 and 105 dB in different experiments. The noise by itself produces a small, but permanent auditory impairment. The current permissible exposure level for JP-8 is 350 mg/m(3). Additionally, a positive control group received only noise exposure, and a fourth group consisted of untreated control subjects. Exposures occurred either on 1 day or repeatedly on 5 successive days. Impairments in auditory function were assessed using distortion product otoacoustic emissions and compound action potential testing. In other rats, tissues were harvested following JP-8 exposure for assessment of hydrocarbon levels or glutathione (GSH) levels. A single JP-8 exposure by itself at 1000 mg/m(3) did not disrupt auditory function. However, exposure to JP-8 and noise produced an additive disruption in outer hair cell function. Repeated 5-day JP-8 exposure at 1000 mg/m(3) for 4 h produced impairment of outer hair cell function that was most evident at the first postexposure assessment time. Partial though not complete recovery was observed over a 4-week postexposure period. The adverse effects of repeated JP-8 exposures on auditory function were inconsistent, but combined treatment with JP-8 + noise yielded greater impairment of auditory function, and hair cell loss than did noise by itself. Qualitative comparison of outer hair cell loss suggests an increase in outer hair cell death among rats treated with JP-8 + noise for 5 days as compared to noise alone. In most instances, hydrocarbon constituents of the fuel were largely eliminated in all tissues by 1-h postexposure with the exception of fat. Finally, JP-8 exposure did result in a significant depletion of total GSH that was observable in liver with a nonsignificant trend toward depletion in the brain and lung raising the possibility that the promotion of noise-induced hearing loss by JP-8 might have resulted from oxidative stress.

Biweekly cetuximab in combination with FOLFOX-4 in the first-line treatment of wild-type KRAS metastatic colorectal cancer: final results of a phase II, open-label, clinical trial (OPTIMIX-ACROSS Study).

PubMed

Fernandez-Plana, Julen; Pericay, Carlos; Quintero, Guillermo; Alonso, Vicente; Salud, Antonieta; Mendez, Miguel; Salgado, Mercedes; Saigi, Eugeni; Cirera, Luis

2014-11-22

This phase II study aims to evaluate the efficacy and safety of biweekly cetuximab in combination with oxaliplatin, leucovorin, and fluorouracil (FOLFOX-4) as first-line treatment of metastatic wild-type KRAS colorectal cancer. Previously untreated patients with wild-type KRAS tumours received biweekly cetuximab (500 mg/m2 on day 1) plus FOLFOX-4 (oxaliplatin 85 mg/m2 on day 1, leucovorin 200 mg/m2 on days 1 and 2, and fluorouracil as a 400 mg/m2 bolus followed by a 22-hour 600 mg/m2 infusion on day 1 and 2). Treatment was continued until disease progression, onset of unacceptable toxicities, metastases surgery, or discontinuation request. The primary endpoint was ORR. The intention-to-treat population included 99 patients with a median age of 64.1 years (range, 34-82). The ORR was 60.6% (95% CI, 50.3% to 70.3%). The median follow-up was 17.8 months; the median OS and PFS were 20.8 and 10.1 months, respectively. Metastases from colorectal cancer were surgically resected in 26 (26.3%) patients, with complete resection achieved in 18 (69.2%) patients. Median PFS and OS in patients undergoing metastatic resection were 12.6 and 29.5 months, respectively. The most common grade 3-4 toxicities were neutropenia (32.3%), acne-like rash (15.2%) and diarrhoea (11.1%). The efficacy of the biweekly combination of cetuximab with FOLFOX-4 in patients with wild-type KRAS tumours supports the administration of cetuximab in a dosing regimen more convenient for patients and healthcare providers. The activity of the biweekly administration is similar to what has been reported for the weekly regimen. Reported toxicity was also consistent with the known toxicity profile of weekly cetuximab. EudraCT Number 200800690916.

Phase I Study of LY2606368, a Checkpoint Kinase 1 Inhibitor, in Patients With Advanced Cancer

PubMed Central

Infante, Jeffrey; Janku, Filip; Jones, Suzanne; Nguyen, Ly M.; Burris, Howard; Naing, Aung; Bauer, Todd M.; Piha-Paul, Sarina; Johnson, Faye M.; Kurzrock, Razelle; Golden, Lisa; Hynes, Scott; Lin, Ji; Lin, Aimee Bence; Bendell, Johanna

2016-01-01

Purpose The primary objective was to determine safety, toxicity, and a recommended phase II dose regimen of LY2606368, an inhibitor of checkpoint kinase 1, as monotherapy. Patients and Methods This phase I, nonrandomized, open-label, dose-escalation trial used a 3 + 3 dose-escalation scheme and included patients with advanced solid tumors. Intravenous LY2606368 was dose escalated from 10 to 50 mg/m2 on schedule 1 (days 1 to 3 every 14 days) or from 40 to 130 mg/m2 on schedule 2 (day 1 every 14 days). Safety measures and pharmacokinetics were assessed, and pharmacodynamics were measured in blood, hair follicles, and circulating tumor cells. Results Forty-five patients were treated; seven experienced dose-limiting toxicities (all hematologic). The maximum-tolerated doses (MTDs) were 40 mg/m2 (schedule 1) and 105 mg/m2 (schedule 2). The most common related grade 3 or 4 treatment-emergent adverse events were neutropenia, leukopenia, anemia, thrombocytopenia, and fatigue. Grade 4 neutropenia occurred in 73.3% of patients and was transient (typically < 5 days). Febrile neutropenia incidence was low (7%). The LY2606368 exposure over the first 72 hours (area under the curve from 0 to 72 hours) at the MTD for each schedule coincided with the exposure in mouse xenografts that resulted in maximal tumor responses. Minor intra- and intercycle accumulation of LY2606368 was observed at the MTDs for both schedules. Two patients (4.4%) had a partial response; one had squamous cell carcinoma (SCC) of the anus and one had SCC of the head and neck. Fifteen patients (33.3%) had a best overall response of stable disease (range, 1.2 to 6.7 months), six of whom had SCC. Conclusion An LY2606368 dose of 105 mg/m2 once every 14 days is being evaluated as the recommended phase II dose in dose-expansion cohorts for patients with SCC. PMID:27044938

Role of Chinese cooking emissions on ambient air quality and human health.

PubMed

Wang, Lina; Xiang, Zhiyuan; Stevanovic, Svetlana; Ristovski, Zoran; Salimi, Farhad; Gao, Jun; Wang, Hongli; Li, Li

2017-07-01

Chinese-style cooking often involves volatilization of oils which can potentially produce a large number of pollutants, which have adverse impact on environment and human health. Therefore, we have reviewed 75 published studies associated with research topic among Mainland China, Hong Kong and Taiwan, involving studies on the roles of food ingredients and oil type, cooking style impacting on generated pollutants, and human health. The highest concentration occurred including: 1) when peat, wood, and raw coal were used in stoves; 2) olive oil was adopted; 3) cooking with high temperatures; and 4) without cleaning technology. We conclude that PM concentrations for cooking emissions were between 0.14 and 24.46mg/cm 3 . VOC concentrations varied from 0.35 to 3.41mg/m 3 . Barbeque produced the greatest mass concentrations compared to Sichuan cuisine, canteen and other restaurants. The PAHs concentration emitted from the exhaust stacks, dining area and kitchen ranged from 0.0175μg/m 3 to 83μg/m 3 . The largest amount of gaseous pollutants emitted was recorded during incomplete combustion of fuel or when a low combustion efficiency (CO2/ (CO+CO2)<0.5) was observed. The variation range was 6.27-228.89mg/m 3 , 0.16-0.80mg/m 3 , 0.69-4.33mg/m3, 0.70-21.70mg/m 3 for CO, CO 2 , NO 2 and SO 2 respectively. In regards to the toxicity and exposure, current findings concluded that both the dose and exposure time are significant factors to be considered. Scientific research in this area has been mainly driven by comparison among emissions from various ingredients and cooking techniques. There is still a need for more comprehensive studies to fully characterise the cooking emissions including their physical and chemical transformations which is crucial for accurate estimation of their impacts on the environment and human health. Copyright © 2017 Elsevier B.V. All rights reserved.

PHOTODYNAMIC THERAPY (PDT) USING HPPH FOR THE TREATMENT OF PRECANCEROUS LESIONS ASSOCIATED WITH BARRETT’S ESOPHAGUS

PubMed Central

Nava, Hector R; Allamaneni, Shyam S; Dougherty, Thomas J; Cooper, Michele T; Tan, Wei; Wilding, Gregory; Henderson, Barbara W

2011-01-01

Background and Objectives Photodynamic therapy (PDT) with porfimer sodium, FDA approved to treat premalignant lesions in Barrett’s esophagus, causes photosensitivity for 6-8 weeks. HPPH (2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) shows minimal photosensitization of short duration and promising efficacy in preclinical studies. Here we explore toxicity and optimal drug and light dose with endoscopic HPPH-PDT. We also want to know the efficacy of one time treatment with HPPH-PDT. Study Design/Materials and Methods Two nonrandomized dose escalation studies were performed (18 patients each) with biopsy-proven high grade dysplasia or early intramucosal adenocarcinoma of esophagus. HPPH doses ranged from 3 to 6 mg/m2. At 24 or 48 hours after HPPH administration the lesions received one endoscopic exposure to 150, 175 or 200 J/cm of 665 nm light. Results Most patients experienced mild to moderate chest pain requiring symptomatic treatment only. Six patients experienced Grade 3 & 4 adverse events (16.6%). Three esophageal strictures were treated with dilatation. No clear pattern of dose dependence of toxicities emerged. In the drug dose ranging study (light dose of 150 J/cm at 48 h), 3 and 4 mg/m2 of HPPH emerged as most effective. In the light dose ranging study (3 or 4 mg/m2 HPPH, light at 24 h), complete response rates (disappearance of high grade dysplasia and early carcinoma) of 72% were achieved at 1 year, with all patients treated with 3 mg/m2 HPPH plus 175 J/cm and 4 mg/m2 HPPH plus 150 J/cm showing complete responses at 1 year. Conclusions HPPH-PDT for precancerous lesions in Barrett’s esophagus appears to be safe and showing promising efficacy. Further clinical studies are required to establish the use of HPPH-PDT. PMID:22057498

Neoadjuvant chemotherapy with ifosfamide, cisplatin, and vinorelbine in advanced squamous cell carcinoma of the cervix.

PubMed

Vallejo, C T; Pérez, J E; Domínguez, M E; Leone, B A; Machiavelli, M R; Lacava, J A; Romero, A O; Ortiz, E H; Grasso, S; Amato, S; Rodríguez, R; Barbieri, M; Romero Acuña, J; Focaccia, G; Suttora, G; Scenna, M; Boughen, J M; Romero Acuña, L A; Langhi, M J

2000-10-01

A phase II trial was performed to assess the efficacy and toxicity of a combination of ifosfamide (IFX), cisplatin (CDDP), and vinorelbine (VNB) as neoadjuvant chemotherapy (NAC) for untreated advanced cervical carcinoma (ACC). Between October 1995 and February 1998, 40 patients were entered in this study. Their median age was 43 years (range: 23-74 years). International Federation of Gynecology and Obstetrics stages were: IIB, 23; IIIB, 13; and IVA, 4. Therapy consisted of: IFX 2,000 mg/m2 1-hour (H) IV infusion days 1 to 3; 2-mercaptoethanesulfonic acid sodium salt (mesna) 400 mg/m2 IV bolus H 0 and 4, and 800 mg/m2 by mouth H 8, days 1 to 3; VNB 25 mg/m2 20-minute IV infusion days 1 and 8; and CDDP 75 mg/m2 IV day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response (R) assessment were performed by a multidisciplinary team. An objective response (OR) was observed in 24 of 40 patients (60%; 95% confidence interval, 45-75%). Four patients achieved complete response (CR) (10%); 20 partial response (50%); 12 patients stable disease (30%); and 4 progressive disease (10%). Eight of 24 patients (33%) with OR underwent radical surgery, and histologic CRs were recorded in 2 of them. The remaining patients received definitive radiotherapy after NAC. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 32 patients (80%) and was grade III or IV in 14 patients (36%). Peripheral neuropathy occurred in 9 patients (22%), whereas myalgias occurred in 10 (25%). Constipation was observed in 9 patients (23%); emesis occurred in 35 patients (88%). There were no therapy-related deaths. These results indicate that IFX/CDDP/VNB is an active combination for ACC with moderate toxicity. Implementation of this regimen in a multimodal therapy protocol deserves further study.

Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil With Bevacizumab in Patients With Metastatic Gastroesophageal Adenocarcinoma

PubMed Central

Shah, Manish A.; Jhawer, Minaxi; Ilson, David H.; Lefkowitz, Robert A.; Robinson, Edric; Capanu, Marinela; Kelsen, David P.

2011-01-01

Purpose To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF) with bevacizumab in patients with advanced gastroesophageal malignancies. Patients and Methods Previously untreated patients with metastatic gastroesophageal adenocarcinoma received bevacizumab 10 mg/kg, docetaxel 40 mg/m2, fluorouracil 400 mg/m2, leucovorin 400 mg/m2 on day 1, fluorouracil 1,000 mg/m2/d × 2 days intravenous continuous infusion beginning on day 1, and cisplatin 40 mg/m2 on day 3. The primary objective was to improve 6-month progression-free survival (PFS) from 43% (historical DCF control) to 63% with the addition of bevacizumab. The target accrual was 44 patients to have 10% type I and II error rates. Results In total, 44 eligible patients with cancer were enrolled from October 2006 to October 2008: 22 gastric, 20 gastroesophageal junction (GEJ), and two esophagus. In 39 patients with measurable disease, the confirmed response rate was 67% (95% CI, 50% to 81%). Six-month PFS was 79% (95% CI, 63% to 88%), and median PFS was 12 months (95% CI, 8.8 to 18.2 months). With 26-month follow-up, median overall survival (OS) was 16.8 months (95% CI, 12.1 to 26.1 months), and 2-year survival was 37%. Treatment-related grade 3 to 4 toxicity was as follows: neutropenia without fever (50%), fatigue (25%), venous thromboembolism (39%), and nausea, vomiting, mucositis, neuropathy, and febrile neutropenia less than 10% each. In subset analysis, diffuse gastric cancer had significantly worse PFS and OS, and the response rate in proximal/GEJ tumors was 85% (95% CI, 62% to 97%). Conclusion mDCF with bevacizumab appears tolerable and has notable patient outcomes in patients with advanced gastroesophageal adenocarcinoma. Six-month PFS was 79%, surpassing our predefined efficacy end point, and median and 2-year OS were 16.8 months and 37%, respectively. PMID:21189380

A phase I report of paclitaxel dose escalation combined with a fixed dose of carboplatin in the treatment of head and neck carcinoma.

PubMed

Dunphy, F R; Boyd, J H; Kim, H J; Dunphy, C H; Harrison, B R; Dunleavy, T L; Rodriguez, J J; McDonough, E M; Minster, J R; Hilton, J G

1997-05-15

Standard therapy for advanced head and neck carcinoma is surgery and radiation, and the subsequent 5-year survival with this treatment has been less than 50%. New combined modality treatment strategies are being tested to improve survival. New chemotherapy combinations are being developed and administered simultaneously with, or sequenced with, radiation and surgery. This article reports the Phase I results of administering paclitaxel and carboplatin preoperatively. The authors' objective was to develop an outpatient chemotherapy that would downstage tumors and allow organ preservation with equal or improved survival as compared with standard therapy. Thirty-six patients with untreated Stage III/IV head and neck carcinoma were treated and were evaluable for toxicity. All patients had lesions that were measurable in perpendicular planes. A nonrandomized, Phase I design was used, according to which cohorts of patients were treated every 21 days with escalating doses of paclitaxel (150-265 mg/m2) given as a 3-hour infusion immediately preceding carboplatin. Premedication was used to avoid acute hypersensitivity reactions. Carboplatin was administered intravenously over 1 hour at a constant dose calculated with the Calvert formula (area under the curve, 7.5). The dose-limiting toxicities were neuropathy and thrombocytopenia at a paclitaxel dose of 265 mg/m2. Neutropenic fever was observed in 30% of patients at a paclitaxel dose of 250-265 mg/m2. Other observed adverse effects included pruritus, myalgia, arthralgia, alopecia, nausea, and vomiting. Toxicity was acceptable. The maximum tolerated dose of paclitaxel was 230 mg/m2 without hematopoietic growth factor, or 250 mg/m2 with hematopoietic growth factor, the carboplatin dose held constant, calculated at area under the curve of 7.5. Phase II studies of this combination are warranted in the treatment of these carcinomas.

BCNU wafer placement with temozolomide (TMZ) in the immediate postoperative period after tumor resection followed by radiation therapy with TMZ in patients with newly diagnosed high grade glioma: final results of a prospective, multi-institutional, phase II trial.

PubMed

Burri, Stuart H; Prabhu, Roshan S; Sumrall, Ashley L; Brick, Wendy; Blaker, Brian D; Heideman, Brent E; Boltes, Peggy; Kelly, Renee; Symanowski, James T; Wiggins, Walter F; Ashby, Lynn; Norton, H James; Judy, Kevin; Asher, Anthony L

2015-06-01

Temozolomide (TMZ) and BCNU have demonstrated anti-glioma synergism in preclinical models. We report final data from a prospective, multi-institutional study of BCNU wafers and early TMZ followed by radiation therapy with TMZ in patients with newly diagnosed malignant glioma. 65 patients were consented in 4 institutions, and 46 patients (43 GBM, 3 AA) were eligible for analysis. After resection and BCNU wafer placement, TMZ began on day four postoperatively. Radiation and TMZ (RT/TMZ) were then administered, followed by monthly TMZ at 200 mg/m2 for the first 26 patients, which was reduced to 150 mg/m2 for the remaining 20 patients. Non-hematologic toxicities were minimal. Nine of 27 patients (33 %) who received 200 mg/m2 TMZ, but only 1 of 20 (5 %) who received 150 mg/m2, experienced grade 3/4 thrombocytopenia. Median progression free survival (PFS) and overall survival (OS) period was 8.5 and 18 months, respectively. The 1-year OS rate was 76 %, which is a significant improvement compared with the historical control 1-year OS rate of 59 % (p = 0.023). However, there was no difference in 1-year OS compared with standard RT/TMZ (p = 0.12) or BCNU wafer followed by RT/TMZ (p = 0.87) in post hoc analyses. Early post-operative TMZ can be safely administered with BCNU wafers following resection of malignant glioma at the 150 mg/m2 dose level. Although there was an OS benefit compared to historical control, there was no indication of benefit for BCNU wafers and early TMZ in addition to standard RT/TMZ or early TMZ in addition to regimens of BCNU wafers followed by RT/TMZ.

Components of a Fanconi-like pathway control Pso2-independent DNA interstrand crosslink repair in yeast.

PubMed

Ward, Thomas A; Dudášová, Zuzana; Sarkar, Sovan; Bhide, Mangesh R; Vlasáková, Danuša; Chovanec, Miroslav; McHugh, Peter J

2012-01-01

Fanconi anemia (FA) is a devastating genetic disease, associated with genomic instability and defects in DNA interstrand cross-link (ICL) repair. The FA repair pathway is not thought to be conserved in budding yeast, and although the yeast Mph1 helicase is a putative homolog of human FANCM, yeast cells disrupted for MPH1 are not sensitive to ICLs. Here, we reveal a key role for Mph1 in ICL repair when the Pso2 exonuclease is inactivated. We find that the yeast FANCM ortholog Mph1 physically and functionally interacts with Mgm101, a protein previously implicated in mitochondrial DNA repair, and the MutSα mismatch repair factor (Msh2-Msh6). Co-disruption of MPH1, MGM101, MSH6, or MSH2 with PSO2 produces a lesion-specific increase in ICL sensitivity, the elevation of ICL-induced chromosomal rearrangements, and persistence of ICL-associated DNA double-strand breaks. We find that Mph1-Mgm101-MutSα directs the ICL-induced recruitment of Exo1 to chromatin, and we propose that Exo1 is an alternative 5'-3' exonuclease utilised for ICL repair in the absence of Pso2. Moreover, ICL-induced Rad51 chromatin loading is delayed when both Pso2 and components of the Mph1-Mgm101-MutSα and Exo1 pathway are inactivated, demonstrating that the homologous recombination stages of ICL repair are inhibited. Finally, the FANCJ- and FANCP-related factors Chl1 and Slx4, respectively, are also components of the genetic pathway controlled by Mph1-Mgm101-MutSα. Together this suggests that a prototypical FA-related ICL repair pathway operates in budding yeast, which acts redundantly with the pathway controlled by Pso2, and is required for the targeting of Exo1 to chromatin to execute ICL repair.

First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5-fluorouracil (DCF) plus panitumumab in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction: final results and biomarker analysis from an Italian oncology group for clinical research (GOIRC) phase II study.

PubMed

Tomasello, Gianluca; Valeri, Nicola; Ghidini, Michele; Smyth, Elizabeth C; Liguigli, Wanda; Toppo, Laura; Mattioli, Rodolfo; Curti, Alessandra; Hahne, Jens C; Negri, Federica M; Panni, Stefano; Ratti, Margherita; Lazzarelli, Silvia; Gerevini, Fabiana; Colombi, Chiara; Panni, Andrea; Rovatti, Massimo; Treccani, Leonardo; Martinotti, Mario; Passalacqua, Rodolfo

2017-12-19

Survival for patients with advanced gastroesophageal cancer (AGC) using standard treatment regimens is poor. EGFR overexpression is common in AGC and associated with poor prognosis. We hypothesized that increasing the dose intensity of chemotherapy and adding panitumumab could improve efficacy. HER2 negative, PS 0-1 patients, received up to 4 cycles of panitumumab 6 mg/kg d 1, docetaxel 60 mg/m2 d 1, cisplatin 50 mg/m2 d 1, l-folinic acid 100 mg/m2 d 1-2, followed by 5-FU 400 mg/m2 bolus d 1-2, and then 600 mg/m2 as a 22 h c.i. on d 1-2, q15 d, plus pegfilgrastim 6 mg on d 3. Patients with disease control after 4 cycles received panitumumab until progression. From 05/2010 to 01/2014, 52 patients (75% male; median age 64.5 y; metastatic 90%, locally advanced 10%; 96% adenocarcinoma; 25% GEJ) were recruited. Three CR, 29 PR, 10 SD and 8 PD were observed, for an ORR by ITT (primary endpoint) of 62% (95% CI, 48%-75%) and a DCR of 81%. Median TTP was 4.9 months (95% CI, 4.2-7.0) and mOS 10 months (95% CI, 8.2- 13.5). Most frequent G3-4 toxicities: leucopenia (29%), asthenia (27%), skin rash (25%), neutropenia (19%), anorexia (17%), febrile neutropenia (13%), and diarrhea (15%). EGFR expression tested both with dd-PCR and FISH was not associated with any significant clinical benefit from treatment. Dose-dense DCF plus panitumumab is an active regimen. However, the toxicity profile of this limits further development. Further research on predictive biomarkers for treatment efficacy in AGC is required.Clinical trial information: 2009-016962-10.

First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5-fluorouracil (DCF) plus panitumumab in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction: final results and biomarker analysis from an Italian oncology group for clinical research (GOIRC) phase II study

PubMed Central

Tomasello, Gianluca; Valeri, Nicola; Ghidini, Michele; Smyth, Elizabeth C.; Liguigli, Wanda; Toppo, Laura; Mattioli, Rodolfo; Curti, Alessandra; Hahne, Jens C.; Negri, Federica M.; Panni, Stefano; Ratti, Margherita; Lazzarelli, Silvia; Gerevini, Fabiana; Colombi, Chiara; Panni, Andrea; Rovatti, Massimo; Treccani, Leonardo; Martinotti, Mario; Passalacqua, Rodolfo

2017-01-01

Background Survival for patients with advanced gastroesophageal cancer (AGC) using standard treatment regimens is poor. EGFR overexpression is common in AGC and associated with poor prognosis. We hypothesized that increasing the dose intensity of chemotherapy and adding panitumumab could improve efficacy. Methods HER2 negative, PS 0-1 patients, received up to 4 cycles of panitumumab 6 mg/kg d 1, docetaxel 60 mg/m2 d 1, cisplatin 50 mg/m2 d 1, l-folinic acid 100 mg/m2 d 1-2, followed by 5-FU 400 mg/m2 bolus d 1-2, and then 600 mg/m2 as a 22 h c.i. on d 1-2, q15 d, plus pegfilgrastim 6 mg on d 3. Patients with disease control after 4 cycles received panitumumab until progression. Results From 05/2010 to 01/2014, 52 patients (75% male; median age 64.5 y; metastatic 90%, locally advanced 10%; 96% adenocarcinoma; 25% GEJ) were recruited. Three CR, 29 PR, 10 SD and 8 PD were observed, for an ORR by ITT (primary endpoint) of 62% (95% CI, 48%-75%) and a DCR of 81%. Median TTP was 4.9 months (95% CI, 4.2-7.0) and mOS 10 months (95% CI, 8.2- 13.5). Most frequent G3-4 toxicities: leucopenia (29%), asthenia (27%), skin rash (25%), neutropenia (19%), anorexia (17%), febrile neutropenia (13%), and diarrhea (15%). EGFR expression tested both with dd-PCR and FISH was not associated with any significant clinical benefit from treatment. Conclusions Dose-dense DCF plus panitumumab is an active regimen. However, the toxicity profile of this limits further development. Further research on predictive biomarkers for treatment efficacy in AGC is required. Clinical trial information: 2009-016962-10. PMID:29340092

Inotuzumab ozogamicin in adults with relapsed or refractory CD22-positive acute lymphoblastic leukemia: a phase 1/2 study.

PubMed

DeAngelo, Daniel J; Stock, Wendy; Stein, Anthony S; Shustov, Andrei; Liedtke, Michaela; Schiffer, Charles A; Vandendries, Erik; Liau, Katherine; Ananthakrishnan, Revathi; Boni, Joseph; Laird, A Douglas; Fostvedt, Luke; Kantarjian, Hagop M; Advani, Anjali S

2017-06-27

This study evaluated the safety, antitumor activity, pharmacokinetics, and pharmacodynamics of inotuzumab ozogamicin (InO) for CD22-positive relapsed/refractory acute lymphoblastic leukemia. In phase 1, patients received InO 1.2 (n = 3), 1.6 (n = 12), or 1.8 (n = 9) mg/m 2 per cycle on days 1, 8, and 15 over a 28-day cycle (≤6 cycles). The recommended phase 2 dose (RP2D) was confirmed (expansion cohort; n = 13); safety and activity of InO were assessed in patients receiving the RP2D in phase 2 (n = 35) and in all treated patients (n = 72). The RP2D was 1.8 mg/m 2 per cycle (0.8 mg/m 2 on day 1; 0.5 mg/m 2 on days 8 and 15), with reduction to 1.6 mg/m 2 per cycle after complete remission (CR) or CR with incomplete marrow recovery (CRi). Treatment-related toxicities were primarily cytopenias. Four patients experienced treatment-related venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS; 1 fatal). Two VOD/SOS events occurred during treatment without intervening transplant; of 24 patients proceeding to poststudy transplant, 2 experienced VOD/SOS after transplant. Forty-nine (68%) patients had CR/CRi, with 41 (84%) achieving minimal residual disease (MRD) negativity. Median progression-free survival was 3.9 (95% confidence interval, 2.9-5.4) months; median overall survival was 7.4 (5.7-9.2) months for all treated patients, with median 23.7 (range, 6.8-29.8) months of follow-up for all treated patients alive at data cutoff. Achievement of MRD negativity was associated with higher InO exposure. InO was well tolerated and demonstrated high single-agent activity and MRD-negativity rates. This trial was registered at www.clinicaltrials.gov as #NCT01363297.

East Asian Subgroup Analysis of a Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-small Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL).

PubMed

Park, Keunchil; Kim, Joo-Hang; Cho, Eun Kyung; Kang, Jin-Hyoung; Shih, Jin-Yuan; Zimmermann, Annamaria Hayden; Lee, Pablo; Alexandris, Ekaterine; Puri, Tarun; Orlando, Mauro

2016-10-01

REVEL demonstrated improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) with docetaxel+ramucirumab versus docetaxel+placebo in 1,253 intent-to-treat (ITT) stage IV non-small cell lung cancer patients with disease progression following platinum-based chemotherapy. Results from the East Asian subgroup analysis are reported. Subgroup analyses were performed in the East Asian ITT population (n=89). Kaplan-Meier analysis and Cox proportional hazards regression were performed for OS and PFS, and the Cochran-Mantel-Haenszel test was performed for response rate. In docetaxel+ramucirumab (n=43) versus docetaxel+placebo (n=46), median OS was 15.44 months versus 10.17 months (hazard ratio [HR], 0.762; 95% confidence interval [CI], 0.444 to 1.307), median PFS was 4.88 months versus 2.79 months (HR, 0.658; 95% CI, 0.408 to 1.060), and ORR was 25.6% (95% CI, 13.5 to 41.2) versus 8.7% (95% CI, 2.4 to 20.8). Due to increased incidence of neutropenia and febrile neutropenia in East Asian patients, starting dose of docetaxel was reduced for newly enrolled East Asian patients (75 to 60 mg/m 2 , n=24). In docetaxel+ramucirumab versus docetaxel+placebo, incidence of neutropenia was 84.4% versus 72.7% (75 mg/m 2 ) and 54.5% versus 38.5% (60 mg/m 2 ). Incidence of febrile neutropenia was 43.8% versus 12.1% (75 mg/m 2 ) and 0% versus 7.7% (60 mg/m 2 ). Results of this subgroup analysis showed a trend favoring ramucirumab+docetaxel for median OS, PFS, and improved ORR in East Asian patients, consistent with ITT population results. Reduction of starting dose of docetaxel in East Asian patients was associated with improved safety.

East Asian Subgroup Analysis of a Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-small Cell Lung Cancer Following Disease Progression after One Prior Platinum-Based Therapy (REVEL)

PubMed Central

Park, Keunchil; Kim, Joo-Hang; Cho, Eun Kyung; Kang, Jin-Hyoung; Shih, Jin-Yuan; Zimmermann, Annamaria Hayden; Lee, Pablo; Alexandris, Ekaterine; Puri, Tarun; Orlando, Mauro

2016-01-01

Purpose REVEL demonstrated improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) with docetaxel+ramucirumab versus docetaxel+placebo in 1,253 intent-to-treat (ITT) stage IV non-small cell lung cancer patients with disease progression following platinum-based chemotherapy. Results from the East Asian subgroup analysis are reported. Materials and Methods Subgroup analyses were performed in the East Asian ITT population (n=89). Kaplan-Meier analysis and Cox proportional hazards regression were performed for OS and PFS, and the Cochran-Mantel-Haenszel test was performed for response rate. Results In docetaxel+ramucirumab (n=43) versus docetaxel+placebo (n=46), median OS was 15.44 months versus 10.17 months (hazard ratio [HR], 0.762; 95% confidence interval [CI], 0.444 to 1.307), median PFS was 4.88 months versus 2.79 months (HR, 0.658; 95% CI, 0.408 to 1.060), and ORR was 25.6% (95% CI, 13.5 to 41.2) versus 8.7% (95% CI, 2.4 to 20.8). Due to increased incidence of neutropenia and febrile neutropenia in East Asian patients, starting dose of docetaxel was reduced for newly enrolled East Asian patients (75 to 60 mg/m2, n=24). In docetaxel+ramucirumab versus docetaxel+placebo, incidence of neutropenia was 84.4% versus 72.7% (75 mg/m2) and 54.5% versus 38.5% (60 mg/m2). Incidence of febrile neutropenia was 43.8% versus 12.1% (75 mg/m2) and 0% versus 7.7% (60 mg/m2). Conclusion Results of this subgroup analysis showed a trend favoring ramucirumab+docetaxel for median OS, PFS, and improved ORR in East Asian patients, consistent with ITT population results. Reduction of starting dose of docetaxel in East Asian patients was associated with improved safety. PMID:26910471

Long-term maintenance combination chemotherapy with OPEC/MPEC (vincristine or methotrexate, prednisolone, etoposide and cyclophosphamide) or with daily oral etoposide and prednisolone can improve survival and quality of life in adult T-cell leukemia/lymphoma.

PubMed

Matsushita, K; Matsumoto, T; Ohtsubo, H; Fujiwara, H; Imamura, N; Hidaka, S; Kukita, T; Tei, C; Matsumoto, M; Arima, N

1999-12-01

Acute leukemia and lymphoma varieties of adult T-cell leukemia/lymphoma (ATL) usually carry a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination protocol, OPEC/MPEC (weekly doses of vincristine, 0.7 mg/m2 or methotrexate, 14 mg/m2; prednisolone, 20 mg/m2; etoposide, 70 mg/m2 and cyclophosphamide, 200 mg/m2). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPEC/MPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.

A phase I study of amrubicin and fixed dose of irinotecan (CPT-11) in relapsed small cell lung cancer: Japan multinational trial organization LC0303.

PubMed

Kawahara, Masaaki; Kubo, Akihito; Komuta, Kiyoshi; Fujita, Yuka; Sasaki, Yoshiaki; Fukushima, Masanori; Daimon, Takashi; Furuse, Kiyoyuki; Mishima, Michiaki; Mio, Tadashi

2012-12-01

To determine the maximum tolerated dose of amrubicin (AMR) with a fixed dose of irinotecan (CPT-11). Patients having pathologically proven small cell lung cancer (SCLC) relapsed after one or two chemotherapies, and Eastern Cooperative Oncology Group performance status of 0 to 2 were eligible for the study. CPT-11 was delivered as 50 mg/m2 on days 1 and 8, every 21 days. AMR was delivered on day 1. Doses of AMR were level 1: 80 mg/m2, level 2: 90 mg/m2, and level 3: 100 mg/m2. Dose elevation was determined using the modified continuous reassessment method. Tolerability was assessed after the first cycle. Another two cycles were conducted when disease progression or unacceptable toxicities were not observed. Eighteen patients (mean age: 66.3 years) were enrolled. A total of 40 courses were conducted. Grade 3/4 toxicities of the first cycle were leukocytopenia: 11 (61%, grade 3/4: 8/3); neutropenia: 15 (83%, grade 3/4: 6/9); and thrombocytopenia: three (17%, grade 3/4: 2/1). Other grade 3 toxicities observed were febrile neutropenia, one; infection, three; diarrhea, one; and dyspnea, one. Dose-limiting toxicity was observed in two of six patients at level 2 (neutropenia and febrile neutropenia) and in one of six at level 3 (thrombocytopenia and infection). The maximum tolerated dose was level 3, and so, the recommended dose for phase II trials was judged to be 90 mg/m2. Objective response was obtained in four of eight patients who were able to evaluate responses. Median survival time was 13 months, with 68% at 1-year survival rate. This combination was well tolerated and showed encouraging activities in SCLC. Randomized phase II trials are being planned in chemonaive SCLC.

Sublethal Ciprofloxacin Treatment Leads to Rapid Development of High-Level Ciprofloxacin Resistance during Long-Term Experimental Evolution of Pseudomonas aeruginosa

PubMed Central

Jørgensen, Karin Meinike; Wassermann, Tina; Jensen, Peter Østrup; Hengzuang, Wang; Molin, Søren; Høiby, Niels

2013-01-01

The dynamics of occurrence and the genetic basis of ciprofloxacin resistance were studied in a long-term evolution experiment (940 generations) in wild-type, reference strain (PAO1) and hypermutable (PAOΔmutS and PAOMY-Mgm) P. aeruginosa populations continuously exposed to sub-MICs (1/4) of ciprofloxacin. A rapid occurrence of ciprofloxacin-resistant mutants (MIC of ≥12 μg/ml, representing 100 times the MIC of the original population) were observed in all ciprofloxacin-exposed lineages of PAOΔmutS and PAOMY-Mgm populations after 100 and 170 generations, respectively, and in one of the PAO1 lineages after 240 generations. The genetic basis of resistance was mutations in gyrA (C248T and G259T) and gyrB (C1397A). Cross-resistance to beta-lactam antibiotics was observed in the bacterial populations that evolved during exposure to sublethal concentrations of ciprofloxacin. Our study shows that mutants with high-level ciprofloxacin resistance are selected in P. aeruginosa bacterial populations exposed to sub-MICs of ciprofloxacin. This can have implications for the long-term persistence of resistant bacteria and spread of antibiotic resistance by exposure of commensal bacterial flora to low antibiotic concentrations. PMID:23774442

Vincristine and irinotecan in children with relapsed hepatoblastoma: a single-institution experience.

PubMed

Zhang, Yu-tong; Feng, Li-hua; Zhong, Xiao-dan; Wang, Li-zhe; Chang, Jian

2015-02-01

This study was to determine the efficacy of vincristine and irinotecan in children with relapsed hepatoblastoma (HB). A total of 10 patients with relapsed HB were enrolled. Three patients were excluded. Patients received irinotecan 50 mg/m(2)/day, day 1-5 and vincristine 1.5 mg/m(2)/day, day 1, repeated every 3 weeks. The maximum cycles were eight. Reevaluation of tumor was performed every two cycles. The primary outcome was the rate of complete resection. Secondary outcomes were event-free survival (EFS) and overall survival (OS). Of the seven patients assessable for response, one patient with normal AFP level showed a progressive disease and withdrew. He finally died 6 months later. Four had PR, all of them underwent a second surgery and achieved complete resection. Two patients had SD, one patient relapsed 6 months after orthotopic liver transplantation and died, the other one undergoing surgery had micro margin positive, he relapsed again but alive. The rate of complete resection was 71.4% (including orthotopic liver transplantation). The 2-year EFS and OS for the whole group were 57.1% (95% CI, 12.7% to 34.2%) and 71.4% (95% CI, 16.39% to 37.4%), respectively. The combination of irinotecan and vincristine has a significant antitumor activity and acceptable toxicity in children with relapsed HB.

Emission characteristics of plastic syringes sterilized with ethylene oxide--a controlled study.

PubMed

Chien, Yeh-Chung; Su, Po-Chi; Lee, Lien-Hsiung; Chen, Chang-Yuh

2009-11-01

This study examined the emission characteristics of ethylene oxide (EO)-sterilized syringes under various environmental conditions, aiming to develop control strategies to minimize worker exposure. Experiments were performed in a facility in which temperature, relative humidity (RH), and air change rate (ACR) were controlled. Analytical results indicate that the main effects of the four test variables on kinetic parameters were statistically significant (p < 0.05), except for the effect of the product on the decay rate constant, the effect of ACR on maximum EO concentration, and effect of RH on the area under the curve-days 1 and 2. The interactive effects among test variables were also evident, indicating complex emission behaviors. The mean EO emission factors during the days 1 and 2 and at the 48th hour for the 1- and 30-ml products were 2302, 1301, and 1031 mg/m(3)/h, and 871, 490, and 381 mg/m(3)/h, respectively. The times required for air EO concentrations from tested products to return to approximately 0 and 1 ppm (permissible limit) were 417 and 218 h, respectively. Plastic content, temperature, RH, and ACR affected EO emissions. ACR is an achievable means of control; however, the aeration area/system should be isolated to ensure adequate ventilation is achieved.

Concentration Levels of Particulate Matter of Common Dental Lab Materials in a Military Dental Lab

DTIC Science & Technology

2016-05-01

to cause contact type dermatitis in some dental laboratory technicans. 22 In both experimental animals and humans, methyl methacrylate is rapidly...being measured out and mixed. As cases of generalized neuropathy, asthma and contact dermatitis have been documented in dental laboratory technicians... contact .45 The sampling for paraffin wax particulate in the current study resulted in a REL 8-TWA of 0.2056 mg/m 3 which is well below the 2 mg/m 3

New alleles of mgm1: a gene encoding a protein with a GTP-binding domain related to dynamin.

PubMed

Backer, J S

1995-10-01

Three previously described genes that affect baker's yeast (Saccharomyces cerevisiae) mitochondrial DNA (mtDNA) or mitochondrial RNA, tpm2-1, mna1-1, and mgm-1-1, are shown to be alleles of the same gene. This report demonstrates that tpm2-1 does not affect recombination of mtDNA. Therefore, there is no evidence that this dynamin-like protein is involved in movement of mtDNA within a cell.

Gemcitabine-Based Chemoradiation in the Treatment of Locally Advanced Head and Neck Cancer: Systematic Review of Literature and Meta-Analysis

PubMed Central

Szturz, Petr; Specenier, Pol; Merlano, Marco C.; Benasso, Marco; Van Gestel, Dirk; Wouters, Kristien; Van Laer, Carl; Van den Weyngaert, Danielle; Peeters, Marc; Vermorken, Jan

2016-01-01

Background. Platinum-based concurrent chemoradiation (CCRT) improves locoregional control and overall survival of locoregionally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) when compared to radiotherapy alone, but this approach is hampered by significant toxicity. Therefore, alternative ways to enhance the radiation effects are worth investigating. Gemcitabine (2′,2′-difluorodeoxycytidine), in addition to its activity against a variety of solid tumors, including SCCHN, is one of the most potent radiosensitizers, and it has an overall favorable safety profile. In this paper, the clinical experience with gemcitabine-based chemoradiation in the treatment of patients with LA-SCCHN is reviewed. Methods. We conducted a review of the literature on the clinical experience with radiotherapy combined with either single-agent gemcitabine or gemcitabine/cisplatin-based polychemotherapy for the treatment of patients with LA-SCCHN. We also searched abstracts in databases of major international oncology meetings from the last 20 years. A meta-analysis was performed to calculate pooled proportions with 95% confidence intervals (CIs) for complete response rate and grade 3–4 acute mucositis rate. Results. A total of 13 papers were eligible for the literature review. For schedules using a gemcitabine dose intensity (DI) below 50 mg/m2 per week, the complete response rate was 86% (95% CI, 74%–93%) with grade 3–4 acute mucositis rate of 38% (95% CI, 27%–50%) and acceptable late toxicity. In one of the studies employing such low DIs, survival data were provided showing a 3-year overall survival of 50%. Compared with DI ≥50 mg/m2 per week, there was no difference in the complete response rate (71%; 95% CI, 55%–83%; p = .087) but a significantly higher (p < .001) grade 3–4 acute mucositis rate of 74% (95% CI, 62%–83%), often leading to treatment interruptions (survival data provided in 8 studies; 3-year overall survival, 27%–63%). Late toxicity comprising mainly dysphagia was generally underreported, whereas information about xerostomia and skin fibrosis was scarce. Conclusion. This review highlights the radiosensitizing potential of gemcitabine and suggests that even very low dosages (less than 50 mg/m2 per week) provide a sufficient therapeutic ratio and therefore should be further investigated. Refinements in radiation schemes, including intensity-modulated radiation therapy, in combination with low-dose gemcitabine and targeted agents, such as cetuximab, are currently being investigated. Implications for Practice: Cisplatin-based concurrent chemoradiation (CCRT) has become the standard treatment of locally advanced head and neck cancer (LAHNC). This approach is hampered by significant toxicity. This paper reviews the studies using gemcitabine as an alternative radio-sensitizer for CCRT in patients with LAHNC. In this capacity, despite its mild intrinsic toxicity, gemcitabine comes with high rates of severe mucositis when used in dosages exceeding 50 mg/m2 per week. CCRT with low-dose gemcitabine provides a sufficient therapeutic ratio, combining clinical activity, similar to the higher-dose regimens, with lower toxicity. Further investigation is warranted. PMID:26712958

Exposure to airborne microorganisms, dust and endotoxin during processing of valerian roots on farms.

PubMed

Skórska, Czesława; Sitkowska, Jolanta; Krysińska-Traczyk, Ewa; Cholewa, Grazyna; Dutkiewicz, Jacek

2005-01-01

The aim of this study was to determine the levels of microorganisms, dust and endotoxin in the air during various stages of valerian (Valeriana officinalis) roots processing by herb farmers and to examine the species composition of airborne microflora. Air samples were collected on glass fibre filters by use of personal samplers on 15 farms owned by valerian cultivating farmers, located in Lublin province (eastern Poland). The concentrations of total viable microorganisms (bacteria + fungi) in the air showed a marked variability and were within a range of 0.95-7,966.6 x 10(3) cfu/m (3). Though median was relatively low (10.75 x 10(3) cfu/m (3)), on 4 farms the concentrations exceeded the level of 10(5) cfu/m (3) and on 1 farm the level of 10(6) cfu/m (3). During the processing of valerian roots, distinct changes could be observed in the composition of airborne microflora. In the first stages of processing, the freshly dug and washed roots until shaking in the drying room, the most numerous were Gram-negative bacteria of the family Pseudomonadaceae (mostly Stenotrophomonas maltophilia, Pseudomonas chlororaphis and Pseudomonas fluorescens). After drying, the dominant organisms were thermo-resistant endospore-forming bacilli (Bacillus spp.) and fungi, among which prevailed Aspergillus fumigatus. Altogether, 29 species or genera of bacteria and 19 species or genera of fungi were identified in the farm air during valerian processing, of these, 10 and 12 species or genera respectively were reported as having allergenic and/or immunotoxic properties. The concentrations of airborne dust and endotoxin on the examined farms were very large and ranged from 10.0-776.7 mg/m (3), and from 0.15-24,448.2 microg/m (3), respectively (medians 198.3 mg/m (3) and 40.48 microg/m (3)). In conclusion, farmers cultivating valerian could be exposed during processing of valerian roots to large concentrations of airborne microorganisms, dust and endotoxin posing a risk of work-related respiratory disease.

Essential thrombocythaemia in two dogs.

PubMed

Favier, R P; van Leeuwen, M; Teske, E

2004-06-01

In this report two dogs with essential thrombocythaemia (ET) are described. Both dogs were presented more or less at the same time with a combination of reduced exercise tolerance and pale mucous membranes without any report of blood loss. Moderate-to-severe, Coomb's-negative anaemia and thrombocytosis (> 1249 x 10'/l) were present. In addition, the peripheral blood smear revealed the presence of basophilia and large numbers of abnormally shaped megakaryocytes in the bone marrow of both dogs. Treatment with vincristine (0.7 mg/m2 once intravenously) and hydroxyurea (500 mg/m2 p.o. per day) was started. Because of insufficient response to treatment after 3 weeks, the dosage of hydroxyurea was increased in both dogs to 2000 mg/m2 p.o. per day. The dogs deteriorated further, however, and were euthanized at 6 weeks after the start of treatment. Blood examination revealed pancytopenia in both dogs, most likely due to the myelosuppressive effects of high-dose hydroxyurea. A survey of veterinary literature on ET is presented, including a comparison of ET in humans.

Phase I and pharmacokinetic evaluation of floxuridine/leucovorin given on the Roswell Park weekly regimen.

PubMed

Creaven, P J; Rustum, Y M; Petrelli, N J; Meropol, N J; Raghavan, D; Rodriguez-Bigas, M; Levine, E G; Frank, C; Udvary-Nagy, S; Proefrock, A

1994-01-01

A phase I and pharmacokinetics study was carried out of floxuridine (FdUrd) modulated by leucovorin (LV) given on the Roswell Park regimen (LV given at 500 mg/m2 by 2-h infusion and FdUrd given by i.v. push at 1 h after the start of LV infusion, treatment being given weekly x 6). The dose-limiting toxicity was diarrhea; the MTD and recommended dose for phase II studies was 1,650 mg/m2 per week of FdUrd. The dose-response curve was steep, with 3/3 patients treated at a dose of 1,750 mg/m2 developing grade IV diarrhea. With this schedule there was no significant mucositis. Pharmacokinetic parameters showed very wide interpatient variability. Plasma decay was biphasic with a t1/2 beta of approximately 2 h. Plasma clearance was high (> 200 1 h-1). No correlation between pharmacokinetic parameters and toxicity could be identified.

Combined treatment in carcinoma of the nasopharynx

DOE Office of Scientific and Technical Information (OSTI.GOV)

Souhami, L.; Rabinowits, M.

1988-08-01

From October 1982 to August 1984, 30 previously untreated patients with biopsy-proven carcinoma of the nasopharynx, stage III (26.5%) and stage IV (73.5%), received combined radiotherapy (6,000 to 7,000 cGy over a period of 7 to 7.5 weeks) and chemotherapy (mitomycin-C 10 mg/M2, IV; 5-fluorouracil 750 mg/M2, IV; and methotrexate 30 mg/M2, IV) concomitantly. There were 20 males and 10 females, with a median age of 40 years. Minimal follow-up duration was 24 months. Actuarial overall survival rate at 48 months was 49%. Complete local response was achieved in 75% of the patients, with 31% of the cases failing distantly.more » The complication rate was high and included severe mucositis, xerostomia, and septicemia (fatal in two cases). Despite high local disease control, survival rate did not increase. A randomized trial is urgently needed to establish whether or not combined treatment is of value in advanced carcinoma of the nasopharynx.« less

Prospective study of etoposide scheduling in combination chemotherapy for limited disease small cell lung carcinoma.

PubMed

Abratt, R P; Willcox, P A; de Groot, M; Goodman, H T; Jansen, E R; Salton, D G

1991-01-01

78 patients with limited disease small cell lung carcinoma (SCLC) were entered into a prospective randomised study of two combination regimens (AVE-5 and AVE-1) that differed only in the scheduling of etoposide. Patients in the AVE-5 arm received etoposide intravenously 60 mg/m2 on day 1 and orally 120 mg/m2 on days 2-5 of each cycle. Patients in the AVE-1 arm received etoposide 300 mg/m2 intravenously on day 1. Patients in both arms received doxorubicin and vincristine on day 1 of each cycle. The complete (53% vs. 26%) and the overall (75% vs. 52%) response rates were significantly higher in the AVE-5 arm. Median survival was also increased from 11 to 14 months in this arm. Toxicity was low and similar in both groups. The daily administration of etoposide in low toxicity combination therapy for SCLC is important. This can be conveniently achieved by using etoposide orally.

Twice-daily dosing of temozolomide in combination with fotemustine for the treatment of patients with refractory glioblastoma.

PubMed

Santoni, M; Paccapelo, A; Burattini, L; Onofri, A; Cascinu, S

2012-03-01

Alkylating agents, such as temozolomide (TMZ) and fotemustine (FTM) are widely used in recurrent glioblastoma (GBM) regimes. Several strategies have been proposed to prevent resistance to these agents, by combining or sequencing them. We report the results of a pilot study of patients with refractory GBM receiving a regime of twice-daily dosing of temozolomide administered on day 1, (with an initial oral dose of 200 mg/m(2) and a second oral dose of 75 mg/m(2) 12 h later), followed by fotemustine in a single i.v. infusion at 75 mg/m(2) on day 2, repeated every four weeks. Enrolment was stopped at 15 patients due to lack of effectiveness of this schedule for patients with GBM. Toxicity was mild, with no grade 4 side effects reported. Results indicate that our temozolomide -FTM combined schedule is not effective, although well tolerated, in non responsive patients with GBM. Further strategies are required to improve the outcome of these patients.

KETAMINE ABREACTION : A NEW APPROACH TO NARCOANALYSIS

PubMed Central

Golechha, G.R.; Sethi, I.C.; Misra, S.L.; Jayaprakash, N.P.

1986-01-01

SUMMARY Ketamine is a parenterally administered non barbiturate anaesthetic agent, in use for more than a decade. It is a safer than Na Pentothal. Administered intramuscularly, in dose of 6 to 15 mgm/Kg body wt. it produces dissociative anaesthesia. But, in smaller sub anaesthetic doses it may act as an abreactant. We report in this study the abreaction effect of Ketamine in dose of .5 to 1.5 mgm/kg body wt. given intramuscularly in 30 selected psychiatric cases requiring narcoanalysis for diagnostic or therapeutic purpose. The results are compared with another ten cases subjected to pentothal interview and five cases subjected to narcoanalysis with intravenous Na Amytal and methidrine. Our findings suggest that Ketamine has property of an efficacious abreactant in doses of 1 to 1.5 mgm/kg body wt. administered intramuscularly and can successfully be used for narcoanalysis in properly selected cases as a good substitute for intravenous pentothal or sodium amytal with methidrine. The relative cardio respiratory safety and ease of administration are its two added advantages. PMID:21927193

Respiratory symptoms in insect breeders.

PubMed

Harris-Roberts, J; Fishwick, D; Tate, P; Rawbone, R; Stagg, S; Barber, C M; Adisesh, A

2011-08-01

A number of specialist food suppliers in the UK breed and distribute insects and insect larvae as food for exotic pets, such as reptiles, amphibians and invertebrates. To investigate the extent of work-related (WR) symptoms and workplace-specific serum IgE in workers potentially exposed to a variety of biological contaminants, including insect and insect larvae allergens, endotoxin and cereal allergens at a UK specialist insect breeding facility. We undertook a study of respiratory symptoms and exposures at the facility, with subsequent detailed clinical assessment of one worker. All 32 workers were assessed clinically using a respiratory questionnaire and lung function. Eighteen workers consented to provide serum for determination of specific IgE to workplace allergens. Thirty-four per cent (11/32) of insect workers reported WR respiratory symptoms. Sensitization, as judged by specific IgE, was found in 29% (4/14) of currently exposed workers. Total inhalable dust levels ranged from 1.2 to 17.9 mg/m(3) [mean 4.3 mg/m(3) (SD 4.4 mg/m(3)), median 2.0 mg/m(3)] and endotoxin levels of up to 29435 EU/m(3) were recorded. Exposure to organic dusts below the levels for which there are UK workplace exposure limits can result in respiratory symptoms and sensitization. The results should alert those responsible for the health of similarly exposed workers to the potential for respiratory ill-health and the need to provide a suitable health surveillance programme.

Benthic iron and phosphorus release from river dominated shelf sediments under varying bottom water O2 concentrations.

NASA Astrophysics Data System (ADS)

Ghaisas, N. A.; Maiti, K.; White, J. R.

2017-12-01

Phosphorus (P) cycling in coastal ocean is predominantly controlled by river discharge and biogeochemistry of the sediments. In coastal Louisiana, sediment biogeochemistry is strongly influenced by seasonally fluctuating bottom water O2, which, in turn transitions the shelf sediments from being a sink to source of P. Sediment P-fluxes were 9.73 ± 0.76 mg / m2 /d and 0.67±0.16 mg/m2/d under anaerobic and aerobic conditions respectively, indicating a 14 times higher P-efflux from oxygen deprived sediments. A high sedimentary oxygen consumption rate of 889 ± 33.6 mg/m2/d was due to organic matter re-mineralization and resulted in progressively decreasing the water column dissolved O2 , coincident with a P-flux of 7.2 ± 5.5 mg/m2/d from the sediment. Corresponding water column flux of Fe total was 19.7 ± 7.80 mg/m2/d and the sediment-TP decreased from 545 mg/Kg to 513 mg/Kg. A simultaneous increase in pore water Fe and P concentrations in tandem with a 34.6% loss in sedimentary Fe-bound P underscores the importance of O2 on coupled Fe- P biogeochemistry. This study suggests that from a 14,025 sq. km hypoxia area, Louisiana shelf sediments can supply 1.33x105 kg P/day into the water column compared to 0.094 x 105 kg P/day during the fully aerobic water column conditions.

Safety assessments of subcutaneous doses of aragonite calcium carbonate nanocrystals in rats

NASA Astrophysics Data System (ADS)

Jaji, Alhaji Zubair; Zakaria, Zuki Abu Bakar; Mahmud, Rozi; Loqman, Mohamad Yusof; Hezmee, Mohamad Noor Mohamad; Abba, Yusuf; Isa, Tijani; Mahmood, Saffanah Khuder

2017-05-01

Calcium carbonate nanoparticles have shown promising potentials in the delivery of drugs and metabolites. There is however, a paucity of information on the safety of their intentional or accidental over exposures to biological systems and general health safety. To this end, this study aims at documenting information on the safety of subcutaneous doses of biogenic nanocrystals of aragonite polymorph of calcium carbonate derived from cockle shells (ANC) in Sprague-Dawley (SD) rats. ANC was synthesized using the top-down method, characterized using the transmission electron microscopy and field emission scanning electron microscope and its acute and repeated dose 28-day trial toxicities were evaluated in SD rats. The results showed that the homogenous 30 ± 5 nm-sized spherical pure aragonite nanocrystals were not associated with mortality in the rats. Severe clinical signs and gross and histopathological lesions, indicating organ toxicities, were recorded in the acute toxicity (29,500 mg/m2) group and the high dose (5900 mg/m2) group of the repeated dose 28-day trial. However, the medium- (590 mg/m2 body weight) and low (59 mg/m2)-dose groups showed moderate to mild lesions. The relatively mild lesions observed in the low toxicity dosage group marked the safety margin of ANC in SD rats. It was concluded from this study that the toxicity of CaCO3 was dependent on the particulate size (30 ± 5 nm) and concentration and the route of administration used.

Health assessment of gasoline and fuel oxygenate vapors: reproductive toxicity assessment.

PubMed

Gray, Thomas M; Steup, David; Roberts, Linda G; O'Callaghan, James P; Hoffman, Gary; Schreiner, Ceinwen A; Clark, Charles R

2014-11-01

Vapor condensates of baseline gasoline (BGVC), or gasoline-blended with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA) were evaluated for reproductive toxicity in rats at target concentrations of 2000, 10,000, or 20,000mg/m(3), 6h/day, 7days/week. BGVC and G/MTBE were assessed over two generations, the others for one generation. BGVC and G/MTBE F1 offspring were evaluated for neuropathology and changes in regional brain glial fibrillary acidic protein content. No neurotoxicity was observed. Male kidney weight was increased consistent with light hydrocarbon nephropathy. In adult rats, decreased body weight gain and increased liver weight were seen. Spleen weight decreased in adults and pups exposed to G/TBA. No pathological changes to reproductive organs occurred in any study. Decreased food consumption was seen in G/TAME lactating females. Transient decreases in G/TAME offspring weights were observed during lactation. Except for a minor increase in time to mating in G/TBA which did not affect other reproductive parameters, there were no adverse reproductive findings. The NOAEL for reproductive and offspring parameters was 20,000mg/m(3) for all vapor condensates except for lower offspring NOAELs of 10,000mg/m(3) for G/TBA and 2000mg/m(3) for G/TAME. Copyright © 2014 Elsevier Inc. All rights reserved.

Health assessment of gasoline and fuel oxygenate vapors: Reproductive toxicity assessment

PubMed Central

Gray, Thomas M.; Steup, David; Roberts, Linda G.; O'Callaghan, James P.; Hoffman, Gary; Schreiner, Ceinwen A.; Clark, Charles R.

2016-01-01

Vapor condensates of baseline gasoline (BGVC), or gasoline-blended with methyl tertiary butyl ether (G/MTBE), ethyl t-butyl ether (G/ETBE), t-amyl methyl ether (G/TAME), diisopropyl ether (G/DIPE), ethanol (G/EtOH), or t-butyl alcohol (G/TBA) were evaluated for reproductive toxicity in rats at target concentrations of 2000, 10,000, or 20,000 mg/m3, 6 h/day, 7 days/week. BGVC and G/MTBE were assessed over two generations, the others for one generation. BGVC and G/MTBE F1 offspring were evaluated for neuropathology and changes in regional brain glial fibrillary acidic protein content. No neurotoxicity was observed. Male kidney weight was increased consistent with light hydrocarbon nephropathy. In adult rats, decreased body weight gain and increased liver weight were seen. Spleen weight decreased in adults and pups exposed to G/TBA. No pathological changes to reproductive organs occurred in any study. Decreased food consumption was seen in G/TAME lactating females. Transient decreases in G/TAME off-spring weights were observed during lactation. Except for a minor increase in time to mating in G/TBA which did not affect other reproductive parameters, there were no adverse reproductive findings. The NOAEL for reproductive and offspring parameters was 20,000 mg/m3 for all vapor condensates except for lower offspring NOAELs of 10,000 mg/m3 for G/TBA and 2000 mg/m3 for G/TAME. PMID:24813181

STS-107 Crew Interviews: Michael Anderson, Mission Specialist

NASA Technical Reports Server (NTRS)

2002-01-01

STS-107 Mission Specialist 3 and Payload Commander Michael Anderson is seen during this preflight interview, where he gives a quick overview of the mission before answering questions about his inspiration to become an astronaut and his career path. He outlines his role in the mission in general, and specifically in conducting onboard science experiments. He discusses the following instruments and sets of experiments in detail: CM2 (Combustion Module 2), FREESTAR (Fast Reaction Enabling Science Technology and Research, MEIDEX (Mediterranean Israeli Dust Experiment) and MGM (Mechanics of Granular Materials). Anderson also mentions on-board activities and responsibilities during launch and reentry, mission training, and microgravity research. In addition, he touches on the dual work-shift nature of the mission, the use of crew members as research subjects including pre and postflight monitoring activities, the emphasis on crew safety during training and the value of international cooperation.

Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial.

PubMed

Waddell, Tom; Chau, Ian; Cunningham, David; Gonzalez, David; Okines, Alicia Frances Clare; Frances, Alicia; Okines, Clare; Wotherspoon, Andrew; Saffery, Claire; Middleton, Gary; Wadsley, Jonathan; Ferry, David; Mansoor, Wasat; Crosby, Tom; Coxon, Fareeda; Smith, David; Waters, Justin; Iveson, Timothy; Falk, Stephen; Slater, Sarah; Peckitt, Clare; Barbachano, Yolanda

2013-05-01

EGFR overexpression occurs in 27-55% of oesophagogastric adenocarcinomas, and correlates with poor prognosis. We aimed to assess addition of the anti-EGFR antibody panitumumab to epirubicin, oxaliplatin, and capecitabine (EOC) in patients with advanced oesophagogastric adenocarcinoma. In this randomised, open-label phase 3 trial (REAL3), we enrolled patients with untreated, metastatic, or locally advanced oesophagogastric adenocarcinoma at 63 centres (tertiary referral centres, teaching hospitals, and district general hospitals) in the UK. Eligible patients were randomly allocated (1:1) to receive up to eight 21-day cycles of open-label EOC (epirubicin 50 mg/m(2) and oxaliplatin 130 mg/m(2) on day 1 and capecitabine 1250 mg/m(2) per day on days 1-21) or modified-dose EOC plus panitumumab (mEOC+P; epirubicin 50 mg/m(2) and oxaliplatin 100 mg/m(2) on day 1, capecitabine 1000 mg/m(2) per day on days 1-21, and panitumumab 9 mg/kg on day 1). Randomisation was blocked and stratified for centre region, extent of disease, and performance status. The primary endpoint was overall survival in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. After a preplanned independent data monitoring committee review in October, 2011, trial recruitment was halted and panitumumab withdrawn. Data for patients on treatment were censored at this timepoint. This study is registered with ClinicalTrials.gov, number NCT00824785. Between June 2, 2008, and Oct 17, 2011, we enrolled 553 eligible patients. Median overall survival in 275 patients allocated EOC was 11.3 months (95% CI 9.6-13.0) compared with 8.8 months (7.7-9.8) in 278 patients allocated mEOC+P (hazard ratio [HR] 1.37, 95% CI 1.07-1.76; p=0.013). mEOC+P was associated with increased incidence of grade 3-4 diarrhoea (48 [17%] of 276 patients allocated mEOC+P vs 29 [11%] of 266 patients allocated EOC), rash (29 [11%] vs two [1%]), mucositis (14 [5%] vs none), and hypomagnesaemia (13 [5%] vs none) but reduced incidence of haematological toxicity (grade ≥ 3 neutropenia 35 [13%] vs 74 [28%]). Addition of panitumumab to EOC chemotherapy does not increase overall survival and cannot be recommended for use in an unselected population with advanced oesophagogastric adenocarcinoma. Amgen, UK National Institute for Health Research Biomedical Research Centre. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial. The "Gruppo Oncologico Centro-Sud-Isole' (G.O.C.S.I.).

PubMed

Gridelli, C; Perrone, F; Palmeri, S; D'Aprile, M; Cognetti, F; Rossi, A; Gebbia, V; Pepe, R; Veltri, E; Airoma, G; Russo, A; Incoronato, P; Scinto, A F; Palazzolo, G; Natali, M; Leonardi, V; Gallo, C; De Placido, S; Bianco, A R

1996-10-01

To compare mitomycin C plus vindesine plus etoposide (MEV) vs. mitomycin C plus vindesine plus cisplatin (MVP) in the treatment of stage IV non-small-cell lung cancer. 204 patients were entered in a phase III multicentre randomised trial from June 1990 to December 1994 and stratified according to the ECOG performance status (0-1 vs. 2). MVP was given in the following dosages: mitomycin C 8 mg/m2+vindesine 3 mg/m2+cisplatin 100 mg/m2 i.v. day 1 and vindesine 3 mg/m2 i.v. day 8 with cycles repeated every 4 weeks. MEV was given in the following dosages: mitomycin C 8 mg/m2+vindesine 3 mg/ m2 i.v. day 1 and etoposide 100 mg/m2 i.v. days 1 to 3 with cycles repeated every 3 weeks. For both treatments a maximum of 6 cycles was planned. Response and toxicity were evaluated according to WHO. Subjective responses were assessed by numerical scales. Analyses were made on the basis of intent to treat. The objective response rate was 21.4% (1 CR + 21 PR among 103 patients) in the MEV and 28.7% (1 CR + 28 PR among 101 patients) in the MVP arm (P = 0.48). Symptoms were similar in the two arms. 196 patients progressed and 182 died. The median times to progression were 10 weeks (95% CI 9-12) and 12 weeks (95% CI 10-15) and median survivals were 29 weeks (95% CI 25-36) and 28 weeks (95% CI 25-35) in the MEV and MVP arms, respectively. The relative risks of progressing and of dying were 0.89 (95% CL 0.66-1.20) and 0.96 (95% CL 0.71-1.30), respectively, for patients receiving MVP as compared with those receiving MEV at multivariate analysis adjusted by sex, age, histologic type, number of metastatic sites, performance status at entry, and centre. In the present study, no significant differences were observed in response rate, survival or palliation of symptoms between the MEV and MVP regimens, while toxicity was significantly more frequent and severe with MVP. Thus, MEV should be considered a reasonable alternative to the MVP regimen in the treatment of stage IV NSCLC.

Guadecitabine (SGI-110) in treatment-naive patients with acute myeloid leukaemia: phase 2 results from a multicentre, randomised, phase 1/2 trial.

PubMed

Kantarjian, Hagop M; Roboz, Gail J; Kropf, Patricia L; Yee, Karen W L; O'Connell, Casey L; Tibes, Raoul; Walsh, Katherine J; Podoltsev, Nikolai A; Griffiths, Elizabeth A; Jabbour, Elias; Garcia-Manero, Guillermo; Rizzieri, David; Stock, Wendy; Savona, Michael R; Rosenblat, Todd L; Berdeja, Jesus G; Ravandi, Farhad; Rock, Edwin P; Hao, Yong; Azab, Mohammad; Issa, Jean-Pierre J

2017-10-01

The hypomethylating drugs azacitidine and decitabine have shown efficacy in myelodysplastic syndromes and acute myeloid leukaemia, but complete tumour responses are infrequent and of short duration, possibly because of the short half-lives and suboptimal bone marrow exposure of the drugs. Guadecitabine, a next-generation hypomethylating drug, has a longer half-life and exposure than its active metabolite decitabine. A phase 1 study established 60 mg/m 2 guadecitabine for 5 days as an effective treatment schedule. In this phase 2 study, we aimed to assess the safety and activity of two doses and schedules of guadecitabine in older (≥65 years) patients with treatment-naive acute myeloid leukaemia who were not candidates for intensive chemotherapy. We did a multicentre, randomised, open-label, phase 1/2 study of guadecitabine in cohorts of patients with treatment-naive acute myeloid leukaemia, relapsed or refractory acute myeloid leukaemia, and myelodysplastic syndromes; here we report the phase 2 results from the cohort of treatment-naive patients with acute myeloid leukaemia. We included patients aged at least 65 years from 14 US medical centres (hospitals and specialist cancer clinics) who were not candidates for intensive chemotherapy and randomly assigned them (1:1) using a computer algorithm (for dynamic randomisation) to guadecitabine 60 or 90 mg/m 2 on days 1-5 (5-day schedule) of a 28-day treatment cycle. Treatment allocation was not masked. We also assigned additional patients to guadecitabine 60 mg/m 2 in a 10-day schedule in a 28-day treatment cycle after a protocol amendment. The primary endpoint was composite complete response (complete response, complete response with incomplete platelet recovery, or complete response with incomplete neutrophil recovery regardless of platelets). Response was assessed in all patients (as-treated) who received at least one dose of guadecitabine. We present the final analysis, although at the time of the database lock, 15 patients were still in follow-up for overall survival. This study is registered with ClinicalTrials.gov, number NCT01261312. Between Aug 24, 2012, and Sept 15, 2014, 107 patients were enrolled: 54 on the 5-day schedule (26 randomly assigned to 60 mg/m 2 and 28 to 90 mg/m 2 ) and 53 were assigned to the 10-day schedule. Median age was 77 years (range 62-92), and median follow-up was 953 days (IQR 721-1040). All treated patients were assessable for a response. The number of patients who achieved a composite complete response did not differ between dose groups or schedules (13 [54%, 95% CI 32·8-74·4] with 60 mg/m 2 on the 5-day schedule; 16 [59%; 38·8-77·6] with 90 mg/m 2 on the 5-day schedule; and 26 [50%, 35·8-64·2] with 60 mg/m 2 on the 10-day schedule). The most frequent grade 3 or worse adverse events, regardless of relationship to treatment, were febrile neutropenia (31 [61%] of 51 patients on the 5-day schedule vs 36 [69%] of 52 patients on the 10-day schedule), thrombocytopenia (25 [49%] vs 22 [42%]), neutropenia (20 [39%] vs 18 [35%]), pneumonia (15 [29%] vs 19 [37%]), anaemia (15 [29%] vs 12 [23%]), and sepsis (eight [16%] vs 14 [27%]). The most common serious adverse events, regardless of relationship to treatment, for the 5-day and 10-day schedules, respectively, were febrile neutropenia (27 [53%] vs 25 [48%]), pneumonia (14 [27%] vs 16 [31%]), and sepsis (eight [16%] vs 14 [27%]). 23 (22%) patients died because of adverse events (mainly from sepsis, eight [8%]; and pneumonia, five [5%]); four deaths were from adverse events deemed treatment-related (pneumonia, two [2%]; multiorgan failure, one [1%]; and sepsis, one [1%], all in the 10-day cohort). More than half of older treatment-naive patients with acute myeloid leukaemia achieved a composite complete response with guadecitabine at all drug doses and schedules investigated, with tolerable toxicity. The recommended guadecitabine regimen for this population is 60 mg/m 2 in a 5-day schedule. A phase 3 study in this patient population is ongoing (NCT02348489) to assess guadecitabine 60 mg/m 2 in a 5-day schedule versus standard of care. Astex Pharmaceuticals and Stand Up To Cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Multisensory connections of monkey auditory cerebral cortex

PubMed Central

Smiley, John F.; Falchier, Arnaud

2009-01-01

Functional studies have demonstrated multisensory responses in auditory cortex, even in the primary and early auditory association areas. The features of somatosensory and visual responses in auditory cortex suggest that they are involved in multiple processes including spatial, temporal and object-related perception. Tract tracing studies in monkeys have demonstrated several potential sources of somatosensory and visual inputs to auditory cortex. These include potential somatosensory inputs from the retroinsular (RI) and granular insula (Ig) cortical areas, and from the thalamic posterior (PO) nucleus. Potential sources of visual responses include peripheral field representations of areas V2 and prostriata, as well as the superior temporal polysensory area (STP) in the superior temporal sulcus, and the magnocellular medial geniculate thalamic nucleus (MGm). Besides these sources, there are several other thalamic, limbic and cortical association structures that have multisensory responses and may contribute cross-modal inputs to auditory cortex. These connections demonstrated by tract tracing provide a list of potential inputs, but in most cases their significance has not been confirmed by functional experiments. It is possible that the somatosensory and visual modulation of auditory cortex are each mediated by multiple extrinsic sources. PMID:19619628

NTP Toxicology and Carcinogenesis Studies of Molybdenum Trioxide (CAS No. 1313-27-5) in F344 Rats and B6C3F1 Mice (Inhalation Studies).

PubMed

1997-04-01

Molybdenum is an essential element for the function of nitrogenase in plants and as a cofactor for enzymes including xanthine oxidoreductase, aldehyde oxidase, and sulfide oxidase in animals. Molybdenum trioxide is used primarily as an additive to steel and corrosion-resistant alloys. It is also used as a chemical intermediate for molybdenum products; an industrial catalyst; a pigment; a crop nutrient; components of glass, ceramics, and enamels; a flame retardant for polyester and polyvinyl chloride resins; and a reagent in chemical analyses. Molybdenum trioxide was nominated by the NCI for toxicity and carcinogenicity studies as a representative inorganic molybdenum compound. The production of molybdenum trioxide is the largest of all the molybdenum compounds examined. Male and female F344/N rats and B6C3F1 mice were exposed to molybdenum trioxide (approximately 99% pure) by inhalation for 14 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and cultured Chinese hamster ovary cells. 14-DAY STUDY IN RATS: Groups of five male and five female F344/N rats were exposed to 0, 3, 10, 30, 100, or 300 mg molybdenum trioxide/m(3). Rats were exposed for 6 hours per day, 5 days per week, for a total of 10 exposure days during a 14-day period. All rats survived to the end of the study. The final mean body weights of male rats exposed to 100 mg/m(3) and male and female rats exposed to 300 mg/m(3) were significantly lower than those of the control groups. Male rats exposed to 300 mg/m(3) lost weight during the study. There were no clinical findings related to exposure to molybdenum trioxide. No chemical-related lesions were observed. 14-DAY STUDY IN MICE: Groups of five male and five female B6C3F1 mice were exposed to 0, 3, 10, 30, 100, or 300 mg molybdenum trioxide/m(3). Mice were exposed 6 hours per day, 5 days per week, for a total of 10 exposure days during a 14-day period. All mice survived to the end of the study. Final mean body weights of male and female mice exposed to 300 mg/m(3) were significantly lower than those of the control groups. Male mice exposed to 300 mg/m(3) lost weight during the study. There were no clinical findings related to exposure to molybdenum trioxide. No chemical-related lesions were observed. 13-WEEK STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were exposed to molybdenum trioxide by inhalation at concentrations of 0, 1, 3, 10, 30, or 100 mg/m(3) for 6.5 hours per day, 5 days per week, for 13 weeks. All rats survived to the end of the study. The final mean body weights of exposed rats were similar to those of the control groups. No clinical findings related to molybdenum trioxide exposure were observed. There were no significant chemical-related differences in absolute or relative organ weights, hematology or clinical chemistry parameters, sperm counts or motility, or liver copper concentrations between control and exposed rats. No chemical-related lesions were observed. 13-WEEK STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were exposed to molybdenum trioxide by inhalation at concentrations of 0, 1, 3, 10, 30, or 100 mg/m(3) for 6.5 hours per day, 5 days per week, for 13 weeks. All mice survived to the end of the study. The final mean body weights of exposed mice were similar to those of the control groups. There were no chemical-related clinical findings. There were no significant differences in absolute or relative organ weights or sperm counts or motility between control and exposed mice. There were significant increases in liver copper concentrations in female mice exposed to 30 mg/m(3) and in male and female mice exposed to 100 mg/m(3) compared to those of the control groups. No chemical-related lesions were observed. 2-YEAR STUDIES IN RATS: Groups of 50 male and 50 female F344/N rats were exposed to molybdenum trioxide by inhalation at concentrations of 0, 10, 30, or 100 mg/m(3). Rats were exposed for 6 hours per day, 5 days per week, for 106 weeks. Survival, Body Weights, and Special Studies: Survival rates of exposed maleed male and female rats were similar to those of the control groups. Mean body weights of exposed groups of male and female rats were similar to those of the control groups throughout the study. There was a significant exposure-dependent increase in blood molybdenum concentration in exposed rats. Blood concentrations of molybdenum in exposed male rats were greater than those in exposed female rats. There were no toxicologically significant differences in bone density or curvature between control and exposed rats. Pathology Findings: The incidences of alveolar/bronchiolar adenoma or carcinoma (combined) were increased in male rats with a marginally significant positive trend. No increase in the incidences of lung neoplasms occurred in female rats. Incidences of chronic alveolar inflammation in male and female rats exposed to 30 or 100 mg/m(3) were significantly greater than those in the control groups. No nasal or laryngeal neoplasms were attributed to exposure to molybdenum trioxide. Incidences of hyaline degeneration in the nasal respiratory epithelium in 30 and 100 mg/m(3) males and in all exposed groups of females were significantly greater than those in the control groups. The incidences of hyaline degeneration in the nasal olfactory epithelium of all exposed groups of females were significantly greater than that in the control group. In the larynx, incidences of squamous metaplasia of the epithelium lining the base of the epiglottis in all exposed groups of male and female rats were significantly greater than those in the control groups and increased with increasing exposure concentration. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female B6C3F1 mice were exposed to molybdenum trioxide by inhalation at concentrations of 0, 10, 30, or 100 mg/m(3). Mice were exposed for 6 hours per day, 5 days per week, for 105 weeks. Survival, Body Weights, and Special Studies: The survival rate of male mice exposed to 30 mg/m(3) was marginally lower than that of the control group; survival rates of 10 and 100 mg/m(3) males and of all exposed groups of females were similar to those of the control groups. Mean body weights of exposed male mice were generally similar to those of the control group throughout the study. Mean body weights of exposed female mice were generally greater than those of the control group from week 11 until the end of the study. There was a significant exposure-dependent increase in blood molybdenum concentration in exposed mice. There were no toxicologically significant differences in bone density or curvature between control and exposed mice. Pathology Findings: The incidences of alveolar/bronchiolar carcinoma in all exposed groups of males were significantly greater than that in the control group. Incidences of alveolar/bronchiolar adenoma in females in the 30 and 100 mg/m(3) groups were significantly greater than that in the control group. Incidences of alveolar/bronchiolar adenoma or carcinoma (combined) in 10 and 30 mg/m(3) males and in 100 mg/m(3) females were significantly greater than those in the control groups and exceeded the historical control ranges for 2-year NTP inhalation studies. Incidences of metaplasia of the alveolar epithelium of minimal severity in the centriacinar region of the lung were significantly increased in all exposed groups of mice. The incidences of histiocyte cellular infiltration in all exposed groups of males were significantly greater than that in the control group. Incidences of hyaline degeneration of the respiratory epithelium of the nasal cavity in 100 mg/m(3) males and females and hyaline degeneration of the olfactory epithelium of the nasal cavity in 100 mg/m(3) females were significantly greater than those in the control groups. The incidences of squamous metaplasia of the epithelium lining the base of the epiglottis were significantly increased in all exposed groups of males and females. In both male and female mice, the incidences of hyperplasia of the laryngeal epithelium in level II of the larynx increased with increasing exposure concentration. The increase was statistically significant only in mice exposed to 100 mg/m(3) with 82% of male and 70% of female mice affected. GENETIC TOXICOLOGY: Molybdenum trioxide was not mutagenic in any of five strains of Salmonella typhimurium, and it did not induce sister chromatid exchanges or chromosomal aberrations in cultured Chinese hamster ovary cells in vitro. All tests were conducted with and without S9 metabolic activation enzymes. CONCLUSIONS: Under the conditions of these 2-year inhalation studies, there was equivocal evidence of carcinogenic activity of molybdenum trioxide in male F344/N rats based on a marginally significant positive trend of alveolar/bronchiolar adenoma or carcinoma (combined). There was no evidence of carcinogenic activity of molybdenum trioxide in female F344/N rats exposed to 10, 30, or 100 mg/m(3). There was some evidence of carcinogenic activity of molybdenum trioxide in male B6C3F1 mice based on increased incidences of alveolar/bronchiolar carcinoma and adenoma or carcinoma (combined). There was some evidence of carcinogenic activity of molybdenum trioxide in female B6C3F1 mice based on increased incidences of alveolar/bronchiolar adenoma and adenoma or carcinoma (combined). Exposure of male and female rats to molybdenum trioxide by inhalation resulted in increased incidences of chronic alveolar inflammation, hyaline degeneration of the respiratory epithelium, hyaline degeneration of the olfactory epithelium (females), and squamous metaplasia of the epiglottis. Exposure of male and female mice to molybdenum trioxide by inhalation resulted in increased incidences of metaplasia of the alveolar epithelium, histiocyte cellular infiltration (males), hyaline degeneration of the respiratory epithelium, hyaline degeneration of the olfactory epithelium (females), squamous metaplasia of the epiglottis, and hyperplasia of the larynx. Synonyms: Molybdic oxide; molybdic trioxide; molybdic anhydride; molybdenum (VI) oxide; molybdenum peroxide; molybdic acid anhydride; molybdenum anhydride; natural molybdite; molybdena

Phase I study of 6-diazo-5-oxo-L-norleucine (DON).

PubMed

Sklaroff, R B; Casper, E S; Magill, G B; Young, C W

1980-01-01

We conducted a phase I study of 6-diazo-5-oxo-L-norleucine given iv on a twice weekly schedule. Twenty-six evaluable patients received 31 courses of the drug. Doses ranged from 100 to 500 mg/m2. Nausea with vomiting was the dose-limiting toxic effect, transient thrombocytopenia was seen frequently, and mucositis occurred in 39% of the patients. No definite therapeutic responses were observed in 18 patients with measurable lesions. The recommended dose for phase II studies is 200-300 mg/m2 iv twice weekly.

Selenium mobilization during a flood experiment in a contaminated wetland: Stewart Lake Waterfowl Management Area, Utah

USGS Publications Warehouse

Naftz, D.L.; Yahnke, J.; Miller, J.; Noyes, S.

2005-01-01

Constructed and natural wetlands can accumulate elevated levels of Se; however, few data are available on cost-effective methods for remobilization and removal of Se from these areas. A field experiment was conducted to assess the effectiveness of flooding on the removal of Se from dry surface sediments. The 83-m2 flood-experiment plot contained 10 monitoring wells, a water-quality minimonitor (continuous measurement of pH, specific conductance, water temperature, and dissolved O2), a down-hole Br electrode, and 2 pressure transducers. Flooding was initiated on August 27, 2002, and a Br tracer was added to water delivered through a pipeline to the flood plot during the first 1.2 h. Standing water depth in the flood plot was maintained at 0.3 m through September 1, 2002. The Br tracer data indicate a dual porosity system that includes fracture (mud cracks) and matrix flow components. Mean vertical water velocities for the matrix flow component were estimated to range from 0.002 to 0.012 m/h. Dissolved (less than 0.45 ??m) Se increased from pre-flood concentrations of less than 10 ??g/L to greater than 800 ??g/L during flooding in samples from deep (2.0 m below land surface) ground water. Selenium concentrations exceeded 5500 ??g/L in samples from shallow (0.8 m below land surface) ground water. Ratios of Se to Br in water samples indicate that Se moved conservatively during the experiment and was derived from leaching of near-surface sediments. Cumulative Se flux to the deep ground water during the experiment ranged from 9.0 to 170 mg/m2. Pre- and post-flood surface soil sampling indicated a mean Se flux of 720 mg/m2 through the top 15 cm of soil. Ground-water samples collected 8 months after termination of the flood experiment contained Se concentrations of less than 20 ??g/L. The minimonitor data indicate a rapid return to chemically reducing conditions in the deep ground water, limiting the mobility of the Se dissolved in the water pulse introduced during the flood experiment. Ratios of Se to Br in deep ground-water samples collected 8 months after the experiment confirmed the removal of Se from the aqueous phase. Based on the median Se flux rate estimated during the experiment of 0.65 mg/h/m2 (n = 52), 7 flooding cycles would be required to meet the 4 ??g/g remediation goal in surface soils from the SLWMA wetland.

Recurrent exposure to welding fumes induces insufficient recovery from inflammation.

PubMed

Yang, Mi Jin; Yang, Young Su; Sung, Jae Hyuck; Kim, Jin Sung; Cho, Kyu Hyuk; Lim, Chae Woong; Chung, Yong Hyun; Kim, Hyeon Yeong; Yang, Jung Sun; Yu, Il Je; Song, Chang Woo

2009-02-01

Previous studies on welding-fume-induced lung fibrosis have indicated that recovery is possible when the degree of exposure is short-term and moderate. However, this study investigated the recovery after recurrent exposure to welding fumes, as welders are invariably re-exposed to welding fumes after recovering from radiographic pneumoconiosis. Thus, to investigate the disease and recovery processes of welding-fume-induced pneumoconiosis in the case of recurrent welding-fume exposure, rats were exposed to manual metal arc-stainless steel (MMA-SS) welding fumes with a total suspended particulate (TSP) concentration of 51.4 +/- 2.8 mg/m(3) (low dose) or 84.6 +/- 2.9 mg/m(3) (high dose) for 2 h/day in an inhalation chamber for 1 mo and then allowed to recover from the inflammation for 1 mo. Thereafter, the rats were exposed again to MMA-SS with a TSP concentration of 44.1 +/- 8.8 mg/m(3) (low dose) or 80.1 +/- 9.8 mg/m(3) (high dose) for another 30 d and then allowed to recover from the inflammation for 1 mo. The recovery from the first exposure was then compared with that from the second exposure. The first and second exposures to MMA-SS welding fumes were found to produce significant increases in the lung weights and inflammatory parameters, including total cell numbers, alveolar macrophages (AMs), polymorphonuclear cells (PMNs), lymphocytes, and lactate dehydrogenase (LDH) in the bronchoalveolar lavage fluid (BALF) when compared with the unexposed controls. Following the first and second recovery, a significant reduction in inflammatory parameters of BALF was observed between the exposure and recovery groups. Histopathological observations showed foamy or pigmented macrophage accumulation, cellular debris, or pigment from burst macrophages after the first or second exposure. Following the first or second recovery, cellular debris or pigment from burst macrophages was cleared away from the lungs and accumulation of foamy or pigmented macrophages was decreased when compared to previous exposure. Reactive hyperplasia was noticed after second exposure or either recovery. However, significant differences were observed between the first and second exposure or the first and second recovery. In particular, the number of PMNs was significantly higher after the second exposure than after the first exposure. Also, all cell types in the BALF were significantly elevated in the high-dose second recovery group than in the first recovery group, indicating an incomplete recovery from second exposure. In conclusion, these results indicated that the lung damage caused by the second welding-fume exposure was more difficult to recover from than the first exposure.

Ototoxic potential of JP-8 and a Fischer-Tropsch synthetic jet fuel following subacute inhalation exposure in rats.

PubMed

Fechter, Laurence D; Gearhart, Caroline A; Fulton, Sherry

2010-07-01

This study was undertaken to identify the ototoxic potential of two jet fuels presented alone and in combination with noise. Rats were exposed via a subacute inhalation paradigm to JP-8 jet fuel, a kerosene-based fuel refined from petroleum, and a synthetic fuel produced by the Fischer-Tropsch (FT) process. Although JP-8 contains small ( approximately 5%) concentrations of aromatic hydrocarbons some of which known to be ototoxic, the synthetic fuel does not. The objectives of this study were to identify a lowest observed adverse effect level and a no observed adverse effect level for each jet fuel and to provide some preliminary, but admittedly, indirect evidence concerning the possible role of the aromatic hydrocarbon component of petroleum-based jet fuel on hearing. Rats (n = 5-19) received inhalation exposure to JP-8 or to FT fuel for 4 h/day on five consecutive days at doses of 500, 1000, and 2000 mg/m(3). Additional groups were exposed to various fuel concentrations followed by 1 h of an octave band of noise, noise alone, or no exposure to fuel or noise. Significant dose-related impairment in the distortion product otoacoustic emissions (DPOAE) was seen in subjects exposed to combined JP-8 plus noise exposure when JP-8 levels of at least 1000 mg/m(3) were presented. No noticeable impairment was observed at JP-8 levels of 500 mg/m(3) + noise. In contrast to the effects of JP-8 on noise-induced hearing loss, FT exposure had no effect by itself or in combination with noise exposure even at the highest exposure level tested. Despite an observed loss in DPOAE amplitude seen only when JP-8 and noise were combined, there was no loss in auditory threshold or increase in hair cell loss in any exposure group.

Respiratory health effects of fifteen years of improved collective protection in a wheat-processing worker population.

PubMed

Dorribo, Victor; Wild, Pascal; Pralong, Jacques A; Danuser, Brigitta; Reboux, Gabriel; Krief, Peggy; Niculita-Hirzel, Hélène

2015-01-01

Occupational exposure to grain dust causes respiratory symptoms and pathologies. To decrease these effects, major changes have occurred in the grain processing industry in the last twenty years. However, there are no data on the effects of these changes on workers' respiratory health. The aim of this study was to evaluate the respiratory health of grain workers and farmers involved in different steps of the processing industry of wheat, the most frequently used cereal in Europe, fifteen years after major improvements in collective protective equipment due to mechanisation. Information on estimated personal exposure to wheat dust was collected from 87 workers exposed to wheat dust and from 62 controls. Lung function (FEV1, FVC, and PEF), exhaled nitrogen monoxide (FENO) and respiratory symptoms were assessed after the period of highest exposure to wheat during the year. Linear regression models were used to explore the associations between exposure indices and respiratory effects. Acute symptoms - cough, sneezing, runny nose, scratchy throat - were significantly more frequent in exposed workers than in controls. Increased mean exposure level, increased cumulative exposure and chronic exposure to more than 6 mg.m (-3) of inhaled wheat dust were significantly associated with decreased spirometric parameters, including FEV1 and PEF (40 ml and 123 ml.s (-1) ), FEV1 and FVC (0.4 ml and 0.5 ml per 100 h.mg.m (-3) ), FEV1 and FVC (20 ml and 20 ml per 100 h at >6 mg.m (-3) ). However, no increase in FENO was associated with increased exposure indices. The lung functions of wheat-related workers are still affected by their cumulative exposure to wheat dust, despite improvements in the use of collective protective equipment.

Phase III Trial Comparing Intraperitoneal and Intravenous Paclitaxel Plus S-1 Versus Cisplatin Plus S-1 in Patients With Gastric Cancer With Peritoneal Metastasis: PHOENIX-GC Trial.

PubMed

Ishigami, Hironori; Fujiwara, Yoshiyuki; Fukushima, Ryoji; Nashimoto, Atsushi; Yabusaki, Hiroshi; Imano, Motohiro; Imamoto, Haruhiko; Kodera, Yasuhiro; Uenosono, Yoshikazu; Amagai, Kenji; Kadowaki, Shigenori; Miwa, Hiroto; Yamaguchi, Hironori; Yamaguchi, Takuhiro; Miyaji, Tempei; Kitayama, Joji

2018-05-10

Purpose Intraperitoneal paclitaxel plus systemic chemotherapy demonstrated promising clinical effects in patients with gastric cancer with peritoneal metastasis. We aimed to verify its superiority over standard systemic chemotherapy in overall survival. Patients and Methods This randomized phase III trial enrolled patients with gastric cancer with peritoneal metastasis who had received no or short-term (< 2 months) chemotherapy. Patients were randomly assigned at a two-to-one ratio to receive intraperitoneal and intravenous paclitaxel plus S-1 (IP; intraperitoneal paclitaxel 20 mg/m 2 and intravenous paclitaxel 50 mg/m 2 on days 1 and 8 plus S-1 80 mg/m 2 per day on days 1 to 14 for a 3-week cycle) or S-1 plus cisplatin (SP; S-1 80 mg/m 2 per day on days 1 to 21 plus cisplatin 60 mg/m 2 on day 8 for a 5-week cycle), stratified by center, previous chemotherapy, and extent of peritoneal metastasis. The primary end point was overall survival. Secondary end points were response rate, 3-year overall survival rate, and safety. Results We enrolled 183 patients and performed efficacy analyses in 164 eligible patients. Baseline characteristics were balanced between the arms, except that patients in the IP arm had significantly more ascites. The median survival times for the IP and SP arms were 17.7 and 15.2 months, respectively (hazard ratio, 0.72; 95% CI, 0.49 to 1.04; stratified log-rank P = .080). In the sensitivity analysis adjusted for baseline ascites, the hazard ratio was 0.59 (95% CI, 0.39 to 0.87; P = .008). The 3-year overall survival rate was 21.9% (95% CI, 14.9% to 29.9%) in the IP arm and 6.0% (95% CI, 1.6% to 14.9%) in the SP arm. Both regimens were well tolerated. Conclusion This trial failed to show statistical superiority of intraperitoneal paclitaxel plus systemic chemotherapy. However, the exploratory analyses suggested possible clinical benefits of intraperitoneal paclitaxel for gastric cancer.

Randomized phase 3 trial comparing 2 cisplatin dose schedules in 326 patients with locally advanced squamous cell cervical carcinoma: long-term follow-up.

PubMed

Nagy, Viorica Magdalena; Ordeanu, Claudia; Coza, Ovidiu; Alin, Cristian Rancea; Traila, Alexandru; Todor, Nicolae

2012-11-01

The evaluation of 5-year results obtained through 2 radiochemotherapy (RCT) regimens: cisplatin (CDDP), 20 mg/m × 5 days every 21 days; and CDDP, 40 mg/m per week in locally advanced cervical carcinoma. In this single-institution prospective randomized phase 3 study, 326 patients with stage IIB to IIIB squamous cell cervical carcinoma treated from March 2003 to March 2005 were included. One hundred sixty patients (49%) had stage IIB cervical carcinoma, 103 patients (31.5%) had stage IIIA cervical carcinoma, and 63 patients (19.5%) had stage IIIB cervical carcinoma. The patients were randomly assigned to 2 therapeutic arms: 164 patients in arm A (5 days) concurrent RCT with CDDP, 20 mg/m per day, days 1 to 5 every 21 days; and 162 patients in arm B (weekly), concurrent RCT with CDDP, 40 mg/m per day weekly. All patients were treated with external beam radiotherapy on the abdominopelvic region using 15-MV x-rays and a cervical boost using the x-rays arch technique or medium-dose-rate intracavitary brachytherapy. The 5-year survival rate obtained through the 2 RCT regimens are not statistically different, even if a tendency of superiority can be observed in the 5-day arm as far as overall survival (78% in arm A vs 72% in arm B; p = 0.14) and disease-free survival (73% in arm A and 69% in arm B; p = 0.09) are concerned. Five-year local relapse-free survival was significantly superior in the 5-day CDDP arm (87%) in comparison with the weekly CDDP arm (77%); p < 0.01. In the 5-day arm, local relapse rate was twice lower, 21/164 (13%), compared with the weekly arm, 40/162 (25%); p < 0.01). Distance failures were identical in the 2 therapeutic groups: 22/164 (13%) and 21/162 (13%), respectively, which shows the superiority of arm A regarding local control. The results of our study demonstrate that RCT with cisplatin, 20 mg/m × 5 days every 21 days, is superior regarding local efficacy and is less toxic compared with the weekly chemotherapy regimen.

Quantitative crystalline silica exposure assessment for a historical cohort epidemiologic study in the German porcelain industry.

PubMed

Birk, Thomas; Guldner, Karlheinz; Mundt, Kenneth A; Dahmann, Dirk; Adams, Robert C; Parsons, William

2010-09-01

A time-dependent quantitative exposure assessment of silica exposure among nearly 18,000 German porcelain workers was conducted. Results will be used to evaluate exposure-response disease risks. Over 8000 historical industrial hygiene (IH) measurements with original sampling and analysis protocols from 1954-2006 were obtained from the German Berufs- genossenschaft der keramischen-und Glas-Industrie (BGGK) and used to construct a job exposure matrix (JEM). Early measurements from different devices were converted to modern gravimetric equivalent values. Conversion factors were derived from parallel historical measurements and new side-by-side measurements using historical and modern devices in laboratory dust tunnels and active workplace locations. Exposure values were summarized and smoothed using LOESS regression; estimates for early years were derived using backward extrapolation techniques. Employee work histories were merged with JEM values to determine cumulative crystalline silica exposures for cohort members. Average silica concentrations were derived for six primary similar exposure groups (SEGs) for 1938-2006. Over 40% of the cohort accumulated <0.5 mg; just over one-third accumulated >1 mg/m(3)-years. Nearly 5000 workers had cumulative crystalline silica estimates >1.5 mg/m(3)-years. Similar numbers of men and women fell into each cumulative exposure category, except for 1113 women and 1567 men in the highest category. Over half of those hired before 1960 accumulated >3 mg/m(3)-years crystalline silica compared with 4.9% of those hired after 1960. Among those ever working in the materials preparation area, half accumulated >3 mg/m(3)-year compared with 12% of those never working in this area. Quantitative respirable silica exposures were estimated for each member of this cohort, including employment periods for which sampling used now obsolete technologies. Although individual cumulative exposure estimates ranged from background to about 40 mg/m(3)-years, many of these estimates reflect long-term exposures near modern exposure limit values, allowing direct evaluation of lung cancer and silicosis risks near these limits without extrapolation. This quantitative exposure assessment is the largest to date in the porcelain industry.

Phase III Randomized Study of Rituximab/Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) Compared With Iodine-131 Tositumomab/BEAM With Autologous Hematopoietic Cell Transplantation for Relapsed Diffuse Large B-Cell Lymphoma: Results From the BMT CTN 0401 Trial

PubMed Central

Vose, Julie M.; Carter, Shelly; Burns, Linda J.; Ayala, Ernesto; Press, Oliver W.; Moskowitz, Craig H.; Stadtmauer, Edward A.; Mineshi, Shin; Ambinder, Richard; Fenske, Timothy; Horowitz, Mary; Fisher, Richard; Tomblyn, Marcie

2013-01-01

Purpose This clinical trial evaluated standard-dose radioimmunotherapy with a chemotherapy-based transplantation regimen followed by autologous hematopoietic cell transplantation versus rituximab with the same regimen in patients with relapsed diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients with chemotherapy-sensitive persistent or relapsed DLBCL were randomly assigned to receive iodine-131 tositumomab (dosimetric dose of 5 mCi on day −19 and therapeutic dose of 0.75 Gy on day −12), carmustine 300 mg/m2 (day −6), etoposide 100 mg/m2 twice daily (days −5 to −2), cytarabine 100 mg/m2 twice daily (days −5 to −2), and melphalan 140 mg/m2 (day −1; B-BEAM) or rituximab 375 mg/m2 on days −19 and −12 and the same chemotherapy regimen (R-BEAM). Results Two hundred twenty-four patients were enrolled, with 113 patients randomly assigned to R-BEAM and 111 patients assigned to B-BEAM. Two-year progression-free survival (PFS) rates, the primary end point, were 48.6% (95% CI, 38.6% to 57.8%) for R-BEAM and 47.9% (95% CI, 38.2% to 57%; P = .94) for B-BEAM, and the 2-year overall survival (OS) rates were 65.6% (95% CI, 55.3% to 74.1%) for R-BEAM and 61% (95% CI, 50.9% to 69.9%; P = .38) for B-BEAM. The 100-day treatment-related mortality rates were 4.1% (95% CI, 0.2% to 8.0%) for R-BEAM and 4.9% (95% CI, 0.8% to 9.0%; P = .97) for B-BEAM. The maximum mucositis score was higher in the B-BEAM arm (0.72) compared with the R-BEAM arm (0.31; P < .001). Conclusion The B-BEAM and R-BEAM regimens produced similar 2-year PFS and OS rates for patients with chemotherapy-sensitive relapsed DLBCL. No differences in toxicities other than mucositis were noted. PMID:23478060

Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study.

PubMed

Pigneux, Arnaud; Béné, Marie C; Guardiola, Philippe; Recher, Christian; Hamel, Jean-Francois; Sauvezie, Mathieu; Harousseau, Jean-Luc; Tournilhac, Olivier; Witz, Francis; Berthou, Christian; Escoffre-Barbe, Martine; Guyotat, Denis; Fegueux, Nathalie; Himberlin, Chantal; Hunault, Mathilde; Delain, Martine; Lioure, Bruno; Jourdan, Eric; Bauduer, Frederic; Dreyfus, Francois; Cahn, Jean-Yves; Sotto, Jean-Jacques; Ifrah, Norbert

2017-02-01

Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older. Patients and Methods A total of 330 patients with AML de novo or secondary to chemotherapy or radiotherapy were enrolled in the study. Induction therapy included idarubicin 8 mg/m 2 on days 1 to 5, cytarabine 100 mg/m 2 on days 1 to 7, and lomustine 200 mg/m 2 on day 1. Patients in complete remission or partial remission received six reinduction courses, alternating idarubicin 8 mg/m 2 on day 1, cytarabine 100 mg/m 2 on days 1 to 5, and a regimen of methotrexate and mercaptopurine. Patients were randomly assigned to receive norethandrolone 10 or 20 mg/day, according to body weight, or no norethandrolone for a 2-year maintenance therapy regimen. The primary end point was disease-free survival by intention to treat. Secondary end points were event-free survival, overall survival, and safety. This trial was registered at www.ClinicalTrials.gov identifier NCT00700544. Results Random assignment allotted 165 patients to each arm; arm A received norethandrolone, and arm B did not receive norethandrolone. Complete remission or partial remission was achieved in 247 patients (76%). The Schoenfeld time-dependent model showed that norethandrolone significantly improved survival for patients still in remission at 1 year after induction. In arms A and B, respectively, 5-year disease-free survival was 31.2% and 16.2%, event-free survival was 21.5% and 12.9%, and overall survival was 26.3% and 17.2%. Norethandrolone improved outcomes irrelevant to all prognosis factors. Only patients with baseline leukocytes > 30 × 10 9 /L did not benefit from norethandrolone. Conclusion This study demonstrates that maintenance therapy with norethandrolone significantly improves survival in elderly patients with AML without increasing toxicity.

Epigenetic Therapy Using Belinostat for Patients With Unresectable Hepatocellular Carcinoma: A Multicenter Phase I/II Study With Biomarker and Pharmacokinetic Analysis of Tumors From Patients in the Mayo Phase II Consortium and the Cancer Therapeutics Research Group

PubMed Central

Yeo, Winnie; Chung, Hyun C.; Chan, Stephen L.; Wang, Ling Z.; Lim, Robert; Picus, Joel; Boyer, Michael; Mo, Frankie K.F.; Koh, Jane; Rha, Sun Y.; Hui, Edwin P.; Jeung, Hei C.; Roh, Jae K.; Yu, Simon C.H.; To, Ka F.; Tao, Qian; Ma, Brigette B.; Chan, Anthony W.H.; Tong, Joanna H.M.; Erlichman, Charles; Chan, Anthony T.C.; Goh, Boon C.

2012-01-01

Purpose Epigenetic aberrations have been reported in hepatocellular carcinoma (HCC). In this study of patients with unresectable HCC and chronic liver disease, epigenetic therapy with the histone deacetylase inhibitor belinostat was assessed. The objectives were to determine dose-limiting toxicity and maximum-tolerated dose (MTD), to assess pharmacokinetics in phase I, and to assess activity of and explore potential biomarkers for response in phase II. Patients and Methods Major eligibility criteria included histologically confirmed unresectable HCC, European Cooperative Oncology Group performance score ≤ 2, and adequate organ function. Phase I consisted of 18 patients; belinostat was given intravenously once per day on days 1 to 5 every 3 weeks; dose levels were 600 mg/m2 per day (level 1), 900 mg/m2 per day (level 2), 1,200 mg/m2 per day (level 3), and 1,400 mg/m2 per day (level 4). Phase II consisted of 42 patients. The primary end point was progression-free survival (PFS), and the main secondary end points were response according to Response Evaluation Criteria in Solid Tumors (RECIST) and overall survival (OS). Exploratory analysis was conducted on pretreatment tumor tissues to determine whether HR23B expression is a potential biomarker for response. Results Belinostat pharmacokinetics were linear from 600 to 1,400 mg/m2 without significant accumulation. The MTD was not reached at the maximum dose administered. Dose level 4 was used in phase II. The median number of cycles was two (range, one to 12). The partial response (PR) and stable disease (SD) rates were 2.4% and 45.2%, respectively. The median PFS and OS were 2.64 and 6.60 months, respectively. Exploratory analysis revealed that disease stabilization rate (complete response plus PR plus SD) in tumors having high and low HR23B histoscores were 58% and 14%, respectively (P = .036). Conclusion Epigenetic therapy with belinostat demonstrates tumor stabilization and is generally well-tolerated. HR23B expression was associated with disease stabilization. PMID:22915658

A phase I study of gefitinib with concurrent dose-escalated weekly docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel and maintenance gefitinib for patients with stage III non-small cell lung cancer.

PubMed

Center, Brian; Petty, William Jeffrey; Ayala, Diandra; Hinson, William H; Lovato, James; Capellari, James; Oaks, Timothy; Miller, Antonius A; Blackstock, Arthur William

2010-01-01

Concurrent radiation and chemotherapy is the standard of care for good performance status patients with stage III non-small cell lung cancer. Locoregional control remains a significant factor relating to poor outcome. Preclinical and early clinical data suggest that docetaxel and gefitinib have radiosensitizing activity. This study sought to define the maximum tolerated dose of weekly docetaxel that could be given with daily gefitinib and concurrent thoracic radiation therapy. Patients with histologically confirmed, inoperable stage III non-small cell lung cancer and good performance status (Eastern Cooperative Oncology Group 0-1) were eligible for this study. Patients received three-dimensional conformal thoracic radiation to a dose of 70 Gy concurrently with oral gefitinib at a dose of 250 mg daily and intravenous, weekly docetaxel at escalating doses from 15 to 30 mg/m2 in cohorts of patients. Patients were given a 2-week rest period after the concurrent therapy, during which they received only gefitinib. After the 2-week rest period, patients received consolidation chemotherapy with docetaxel 75 mg/m2 given every 21 days for two cycles. Maintenance gefitinib was continued until disease progression or study completion. Sixteen patients were enrolled on the study between December 2003 and April 2007 with the following characteristics: median age, 64 years (range 43-79 years); M/F: 9/7; and performance status 0/1, 1/15. Dose-limiting pulmonary toxicity and esophagitis were encountered at a weekly docetaxel dose of 25 mg/m2, resulting in a maximum tolerated dose of 20 mg/m2/wk. Overall, grade 3/4 hematologic toxicity was observed in 27% of patients. Grade 3/4 esophageal and pulmonary toxicities were reported in 27% and 20% of patients, respectively. The overall response rate was 46%, and the median survival for all patients was 21 months. Concurrent thoracic radiation with weekly docetaxel and daily gefitinib is feasible but results in moderate toxicity. For further studies, the recommended weekly docetaxel dose for this chemoradiation regimen is 20 mg/m2.

Final Results of NRG Oncology RTOG 0246: An Organ-Preserving Selective Resection Strategy in Esophageal Cancer Patients Treated with Definitive Chemoradiation.

PubMed

Swisher, Stephen G; Moughan, Jennifer; Komaki, Ritsuko U; Ajani, Jaffer A; Wu, Tsung T; Hofstetter, Wayne L; Konski, Andre A; Willett, Christopher G

2017-02-01

The impact of selective surgical resection for patients with esophageal cancer treated with definitive chemoradiation has not been clearly evaluated long-term. NRG (National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, Gynecologic Oncology Group) Oncology Radiation Therapy Oncology Group 0246 was a multi-institutional, single-arm, open-label, nonrandomized phase II study that enrolled 43 patients from September 2003 to March 2008 with clinical stage T1-4N0-1M0 squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction from 19 sites. Patients received induction chemotherapy with fluorouracil (650 mg/m 2 /d), cisplatin (15 mg/m 2 /d), and paclitaxel (200 mg/m 2 /d) for two cycles followed by concurrent chemoradiation consisting of 50.4 Gy of radiation (1.8 Gy per fraction) and daily fluorouracil (300 mg/m 2 /d) with cisplatin (15 mg/m 2 /d) over the first 5 days. After definitive chemoradiation, patients were evaluated for residual disease. Selective esophagectomy was considered only for patients with residual disease after chemoradiation (clinical incomplete response) or recurrent disease on surveillance. This report looks at the long-term outcome of this selective surgical strategy. With a median follow-up of 8.1 years (minimum to maximum for 12 alive patients 7.2-9.8 years), the estimated 5- and 7-year survival rates are 36.6% (95% confidence interval [CI]: 22.3-51.0) and 31.7% (95% CI: 18.3-46.0). Clinical complete response was achieved in 15 patients (37%), with 5- and 7-yearr survival rates of 53.3% (95% CI: 26.3-74.4) and 46.7% (95% CI: 21.2-68.7). Esophageal resection was not required in 20 of 41 patients (49%) on this trial. The long-term results of NRG Oncology Radiation Therapy Oncology Group 0246 demonstrate promising efficacy of a selective surgical resection strategy and suggest the need for larger randomized studies to further evaluate this organ-preserving approach. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Pharmacokinetics and Safety of Bortezomib in Patients with Advanced Malignancies and Varying Degrees of Liver Dysfunction: Phase 1 NCI Organ Dysfunction Working Group Study NCI-6432

PubMed Central

LoRusso, Patricia M; Venkatakrishnan, Karthik; Ramanathan, Ramesh K; Sarantopoulos, John; Mulkerin, Daniel; Shibata, Stephen I; Hamilton, Anne; Dowlati, Afshin; Mani, Sridhar; Rudek, Michelle A; Takimoto, Chris H; Neuwirth, Rachel; Esseltine, Dixie-Lee; Ivy, Percy

2013-01-01

Purpose The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations. Methods Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m2 standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m2, respectively, up to a 1.3 mg/m2 maximum. Serial blood samples were collected for 24 hours post-dose on days 1 and 8, cycle 1, for bortezomib plasma concentration measurements. Results Sixty-one patients were treated, including 14 with normal hepatic function and 17, 12, and 18 with mild, moderate, and severe impairment, respectively. Mild hepatic impairment did not alter dose-normalized bortezomib exposure (AUC0-tlast) or Cmax compared with patients with normal function. Mean dose-normalized AUC0-tlast was increased by approximately 60% on day 8 in patients with moderate or severe impairment. Conclusions Patients with mild hepatic impairment do not require a starting dose adjustment of bortezomib. Patients with moderate or severe hepatic impairment should be started at a reduced dose of 0.7 mg/m2. PMID:22394984

Double-modulation of 5-Fluorouracil by methotrexate and leucovorin in advanced colorectal-carcinoma.

PubMed

Leone, B; Romero, A; Rabinovich, M; Vallejo, C; Bianco, A; Perez, J; Rodriguez, R; Cuevas, M; Machiavelli, M; Paris, A; Lacava, J

1993-11-01

A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and leucovorin (LV) as first line chemotherapy in advanced colorectal carcinoma. Between January 1990, and April 1992, 42 patients with metastatic or advanced recurrent (inoperable) colorectal cancer were entered into the study. Therapy consisted of a sequential combination of MTX, LV and 5-FU. MTX was administered at a dose of 150 mg/m2 over 20 minutes I.V. infusion at hour (h) 0, followed 19 h later by LV 50 mg/m2 over 2 h infusion. 5-FU 900 mg/m2 was given by I.V. push injection at h 20. Starting 24 h after MTX administration all patients received LV 15 mg/m2 intramuscularly every 6 h for six doses. Treatment was repeated every 15 days until progressive disease, severe toxicity, or death. Four patients were considered not evaluable for response. Objective regression (OR) was observed in 14 of 38 patients (37%, 95% confidence interval 23-53%). Two patients (5%) obtained complete response (CR) and 12 (32%) partial response (PR). Median time to treatment failure was 6 months (range 1-21). Median survival for the whole group of patients was 13 months (range 1-27). Toxicity was within acceptable limits but one therapy-related death due to severe leukopenia and sepsis was observed. Double modulation of 5-FU with MTX and low dose of LV is an active regimen against advanced colorectal carcinoma and represents a promising strategy that should be further explored.

Seasonal changes in the chemistry and biology of a meromictic lake (Big Soda Lake, Nevada, U.S.A.)

USGS Publications Warehouse

Cloern, J.E.; Cole, B.E.; Oremland, R.S.

1983-01-01

Big Soda Lake is an alkaline, saline lake with a permanent chemocline at 34.5 m and a mixolimnion that undergoes seasonal changes in temperature structure. During the period of thermal stratification, from summer through fall, the epilimnion has low concentrations of dissolved inorganic nutrients (N, Si) and CH4, and low biomass of phytoplankton (chlorophyll a ca. 1 mgm -3). Dissolved oxygen disappears near the compensation depth for algal photosynthesis (ca. 20 m). Surface water is transparent so that light is present in the anoxic hypolimnion, and a dense plate of purple sulfur photosynthetic bacteria (Ectothiorhodospira vacuolata) is present just below 20 m (Bchl a ca. 200 mgm-3). Concentrations of N H4+, Si, and CH4 are higher in the hypolimnion than in the epilimnion. As the mixolimnion becomes isothermal in winter, oxygen is mixed down to 28 m. Nutrients (NH4+, Si) and CH4 are released from the hypolimnion and mix to the surface, and a diatom bloom develops in the upper 20 m (chlorophyll a > 40 mgm-3). The deeper mixing of oxygen and enhanced light attenuation by phytoplankton uncouple the anoxic zone and photic zone, and the plate of photosynthetic bacteria disappears (Bchl a ca.10mgm-3). Hence, seasonal changes in temperature distribution and mixing create conditions such that the primary producer community is alternately dominated by phytoplankton and photosynthetic bacteria: the phytoplankton may be nutrient-limited during periods of stratification and the photosynthetic bacteria are light-limited during periods of mixing. ?? 1983 Dr W. Junk Publishers.

Effect of temperature on the breakthrough of a charcoal tube during vinyl chloride monomer sampling.

PubMed

Roh, J; Park, Y J; Kim, C N; Lim, N G; Lee, S H; Song, J S; Won, J U; Talaska, G

2000-01-01

This study evaluated the effects of temperature on breakthrough of two standard collection media at various concentrations during vinyl chloride monomer (VCM) sampling. The National Institute for Occupational Safety and Health (NIOSH) and Occupational Safety and Health Administration (OSHA) methods were evaluated. To determine whether breakthrough of VCM would occur at the extremes of exposure and temperature that might be encountered in some workplaces, air samples containing 4 ppm (10.24 mg/m3), 8 ppm (20.45 mg/m3), 16 ppm (40.98 mg/m3), and 32 ppm (81.80 mg/m3) of VCM were collected at temperatures of 4, 22, and 40 degrees C. Five liters of air was sampled at the rate of 0.05 L/min for 100 min using the activated charcoal tube recommended by NIOSH. A second tube was added to the sampling train to collect any VCM that might not have been absorbed in the first tube. To collect VCM air samples by the OSHA method, two carbon molecular sieve tubes were connected serially and 3 L of air was sampled at the rate of 0.05 L/min for 60 min. A gas chromatograph with a flame ionization detector and ultra 2 capillary column was used to analyze VCM. Significant breakthrough was found when sampling at higher temperatures with the NIOSH method. No breakthrough was found when samples were collected using the OSHA media at different temperatures and concentrations. Therefore, under hot ambient conditions (>22 degrees C), the possibility of breakthrough should be considered when sampling VCM by the NIOSH method.

Weekly docetaxel versus CMF as adjuvant chemotherapy for elderly breast cancer patients: safety data from the multicentre phase 3 randomised ELDA trial.

PubMed

Nuzzo, Francesco; Morabito, Alessandro; De Maio, Ermelinda; Di Rella, Francesca; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Pacilio, Carmen; Piccirillo, Maria Carmela; Rossi, Emanuela; D'Aiuto, Giuseppe; Thomas, Renato; Gori, Stefania; Colozza, Mariantonietta; De Placido, Sabino; Lauria, Rossella; Signoriello, Giuseppe; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2008-05-01

Within an ongoing multicentre phase 3 randomised trial (ELDA, cancertrials.gov ID: NCT00331097), early breast cancer patients, 65-79 years old, with average to high risk of recurrence, are randomly assigned to receive CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, fluorouracil 600 mg/m2, days 1-8) or docetaxel (35 mg/m2 days 1-8-15), every 4 weeks. Here we report an unplanned safety analysis prompted by an amendment introducing creatinine clearance as a tool to adjust methotrexate dose. Before such change, 101 patients with a median age of 70 were randomly assigned CMF (53 patients) or docetaxel (48 patients). At least one grades 3-4 toxic event of any type was reported in 40 (75.5%) and 19 (39.6%) patients with CMF and docetaxel, respectively (p=0.0002). Grades 3-4 hematological events were observed in 37 (69.8%) vs. 4 (8.3%) cases (p<0.0001) and grades 3-4 non-hematological toxicity in 12 (22.6%) vs. 15 (31.2%) patients (p=0.11), with CMF and docetaxel, respectively. A higher incidence of anemia, neutropenia, thrombocytopenia and febrile neutropenia was reported with CMF. Constipation, mucositis, nausea and vomiting were more common with CMF; diarrhoea, abdominal pain, dysgeusia, neuropathy and liver toxicity were more frequent with docetaxel. No significant interaction was found between the occurrence of severe toxicity and baseline variables, including creatinine clearance and geriatric activity scales. In conclusion, weekly docetaxel appears to be less toxic than CMF in terms of hematological toxicity.

Unmetabolized VOCs in urine as biomarkers of low level occupational exposure.

PubMed

Janasik, Beata; Jakubowski, Marek; Wesołowski, Wiktor; Kucharska, Małgorzata

2010-01-01

To compare the usefulness of determining unchanged forms of volatile organic compounds (VOCs), namely toluene (TOL), ethylbenzene (EB) and xylene (XYL), in urine with the effectiveness of the already used biomarkers of occupational exposure. Surveys were conducted in two workplaces (paint factory and footwear factory). In total, 65 subjects participated in the study. Air samples were collected using individual samplers during work shift. Urine and blood samples were collected at the end of work shift. Urine samples were analyzed for unchanged compounds and selected metabolites, while blood samples were tested for unchanged compounds. VOCs in blood and urine were determined by solid phase microextraction gas chromatography (SPME-GC-MS). In the paint factory, the geometric mean (GM) concentrations of VOCs in the air ranged as follows: 0.2-4.7 mg/m(3) for TOL, 0.4-40.9 mg/m(3) for EB and 0.1-122.6 mg/m(3) for XYL. In the footwear factory, the GM concentration of TOL in the air amounted to 105.4 mg/m(3). A significant correlation (p < 0.05) was observed between VOCs in blood, urine and air. The regression analyses performed for paint factory workers showed that TOL-U and TOL-B were better biomarkers of exposure (r = 0.72 and r = 0.81) than benzoic acid (r = 0.12) or o-cresol (r = 0.55). The findings of the study point out that the concentration of unchanged VOCs in urine can be a reliable biological indicator of low level occupational exposure to these compounds.

Characteristics of GHG flux from water-air interface along a reclaimed water intake area of the Chaobai River in Shunyi, Beijing

NASA Astrophysics Data System (ADS)

He, Baonan; He, Jiangtao; Wang, Jian; Li, Jie; Wang, Fei

2018-01-01

To understand greenhouse gas (GHG) flux in reclaimed water intake area impact on urban climate, 'static chamber' method was used to investigate the spatio-diurnal variations and the influence factors of GHG fluxes at water-air interface from Jian River to Chaobai River. Results showed that the average fluxes of CO2 from the Jian River and the Chaobai River were 73.46 mg(m2·h)-1 and -64.75 mg(m2·h)-1, respectively. CO2 was emitted the most in the Jian River, but it was absorbed from the atmosphere in the Chaobai River. Unary linear regression analyses demonstrated that Chlorophyll a (Chl a) and pH variation controlled the carbon source and sink from the Jian River to the Chaobai River. The diurnal variation of CO2 fluxes was higher at night than in the daytime in the Jian River, and it was the inverse in the Chaobai River, which highly correlated with dissociative CO2 and HCO3- transformation to CO32-. The average fluxes of CH4 from the Jian River and Chaobai River were 0.973 mg(m2·h)-1 and 5.556 mg(m2·h)-1, respectively, which increased along the water flow direction. Unary and multiple linear regression analyses demonstrated that Chl a and total organic carbon (TOC) controlled the increase of CH4 along the flow direction. The diurnal variation of CH4 fluxes was slightly higher in the daytime than at night due to the effect of water temperature.

Chlorambucil plus Rituximab as Front-Line Therapy in Elderly/Unfit Patients Affected by B-Cell Chronic Lymphocytic Leukemia: Results of a Single-Centre Experience

PubMed Central

Laurenti, Luca; Vannata, Barbara; Innocenti, Idanna; Autore, Francesco; Santini, Francesco; Piccirillo, Nicola; Za, Tommaso; Bellesi, Silvia; Marietti, Sara; Sica, Simona; Efremov, Dimitar G.; Leone, Giuseppe

2013-01-01

The current standard first line therapy for fit patients with B-CLL/SLL is based on combination of fludarabine-cyclophosphamide and rituximab. However, elderly patients or patients with comorbidities poorly tolerate purine analogue-based chemotherapy and they are often treated with Chlorambucil (Chl) only. However, complete response (CR) and overall response (OR) rates with Chl are relatively low. We now investigated whether the addition of Rituximab to Chl will improve the efficacy without impairing the tolerability in elderly and unfit patients. We included in our study 27 elderly or unfit patients that had not received prior therapy. All patients were treated with Chl (1mg/Kg per 28-day cycle for 8 cycles) plus Rituximab (375 mg/m2 for the first course and 500 mg/m2 for subsequent cycles until the 6th cycle). We obtained an OR rate of 74%. The most frequent adverse effect was grade 3–4 neutropenia, which occurred in 18.5% of the patients. Infections or grade 3–4 extra-hematological side effects were not recorded. None of the patients required reduction of dose, delay of therapy or hospitalization. Overall, these data suggest that Chl-R is an effective and well tolerated regimen in elderly/unfit patients with CLL. PMID:23667729

Breast metastasis of gastric signet-ring cell carcinoma: a case report and literature review.

PubMed

He, Chun-Lan; Chen, Ping; Xia, Bing-Lan; Xiao, Qin; Cai, Feng-Lin

2015-03-26

Cases of primary gastric adenocarcinoma with metastasis to the breast are extremely rare. Till now, only 38 cases have been reported in PubMed since 1908. We herein reported a race case of gastric adenocarcinoma with metastasis to the right breast. Breast biopsy showed invasive signet-ring cell breast carcinoma in the right breast. She was given a TEC regimen (docetaxel 75 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 600 mg/m(2) every 3 weeks) for one cycle but showed no objective response. Upper gastrointestinal endoscopy demonstrated an ulcerative mass in the gastric body. Biopsy demonstrated low-grade gastric adenocarcinoma with signet-ring features. In immunohistochemistry, mammary malignant cells were positive for cytokeratin 7, cytokeratin 20, villin, and ErbB2/HER2, but negative for gross cystic disease fluid protein-15, estrogen receptor, and progesterone receptor. The diagnosis of metastatic poorly differentiated signet-ring cell adenocarcinoma of the right breast identical to gastric primary was confirmed finally. Gastric cancer with metastasis to the breast can be diagnosed by clinical history, histological findings, and immunohistochemical markers.

[Adriamycin, cyclophosphamide, ftorafur and tamoxifen (ACFT) in patients with advanced breast cancer].

PubMed

Imajo, K; Ogawa, M; Horikoshi, N; Inoue, K; Mukaiyama, T; Ozeki, H; Nagamine, D; Shinagawa, K; Fukutani, H

1988-01-01

One hundred and six patients with advanced breast cancer were treated with chemoendocrine therapy consisting of adriamycin (40 mg/m2) i.v. on day 1 and cyclophosphamide (130 mg/m2) i.v. daily for 5 days every 3 weeks, ftorafur (500 mg/m2) and tamoxifen (40 mg) orally daily. Of 82 evaluable patients, 16 showed complete response (20%), 32 partial response (39%), 32 no change (39%), and two progressive disease (2%). The overall response rate was 59%, and the median duration of response was 16.3 (3.5-67+) months with a median survival time from the start of chemoendocrine therapy of 25.5 (3.5-67+) months. The median survival time of responders (32.5 months) was significantly longer than that of non-responders (15.3 months). The major toxicities were hair loss, G1 symptoms, and hematological toxicity, but these were clinically well tolerated. No serious cardiac, renal or liver damage was seen. These results indicated that the addition of tamoxifen to the ACF regimen increased the number of complete responses and prolonged the survival time of responders.

[Quantitative evaluation of health risk associated with occupational inhalation exposure to vinyl chloride at production plants in Poland].

PubMed

Szymczak, W

1997-01-01

Vinyl chloride is classified by the IARC in group 1-human carcinogens. In Poland occupational exposure to vinyl chloride is found among workers employed in many branches of industry, among others in the industry of vinyl chloride synthesis and polymerization as well as in the plastics, footwear, rubber, pharmaceutical and metallurgical industries. Concentrations observed range from the noon-determinable level to 90 mg/m3, at the MAC value equal to 5 mg/m3. Neoplasm of liver is a major carcinogenic effect of vinyl chloride. Hence, the health assessment focused on this critical risk. Four different linear dose-response models, developed by several authors and based on results of different epidemiological studies, were used to characterise the extent of cancer risk depending on the level of vinyl chloride concentrations. The estimated risk related to a forty-year employment under exposure equal to MAC values (5 mg/m3) fell within the range from 2.9.10(-4) to 2.6.10(-3). As the figures depict it did not exceed the acceptable level (10(-3)).

NEOADJUVANT СHEMOTHERAPY FOR LOCALLY ADVANCED BREAST CANCER.

PubMed

Fomenko, Y; Sirota, V; Omarova, I; Kabildina, N; Amanov, A

2017-03-01

93 patients with LABC (T2N1-2M0, T3N0-2M0) at the age from 35 to 75 years were included in the trial. With 2 stage - 60 patients, with the third stage - 33 patients. All patients were randomized into 3 groups: The I control group (n=36) received 4 courses of neoadjuvant chemotherapy according to AC-protocol (doxorubicin 50 mg/m2, cyclophosphan-500 mg/m2 on day 1, repeated every three weeks) followed by radical mastectomy, 4 courses of adjuvant chemotherapy (АС), radiotherapy and hormone therapy if indicated. II investigative group (n=30) received the same CTX but in combination with Arglabin at a dose of 370 mg/m2 for 7 days. III investigative group (n=27) received Arglabin as monotherapy. The clinical efficacy of neoadjuvant chemotherapy according to the scheme of AC and AC + arglabin was the same and significantly exceeded Arlabine monotherapy. There was no statistically significant difference in pathological response in patients of all three groups. Arglabin has very low toxicity and eliminates the toxic effects of standard chemotherapy.

Induction gemcitabine and oxaliplatin therapy followed by a twice-weekly infusion of gemcitabine and concurrent external-beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer: a single institutional experience.

PubMed

Leone, Francesco; Gatti, Marco; Massucco, Paolo; Colombi, Federica; Sperti, Elisa; Campanella, Delia; Regge, Daniele; Gabriele, Pietro; Capussotti, Lorenzo; Aglietta, Massimo

2013-01-15

Chemoradiotherapy (CRT) may render curative resection feasible in patients with locally advanced pancreatic carcinoma (LAPC). The authors previously demonstrated the achievement of significant disease control and a median survival of 14 months by CRT in patients with LAPC. In this study, they evaluated the use of induction chemotherapy followed by a CRT neoadjuvant protocol. Patients first received induction gemcitabine and oxaliplatin (GEMOX) (gemcitabine 1000 mg/m(2), oxaliplatin 100 mg/m(2)). Patients without disease progression then received gemcitabine twice weekly (50 mg/m(2) daily) concurrent with radiotherapy (50.4 grays) and were re-evaluated for resectability. Thirty-nine patients (15 with borderline resectable disease and 24 with unresectable disease) entered the study. The treatment was well tolerated. Disease control was obtained in 29 of 39 patients. Two patients progressed after GEMOX, and 7 progressed after CRT. After a median follow-up of 13 months, the median progression-free survival (PFS) was 10.2 months. The median PFS of patients with borderline resectable and unresectable disease was 16.6 and 9.1 months, respectively (P = .056). For the whole group, the median overall survival (OS) was 16.7 months (27.8 months for patients with borderline resectable disease, 13.3 for patients with unresectable disease; P = .045). Eleven patients (9 with borderline resectable disease and 2 with unresectable disease at diagnosis) underwent successful resection. Patients who underwent resection had a significantly longer median PFS compared with nonresected patients (19.7 months vs 7.6 months, respectively). The median OS among resected and nonresected patients was 31.5 months and 12.3 months, respectively (P < .001). The current results indicated that induction GEMOX followed by CRT is feasible in patients with LAPC. Both those with borderline resectable disease and those with unresectable disease received clinical benefit, a chance to obtain resectability, and improved survival. The authors concluded that this protocol warrants further evaluation. Copyright © 2012 American Cancer Society.

An evaluation of the GCA respirable dust monitor 101-1.

PubMed

Marple, V A; Rubow, K L

1978-01-01

The GCA RDM 101-1 has been evaluated using aerosols of coal, Arizona road dust, silica, potash, and rock (copper ore) particles. The effects of the dust mass concentration, particle size distribution, and dust material on the instrument response were investigated. The instrument was found to measure the mass concentrations of respirable dust aerosols up to about 16 mg/m3 for coal and rock dust and about 20 mg/m3 for silica, potash, and Arizona road dust, providing there is not appreciable mass in the size range below approximateley 0.7 micrometer aerodynamic diameter.

Environmental Assessment for Beddown of Air Force Reserve Command Classic Associate Unit on A/OA-10 Operations and Maintenance Moody Air Force Base, Georgia

DTIC Science & Technology

2008-09-01

Code of Federal Regulations CO carbon monoxide CSAF Chief of Staff of the Air Force dB decibels DNL day-night average sound level DNLmr onset rate...the health and welfare of the general public. These seven pollutants (the “criteria pollutants”) include ozone, carbon monoxide (CO), nitrogen... Monoxide 9 ppm (10 mg/m3) 8-hour (1) None 35 ppm (40 mg/m3) 1-hour (1) None Lead 1.5 µg/m3 Quarterly Average Same as Primary Nitrogen Dioxide 0.053

Dust exposure and pneumoconiosis in a South African pottery. 1. Study objectives and dust exposure.

PubMed Central

Rees, D; Cronje, R; du Toit, R S

1992-01-01

Dust exposure and pneumoconiosis were investigated in a South African pottery that manufactured wall tiles and bathroom fittings. This paper describes the objectives of the investigation and presents dust measurement data. x Ray diffraction showed that the clays used by the pottery had a high quartz content (range 58%-23%, mean 38%). Exposure to respirable dust was measured for 43 workers and was highest (6.6 mg/m3) in a bathroom fitting fettler. Quartz concentrations in excess of 0.1 mg/m3 were found in all sections of the manufacturing process from slip production to biscuit firing and sorting. The proportion of quartz in the respirable dust of these sections was 24% to 33%. This is higher than is usually reported in English potteries. Four hundred and six (80%) of the 509 workers employed at the pottery were potentially at risk of occupational lung disease. The finding of large numbers of pottery workers exposed to unacceptable dust concentrations is not surprising as poor dust control was found in all six wall tile and sanitary ware factories surveyed by the National Centre for Occupational Health between 1973 and 1989. Dust related occupational disease can be expected in potters for many years to come. PMID:1637705

Dust exposure and pneumoconiosis in a South African pottery. 1. Study objectives and dust exposure.

PubMed

Rees, D; Cronje, R; du Toit, R S

1992-07-01

Dust exposure and pneumoconiosis were investigated in a South African pottery that manufactured wall tiles and bathroom fittings. This paper describes the objectives of the investigation and presents dust measurement data. x Ray diffraction showed that the clays used by the pottery had a high quartz content (range 58%-23%, mean 38%). Exposure to respirable dust was measured for 43 workers and was highest (6.6 mg/m3) in a bathroom fitting fettler. Quartz concentrations in excess of 0.1 mg/m3 were found in all sections of the manufacturing process from slip production to biscuit firing and sorting. The proportion of quartz in the respirable dust of these sections was 24% to 33%. This is higher than is usually reported in English potteries. Four hundred and six (80%) of the 509 workers employed at the pottery were potentially at risk of occupational lung disease. The finding of large numbers of pottery workers exposed to unacceptable dust concentrations is not surprising as poor dust control was found in all six wall tile and sanitary ware factories surveyed by the National Centre for Occupational Health between 1973 and 1989. Dust related occupational disease can be expected in potters for many years to come.

Determination of exposure to respirable quartz in the stone crushing units at Azendarian-West of Iran.

PubMed

Bahrami, Abdul Rahman; Golbabai, Faridah; Mahjub, Hossien; Qorbani, Farshid; Aliabadi, Mohsan; Barqi, Mohamadali

2008-08-01

The purpose of this study is to describe the personal exposure to respirable dust and quartz and in stone crushing units located at west of Iran. A size of 40 personal samples and 40 stationary samples were obtained and analysis was done by X-ray diffraction (XRD). The results of personal sampling were shown the concentrations of respirable dust exposure level in workers of process, hopper and drivers were 1.90, 2.22, 1.41 times greater than Occupational Safety and Health Administration permissible exposure limit (OSHA PEL). The average value of total dust and respirable dust emission from stationary sources was 9.46 mg/m(3), 1.24 mg/m(3) respectively, showing that 13.8 % of total dust is respirable. The efficiency of local exhaust ventilation (LEV) to control of particles inside of industrial units was greater than 99%. It is concluded from this research the particulate generated from stone crushing activities contain a significant amount of respirable particle. The amount of free silica in stone quartz is 85 to 97 percent that emission of particles effect to health workers. LEV has important effect in the removal of silica particles in stone crushing units. The worker of hoppers still exposed to silica more than standard limits.

Atmospheric corrosion performance of different steels in early exposure in the coastal area region West Java, Indonesia

NASA Astrophysics Data System (ADS)

Nuraini, Lutviasari; Prifiharni, Siska; Priyotomo, Gadang; Sundjono, Gunawan, Hadi; Purawiardi, Ibrahim

2018-05-01

The performance of carbon steel, galvanized steel and aluminium after one month exposed in the atmospheric coastal area, which is in Limbangan and Karangsong Beach, West Java, Indonesia was evaluated. The corrosion rate was determined by weight loss method and the morphology of the steel after exposed was observed by Scanning Electron Microscopy(SEM)/Energy Dispersive X-Ray Analysis(EDX). The site was monitored to determine the chloride content in the marine atmosphere. Then, the corrosion products formed at carbon steel were characterized by X-Ray diffraction (XRD). The result showed the aggressively corrosion in Karangsong beach, indicated from the corrosion rate of carbon steel, galvanized steel and aluminium were 38.514 mpy; 4.7860 mpy and 0.5181 mpy, respectively. While in Limbangan Beach the corrosion rate of specimen carbon steel, galvanized steel and aluminium were 3.339; 0.219 and 0.166 mpy, respectively. The chloride content was found to be the main factor that influences in the atmospheric corrosion process in this area. Chloride content accumulated in Karangsong and Limbangan was 497 mg/m2.day and 117 mg/m2.day, respectively. The XRD Analysis on each carbon steel led to the characterization of a complex mixture of iron oxides phases.

Mitochondrial shaping cuts.

PubMed

Escobar-Henriques, Mafalda; Langer, Thomas

2006-01-01

A broad range of cellular processes are regulated by proteolytic events. Proteolysis has now also been established to control mitochondrial morphology which results from the balanced action of fusion and fission. Two out of three known core components of the mitochondrial fusion machinery are under proteolytic control. The GTPase Fzo1 in the outer membrane of mitochondria is degraded along two independent proteolytic pathways. One controls mitochondrial fusion in vegetatively growing cells, the other one acts upon mating factor-induced cell cycle arrest. Fusion also depends on proteolytic processing of the GTPase Mgm1 by the rhomboid protease Pcp1 in the inner membrane of mitochondria. Functional links of AAA proteases or other proteolytic components to mitochondrial dynamics are just emerging. This review summarises the current understanding of regulatory roles of proteolytic processes for mitochondrial plasticity.

Terpene exposure and respiratory effects among workers in Swedish joinery shops.

PubMed

Eriksson, K A; Levin, J O; Sandström, T; Lindström-Espeling, K; Lindén, G; Stjernberg, N L

1997-04-01

Exposure to monoterpenes (alpha-pinene, beta-pinene and delta 3-carene) in joinery shops was studied in Sweden during the processing of Scot's pine, and the acute respiratory effects among the employees were evaluated. A cross-sectional study of 38 workers was carried out in 4 joinery shops. The investigation included personal air sampling of monoterpenes, biological monitoring of metabolites of alpha-pinene in the workers' urine, interviews following a standardized questionnaire, and dynamic spirometry. The personal exposure to monoterpenes in the joinery shops was 10-214 mg/m3. The correlation (correlation coefficient = 0.69) between exposure to alpha-pinene and verbenols (metabolites from alpha-pinene) in urine was relatively good. No acute effects on forced vital capacity or forced expiratory volume during 1 s were detected. The workers had significantly reduced preshift lung function values when compared with the values of a local reference group, even when smokers and ex-smokers were excluded. Personal exposure to the monoterpenes alpha-pinene, and delta 3-carene in joinery shops may exceed the present Swedish occupational exposure limit of 150 mg/m3 during the winter season when workroom air is commonly recirculated. The determination of metabolites of alpha-pinene (verbenols) in urine can be used as an index of exposure to fumes released during wood-treating processes. The results from the lung function tests indicate chronic rather than acute reactions in the airways. The fact that there were no major changes in lung function over a workshift indicates chronic reaction in the airways.

A Phase I Study of Reduced-Intensity Conditioning and Allogeneic Stem Cell Transplantation Followed by Dose Escalation of Targeted Consolidation Immunotherapy with Gemtuzumab Ozogamicin in Children and Adolescents with CD33+ Acute Myeloid Leukemia.

PubMed

Zahler, Stacey; Bhatia, Monica; Ricci, Angela; Roy, Sumith; Morris, Erin; Harrison, Lauren; van de Ven, Carmella; Fabricatore, Sandra; Wolownik, Karen; Cooney-Qualter, Erin; Baxter-Lowe, Lee Ann; Luisi, Paul; Militano, Olga; Kletzel, Morris; Cairo, Mitchell S

2016-04-01

Myeloablative conditioning and allogeneic hematopoietic stem cell transplant (alloHSCT) in children with acute myeloid leukemia (AML) in first complete remission (CR1) may be associated with significant acute toxicity and late effects. Reduced-intensity conditioning (RIC) and alloHSCT in children is safe, feasible, and may be associated with less adverse effects. Gemtuzumab ozogamicin (GO) induces a response in 30% of patients with CD33+ relapsed/refractory AML. The dose of GO is significantly lower when combined with chemotherapy. We examined the feasibility and toxicity of RIC alloHSCT followed by GO targeted immunotherapy in children with CD33+ AML in CR1/CR2. Conditioning consisted of fludarabine 30 mg/m2 × 6 days, busulfan 3.2 to 4 mg/kg × 2 days ± rabbit antithymocyte globulin 2 mg/kg × 4 days followed by alloHSCT from matched related/unrelated donors. GO was administered ≥60 days after alloHSCT in 2 doses (8 weeks apart), following a dose-escalation design (4.5, 6, 7.5, and 9 mg/m2). Fourteen patients with average risk AML received RIC alloHSCT and post-GO consolidation: median age 13.5 years at transplant (range, 1 to 21), male-to-female 8:6, and disease status at alloHSCT 11 CR1 and 3 CR2. Eleven patients received alloHSCT from 5-6/6 HLA-matched family donors: 8 received peripheral blood stem cells, 2 received bone marrow, and 1 received related cord blood transplantation. Three patients received an unrelated allograft (two 4-5/6 and one 9/10) from unrelated cord blood unit and bone marrow, respectively. Neutrophil and platelet engraftment was observed in all assessable patients (100%), achieved at median 15.5 days (range, 7 to 31) and 21 days (range, 10 to 52), respectively. Three patients received GO at dose level 1 (4.5 mg/m2 per dose), 5 at dose level 2 (6 mg/m2 per dose), 3 at dose level 3 (7.5 mg/m2 per dose), and 3 at dose level 4 (9 mg/m2 per dose). Three of 14 patients received only 1 dose of GO after alloHSCT. One patient experienced grade III transaminitis, which resolved; no grade IV transaminitis, no grade III/IV hyperbilirubinemia, or sinusoidal obstructive syndrome were observed. The second dose of GO was given at median of 143 days (range, 120 to 209) after alloHSCT. Probability of grades II to IV acute and chronic graft-versus-host disease were 21% and 33.5%, respectively. Probability of overall survival after RIC alloHSCT and GO consolidation at 1 and 5 years was 78% and 61%, respectively. Probability of 5-year event-free survival after RIC alloHSCT and GO consolidation in patients in CR1 was 78%. No dose-limiting toxicities probably or directly related to GO were observed in this cohort. This preliminary data demonstrate that RIC followed by alloHSCT and consolidation with GO appears to be safe in children and adolescents with CD33+ AML in CR1/CR2. A phase II trial is currently underway investigating this approach with a GO dose of 9 mg/m2 per dose. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Inhalation toxicity of potassium octatitanate fibers (TISMO) in rats following 13 weeks of aerosol exposure.

PubMed

Ikegami, T; Taniguchi, M; Singer, A W; Brooker, M J; Yarrington, J; Placke, M E; Lee, K P

2000-05-01

One hundred and forty male and 140 female rats were divided into 1 control and 3 test groups of 35 rats each, per sex, and exposed by whole-body inhalation to test compound at target concentrations of 0, 1 mg/m(3) (1700 fibers/cm(3), 123 WHO fibers/cm(3)), 10 mg/m(3) (5900 fibers/cm(3), 952 WHO fibers/cm(3)), and 100 mg/m(3) (112,700 fibers/cm(3), 7440 WHO fibers/cm(3)) for 6 h/day, 5 days/wk for 13 wk. Ten rats from each group were killed after 13 wk of exposure and 13 wk of recovery, respectively, for histopathological evaluation. The other 15 rats from each group were killed to study lung clearance after 91 days of exposure, and approximately 1.5 and 3 mo of recovery following the end of the 13 wk of exposure. The mean fiber length of the chamber atmosphere was 2.8, 2.7, and 2.8 microm, while the mean fiber width was 0.48, 0.48, and 0.45 microm for the 1-, 10-, and 100-mg/m(3) chambers, respectively. In the 1-mg/m(3) (123 WHO fibers/cm(3)) exposure group, inhaled particles were mostly retained in a few fiber-laden alveolar macrophages (AMs) within the alveoli adjacent to alveolar ducts without any adverse tissue response throughout 13 wk of exposure and following 13 wk of recovery. This exposure concentration was considered to be a no-observable-adverse-effect level (NOAEL), since the alveoli containing fiber-laden AMs preserved normal structure. After 13 wk of exposure to 10 mg/m(3) (952 WHO fibers/cm(3)), fiber-laden AMs were mainly retained at the alveoli adjacent to the alveolar ducts. Infrequently, slight fibrotic thickening was observed in the alveolar ducts and adjoining alveoli, with proliferating fibroblasts and hyperplastic Type II pneumocytes, and microgranulomas. Occasionally, trace amounts of collagenous material were deposited in the thickened alveolar ducts and adjoining alveolar walls. In addition, minimal alveolar bronchiolarization was occasionally found in the alveoli adjacent to the terminal bronchioles. The peribronchial lymphoid tissue and thymic lymph nodes contained migrated fiber-laden AMs. After 13 wk of recovery, fiber-laden AMs had mostly disappeared from alveoli located in the peripheral acini, but they localized in the alveolar ducts region, suggesting there was active lung clearance of fibers by the AMs via airways. Thickened alveolar ducts and adjacent alveoli were decreased in thickness, a reversible change manifested by reduction of proliferating Type II pneumocytes and fibroblasts. Collagenized fibrosis was slightly more pronounced in the thickened alveolar ducts and adjoining alveoli. The lung response following 13 wk of exposure to 100 mg/m(3) (7440 WHO fibers/cm(3)) and after 13 wk of recovery was similar to those findings of the 952 WHO fibers/cm(3) group but more pronounced, demonstrating a clear concentration-related response. Alveolar ducts and adjoining alveolar walls in the central acini were irregularly thickened with more frequent evidence of minimal collagenized fibrosis. The lung burden and clearance of fibers were estimated by measuring the total content of titanium (Ti) in the lungs, but high variability of Ti content in control and exposed groups prevented meaningful lung clearance analysis.

SAFETY, EFFICACY, PHARMACOKINETICS AND PHARMACODYNAMICS OF THE COMBINATION OF SORAFENIB AND TANESPIMYCIN

PubMed Central

Vaishampayan, Ulka N.; Burger, Angelika M.; Sausville, Edward A.; Heilbrun, Lance K.; Li, Jing; Horiba, Naomi; Egorin, Merrill J.; Ivy, Percy; Pacey, Simon; Lorusso, Patricia M.

2010-01-01

PURPOSE Heat shock protein 90 inhibition affects the Raf-kinase signaling pathway and could enhance anti-tumor effects of sorafenib, a Raf-kinase inhibitor. The combination of sorafenib and tanespimycin (17-AAG/17-allyl-amino-geldanamycin; NSC # 330507/KOS-953) was evaluated in a phase I trial with the primary objective of defining a phase II dose PATIENTS AND METHODS The dose cohorts consisted of fixed continuous oral dosing of sorafenib 400 mg twice daily, starting 14 days prior to tanespimycin which was administered intravenously, at escalating doses, (starting at 300 mg/m,2 with 50 mg/m2 increments), on days 1, 8 and 15, in a 28-day cycle. Toxicity was assessed weekly; response was evaluated every 2 cycles. RESULTS Twenty-seven toxicity-evaluable patients were enrolled and treated at four dose levels. Predominant primary malignancies were: renal cancer (12), melanoma (6) and colorectal cancer (4). Dose-limiting toxicities of grade 4 transaminitis and grade 3 hand-foot syndrome in 1 patient each were observed at 450 mg/m2 of tanespimycin. 114 cycles were administered with a median of four cycles (range 1–17 cycles). Plasma concentrations of sorafenib and metabolites reached steady-state after 7 days. Tanespimycin did not alter sorafenib concentrations. Pharmacodynamics showed a decrease in Hsp90 levels and induction of Hsp70. Clinical efficacy was observed in 9 of 12 renal cancer patients and 4 of 6 melanoma patients CONCLUSIONS Recommended phase II doses of this combination are sorafenib 400 mg twice daily and tanespimycin 400 mg/m2 on days 1, 8 and 15 every 28 days. Clinical and pharmacodynamic activity was observed in kidney cancer and melanoma. PMID:20525756

Exposure to respirable dust and manganese and prevalence of airways symptoms, among Swedish mild steel welders in the manufacturing industry.

PubMed

Hedmer, Maria; Karlsson, Jan-Eric; Andersson, Ulla; Jacobsson, Helene; Nielsen, Jörn; Tinnerberg, Håkan

2014-08-01

Welding fume consists of metal fumes, e.g., manganese (Mn) and gases, e.g., ozone. Particles in the respirable dust (RD) size range dominate. Exposure to welding fume could cause short- and long-term respiratory effects. The prevalence of work-related symptoms among mild steel welders was studied, and the occupational exposure to welding fumes was quantified by repeated measurements of RD, respirable Mn, and ozone. Also the variance components were studied. A questionnaire concerning airway symptoms and occupational history was answered by 79% of a cohort of 484 welders. A group of welders (N = 108) were selected and surveyed by personal exposure measurements of RD and ozone three times during 1 year. The welders had a high frequency of work-related symptoms, e.g., stuffy nose (33%), ocular symptoms (28%), and dry cough (24%). The geometric mean exposure to RD and respirable Mn was 1.3 mg/m(3) (min-max 0.1-38.3 mg/m(3)) and 0.08 mg/m(3) (min-max <0.01-2.13 mg/m(3)), respectively. More than 50% of the Mn concentrations exceeded the Swedish occupational exposure limit (OEL). Mainly, low concentrations of ozone were measured, but 2% of the samples exceeded the OEL. Of the total variance for RD, 30 and 33% can be attributed to within-worker variability and between-company variability, respectively. Welders had a high prevalence of work-related symptom from the airways and eyes. The welders' exposure to Mn was unacceptably high. To reduce the exposure further, control measures in the welding workshops are needed. Correct use of general mechanical ventilation and local exhaust ventilation can, for example, efficiently reduce the exposure.

A Phase I Study of Hepatic Arterial Infusion of Nab-Paclitaxel in Combination with Intravenous Gemcitabine and Bevacizumab for Patients with Advanced Cancers and Predominant Liver Metastases

PubMed Central

Tsimberidou, Apostolia M.; Ye, Yang; Wheler, Jennifer; Naing, Aung; Hong, David; Nwosu, Uchechi; Hess, Kenneth R.; Wolff, Robert A.

2014-01-01

PURPOSE We conducted a Phase I clinical trial for patients with advanced cancer and predominant liver disease. EXPERIMENTAL DESIGN Patients were treated with HAI nab-paclitaxel (120-210 mg/m2; day 1); intravenous bevacizumab (10 mg/kg; day 1); and intravenous gemcitabine (600-800 mg/m2; days 1 and 8). A conventional “3 + 3” study design was used. RESULTS Fifty patients with advanced cancer and predominant liver metastases were treated (median age, 58 years; 27 women, 23 men; median number of prior therapies, 3 [range, 0-12]). The most common cancers were breast (n=9) and pancreatic (n=9). Overall, 264 cycles were administered (median/patient, 4; range, 1-17). No dose-limiting toxicities were noted during the escalation phase. On dose level 4, 3 patients were unable to receive gemcitabine on day 8 because of severe thrombocytopenia. Dose level 3 was selected as the maximum tolerated dose (HAI nab-paclitaxel 180 mg/m2 and intravenous gemcitabine 800 mg/m2 and bevacizumab 10 mg/kg); Thirty-two patients were treated in the expansion phase. The most common treatment-related toxicities were thrombocytopenia (n=17), neutropenia (n=10), and fatigue (n=12). Of 46 patients evaluable for response, 9 (20%) had a partial response [1] and 9 (20%) had stable disease for {greater than or equal to} 6 months. The median overall survival duration was 7.0 months (95% CI: 4, 22 months) and the median progression-free survival duration was 4.2 months (95% CI: 2.7, 8.6 months). CONCLUSIONS HAI nab-paclitaxel in combination with gemcitabine and bevacizumab was well tolerated and had antitumor activity in selected patients with advanced cancer and liver metastases. PMID:23377373

Development of a job-exposure matrix for exposure to total and fine particulate matter in the aluminum industry

PubMed Central

Noth, Elizabeth M.; Dixon-Ernst, Christine; Liu, Sa; Cantley, Linda; Tessier-Sherman, Baylah; Eisen, Ellen A.; Cullen, Mark R.; Hammond, S. Katharine

2014-01-01

Increasing evidence indicates that exposure to particulate matter (PM) at environmental concentrations increases the risk of cardiovascular disease, particularly PM with an aerodynamic diameter of less than 2.5μm (PM2.5). Despite this, the health impacts of higher occupational exposures to PM2.5 have rarely been evaluated. In part, this research gap derives from the absence of information on PM2.5 exposures in the workplace. To address this gap, we have developed a job-exposure matrix (JEM) to estimate exposure to two size fractions of PM in the aluminum industry. Measurements of total PM (TPM) and PM2.5 were used to develop exposure metrics for an epidemiologic study. TPM exposures for distinct exposure groups (DEGs) in the JEM were calculated using 8,385 personal TPM samples collected at 11 facilities (1980-2011). For 8 of these facilities, simultaneous PM2.5 and TPM personal monitoring was conducted from 2010-2011 to determine the percent of TPM that is composed of PM2.5 (%PM2.5) in each DEG. The mean TPM from the JEM was then multiplied by %PM2.5 to calculate PM2.5 exposure concentrations in each DEG. Exposures in the smelters were substantially higher than in fabrication units; mean TPM concentrations in smelters and fabrication facilities were 3.86 mg/m3 and 0.76 mg/m3, and the corresponding mean PM2.5 concentrations were 2.03 mg/m3 and 0.40 mg/m3. Observed occupational exposures in this study generally exceeded environmental PM2.5 concentrations by an order of magnitude. PMID:24022670

Double modulation of 5-fluorouracil by methotrexate and high-dose L-leucovorin in advanced colorectal cancer.

PubMed

Romero, A O; Perez, J E; Cuevas, M A; Lacava, J A; Sabatini, C L; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Salvadori, M A; Acuña, L A; Acuña, J M; Langhi, M J; Amato, S; Machiavelli, M R; Leone, B A; Vallejo, C T; Lorusso, V; DeLena, M

1998-02-01

A phase II trial was performed to evaluate the efficacy and toxicity of a double modulation of 5-fluorouracil (5-FU) by methotrexate (MTX) and L-leucovorin (L-LV) in patients with advanced recurrent (inoperable) or metastatic colorectal carcinoma (ACC). Between July 1993 and October 1995, 41 patients with ACC received a regimen that consisted of MTX 150 mg/m2 i.v., infused over a 20-minute period at hour 0, followed 19 hours later by L-LV 250 mg/m2 in a 2-hour i.v. infusion. 5-FU, 900 mg/m2, was administered by i.v. push injection at hour 20. Beginning 24 hours after MTX administration, all patients received four doses of L-LV, 15 mg/m2 i.m., every 6 hours. Cycles were repeated every 15 days. Two patients were not assessable for response. Objective regression was observed in 11 of 39 (28%) patients, [95% confidence interval (CI), 14-42%]. One (2%) patient achieved complete response (CR) and 10 (26%) partial response (PR). No change was recorded in 15 (39%) patients and progressive disease was noted in 13 (33%) patients. The median time to treatment failure was 6 months and the median survival time was 10 months. Toxicity was within acceptable limits, but one therapy-related death due to severe leukopenia was observed. The dose-limiting toxicity was mucositis. Eight episodes of grade 3 or 4 stomatitis were observed, and were responsible for dosage modifications of MTX and 5-FU. In conclusion, further in experimental and clinical studies are clearly necessary in order to design the best modulatory strategy of 5-FU.

Ifosfamide and vinorelbine as first-line chemotherapy for metastatic breast cancer.

PubMed

Leone, B A; Vallejo, C T; Romero, A O; Perez, J E; Cuevas, M A; Lacava, J A; Sabatini, C L; Dominguez, M E; Rodriguez, R; Barbieri, M R; Ortiz, E H; Salvadori, M A; Acuña, L A; Acuña, J M; Langhi, M J; Amato, S; Machiavelli, M R

1996-11-01

To evaluate the efficacy and toxicity of the combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in metastatic breast cancer (MBC). Between August 1993 and August 1995, 45 patients with untreated MBC received a regimen that consisted of IFX 2 g/m2 by 1-hour intravenous (i.v.) infusion on days 1 to 3, mesna 400 mg/m2 by i.v. bolus at hours 0 and 4 and 800 mg/m2 orally at hour 8 on days 1 to 3, and VNB 35 mg/m2 by 20-minute i.v. infusion on days 1 and 15. Courses were repeated every 28 days. During the first course only, half-dose VNB (17.5 mg/m2) was administered on days 8 and 22. The median age was 53 years and 30 patients (67%) were postmenopausal. Dominant sites of disease were soft tissue in nine patients, bone in seven, and visceral in 29. Objective responses (ORs) were recorded in 25 of 43 assessable patients (58%; 95% confidence interval, 43% to 73%). Complete remissions (CRs) occurred in six patients (14%) and partial remissions (PRs) in 19 (44%). No change (NC) was recorded in 10 patients (23%) and progressive disease (PD) in eight patients (19%). The median time to treatment failure was 12 months and the median survival duration 19 months. Myelosuppression was the limiting toxicity, mainly leukopenia in 32 patients (74%). In contrast, anemia and thrombocytopenia were mild. Other significant toxicities included peripheral neuropathy in nine patients (21%), constipation in 15 (35%), and myalgias in 11 (26%). IFX/VNB is an active combination against MBC with moderate toxicity and deserves further evaluation.

Respiratory exposures associated with silicon carbide production: estimation of cumulative exposures for an epidemiological study.

PubMed Central

Smith, T J; Hammond, S K; Laidlaw, F; Fine, S

1984-01-01

Silicon carbide is produced by heating a mixture of petroleum coke and silica sand to approximately 2000 degrees C in an electric furnace for 36 hours. During heating, large amounts of carbon monoxide are released, sulphur dioxide is produced from residual sulphur in the coke, and hydrocarbon fume is produced by pyrolysis of the coke. Loading and unloading furnaces causes exposures to respirable dust containing crystalline silica, silicon carbide, and hydrocarbons. In the autumn of 1980 extensive measurements were made of personal exposures to air contaminants. Eight hour time weighted exposures to sulphur dioxide ranged from less than 0.1 ppm to 1.5 ppm and respirable participate exposures ranged from 0.01 mg/m3 to 9.0 mg/m3. Geometric mean particulate exposures for jobs ranged from 0.1 mg/m3 to 1.46 mg/m3. The particulate contained varying amounts of alpha-quartz, ranging from less than 1% to 17%, and most quartz exposures were substantially below the threshold limit value of 100 micrograms/m3. Only traces of cristobalite (less than 1%) were found in the particulate. Median exposures to air contaminants in each job were estimated. Since the operations at the plant had been stable over the past 30 years, it was possible to estimate long term exposures of workers to sulphur dioxide, respirable particulate, quartz, total inorganic material, and extractable organic material. Cumulative exposure (average concentration times exposure duration) for each of the air contaminants was estimated for each worker using his job history. There was sufficient independent variability in the sulphur dioxide and respirable particulate cumulative exposures to make an assessment of their independent effects feasible. The theoretical basis for using the cumulative exposure index and its shortcomings for epidemiological applications were presented. PMID:6691927

Randomized phase II study comparing gemcitabine plus dacarbazine versus dacarbazine alone in patients with previously treated soft tissue sarcoma: a Spanish Group for Research on Sarcomas study.

PubMed

García-Del-Muro, Xavier; López-Pousa, Antonio; Maurel, Joan; Martín, Javier; Martínez-Trufero, Javier; Casado, Antonio; Gómez-España, Auxiliadora; Fra, Joaquín; Cruz, Josefina; Poveda, Andrés; Meana, Andrés; Pericay, Carlos; Cubedo, Ricardo; Rubió, Jordi; De Juan, Ana; Laínez, Nuria; Carrasco, Juan Antonio; de Andrés, Raquel; Buesa, José M

2011-06-20

To assess the activity and toxicity of the combination of gemcitabine plus dacarbazine (DTIC) in patients with advanced soft tissue sarcoma (STS) in a randomized, multicenter, phase II study using DTIC alone as a control arm. Patients with previously treated advanced STS were randomly assigned to receive either fixed-dose rate gemcitabine (10 mg/m2/min) at 1800 mg/m2 followed by DTIC at 500 mg/m2 every 2 weeks, or DTIC alone at 1200 mg/m2 every 3 weeks. The primary end point of the study was progression-free rate (PFR) at 3 months. From November 2005 to September 2008, 113 patients were included. PFR at 3 months was 56% for gemcitabine plus DTIC versus 37% for DTIC alone (P = .001). Median progression-free survival was 4.2 months versus 2 months (hazard ratio [HR], 0.58; 95% CI, 0.39 to 0.86; P = .005), and median overall survival was 16.8 months versus 8.2 months (HR, 0.56; 95% CI, 0.36 to 0.90; P = .014); both favored the arm of gemcitabine plus DTIC. Gemcitabine plus DTIC was also associated with a higher objective response or higher stable disease rate than was DTIC alone (49% v 25%; P = .009). Severe toxicities were uncommon, and treatment discontinuation for toxicity was rare. Granulocytopenia was the more common serious adverse event, but febrile neutropenia was uncommon. Asthenia, emesis, and stomatitis were the most frequent nonhematologic effects. The combination of gemcitabine and DTIC is active and well tolerated in patients with STS, providing in this phase II randomized trial superior progression-free survival and overall survival than DTIC alone. This regimen constitutes a valuable therapeutic alternative for these patients.

Oxaliplatin in patients with metastatic colorectal cancer: efficacy and pharmacokinetics parameters.

PubMed

Burz, C; Berindan-Neagoe, I; Balacescu, O; Todor, N; Pelau, D; Floares, C; Kacso, G; Tanaselia, C; Ursu, M; Vlase, L; Leucuta, S E; Cristea, V; Irimie, A

2010-01-01

The aim of this study was to investigate the efficiency of the FOLFOX-4 regimen and to evaluate the pharmacokinetics of oxaliplatin in untreated patients with metastatic colorectal cancer. 43 patients were enrolled in the study. Patients received oxaliplatin 85 mg/m(2) as 2-h i.v. infusion, on day 1, and bolus 5-fluorouracil (5FU) 400 mg/m(2) plus leucovorin (LV) 200 mg/m(2) followed by 5FU 600 mg/m(2) as 22-h infusion on day 1 and 2, every 2 weeks. The pharmacokinetics of oxaliplatin evaluated in 4 patients was performed in blood, plasma and ultrafiltered plasma (UFT) by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The overall response rate and the median time to progression (TTP) were 53.49% and 7.1 months, respectively. Grade 3-4 toxic effects were observed in 11 (25.5%) patients. Grade 3 neuropathy was observed in 13.95% of the cases. In univariate analysis only Eastern Cooperative Oncology Group (ECOG) performance status (PS) was correlated with response. No correlation was found between grade 3-4 adverse events and the patient characteristics. The area under the time-concentration curve (AUC) in UFT was 4.8 + or - 0.72 standard deviation (SD) microg h/ml and the total clearance 30.17 + or - 7.75 l/min. The values for volume of distribution and the maximum concentration were 567 + or - 20 liters and 0.38 + or - 0.17 ug/ml, respectively. FOLFOX-4 was an effective regimen with good tolerability in previously untreated metastatic colorectal cancer patients. The pharmacokinetics of oxaliplatin was triphasic with a short initial distribution phase and a long terminal elimination phase.

[Prospective randomized study of HMVP, MVP, and HVP regimens in treatment of advanced non-small cell lung cancer].

PubMed

Gao, Jian-Fei; Li, Chang-Sheng; Zhang, Bi-Cheng; Du, Guang-Zu; Zhang, Xin-Hua; Wang, Jun; Zhu, Yu-Ze; Ou, Wu-Ling; Yang, Bo

2004-04-01

Non-small cell lung cancer (NSCLC) is hyposensitive to the normal first and second-line chemotherapy regimens. Camptothecin derivative is becoming a hot point in the treatment of advanced NSCLC. The objective of this article was to evaluate the response, toxicity, and survival time of HMVP, MVP, and HVP regimens (detail in below) in the treatment of advanced NSCLC. A total of 134 cases with advanced NSCLC was randomized into three groups: HMVP group [46 patients, hydroxycamptothecin (HCPT) 12 mg/m(2) from d1 to d5, mitomycin C (MMC) 6 mg/m(2) d1, vindesine (VDS) 2.5-3 mg/m(2) d1 and d8, cisplatin (DDP) 50 mg/m(2) d2 and d3], MVP group (44 patients, MMC, VDS and DDP were the same as HMVP group) and HVP group (44 patients, HCPT, VDS, DDP were the same as HMVP group). The response rates were 39.54% (17/43), 35.57% (15/42), and 26.19% (11/42) in HMVP, MVP, and HVP groups, respectively; no significant difference was detected among the three groups (P >0.05). No significant difference was detected in the median time of remission, median survival time, and 1-, 2-year survival rates among the three groups. Moreover, no significant difference was detected in grade III-IV leukopenia, grade III-IV thrombocytopenia, grade III-IV nausea and vomiting and grade III-IV constipation among the three groups. The response rate of MVP regimen is slightly lower than that of HMVP regimen, but HMVP regimen do not show obvious superiority. It may increase toxicities such as leukopenia, nausea/vomiting, and constipation. The response rate of HVP regimen is slightly lower than that of MVP regimen.

[Clinical efficacy and adverse effects of taxol plus carboplatin or gemcitabine plus carboplatin in patients with advanced non-small-cell lung carcinoma].

PubMed

Wang, Xiao-Yun; Zhao, Yu-Liang

2010-12-21

To observe the clinical efficacy and adverse effects of taxol plus carboplatin (TP) or gemcitabine plus carboplatin (GP) in patients with advanced non-small-cell lung carcinoma. A total of 86 patients with advanced non-small-cell lung carcinoma with a histologically confirmed diagnosis at our department were treated with at least two cycles of drug therapy according to the WHO standard. There were 43 cases in TP group and 43 cases in GP group. TP group: taxol 150 mg/m(2), d1, carboplatin 300 mg/m(2) in d1; GP group: gemcitabine 1000 mg/m(2), 30 min, d1, 8, carboplatin 300 mg/m(2) in d1, 3 weeks a cycle. The efficacy and side effects were analyzed after two cycles of chemotherapy. When TP and GP groups were compared, the effective rate was 44.2% vs 39.5%; disease control rate (CR + PR + SD): 81.4% vs 74.4%; median time to progress (TTP): 4.6 vs 4.5 months; medium survivals: 8.6 vs 8.8 months; 1-year survival rates: 17.2% vs 18.1%; 2-year survival rates: 8% vs 10%. The statistic analysis showed that the two groups had no significant difference. The main cytotoxicities of GP and TP groups were predominantly thrombocytopenia and leucopenia respectively. The two groups had no significant statistical difference. The incidences of allergen, alopecia and peripheral neurotoxicity were higher in the TP group. The two groups had statistical difference. Tolerance was excellent in both groups. The therapeutic effect and tolerance are excellent for advanced non-small cell lung carcinoma. The efficacy and survival rate of two groups show no statistical difference.

A Phase II Study of Docetaxel, Cisplatin and 5- Fluorouracil (TPF) In Patients with Locally Advanced Head and Neck Carcinomas.

PubMed

Ansari, M; Omidvari, S; Mosalaei, A; Ahmadloo, N; Mosleh-Shirazi, M A; Mohammadianpanah, M

2011-03-01

The combination of cisplatin and 5-fluorouracil (PF) is currently considered a standard and effective regimen for the treatment of advanced head and neck carcinomas. The aim of this study was to evaluate the efficacy and safety of docetaxel, cisplatin and 5-fluorouracil (TPF) in patients with unresectable head and neck carcinomas. Forty-six patients with previously untreated non-metastatic stage IV head and neck carcinomas were enrolled. All patients received three cycles of induction chemotherapy with docetaxel (75 mg/m(2)), cisplatin (40 mg/m(2)) (days 1-2), and 5-FU (500 mg/m(2), days 1-3), repeated every 21 days. Following induction chemotherapy, all patients underwent concurrent chemoradiotherapy using weekly cisplatin (30 mg/m(2)) and a median total dose of 70 Gy was delivered. Clinical response rate and toxicity were the primary and secondary end-points of the study. There were 31 men and 15 women. All patients had non-metastatic stage IV (T2-3N2-3 or T4N0-3) of disease. Overall and complete response rates were 74% and 24% respectively. Advanced T4 classification was associated with poorer response rate (p value=0.042). The major (grade 3-4) treatment-related toxicities were myelosuppression (78%), anorexia (13%), diarrhea (7%), emesis (11%) and stomatitis/pharyngitis (24%). In comparison with the data of historical published trials of the PF regimen, the TPF regimen was more effective. However, the TPF regimen appears to be associated with a higher incidence of major toxicities. Therefore, our limited findings support the TPF regimen as an alternative chemotherapeutic regimen for advanced head and neck carcinomas.

Palliative chemotherapy with gemcitabine, paclitaxel, and cisplatin as first-line treatment following gemcitabine monotherapy for patients with transitional cell carcinoma of the urothelium.

PubMed

Ecke, T H; Gerullis, H; Bartel, P; Koch, S; Ruttloff, J

2009-03-01

Chemotherapeutic agents are active in transitional cell cancer of the urothelium, and combinations have shown promising results. The objective of this study was to evaluate the palliative chemotherapy with gemcitabine, paclitaxel, and cisplatin for transitional cell carcinoma. Thirty-four patients with advanced transitional cell carcinoma of the urothelium were treated between 2000 and 2007. All patients received chemotherapy with intravenous gemcitabine at a dose of 1000 mg/m2 on days I and VIII, intravenous paclitaxel at a dose of 80 mg/m2 on days I and VIII, and intravenous cisplatin at a dose of 50 mg/m2 on day II. Treatment courses were repeated every 21 days. After completion of four to six courses in this regimen an application of intravenous gemcitabine at a dose of 1000 mg/m2 followed repeating every 28 days. Twelve patients (35.3%) had 1 visceral sites of metastases. Twenty two patients (64.7%) had achieved objective responses to treatment (29.4% complete responses). The median actuarial survival was 18.5 months, and the actuarial one-year and two-year survival rates were 56% and 26% respectively. After a median follow-up of 16.3 months, 18 patients remained alive. The median progression-free survival was 7 months. Median survival time for patients with ECOG status 0, 1, and 2 was 45, 12, and 10.5 months respectively. Grade 3-4 neutropenia occurred in 41.2% of patients. The combination of gemcitabine, paclitaxel, and cisplatin is a highly effective and tolerable regimen for patients with advanced transitional cell carcinoma of the urothelium. This treatment should be considered as a suitable option that deserves further prospective evaluation. ECOG performance status and visceral metastases are important predictive factors for survival.

Manganese distribution in brains of Sprague-Dawley rats after 60 days of stainless steel welding-fume exposure.

PubMed

Yu, Il Je; Park, Jung Duck; Park, Eon Sub; Song, Kyung Seuk; Han, Kuy Tae; Han, Jeong Hee; Chung, Yong Hyun; Choi, Byung Sun; Chung, Kyu Hyuck; Cho, Myung Haing

2003-12-01

Welders working in a confined space, as in the shipbuilding industry, are at risk of being exposed to high concentrations of welding fumes and developing pneumoconiosis or other welding-fume exposure related diseases. Among such diseases, manganism resulting from welding-fume exposure remains a controversial issue, as the movement of manganese into specific brain regions has not yet been clearly established. Accordingly, to investigate the distribution of manganese in the brain after welding-fume exposure, male Sprague-Dawley rats were exposed to welding fumes generated from manual metal arc-stainless steel (MMA-SS) at concentrations of 63.6 +/- 4.1 mg/m(3) (low dose, containing 1.6 mg/m(3) Mn) and 107.1 +/- 6.3 mg/m(3) (high dose, containing 3.5 mg/m(3) Mn) total suspended particulate (TSP) for 2 h per day in an inhalation chamber over a 60-day period. Blood, brain, lung, and liver samples were collected after 2 h, 15, 30, and 60 days of exposure and the tissues analyzed for their manganese concentrations using an atomic absorption spectrophotometer. Although dose- and time-dependent increases in the manganese concentrations were found in the lungs and livers of the rats exposed for 60 days, only slight manganese increases were observed in the blood during this period. Major statistically significant increases in the brain manganese concentrations were detected in the cerebellum after 15 days of exposure and up until 60 days. Slight increases in the manganese concentrations were also found in the substantia nigra, basal ganglia (caudate nucleus, putamen, and globus pallidus), temporal cortex, and frontal cortex, thereby indicating that the pharmacokinetics and distribution of the manganese inhaled from the welding fumes were different from those resulting from manganese-only exposure.

Induction chemotherapy followed by alternating chemo-radiotherapy in non-endemic undifferentiated carcinoma of the nasopharynx: optimal compliance and promising 4-year results.

PubMed

Ponzanelli, Anna; Vigo, Viviana; Marcenaro, Michela; Bacigalupo, Almalina; Gatteschi, Beatrice; Ravetti, Jean-Luis; Corvò, Renzo; Benasso, Marco

2008-08-01

Concomitant chemo-radiotherapy is the standard treatment for advanced nasopharyngeal carcinoma (NPC). Induction chemotherapy may improve the results further by enhancing both loco-regional and distant control. Fifty patients with untreated, stage IV (UICC 1992) undifferentiated NPC were initially treated with three courses of epidoxorubicin, 90 mg/m(2), day 1 and cisplatin, 40 mg/m(2), days 1 and 2, every three weeks and then underwent three courses of cisplatin, 20 mg/m(2)/day, days 1-4 and fluorouracil, 200mg/m(2)/day, days 1-4 (weeks 1, 4, 7), alternated to three splits of radiation (week 2-3, 5-6, 8-9-10) up to 70 Gy. All patients but one received 3 cycles of induction chemotherapy. Toxicities from induction chemotherapy were grade III or IV mucositis (2%), grade III or IV nausea/vomiting (22%), grade III or IV hematological toxicity (6%). At the end of induction phase 12% of CRs, 84% of PRs were recorded. Toxicities from alternating chemo-radiotherapy were grade III or IV mucositis (30%), grade III or IV nausea/vomiting (8%), grade III or IV hematological toxicity (24%). Overall, 86% of CRs and 14% of PRs were observed. Four-year progression free survival and overall survival rates are 71% and 81%, respectively. In a small number of patients studied, no correlation between the level of EGFR overexpression and outcomes was detected. In locally advanced UNPC our combined program including induction chemotherapy followed by alternating chemo-radiotherapy is active and gives promising long-term outcomes with acceptable toxicity and optimal patients' compliance. This program merits to be tested in a phase III trial.

Pharmacokinetics of detomidine following intravenous or oral-transmucosal administration and sedative effects of the oral-transmucosal treatment in dogs.

PubMed

Messenger, Kristen M; Hopfensperger, Marie; Knych, Heather K; Papich, Mark G

2016-04-01

To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs. 12 healthy adult dogs. In phase 1, detomidine was administered by IV (0.5 mg/m(2)) or OTM (1 mg/m(2)) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m(2)) or detomidine gel by OTM administration (0.5 mg/m(2)), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment. Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation. Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.

[Effects of 1-bromopropane on neurological and hematological changes of female exposed workers].

PubMed

Li, Wei-Hua; Zhou, Zhi-Jun; Wang, Qiang-Yi; Ichihara, Gaku; Takeuchi, Yasuhiro; Ding, Xun-Cheng

2010-05-01

To investigate the health effects of 1-bromopropane (1-BP) on female exposed workers. Four 1-BP manufacturing plants were investigated. Workers were interviewed with questionnaire and examined with neurobehavioral core test battery, nerve conduction velocity tests of nervus tibialis and nervus suralis, vibration sensation test, hematological and biochemical tests. Ambient 1-BP concentration was measured with detection tube, and time-weighed average levels of individual workers were estimated with passive samplers. 1-BP concentration in the plants ranged from 0 to 402.40 mg/m3 (Geomean 32.19 mg/m3). Time-weighted average exposure levels (TWA-8 h) ranged from 0.35 to 535.19 mg/m3 (Geomean 14.08 mg/m3). Compared with the control group, 1-BP exposed workers showed reduced motor nerve conduction velocity [(44.8 +/- 8.7) m/s] and sensory nerve conduction velocity [(45.5 +/- 4.9) m/s], prolonged distal latency [(7.5 +/- 2.1) ms], reduced toe vibration perception, and altered neurobehavior parameters(POMS vigor, tension, anxiety, confusion) significantly (P < 0.05). As to hematological and biochemical indicators, the exposed workers showed decreased white blood cell count [(5.6 +/- 2.17) x 10(3)/microl], red blood cell count [(3.9 +/- 0.4) x 10(6)/microl], hemoglobin [(121.1 +/- 14.5) g/L] and creatine kinase [(82.0 +/- 27.5) IU/L] (P < 0.05), and increased serum total protein (8.0 +/- 0.5 g/dl), lactate dehydrogenase [(335.2 +/- 356.6) IU/L], thyroid-stimulating hormone [(3.6 +/- 2.3) microIU/ml] and follicle-stimulating hormone levels (18.7 +/- 24.4 mIU/ml) (P < 0.05). 1-BP exposure may affect peripheral nerves and central nervous system, and lead to abnormal hematological and biomedical indicators.

A phase I study evaluating the role of the anti-epidermal growth factor receptor (EGFR) antibody cetuximab as a radiosensitizer with chemoradiation for locally advanced pancreatic cancer

PubMed Central

Arnoletti, J. P.; Frolov, A.; Eloubeidi, M.; Keene, K.; Posey, J.; Wood, T.; Greeno, Edward; Jhala, N.; Varadarajulu, S.; Russo, S.; Christein, J.; Oster, R.; Buchsbaum, D. J.; Vickers, S. M.

2012-01-01

Purpose (1) To determine the safety of the epidermal growth factor receptor (EGFR) antibody cetuximab with concurrent gemcitabine and abdominal radiation in the treatment of patients with locally advanced adenocarcinoma of the pancreas. (2) To evaluate the feasibility of pancreatic cancer cell epithelial–mesenchymal transition (EMT) molecular profiling as a potential predictor of response to anti-EGFR treatment. Methods Patients with non-metastatic, locally advanced pancreatic cancer were treated in this dose escalation study with gemcitabine (0–300 mg/m2/week) given concurrently with cetuximab (400 mg/m2 loading dose, 250 mg/m2 weekly maintenance dose) and abdominal irradiation (50.4 Gy). Expression of E-cadherin and vimentin was assessed by immunohistochemistry in diagnostic endoscopic ultrasound fine-needle aspiration (EUS-FNA) specimens. Results Sixteen patients were enrolled in 4 treatment cohorts with escalating doses of gemcitabine. Incidence of grade 1–2 adverse events was 96%, and incidence of 3–4 adverse events was 9%. There were no treatment-related mortalities. Two patients who exhibited favorable treatment response underwent surgical exploration and were intraoperatively confirmed to have unresectable tumors. Median overall survival was 10.5 months. Pancreatic cancer cell expression of E-cadherin and vimentin was successfully determined in EUS-FNA specimens from 4 patients. Conclusions Cetuximab can be safely administered with abdominal radiation and concurrent gemcitabine (up to 300 mg/m2/week) in patients with locally advanced adenocarcinoma of the pancreas. This combined therapy modality exhibited limited activity. Diagnostic EUS-FNA specimens could be analyzed for molecular markers of EMT in a minority of patients with pancreatic cancer. PMID:20589377

Diffusive emission of methane and carbon dioxide from two hydropower reservoirs in Brazil.

PubMed

Marcelino, A A; Santos, M A; Xavier, V L; Bezerra, C S; Silva, C R O; Amorim, M A; Rodrigues, R P; Rogerio, J P

2015-05-01

The role of greenhouse gas emissions from freshwater reservoirs and their contribution to increase greenhouse gas concentrations in the atmosphere is currently under discussion in many parts of the world. We studied CO2 and CH4 diffusive fluxes from two large neotropical hydropower reservoirs with different climate conditions. We used floating closed-chambers to estimate diffusive fluxes of these gaseous species. Sampling campaigns showed that the reservoirs studied were sources of greenhouse gases to the atmosphere. In the Serra da Mesa Reservoir, the CH4 emissions ranged from 0.530 to 396.96 mg.m(-2).d(-1) and CO2 emissions ranged from -1,738.33 to 11,166.61 mg.m(-2).d(-1) and in Três Marias Reservoir the CH4 fluxes ranged 0.720 to 2,578.03 mg.m(-2).d(-1) and CO2 emission ranged from -3,037.80 to 11,516.64 to mg.m(-2).d(-1). There were no statistically significant differences of CH4 fluxes between the reservoirs, but CO2 fluxes from the two reservoirs studied were significantly different. The CO2 emissions measured over the periods studied in Serra da Mesa showed some seasonality with distinctions between the wet and dry transition season. In Três Marias Reservoir the CO2 fluxes showed no seasonal variability. In both reservoirs, CH4 emissions showed a tendency to increase during the study periods but this was not statistically significant. These results contributed to increase knowledge about the magnitude of CO2 and CH4 emission in hydroelectric reservoirs, however due to natural variability of the data future sampling campaigns will be needed to better elucidate the seasonal influences on the fluxes of greenhouse gases.

Assessment of low-dose cisplatin as a model of nausea and emesis in beagle dogs, potential for repeated administration.

PubMed

Kenward, Hannah; Pelligand, Ludovic; Elliott, Jonathan

2014-08-01

Cisplatin is a highly emetogenic cancer chemotherapy agent, which is often used to induce nausea and emesis in animal models. The cytotoxic properties of cisplatin also cause adverse events that negatively impact on animal welfare preventing repeated administration of cisplatin. In this study, we assessed whether a low (subclinical) dose of cisplatin could be utilized as a model of nausea and emesis in the dog while decreasing the severity of adverse events to allow repeated administration. The emetic, nausea-like behavior and potential biomarker response to both the clinical dose (70 mg/m2) and low dose (15 mg/m2) of cisplatin was assessed. Plasma creatinine concentrations and granulocyte counts were used to assess adverse effects on the kidneys and bone marrow, respectively. Nausea-like behavior and emesis was induced by both doses of cisplatin, but the latency to onset was greater in the low-dose group. No significant change in plasma creatinine was detected for either dose groups. Granulocytes were significantly reduced compared with baseline (P = 0.000) following the clinical, but not the low-dose cisplatin group. Tolerability of repeated administration was assessed with 4 administrations of an 18 mg/m2 dose cisplatin. Plasma creatinine did not change significantly. Cumulative effects on the granulocytes occurred, they were significantly decreased (P = 0.03) from baseline at 3 weeks following cisplatin for the 4th administration only. Our results suggest that subclinical doses (15 and 18 mg/m2) of cisplatin induce nausea-like behavior and emesis but have reduced adverse effects compared with the clinical dose allowing for repeated administration in crossover studies.

Vincristine, cisplatin, teniposide, and cyclophosphamide combination in the treatment of recurrent or metastatic adrenocortical cancer.

PubMed

Khan, Tanweera S; Sundin, Anders; Juhlin, Claes; Wilander, Erik; Oberg, Kjell; Eriksson, Barbro

2004-01-01

The efficacy and tolerability of a combination of vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) in 11 patients (median age, 45 yr) with recurrent and/or metastatic adrenocortical cancer (ACC) (seven functional and four nonfunctional) were evaluated. All patients received this regimen after the failure of streptozocin and o,p'-DDD (SO) combination therapy. The regimen comprised cyclophosphamide, 600 mg/m2, and vincristine, 1.5 mg/m2, maximum dose 2.0 mg (d 1); cisplatin, 100 mg/m2 (d 2) and teniposide, 150 mg/m2 (d 4). Cycles were repeated every 4 wk. One to eight cycles (median, six cycles) of OPEC were administered to each patient. The median duration of treatment was 6 mo. The overall 2-yr survival rate was 82% and the median survival since diagnosis was 44 mo while it was 21 mo since start of OPEC therapy. Responses were obtained in nine patients: partial response in two patients, and stable disease in seven patients. The median duration of response was 6.75 mo. A total of 60 cycles of chemotherapy were given to all patients; grade 1-2 toxicity occurred in 57 cycles, while grade 3 toxicity was observed only in two cycles, according to NCI's Common Toxicity Criteria. We conclude that the OPEC regimen may be considered in recurrent or metastatic ACC as a second-line medical treatment. However, the combination is accompanied by considerable side effects and dose modifications are necessary in order to be able to recommend the treatment. This regimen needs further evaluation compared with SO therapy preferably in a randomized multicenter trial.

Occupational Exposure to Crystalline Silica Dust in the United States, 1988–2003

PubMed Central

Yassin, Abdiaziz; Yebesi, Francis; Tingle, Rex

2005-01-01

The purposes of this study were a) to summarize measurements of airborne (respirable) crystalline silica dust exposure levels among U.S. workers, b) to provide an update of the 1990 Stewart and Rice report on airborne silica exposure levels in high-risk industries and occupations with data for the time period 1988–2003, c) to estimate the number of workers potentially exposed to silica in industries that the Occupational Safety and Health Administration (OSHA) inspected for high exposure levels, and d) to conduct time trend analyses on airborne silica dust exposure levels for time-weighted average (TWA) measurements. Compliance inspection data that were taken from the OSHA Integrated Management Information System (IMIS) for 1988–2003 (n = 7,209) were used to measure the airborne crystalline silica dust exposure levels among U.S. workers. A second-order autoregressive model was applied to assess the change in the mean silica exposure measurements over time. The overall geometric mean of silica exposure levels for 8-hr personal TWA samples collected during programmed inspections was 0.077 mg/m3, well above the applicable American Conference of Governmental Industrial Hygienists threshold limit value of 0.05 mg/m3. Surgical appliances supplies industry [Standard Industrial Classification (SIC) 3842] had the lowest geometric mean silica exposure level of 0.017 mg/m3, compared with the highest level, 0.166 mg/m3, for the metal valves and pipe fitting industry (SIC 3494), for an 8-hr TWA measurement. Although a downward trend in the airborne silica exposure levels was observed during 1988–2003, the results showed that 3.6% of the sampled workers were exposed above the OSHA-calculated permissible exposure limit. PMID:15743711

Neoadjuvant and adjuvant chemotherapy with modified mesna, adriamycin, ifosfamide, and dacarbazine (MAID) regimen for adult high-grade non-small round cell soft tissue sarcomas.

PubMed

Ogura, Koichi; Goto, Takahiro; Imanishi, Jungo; Shinoda, Yusuke; Okuma, Tomotake; Tsuda, Yusuke; Kobayashi, Hiroshi; Akiyama, Toru; Hirata, Makoto; Yamamoto, Aiichiro; Kawano, Hirotaka

2013-02-01

Good local control of high-grade non-small round cell soft tissue sarcomas (NSRCSTSs) has been achieved with significant advances in surgical techniques and radiotherapy. However, the role of chemotherapy remains controversial. Our aim was to investigate the efficacy, feasibility and adverse effects of neoadjuvant and adjuvant chemotherapy with modified mesna, adriamycin, ifosfamide and dacarbazine (MAID) regimen for NSRCSTSs. We conducted a retrospective review of 40 consecutive patients (29 men, 11 women; median age 47 years) with high-grade NSRCSTSs treated in two referral centers between 2004 and 2009 (median follow-up 38.5 months). Patients with distant or nodal metastases at diagnosis were excluded. The regimen consisted of ifosfamide 2,500 mg/m(2)/6 h (days 1-3), mesna 2,500 mg/m(2)/6 h (days 1-3), tetrahydropyranyl adriamycin 20 mg/m(2)/0.5 h (days 1-3), and dacarbazine 300 mg/m(2)/1 h (days 1-3). Among the 26 evaluable patients, there were 8 with a partial response, 15 with stable disease, and 3 with progressive disease. Two- and 5-year overall survival rates were 92 and 86%, respectively, and corresponding disease-free survival rates were 80 and 77%. All relapses were metastases without local recurrence. Grade 3-4 neutropenia, anemia and thrombocytopenia were observed in 38, 18, and 21 patients, respectively. No serious infectious complications occurred due to the administration of granulocyte colony-stimulating factor and prophylactic antibiotics. No other life-threatening serious adverse events were observed. The modified MAID regimen achieved a better outcome with less serious adverse events than previously reported and is a potential option in the management of NSRCSTSs. Further evaluation with long-term follow-up is required.

Feasibility of a modified outpatient regimen of intravenous/intraperitoneal chemotherapy in optimally debulked stage III ovarian cancer patients: a GEICO study.

PubMed

Oaknin, Ana; Roda, Desamparado; González-Martín, Antonio; Chiva, Luis; García-Donas, Jesús; de Juan, Ana; Redondo, Andrés; Martínez, Sergio; García, Yolanda; Catot, Sílvia; Ponce, Jordi; Del Campo, J M; Cervantes, Andrés; Poveda, Andrés

2011-08-01

The objective of the study was to assess the feasibility, toxicity, and reasons for early discontinuation of a modified outpatient intraperitoneal/intravenous (IP/IV) chemotherapy regimen for the treatment of patients with optimally debulked stage III ovarian cancer. Between February 2006 and November 2008, 51 consecutive patients from Institutions of the Spanish Ovarian Cancer Group (GEICO) were treated with a modified outpatient IP chemotherapy regimen. Patients received IV paclitaxel 175 mg/m over 3 hours on day 1, followed by IP cisplatin 100 mg/m (or 75 mg/m according to the principal investigator's criteria) on day 2. On day 8, patients received IP paclitaxel 60 mg/m. To homogenize the IP administration and supportive measures, a GEICO guideline for IP chemotherapy was established. Patients were treated with the intention to receive 6 courses of chemotherapy every 21 days. The median age of the patients was 49 years (range, 36-75 years), and most of them had papillary serous ovarian cancer (78%), International Federation of Gynecology and Obstetrics stage IIIC (76%). Thirty-nine patients completed 4 or more IP cycles, and 28 (61%) completed all 6 IP cycles. Twenty-two patients discontinued the IP/IV treatment, mainly because of chemotherapy toxicity (10 patients) and catheter-related complications (5 patients). The most prevalent grade 3/4 toxicities were neutropenia (14 patients; 30%) and gastrointestinal events (12 patients; 26%). The GEICO outpatient modified regimen resulted in a lesser toxicity and a greater rate of treatment completion than previously reported. The accurate selection of patients and the administration following well-defined guidelines can increase the feasibility of IP chemotherapy administration.

A phase III concurrent chemoradiotherapy trial with cisplatin and paclitaxel or docetaxel or gemcitabine in unresectable non-small cell lung cancer: KASLC 0401.

PubMed

Oh, In-Jae; Kim, Kyu-Sik; Kim, Young-Chul; Ban, Hee-Jung; Kwon, Yong-Soo; Kim, Yu-Il; Lim, Sung-Chul; Chung, Woong-Ki; Nam, Taek-Keun; Song, Joo-Young; Yoon, Mee-Sun; Ahn, Sung-Ja

2013-12-01

Concurrent chemoradiotherapy (CCRT) is recommended for the management of patients with unresectable non-small cell lung cancer (NSCLC). This prospective study aimed to compare the efficacy of concurrently delivered cisplatin doublets with paclitaxel, or docetaxel, or gemcitabine. The main eligibility criteria consisted of previously untreated stage IIIB NSCLC. The subjects were randomized into three arms: paclitaxel 45 mg/m(2)/week (TP), docetaxel 20 mg/m(2)/week (DP), and gemcitabine 350 mg/m(2)/week (GP) in addition to cisplatin 20 mg/m(2)/week. Three-dimensional conformal radiotherapy was given once daily, weekly 5 fractions and the total prescription dose was 60-66 Gy. The primary endpoint was response rate, and the secondary endpoints were survival and toxicity. A total of 101 patients were recruited into this trial of whom 93 (TP: 33, DP: 29, GP: 31) patients were treated with CCRT from March 2005 to July 2007. Similar response rates were observed across arms: TP: 63.6 %, DP: 72.4 %, GP: 61.3 % (p = 0.679). There was no statistically significant difference of median survival (TP: 27.3, DP: 27.6, GP: 16.5 months, p = 0.771). In subgroup analysis, a survival benefit of consolidation chemotherapy was not seen, but leucopenia (63.2 %) and neutropenia (68.4 %) more than grade 3 were significantly high in DP arm. The grade ≥3 radiation esophagitis was more frequent in the GP arm (22.6 %, p = 0.163). Among the three arms, no statistically significant difference in response rate, survival, and toxicity was observed. However, clinically significant radiation toxicity was more frequent in the GP arm.

Phase I study of UCN-01 and perifosine in patients with relapsed and refractory acute leukemias and high-risk myelodysplastic syndrome

PubMed Central

Gojo, Ivana; Perl, Alexander; Luger, Selina; Baer, Maria R.; Norsworthy, Kelly J.; Bauer, Kenneth S.; Tidwell, Michael; Fleckinger, Stephanie; Carroll, Martin; Sausville, Edward A.

2013-01-01

Summary Background The PI3K-Akt pathway is frequently activated in acute leukemias and represents an important therapeutic target. UCN-01 and perifosine are known to inhibit Akt activation. Methods The primary objective of this phase I study was to determine the maximum tolerated dose (MTD) of UCN-01 given in combination with perifosine in patients with advanced acute leukemias and myelodysplastic syndrome. Secondary objectives included safety, pharmacokinetics, pharmacodynamics, and efficacy. Perifosine 150 mg every 6 hours was given orally on day 1 followed by 100 mg once a day continuously in 28-day cycles. UCN-01 was given intravenously over 3 hours on day 4 at three dose levels (DL1=40 mg/m2; DL2=65 mg/m2; DL3=90 mg/m2). Results Thirteen patients were treated (DL1, n=6; DL2, n=4; DL3, n=3) according to a traditional “3+3” design. Two patients at the DL3 experienced dose-limiting toxicity including grade 3-4 pericardial effusion, hypotension, hyperglycemia, hyperkalemia, constitutional symptoms and grade 5 pneumonitis. Other frequent toxicities were grade 1-2 nausea, diarrhea, vomiting, fatigue and hyperglycemia. The MTD was determined to be UCN-01 65 mg/m2 with perifosine 100 mg a day. No appreciable direct Akt inhibition could be demonstrated in patients’ mononuclear cells using Western blot, however, reduced phosphorylation of the downstream target ribosomal protein S6 in leukemic blasts was noted by intracellular flow cytometry. No objective responses were observed on this study. Conclusion UCN-01 and perifosine can be safely administered, but this regimen lacked clinical efficacy. This approach may have failed because of insufficient Akt inhibition in vivo. PMID:23443507

Chronic obstructive pulmonary disease and occupational exposure to silica.

PubMed

Rushton, Lesley

2007-01-01

Prolonged exposure to high levels of silica has long been known to cause silicosis This paper evaluates the evidence for an increased risk of chronic obstructive pulmonary disease (COPD) in occupations and industries in which exposure to crystalline silica is the primary exposure, with a focus on the magnitude of risks and levels of exposure causing disabling health effects. The literature suggests consistently elevated risks of developing COPD associated with silica exposure in several occupations, including the construction industry; tunneling; cement industry; brick manufacturing; pottery and ceramic work; silica sand, granite and diatomaceous earth industries; gold mining; and iron and steel founding, with risk estimates being high in some, even after taking into account the effect of confounders like smoking. Average dust levels vary from about 0.5 mg.m3 to over 10 mg.m3 and average silica levels from 0.04 to over 5 mg.m3, often well above occupational standards. Factors influencing the variation from industry to industry in risks associated with exposure to silica-containing dusts include (a) the presence of other minerals in the dust, particularly when associated with clay minerals; (b) the size of the particles and percentage of quartz; (c) the physicochemical characteristics, such as whether the dust is freshly fractured. Longitudinal studies suggest that loss of lung function occurs with exposure to silica dust at concentrations of between 0.1 and 0.2 mg.m3, and that the effect of cumulative silica dust exposure on airflow obstruction is independent of silicosis. Nevertheless, a disabling loss of lung function in the absence of silicosis would not occur until between 30 and 40 years exposure.

A Phase I and Pharmacokinetic Study of the Oral Histone Deacetylase Inhibitor, MS-275, in Patients with Refractory Solid Tumors and Lymphomas

PubMed Central

Gore, Lia; Rothenberg, Mace L.; O'Bryant, Cindy L.; Schultz, Mary Kay; Sandler, Alan B.; Coffin, Denise; McCoy, Candice; Schott, Astrid; Scholz, Catherine; Eckhardt, S. Gail

2010-01-01

Purpose To evaluate the toxicity profile, pharmacologic, and biological properties of 3-pyridylmethyl N-{4-[(2-aminophenyl)carbamoyl]benzyl}carbamate (MS-275), a histone deacetylase inhibitor, when administered orally on three different dosing schedules. Experimental Design Patients with advanced solid malignancies and lymphomas were treated on three dose schedules: once every other week, twice weekly for 3 weeks every 28 days, and once weekly for 3 weeks every 28 days. First-cycle plasma pharmacokinetics and peripheral blood mononuclear cell histone acetylation were determined. Results Twenty-seven patients received ≥149 courses of treatment. Hypophosphatemia and asthenia were dose limiting on the weekly and twice-weekly dosing schedules; there was no dose-limiting toxicity on the every other week schedule. Pharmacokinetic variables revealed dose-dependent and dose-proportional increases. Two of 27 patients showed partial remissions, including one patient with metastatic melanoma who had a partial response and has remained on study for >5 years. Six patients showed prolonged disease stabilization. Levels of histone H3 and H4 acetylation in peripheral blood mononuclear cells increased qualitatively but with a high degree of interpatient variation. Conclusions MS-275 is well tolerated at doses up to 6 mg/m2 every other week or 4 mg/m2 weekly for 3 weeks followed by 1 week of rest and results in biologically relevant plasma concentrations and antitumor activity. Twice-weekly dosing was not tolerable due to asthenia, and further evaluation of this schedule was halted. The recommended dose for further disease-focused studies is 4 mg/m2 given weekly for 3 weeks every 28 days or 2 to 6 mg/m2 given once every other week. PMID:18579665

First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial.

PubMed

Eichhorst, Barbara; Fink, Anna-Maria; Bahlo, Jasmin; Busch, Raymonde; Kovacs, Gabor; Maurer, Christian; Lange, Elisabeth; Köppler, Hubert; Kiehl, Michael; Sökler, Martin; Schlag, Rudolf; Vehling-Kaiser, Ursula; Köchling, Georg; Plöger, Christoph; Gregor, Michael; Plesner, Torben; Trneny, Marek; Fischer, Kirsten; Döhner, Harmut; Kneba, Michael; Wendtner, Clemens-Martin; Klapper, Wolfram; Kreuzer, Karl-Anton; Stilgenbauer, Stephan; Böttcher, Sebastian; Hallek, Michael

2016-07-01

Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab is the standard therapy for physically fit patients with advanced chronic lymphocytic leukaemia. This international phase 3 study compared the efficacy and tolerance of the standard therapy with a potentially less toxic combination consisting of bendamustine and rituximab. Treatment-naive fit patients with chronic lymphocytic leukaemia (aged 33-81 years) without del(17p) were enrolled after undergoing a central screening process. Patients were randomly assigned (1:1) with a computer-generated randomisation list using randomly permuted blocks with a block size of eight and were stratified according to participating country and Binet stage. Patients were allocated to receive six cycles of intravenous fludarabine (25 mg/m(2) per day) and cyclophosphamide (250 mg/m(2) per day) for the first 3 days or to intravenous bendamustine (90 mg/m(2) per day) for the first 2 days of each cycle. Rituximab 375 mg/m(2) was given intravenously in both groups on day 0 of cycle 1 and subsequently was given at 500 mg/m(2) during the next five cycles on day 1. The primary endpoint was progression-free survival with the objective to assess non-inferiority of bendamustine and rituximab to the standard therapy. We aimed to show that the 2-year progression-free survival with bendamustine and rituximab was not 67·5% or less with a corresponding non-inferiority margin of 1·388 for the hazard ratio (HR) based on the 90·4% CI. The final analysis was done by intention to treat. The study is registered with ClinicalTrials.gov, number NCT%2000769522. 688 patients were recruited between Oct 2, 2008, and July 11, 2011, of which 564 patients who met inclusion criteria were randomly assigned. 561 patients were included in the intention-to-treat population: 282 patients in the fludarabine, cyclophosphamide, and rituximab group and 279 in the bendamustine and rituximab group. After a median observation time of 37·1 months (IQR 31·0-45·5) median progression-free survival was 41·7 months (95% CI 34·9-45·3) with bendamustine and rituximab and 55·2 months (95% CI not evaluable) with fludarabine, cyclophosphamide, and rituximab (HR 1·643, 90·4% CI 1·308-2·064). As the upper limit of the 90·4% CI was greater than 1·388 the null hypothesis for the corresponding non-inferiority hypothesis was not rejected. Severe neutropenia and infections were more frequently observed with fludarabine, cyclophosphamide, and rituximab (235 [84%] of 279 vs 164 [59%] of 278, and 109 [39%] vs 69 [25%], respectively) during the study. The increased frequency of infectious complications with fludarabine, cyclophosphamide, and rituximab was more pronounced in patients older than 65 years. The combination of fludarabine, cyclophosphamide, and rituximab remains the standard front-line therapy in fit patients with chronic lymphocytic leukaemia, but bendamustine and rituximab is associated with less toxic effects. Roche Pharma AG, Mundipharma, German Federal Ministry of Education and Research. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of moisture content of combusted wood on the thermal efficiency of a boiler

NASA Astrophysics Data System (ADS)

Dzurenda, Ladislav; Banski, Adrián

2017-03-01

In the paper the influence of moisture content of wood on the heat losses and thermal efficiency of a boiler is analysed. The moisture content of wood has a negative effect, especially on flue gas loss. The mathematical dependence of the thermal efficiency of a boiler is presented for the following boundary conditions: the moisture content of wood 10-60%, range of temperatures of emitted flue gases from the boiler into the atmosphere 120-200 C, the emissions meeting the emission standards: carbon monoxide 250 mgm-3, fly ash 50 mgm-3 and the heat power range 30-100%.

Second-line chemotherapy of disseminated malignant melanoma with cystemustine at 60 mg/m2: a phase II trial.

PubMed

Thivat, Emilie; Durando, Xavier; D'Incan, Michel; Cure, Hervé; Mouret-Reynier, Marie-Ange; Madelmont, Jean-Claude; Souteyrand, Pierre; Chollet, Philippe

2005-10-01

Nitrosoureas possess some anti-tumor activity as a single agent in metastatic melanoma (MM). In a phase II trial, we evaluated the anti-tumor effects of cystemustine chemotherapy, a new nitrosourea, as a second-line treatment. Patients were required to have histologic evidence of disseminated MM and had failed in first-line chemotherapy. Treatment comprised cystemustine given at a dose of 60 mg/m every 2 weeks by a 15-min infusion. From February 1997 to September 1999, 22 patients (median age 66 years) were enrolled and were assessable. Two complete responses, one partial response, three stable diseases and 16 progressions were observed, giving an overall response rate of 13.6%. Median duration of response was 10 months (range 4-63). Median survival of responders and non-responders was 11 and 4 months, respectively. However, hematological toxicity, particularly thrombopenia, was a limiting factor for one-third of patients. We conclude that cystemustine at 60 mg/m is active in patients who progressed after one line of chemotherapy in advanced disease, and offers the possibility of complete responses and long durations of these responses.

Visitor spending effects: assessing and showcasing America's investment in national parks

USGS Publications Warehouse

Koontz, Lynne; Cullinane Thomas, Catherine; Ziesler, Pamela; Olson, Jeffrey; Meldrum, Bret

2017-01-01

This paper provides an overview of the evolution, future, and global applicability of the U.S. National Park Service's (NPS) visitor spending effects framework and discusses the methods used to effectively communicate the economic return on investment in America's national parks. The 417 parks represent many of America's most iconic destinations: in 2016, they received a record 331 million visits. Competing federal budgetary demands necessitate that, in addition to meeting their mission to preserve unimpaired natural and cultural resources for the enjoyment of the people, parks also assess and showcase their contributions to the economic vitality of their regions and the nation. Key approaches explained include the original Money Generation Model (MGM) from 1990, MGM2 used from 2001, and the visitor spending effects model which replaced MGM2 in 2012. Detailed discussion explains the NPS's visitor use statistics system, the formal program for collecting, compiling, and reporting visitor use data. The NPS is now establishing a formal socioeconomic monitoring (SEM) program to provide a standard visitor survey instrument and a long-term, systematic sampling design for in-park visitor surveys. The pilot SEM survey is discussed, along with the need for international standardization of research methods.

Determination of microplastic polyethylene (PE) and polypropylene (PP) in environmental samples using thermal analysis (TGA-DSC).

PubMed

Majewsky, Marius; Bitter, Hajo; Eiche, Elisabeth; Horn, Harald

2016-10-15

Microplastics are increasingly detected in the environment and the consequences on water resources and ecosystems are not clear to date. The present study provides a cost-effective and straightforward method to determine the mass concentrations of polymer types using thermal analysis. Characteristic endothermic phase transition temperatures were determined for seven plastic polymer types using TGA-DSC. Based on that, extracts from wastewater samples were analyzed. Results showed that among the studied polymers, only PE and PP could be clearly identified, while the phase transition signals of the other polymers largely overlap each other. Subsequently, calibration curves were run for PE and PP for qualitative measurements. 240 and 1540mg/m(3) of solid material (12µm to 1mm) was extracted from two wastewater effluent samples of a municipal WWTP of which 34% (81mg/m(3)) and 17% (257mg/m(3)) could be assigned to PE, while PP was not detected in any of the samples. The presented application of TGA-DSC provides a complementary or alternative method to FT-IR analyses for the determination of PE and PP in environmental samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Species Composition and Distribution of Zooplankton from Northeastern Sakhalin Shelf (Sea of Okhotsk)

NASA Astrophysics Data System (ADS)

Kasyan, V. V.

2018-03-01

The species composition, density, biomass, and distribution of zooplankton of the northeastern Sakhalin shelf, Sea of Okhotsk (Chaivo, Pil'tunskii, and Morskoi regions) were studied in October 2014. Zooplankton was represented by 15 taxonomic groups, which were dominated by Copepoda (13 species). The average density and biomass was highest in the Chaivo region (14112 ± 4322 ind./m3, 395 ± 107 mg/m3) and in the Pil'tunskii region (16692 ± 10707 ind./m3, 346 ± 233 mg/m3); the abundance of detected taxonomic groups was minimal (8-12). The average density and biomass of zooplankton was up to 4304 ± 2441 ind./m3, 133 ± 77 mg/m3 in the Morskoi region and increased with depth; the abundance of taxa was maximum (15). Four species of copepods made up the majority of the density and biomass of zooplankton: Acartia hudsonica, Eurytemora herdmani, Pseudocalanus newmani, and Oithona similis. In the Chaivo region, species of the genera Acartia, Eurytemora, and Oithona dominated and subdominated; in Pil'tunskii region, species of the genera Acartia and Oithona dominated and subdominated; and in the Morskoi region, species of the genera Oithona, Pseudocalanus, and Acartia dominated and subdominated.

Neoadjuvant chemotherapy with continuous infusion of cisplatin and 5-fluorouracil, with or without leucovorin, for locally advanced nasopharyngeal carcinoma.

PubMed

Fonseca, E; Cruz, J J; Rodríguez, C A; Gómez-Bernal, A; Martín, G; Sánchez, P; Nieto, A; Soria, P; Vega, M J; Muñoz, A; Pardal, J L

1996-01-01

Cisplatin-based induction chemotherapy has been extensively tested in nasopharyngeal carcinoma for the improvement of local and systemic control and survival of this disease. In this study, we report the results of the treatment with induction chemotherapy in 40 patients with locally advanced carcinoma of the nasopharynx (LANPC) with four courses of cisplatin (P) 25 mg/m2 per day and 5-fluorouracil (F) 1000 mg/m2 per day both in a 4-days continuous infusion, with or without leucovorin (L) 250 mg/m2 per day in 2-hour infusion at the beginning of daily administration of PF, followed by sequential radiotherapy. All except one were in stage IV. The overall response after induction chemotherapy was 93%, with 55% CR and 38% PR. Definitive overall response after radiotherapy was 98%, with 80% CR and 18% PR. At a maximum follow up of 11 years, the overall survival rate is 55%. Induction chemotherapy with continuous infusion of PF with or without leucovorin followed by radiotherapy is a highly active regimen for the treatment of locally advanced nasopharyngeal carcinoma with response and survival rates comparable to other combinations of sequential or simultaneous chemotherapy and radiotherapy.

Factors influencing the nitrification efficiency of fluidized bed filter with a plastic bead medium

USGS Publications Warehouse

Sandu, S.I.; Boardman, G.D.; Watten, B.J.; Brazil, B.L.

2002-01-01

The performance of fluidized bed nitrification filters charged with 2 ?? 4 ABS plastic beads (specific gravity 1.06) was evaluated. Three unique bed-height to diameter ratios were established, in triplicate, using column diameters of 12.7, 15.2 and 17.8 cm. Filters received water spiked with recycled nutrients and ammonia (TAN), from one of the three 500 1 feed tank system. With daily ammonia loading fixed at 8.6 g per system, TAN removal increased with column diameter at each of four tests hydraulic loading rates (6, 8, 10 and 12 Lpm). TAN in recirculated water (influent) rose from 0.5 to 1.0 mg/1 as ammonia loading increased from 180 mg/m2-day to 360 mg/m2-day. When hydraulic loading was fixed at 12 Lpm, TAN removal (%) was maximized with ammonia loadings ranging from 225 to 270 mg/m2-day. Biofilm thickness increased with ammonia loading, but decreased with increased hydraulic loading rates. Fluidized beds of ABS plastic beads were effective in reducing energy costs (head loss) of water treatment. ?? 2002 Elsevier Science B.V. All rights reserved.

Estimation of insecticide persistence, biological activity and mosquito resistance to PermaNet® 2 long-lasting insecticidal nets over three to 32 months of use in Ethiopia.

PubMed

Anshebo, Gedeon Yohannes; Graves, Patricia M; Smith, Stephen C; Wills, Aprielle B; Damte, Mesele; Endeshaw, Tekola; Shargie, Estifanos Biru; Gebre, Teshome; Mosher, Aryc W; Patterson, Amy E; Emerson, Paul M

2014-03-06

Information is needed on the expected durability of insecticidal nets under operational conditions. The persistence of insecticidal efficacy is important to estimate the median serviceable life of nets under field conditions and to plan for net replacement. Deltamethrin residue levels were evaluated by the proxy method of X-ray fluorescence spectrometry on 189 nets used for three to six months from nine sites, 220 nets used for 14-20 months from 11 sites, and 200 nets used for 26-32 months from ten sites in Ethiopia. A random sample of 16.5-20% of nets from each time period (total 112 of 609 nets) were tested by bioassay with susceptible mosquitoes, and nets used for 14-20 months and 26-32 months were also tested with wild caught mosquitoes. Mean insecticide levels estimated by X-ray fluorescence declined by 25.9% from baseline of 66.2 (SD 14.6) mg/m2 at three to six months to 44.1 (SD 21.2) mg/m2 at 14-20 months and by 30.8% to 41.1 (SD 18.9) mg/m2 at 26-32 months. More than 95% of nets retained greater than 10 mg/m2 of deltamethrin and over 79% had at least 25 mg/m2 at all time periods. By bioassay with susceptible Anopheles, mortality averaged 89.0% on 28 nets tested at three to six months, 93.3% on 44 nets at 14-20 months and 94.1% on 40 nets at 26-32 months. With wild caught mosquitoes, mortality averaged 85.4% (range 79.1 to 91.7%) at 14-20 months but had dropped significantly to 47.2% (39.8 to 54.7%) at 26-32 months. Insecticide residue level, as estimated by X-ray fluorescence, declined by about one third between three and six months and 14-20 months, but remained relatively stable and above minimum requirements thereafter up to 26-32 months. The insecticidal activity of PermaNet® 2.0 long-lasting insecticidal nets in the specified study area may be considered effective to susceptible mosquitoes at least for the duration indicated in this study (32 months). However, results indicated that resistance in the wild population is already rendering nets with optimum insecticide concentrations less effective in practice.

Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial.

PubMed

Noronha, Vanita; Joshi, Amit; Patil, Vijay Maruti; Agarwal, Jaiprakash; Ghosh-Laskar, Sarbani; Budrukkar, Ashwini; Murthy, Vedang; Gupta, Tejpal; D'Cruz, Anil K; Banavali, Shripad; Pai, Prathamesh S; Chaturvedi, Pankaj; Chaukar, Devendra; Pande, Nikhil; Chandrasekharan, Arun; Talreja, Vikas; Vallathol, Dilip Harindran; Mathrudev, Vijayalakshmi; Manjrekar, Aparna; Maske, Kamesh; Bhelekar, Arati Sanjay; Nawale, Kavita; Kannan, Sadhana; Gota, Vikram; Bhattacharjee, Atanu; Kane, Shubhada; Juvekar, Shashikant L; Prabhash, Kumar

2018-04-10

Purpose Chemoradiation with cisplatin 100 mg/m 2 given once every 3 weeks is the standard of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed the noninferiority of cisplatin 30 mg/m 2 given once a week compared with cisplatin 100 mg/m 2 given once every 3 weeks, both administered concurrently with curative intent radiotherapy in patients with LAHNSCC. The primary end point was locoregional control (LRC); secondary end points included toxicity, compliance, response, progression-free survival, and overall survival. Results Between 2013 and 2017, we randomly assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m 2 resulted in superior LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m 2 , and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.

Folfirinox in elderly patients with pancreatic or colorectal cancer-tolerance and efficacy.

PubMed

Guion-Dusserre, Jean-Florian; Bertaut, Aurélie; Ghiringhelli, François; Vincent, Julie; Quipourt, Valérie; Marilier, Sophie; Tharin, Zoé; Bengrine-Lefevre, Leila

2016-11-14

To study the tolerance and the efficiency of FOLFIRINOX in elderly patients diagnosed with colorectal or pancreatic cancer. This retrospective study included elderly patients aged over 70 years of age treated at Georges-Francois Leclerc Center by FOLFIRINOX for histological proved colorectal or pancreatic cancer between January 2009 and January 2015. Chemotheapy regimen consisted of oxaliplatin (85 mg/m 2 in over 120 min) followed by leucovorin (400 mg/m 2 in over 120 min), with the addition, after 30 min of irinotecan (180 mg/m 2 in over 90 min) then 5 fluorouracil (5FU) (400 mg/m 2 administred intravenous bolus), followed by 5FU (2400 mg/m 2 intraveinous infusion over 46 h) repeated every 2 wk. Geriatric parameters were recorded at the beginning. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events 4.03. Tumor response was evaluated by CT scan. Treatment continued until disease progression, unacceptable toxicities or patient refusal. Fifty-two patients aged from 70 to 87 years were treated by FOLFIRINOX, 34 had colorectal cancer and 18 had pancreatic cancer. Most of them were in good general condition, 82.7% had a 0-1 performance status and 61.5% had a Charlson Comorbidity Index < 10. The most frequent severe toxicities were neutropenia (17 patients, n = 32.7%) and diarrhea (35 patients n = 67.3%); 10 of the case of neutropenia and 5 of diarrhea registered a grade 4 toxicity. Thirty-nine patients (75%) initially received an adapted dose of chemotherapy. The dosage was adjusted for 26% of patients during the course of treatment. Tumor response evaluated by RECIST criteria showed a controlled disease for 25 patients (48.1%), a stable disease for 13 and a partial response for 12 patients. Time under treatment was higher for colorectal cancer with a median time of 2.44 mo (95%CI: 1.61-3.25). Overall survival was 43.88 mo for colorectal cancer and 12.51 mo for pancreatic cancer. In univariate or multivariate analysis, none of geriatric parameters were linked to overall survival. Only the type of tumor (pancreatic/colorectal) was linked in both analysis. For people over 70 years old, FOLFIRINOX regimen seems to induce manageable toxicities but similar, even higher, median survival rates compared to younger people.

Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial.

PubMed

Alistar, Angela; Morris, Bonny B; Desnoyer, Rodwige; Klepin, Heidi D; Hosseinzadeh, Keyanoosh; Clark, Clancy; Cameron, Amy; Leyendecker, John; D'Agostino, Ralph; Topaloglu, Umit; Boteju, Lakmal W; Boteju, Asela R; Shorr, Rob; Zachar, Zuzana; Bingham, Paul M; Ahmed, Tamjeed; Crane, Sandrine; Shah, Riddhishkumar; Migliano, John J; Pardee, Timothy S; Miller, Lance; Hawkins, Gregory; Jin, Guangxu; Zhang, Wei; Pasche, Boris

2017-06-01

Pancreatic cancer statistics are dismal, with a 5-year survival of less than 10%, and more than 50% of patients presenting with metastatic disease. Metabolic reprogramming is an emerging hallmark of pancreatic adenocarcinoma. CPI-613 is a novel anticancer agent that selectively targets the altered form of mitochondrial energy metabolism in tumour cells, causing changes in mitochondrial enzyme activities and redox status that lead to apoptosis, necrosis, and autophagy of tumour cells. We aimed to establish the maximum tolerated dose of CPI-613 when used in combination with modified FOLFIRINOX chemotherapy (comprising oxaliplatin, leucovorin, irinotecan, and fluorouracil) in patients with metastatic pancreatic cancer. In this single-centre, open-label, dose-escalation phase 1 trial, we recruited adult patients (aged ≥18 years) with newly diagnosed metastatic pancreatic adenocarcinoma from the Comprehensive Cancer Center of Wake Forest Baptist Medical Center (Winston-Salem, NC, USA). Patients had good bone marrow, liver and kidney function, and good performance status (Eastern Cooperative Oncology Group [ECOG] performance status 0-1). We studied CPI-613 in combination with modified FOLFIRINOX (oxaliplatin at 65 mg/m 2 , leucovorin at 400 mg/m 2 , irinotecan at 140 mg/m 2 , and fluorouracil 400 mg/m 2 bolus followed by 2400 mg/m 2 over 46 h). We applied a two-stage dose-escalation scheme (single patient and traditional 3+3 design). In the single-patient stage, one patient was accrued per dose level. The starting dose of CPI-613 was 500 mg/m 2 per day; the dose level was then escalated by doubling the previous dose if there were no adverse events worse than grade 2 within 4 weeks attributed as probably or definitely related to CPI-613. The traditional 3+3 dose-escalation stage was triggered if toxic effects attributed as probably or definitely related to CPI-613 were grade 2 or worse. The dose level for CPI-613 for the first cohort in the traditional dose-escalation stage was the same as that used in the last cohort of the single-patient dose-escalation stage. The primary objective was to establish the maximum tolerated dose of CPI-613 (as assessed by dose-limiting toxicities). This trial is registered with ClinicalTrials.gov, number NCT01835041, and is closed to recruitment. Between April 22, 2013, and Jan 8, 2016, we enrolled 20 patients. The maximum tolerated dose of CPI-613 was 500 mg/m 2 . The median number of treatment cycles given at the maximum tolerated dose was 11 (IQR 4-19). Median follow-up of the 18 patients treated at the maximum tolerated dose was 378 days (IQR 250-602). Two patients enrolled at a higher dose of 1000 mg/m 2 , and both had a dose-limiting toxicity. Two unexpected serious adverse events occurred, both for the first patient enrolled. Expected serious adverse events were: thrombocytopenia, anaemia, and lymphopenia (all for patient number 2; anaemia and lymphopenia were dose-limiting toxicities); hyperglycaemia (in patient number 7); hypokalaemia, hypoalbuminaemia, and sepsis (patient number 11); and neutropenia (patient number 20). No deaths due to adverse events were reported. For the 18 patients given the maximum tolerated dose, the most common grade 3-4 non-haematological adverse events were hyperglycaemia (ten [55%] patients), hypokalaemia (six [33%]), peripheral sensory neuropathy (five [28%]), diarrhoea (five [28%]), and abdominal pain (four [22%]). The most common grade 3-4 haematological adverse events were neutropenia (five [28%] of 18 patients), lymphopenia (five [28%]), anaemia (four [22%], and thrombocytopenia in three [17%]). Sensory neuropathy (all grade 1-3) was recorded in 17 (94%) of the 18 patients and was managed with dose de-escalation or discontinuation per standard of care. No patients died while on active treatment; 11 study participants died, with cause of death as terminal pancreatic cancer. Of the 18 patients given the maximum tolerated dose, 11 (61%) achieved an objective (complete or partial) response. A maximum tolerated dose of CPI-613 was established at 500 mg/m 2 when used in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer. The findings of clinical activity will require validation in a phase 2 trial. Comprehensive Cancer Center of Wake Forest Baptist Medical Center. Copyright © 2017 Elsevier Ltd. All rights reserved.

Creating values-based health care. An interview with ACMPE President Patty Brewster. Interview by Pamela L. Moore.

PubMed

Brewster, P L

1998-01-01

The new president of the American College of Medical Practice Executives (ACMPE), Patricia L. Brewster, FACMPE, regional director; Hughston Clinic, Atlanta, took time to talk to MGM Journal Managing Editor Pamela L. Moore, Ph.D., about her job, the ethics of medical practice management and the role of ACMPE. Brewster has 20 years experience in the medical marketplace. She formerly worked as the administrator at Phoenix: Orthopedic and Sports Medicine, Atlanta, and Orthopaedic Associates of Atlanta. She is also past-president of the MGMA Southern Section. Under her guidance, Hughston Clinic has from two to seven locations, covering a six county area in metropolitan Atlanta.

[The balance of harmful trace contaminants between the air humidity condensate and air in a simulator of the Mir orbit station moisture condensation unit].

PubMed

Zlotopol'skiĭ, V M; Smolenskaia, T S

2000-01-01

Subject of the investigation was the balance of harmful trace contaminants (HTC) between the air moisture condensate and air in a simulator of the MIR moisture condensation unit. Experiments involved various classes of water-solvent compounds including alcohols (C1-C4), ketons (C1-C2), aldehydes (C1-C2), fatty acids (C2-C4), esters (acetates C4-C6), and ammonium. For most of the compounds, removal efficiency correlates with air humidity and virtually does not depend on the HTC concentration within the range of 0.25 to 59.1 mg/m3.

Surface chemistry and reactivity of SiO2 polymorphs: A comparative study on α-quartz and α-cristobalite

NASA Astrophysics Data System (ADS)

Tang, Cuihua; Zhu, Jianxi; Li, Zhaohui; Zhu, Runliang; Zhou, Qing; Wei, Jingming; He, Hongping; Tao, Qi

2015-11-01

Silica minerals are widely used in environmental remediation for their prevalence in soil and sediment. Two common SiO2 polymorphs, α-quartz and α-cristobalite, were investigated for the removal of a typical cationic dye, methylene blue (MB), from aqueous solutions. Their adsorption behaviors were studied in batch experiments as a function of specific surface area (SSA), pH, and temperature. The surface site density of α-quartz (10.6 sites/nm2) was higher than that of α-cristobalite (6.2 sites/nm2) with the Gran plot method, and the adsorption maxima of MB on the two were 0.84 mg/m2 and 0.49 mg/m2, respectively, at 303 K and pH 8. The potentiometric titration showed the capacity of proton-donating by α-quartz was stronger than that by α-cristobalite. A drastic increase of adsorption amount on α-quartz at pH < 3 was caused by its greater quantity of isolated silanols. The negative ΔG and positive ΔH values suggested adsorption of MB on both minerals was spontaneous and endothermic. At three different temperatures (288 K, 298 K, and 303 K), the adsorption capacities of two polymorphs increased with increasing temperature. The surface heterogeneity of α-quartz and α-cristobalite corresponds to their different adsorption behavior, and our work also provides some referential significance in evaluating the overall quality of soils and sediments.

Health economic impact of high-dose versus standard-dose cytarabine induction chemotherapy for acute myeloid leukaemia.

PubMed

Fedele, P L; Avery, S; Patil, S; Spencer, A; Haas, M; Wei, A

2014-08-01

Induction chemotherapy for acute myeloid leukaemia (AML) is one of the most resource-intensive cancer therapies delivered in hospitals. To assess the health resource impact of different chemotherapy approaches for AML commonly used in Australia. A retrospective analysis was undertaken in 63 patients aged 18-55 years with AML given induction with either 7 + 3 (cytarabine 100 mg/m(2) days 1-7 and idarubicin 12 mg/m(2) days 1-3) or HiDAC-3 (high-dose cytarabine 3 g/m(2) twice daily days 1, 3, 5 and 7 and idarubicin 12 mg/m(2) days 1-3) chemotherapy. Average costs of hospitalisation, pathology, radiology, chemotherapy and ancillary drugs were calculated and compared with current Victorian casemix funding. Two consolidation approaches, HiDAC (cytarabine 3 g/m(2) twice daily days 1, 3, 5 and 7) × either three or four cycles (following 7 + 3) and IcE (idarubicin 12,mg/m(2) days 1-2, cytarabine 100 mg/m(2) × 5 days and etoposide 75 mg/m(2) × 5 days) × 2 cycles (following HiDAC-3) were modelled, using a policy of discharge following completion of chemotherapy with outpatient monitoring. The cost (in AUD) of induction was similar between 7 + 3 ($58,037) and HiDAC-3 ($56,902), with bed day costs accounting for 61-62% of the total expense. Blood bank costs ranked second, accounting for 15%. Accumulated costs for HiDAC consolidation were $44,289 for a three-cycle protocol and $59,052 for four cycles ($14,763 per cycle) versus $31,456 for two cycles of IcE consolidation ($15,728 per cycle). Overall, the classical 7 + 3 → HiDAC approach ($102,326/$117,089 for three or four consolidation cycles) incurs a greater cost than a HiDAC-3 → IcE × 2 approach ($88,358). For patients requiring complete hospitalisation until neutrophil recovery, the estimated costs of treatment will be even higher, ranging between $122,282 for HiDAC-3 → IcE × 2, $153,212 for 7 + 3 → HiDAC × 3 and $184,937 for 7 + 3 → HiDAC × 4. State-based casemix funding for non-complicated AML therapy is currently $74,013 for 7 + 3 → HiDAC × 4, $64,177 for 7 + 3 → HiDAC × 3 and $54,340 for HiDAC-3 → IcE × 2 based on outpatient recovery after consolidation chemotherapy. These calculations do not take into account additional resource implications associated with complications of consolidation chemotherapy or reinduction for treatment failure. Regimens minimising the total number of chemotherapy cycles may represent the most efficient use of limited health resources for the treatment of AML. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Characteristics of Sawdust and Cocopeat Beddings, and Their Usefulness According to the Fan and Pen Location for Rearing Hanwoo Cattle.

PubMed

Ahn, Gyu Chul; Jang, Sun Sik; Lee, Kang Yeon; Kwak, Wan Sup; Oh, Young Kyun; Park, Keun Kyu

2016-03-01

This study was designed to examine the characteristics of sawdust and cocopeat bedding materials, including physicochemical properties (Exp. I) and on-farm trial (Exp. II). In Exp. I, the proportion of particle size was in the order of sawdust> cocopeat India>cocopeat Vietnam (p<0.05), and cocopeat contained higher proportion of small particles (250 μm+below 250 μm) than sawdust, causing a dust production problem. Bulk density was cocopeat India>cocopeat Vietnam>sawdust (p<0.05), thus cocopeat treatments showed 4.4 times higher bedding cost than sawdust. The water absorption rates were 702.0% in cocopeat India, 678.3% in cocopeat Vietnam, and 444.0% in sawdust, showing cocopeat had approximately 1.5 times higher water absorption rate than sawdust. Moisture evaporation rates after 12 h of air blowing (2.00 m/s) were higher (p<0.05) in cocopeat Vietnam (80.4%) than sawdust (71.2%) and cocopeat India (72.8%). In vitro ammonia emissions were higher (p<0.05) in sawdust (2.71 mg/m(2)/h) than cocopeat India (1.59 mg/m(2)/h) and Vietnam (1.22 mg/m(2)/h), and total ammonia emissions were higher (p<0.05) in sawdust (37.02 mg/m(2)) than cocopeat India (22.51 mg/m(2)) and Vietnam (13.60 mg/m(2)). In Exp. II, an on-farm trial was conducted with 48 Hanwoo cattle in 16 pens using the same bedding materials as in Exp. I, with fan (blowing 2.00 m/s) and no fan treatments, and feed bunk side (FB) and water supply side (WS) within a pen (4.5 m, width×9.0 m, length). Beddings were replaced with fresh bedding materials when moisture concentrations were over 65%. No interactions among treatments were detected for moisture concentration and increment rates, and ammonia concentrations, but a significant effect was observed (p<0.01) for each of the treatments. Both concentrations and increment rate of moisture were higher (p<0.01) in the beddings without fan than with fan. Moisture concentrations and increment rate within a pen were also higher (p<0.01) in FB than WS. Thus, the whole no-fan-FB and sawdust-fan-FB were replaced with fresh bedding material between 4 to 5 experimental weeks. The ammonia concentrations and pH of beddings were not significantly different among treatments. Therefore, using cocopeat bedding with a blowing fan can extend twice the bedding utilization period, and WS within a pen showed twice the bedding-life compared to FB. Despite the outstanding characteristics of cocopeat compared with sawdust, using cocopeat as an alternative for sawdust bedding is not recommended for cattle management, considering it has 4.4 times higher bedding cost and a dust production problem.

Semen quality and sex hormones among mild steel and stainless steel welders: a cross sectional study.

PubMed Central

Bonde, J P

1990-01-01

Welding may be detrimental to the male reproductive system. To test this hypothesis, semen quality was examined in 35 stainless steel welders, 46 mild steel welders, and 54 non-welding metal workers and electricians. These figures represent a participation rate of 37.1% in welders and 36.7% in non-welding subjects. The mean exposure to welding fume particulates was 1.3 mg/m3 (SD 0.8) in stainless steel welders using tungsten inert gas, 3.2 mg/m3 (SD 1.0) in low exposed mild steel welders using manual metal arc or metal active gas (n = 31), and 4.7 mg/m3 (SD 2.1) in high exposed mild steel welders (n = 15). The semen quality of each participant was defined in terms of the mean values of the particular semen parameters in three semen samples delivered at monthly intervals in a period with occupational exposure in a steady state. The sperm concentration was not reduced in either mild steel or stainless steel welders. The sperm count per ejaculate, the proportion of normal sperm forms, the degree of sperm motility, and the linear penetration rate of the sperm were significantly decreased and the sperm concentration of follicle stimulating hormone (FSH) was non-significantly increased in mild steel welders. A dose response relation between exposure to welding fumes and these semen parameters (sperm count excepted) was found. Semen quality decreased and FSH concentrations increased with increasing exposure. Significant deteriorations in some semen parameters were also observed in stainless steel welders. An analysis of information from questionnaires obtained from the whole population including subjects who declined to participate indicated an underestimation of effects due to selection bias. Potential confounding was treated by restriction and statistical analysis. The results support the hypothesis that mild steel welding and to a lesser extent stainless steel welding with tungsten inert gas is associated with reduced semen quality at exposure in the range of the Danish process specific threshold limit values of welding. PMID:2118383

Semen quality and sex hormones among mild steel and stainless steel welders: a cross sectional study.

PubMed

Bonde, J P

1990-08-01

Welding may be detrimental to the male reproductive system. To test this hypothesis, semen quality was examined in 35 stainless steel welders, 46 mild steel welders, and 54 non-welding metal workers and electricians. These figures represent a participation rate of 37.1% in welders and 36.7% in non-welding subjects. The mean exposure to welding fume particulates was 1.3 mg/m3 (SD 0.8) in stainless steel welders using tungsten inert gas, 3.2 mg/m3 (SD 1.0) in low exposed mild steel welders using manual metal arc or metal active gas (n = 31), and 4.7 mg/m3 (SD 2.1) in high exposed mild steel welders (n = 15). The semen quality of each participant was defined in terms of the mean values of the particular semen parameters in three semen samples delivered at monthly intervals in a period with occupational exposure in a steady state. The sperm concentration was not reduced in either mild steel or stainless steel welders. The sperm count per ejaculate, the proportion of normal sperm forms, the degree of sperm motility, and the linear penetration rate of the sperm were significantly decreased and the sperm concentration of follicle stimulating hormone (FSH) was non-significantly increased in mild steel welders. A dose response relation between exposure to welding fumes and these semen parameters (sperm count excepted) was found. Semen quality decreased and FSH concentrations increased with increasing exposure. Significant deteriorations in some semen parameters were also observed in stainless steel welders. An analysis of information from questionnaires obtained from the whole population including subjects who declined to participate indicated an underestimation of effects due to selection bias. Potential confounding was treated by restriction and statistical analysis. The results support the hypothesis that mild steel welding and to a lesser extent stainless steel welding with tungsten inert gas is associated with reduced semen quality at exposure in the range of the Danish process specific threshold limit values of welding.

Effects of acoustic hood on noise, CFC-11, and particulate matter in a recycling system for waste refrigerator cabinet.

PubMed

Guo, Jie; Fang, Wenxiong; Yang, Yichen; Xu, Zhenming

2014-11-01

The mechanical-physical process was proven to be technologically feasible for waste refrigerator recycling and has been widely used in the typical e-waste recycling factories in China. In this study, effects of the acoustic hood on the reduction of noise level, CFC-11, and heavy metals (Cr, Ni, Cu, Cd, and Pb) in particulate matter (PM) were evaluated. For noise pollution, the noise level inside and outside the acoustic hood was 96.4 and 78.9 dB, respectively. Meanwhile, it had a significant effect on A-weighted sound level with a reduction from 98.3 to 63.6 dB. For CFC-11 exposure, abundant CFC-11 (255 mg/m(3)) was detected in the acoustic hood. However, the mean concentration of CFC-11 at the outline of polyurethane foam collection was obviously diminished to 14 mg/m(3), and no CFC-11 was monitored around the acoustic hood. The concentrations of PM and heavy metals in PM outside the acoustic hood were lower than those inside the acoustic hood due to the physical barriers of the acoustic hood. Based on the risk assessment, only adverse health effect caused by Pb might likely appear. All the results can provide the basic data for pollution control and risk assessment in waste refrigerator recycling system.

Kinetics of Fe2+-Mg order-disorder in orthopyroxene: experimental studies and applications to cooling rates of rocks

NASA Astrophysics Data System (ADS)

Stimpfl, M.; Ganguly, J.; Molin, G.

2005-10-01

We determined the forward rate constant (K+) for the Fe2+-Mg order-disorder between the M2 and M1 sites of orthopyroxene (OPx), which is described by the homogeneous reaction Fe2+ (M2) + Mg(M1) ↔ Mg(M2) + Fe2+ (M1), by both ordering and disordering experiments at isothermal condition and also by continuous cooling experiments. The rate constant was determined as a function of temperature in the range of 550-750°C, oxygen fugacity between quartz-fayalite-iron and Ni-NiO buffers, and at compositions of 16 and 50 mol% ferrosilite component. The K+ value derived from disordering experiment was found to be larger than that derived from ordering experiment at 550°C, while at T>580°C, these two values are essentially the same. The fO2 dependence of the rate constant can be described by the relation K+ α (fO2) n with n=5.5-6.5, which is compatible with the theoretically expected relation. The Arrhenius relation at the WI buffer condition is given by ln (C_{text{o}} {text{K}}^+) = - {41511 - 12600{text{X}}_{{text{Fe}}} }/{{T({text{K}})}} + 28.26 + 5.27{text{X}}_{{text{Fe}}}, min^{-1} where C o represents the total number of M2 + M1 sites occupied by Fe2+ and Mg per unit volume of the crystal. The above relation can be used to calculate the cooling rates of natural OPx crystals around the closure temperature ( T c) of Fe-Mg ordering, which are usually below 300°C for slowly cooled rocks. We determined the Fe-Mg ordering states of several OPx crystals (˜ Fs50) from the Central Gneissic Complex (Khtada Lake), British Columbia, which yields T c ˜290°C. Numerical simulation of the change of Fe2+-Mg ordering in OPx as a function of temperature using the above expression of rate constant and a non-linear cooling model yields quenched values of ordering states that are in agreement with the observed values for cooling rates of 11-17°C/Myr below 300°C. The inferred cooling rate is in agreement with the available geochronological constraints.

Treatment of tumor-bearing dogs with actinomycin D.

PubMed

Hammer, A S; Couto, C G; Ayl, R D; Shank, K A

1994-01-01

Fifty dogs with advanced malignancies were treated with actinomycin D at doses ranging from 0.5 to 1.1 mg/m2 every 3 weeks. The greatest number of responses was noted in dogs with lymphoma, including dogs that had received prior chemotherapy. Other responding tumor types included anal sac adenocarcinoma, perianal adenocarcinoma, squamous cell carcinoma, thyroid carcinoma, and transitional cell carcinoma. The median time to maximum response for dogs with lymphoma was 7 days, with a median duration of 42 days. Gastrointestinal toxicity was the most frequently observed side effect. A dose of 0.6 to 0.7 mg/m2 appears to be appropriate for treating various malignancies in dogs.

Modeling of oil mist and oil vapor concentration in the shale shaker area on offshore drilling installations.

PubMed

Bråtveit, Magne; Steinsvåg, Kjersti; Lie, Stein Atle; Moen, Bente E

2009-11-01

The objective of this study was to develop regression models to predict concentrations of oil mist and oil vapor in the workplace atmosphere in the shale shaker area of offshore drilling installations. Collection of monitoring reports of oil mist and oil vapor in the mud handling areas of offshore drilling installations was done during visits to eight oil companies and five drilling contractors. A questionnaire was sent to the rig owners requesting information about technical design of the shaker area. Linear mixed-effects models were developed using concentration of oil mist or oil vapor measured by stationary sampling as dependent variables, drilling installation as random effect, and potential determinants related to process technical parameters and technical design of the shale shaker area as fixed effects. The dataset comprised stationary measurements of oil mist (n = 464) and oil vapor (n = 462) from the period 1998 to 2004. The arithmetic mean concentrations of oil mist and oil vapor were 3.89 mg/m(3) and 39.7 mg/m(3), respectively. The air concentration models including significant determinants such as viscosity of base oil, mud temperature, well section, type of rig, localization of shaker, mechanical air supply, air grids in outer wall, air curtain in front of shakers, and season explained 35% and 17% of the total variance in oil vapor and oil mist, respectively. The developed models could be used to indicate what impact differences in technical design and changes in process parameters have on air concentrations of oil mist and oil vapor. Thus, the models will be helpful in planning control measures to reduce the potential for occupational exposure.

Ambient air pollution exposure and respiratory, cardiovascular and cerebrovascular mortality in Cape Town, South Africa: 2001–2006.

PubMed

Wichmann, Janine; Voyi, Kuku

2012-11-05

Little evidence is available on the strength of the association between ambient air pollution exposure and health effects in developing countries such as South Africa. The association between the 24-h average ambient PM(10), SO(2) and NO(2) levels and daily respiratory (RD), cardiovascular (CVD) and cerebrovascular (CBD) mortality in Cape Town (2001-2006) was investigated with a case-crossover design. For models that included entire year data, an inter-quartile range (IQR) increase in PM(10) (12 mg/m3) and NO(2) (12 mg/m3) significantly increased CBD mortality by 4% and 8%, respectively. A significant increase of 3% in CVD mortality was observed per IQR increase in NO(2) and SO(2) (8 mg/m3). In the warm period, PM(10) was significantly associated with RD and CVD mortality. NO(2) had significant associations with CBD, RD and CVD mortality, whilst SO(2) was associated with CVD mortality. None of the pollutants were associated with any of the three outcomes in the cold period. Susceptible groups depended on the cause-specific mortality and air pollutant. There is significant RD, CVD and CBD mortality risk associated with ambient air pollution exposure in South Africa, higher than reported in developed countries.

Procarbazine, CCNU, vincristine combination in the treatment of brain tumors.

PubMed

Güllü, I H; Celik, I; Tekuzman, G; Altunbaş, M; Güler, N; Barişta, I; Alkiş, N; Yalçin, S; Kars, A; Baltali, E; Kansu, E; Firat, D

1996-01-01

Forty patients with primary malignant brain tumor were treated by combination chemotherapy after prior treatment with surgery and radiotherapy. The chemotherapy schedule consisted of PCV: procarbazine per os, 100 mg/m2, during 14 consecutive days; CCNU, per os, 80 mg/m2 on day 1 and vincristine, intravenously, 1.4 mg/m2 on days 1 and 14. This protocol was planned to be repeated every 45 days for 6 courses. Median 5 courses (range, 2-6) of chemotherapy was administered to patients. The median relapse free (RFS) and overall survival (OS) rates were found to be 28 and 79+ months, respectively. According to univariate analysis, performance status (PS) of patients was an important prognostic factor on RFS and OS where extent of surgery was an additional significant determinant of OS. Multivariate analysis of pretreatment factors revealed the influence of sex, type of histopathology and PS on RFS and that of PS on OS rates (P < 0.05). The toxicity of this regimen was mild to moderate. The major toxicity noted was myelosuppression. Severe (grade III-IV) neutropenia and thrombocytopenia has been observed in 13 (7%) and 6 courses (3.5%), respectively. In general, PCV is well tolerated and the median RFS and OS times elucidated are comparable with particular trials utilizing combination chemotherapy and longer than using radiotherapy alone.

Urinary excretion of the metabolites of n-hexane and its isomers during occupational exposure.

PubMed Central

Perbellini, L; Brugnone, F; Faggionato, G

1981-01-01

Environmental exposure to commercial hexane (n-hexane, 2-methylpentane, and 3-methylpentane) was tested in several work places in five shoe factories by taking three grap-air samples during the afternoon shift. Individual exposure ranges were 32-500 mg/m3 for n-hexane, 11-250 mg/m3 for 2-methylpentane, and 10-204 mg/m3 for 3-methylpentane. The metabolites of commercial hexane in the urine of 41 workers were measured at the end of the work shift. 2-Hexanol, 2,5-hexanedione, 2,5-dimethylfuran, and gamma-valerolactone were found as n-hexane metabolites and 2-methyl-2-pentanol and 3-methyl-2-pentanol as 2-methylpentane and 3-methylpentane metabolites. The presence of metabolites in the urine was correlated with occupational exposure to solvents. n-Hexane exposure was correlated more positively with 2-hexanol and 2,5-hexanedione than with 2,5-dimethylfuran and gamma-valerolactone. A good correlation was also found between total n-hexane metabolites and n-hexane exposure. 2-Methyl-2-pentanol and 3-methyl-2-pentanol were highly correlated with 2-methylpentane and 3-methylpentane exposure. The results suggest that the urinary excretion of hexane metabolites may be used for monitoring occupational exposure to n-hexane and its isomers. PMID:7470400

Arginine prevents thermal aggregation of hen egg white proteins.

PubMed

Hong, Taehun; Iwashita, Kazuki; Handa, Akihiro; Shiraki, Kentaro

2017-07-01

The control of aggregation and solubilization of hen egg white protein (HEWP) is an important issue for industrial applications of one of the most familiar food protein sources. Here, we investigated the effects of edible amino acids on heat-induced aggregation of HEWP. The addition of 0.6M arginine (Arg) completely suppressed the formation of insoluble aggregates of 1mgmL -1 HEWP following heat treatment, even at 90°C for 20min. In contrast, lysine (Lys), glycine (Gly), and sodium chloride (NaCl) did little to suppress the aggregation of HEWP under the same conditions. SDS-PAGE indicated that Arg suppresses the thermal aggregation of almost all types of HEWP at 1mgmL -1 . However, Arg did not suppress the thermal aggregation of HEWP at concentrations ≥10mgmL -1 and prompted the formation of aggregates. Transmission electron micrographs revealed a high-density structure of unfolded proteins in the presence of Arg. These results indicate that Arg exerts a greater suppressive effect on a protein mixture, such as HEWP, than on a single model protein. These observations may propose Arg as a safe and reasonable additive to HEWP for the elimination of microorganisms by allowing an increase in sterilization temperature. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of pH adjustment by mixing steroid for venous pain in colorectal cancer patients receiving oxaliplatin through peripheral vein: a multicenter randomized phase II study (APOLLO).

PubMed

Hata, Taishi; Honda, Michitaka; Kobayashi, Michiya; Toyokawa, Akihiro; Tsuda, Masahiro; Tokunaga, Yukihiko; Takase, Kozo; Miyake, Masakazu; Morita, Satoshi; Nagata, Naoki; Sakamoto, Junichi; Gosho, Masahiko; Mishima, Hideyuki

2015-12-01

The aim of this phase II clinical trial was to evaluate the preventive effect of dexamethasone mixing injection for venous pain in patients with colorectal cancer during chemotherapy. Patients were randomized to receive a 2-h intravenous infusion of oxaliplatin 130 mg/m(2) on day 1 followed by capecitabine 1000 mg/m(2) (or S-1 40-60 mg/m(2)) twice daily on days 1 through 14 of every 3 weeks with or without dexamethasone 1.65 mg at the infusion on day 1. A total of 53 patients were enrolled. The analysis population consisted of 49 patients (arm A, with dexamethasone N = 24; arm B, without dexamethasone N = 25). The incidence of venous pain ≥grade 2 based on the CTCAE version 4.0 was 33.3 % in arm A and 56.0 % in arm B (relative risk 0.60; 95 % CI 0.31-1.16). The incidences based on the verbal rating scale for arms A and B were 50.0 and 64.0 %, respectively (relative risk 0.78; 95 % CI 0.48-1.28). The primary endpoint was not met in this preliminary study.

An Open-Label, Randomized, Parallel, Phase III Trial Evaluating the Efficacy and Safety of Polymeric Micelle-Formulated Paclitaxel Compared to Conventional Cremophor EL-Based Paclitaxel for Recurrent or Metastatic HER2-Negative Breast Cancer.

PubMed

Park, In Hae; Sohn, Joo Hyuk; Kim, Sung Bae; Lee, Keun Seok; Chung, Joo Seop; Lee, Soo Hyeon; Kim, Tae You; Jung, Kyung Hae; Cho, Eun Kyung; Kim, Yang Soo; Song, Hong Suk; Seo, Jae Hong; Ryoo, Hun Mo; Lee, Sun Ah; Yoon, So Young; Kim, Chul Soo; Kim, Yong Tai; Kim, Si Young; Jin, Mi Ryung; Ro, Jungsil

2017-07-01

Genexol-PM is a Cremophor EL-free formulation of low-molecular-weight, non-toxic, and biodegradable polymeric micelle-bound paclitaxel. We conducted a phase III study comparing the clinical efficacy and toxicity of Genexol-PM with conventional paclitaxel (Genexol). Patients were randomly assigned (1:1) to receive Genexol-PM 260 mg/m 2 or Genexol 175 mg/m 2 intravenously every 3 weeks. The primary outcome was the objective response rate (ORR). The study enrolled 212 patients, of whom 105 were allocated to receive Genexol-PM. The mean received dose intensity of Genexol-PM was 246.8±21.3 mg/m 2 (95.0%), and that of Genexol was 168.3±10.6 mg/m 2 (96.2%). After a median follow-up of 24.5 months (range, 0.0 to 48.7 months), the ORR of Genexol-PM was 39.1% (95% confidence interval [CI], 31.2 to 46.9) and the ORR of Genexol was 24.3% (95% CI, 17.5 to 31.1) (p non-inferiority =0.021, p superiority =0.016). The two groups did not differ significantly in overall survival (28.8 months for Genexol-PM vs. 23.8 months for Genexol; p=0.52) or progression-free survival (8.0 months for Genexol-PM vs. 6.7 months for Genexol; p=0.26). In both groups, the most common toxicities were neutropenia, with 68.6% occurrence in the Genexol-PM group versus 40.2% in the Genexol group (p < 0.01). The incidences of peripheral neuropathy of greater than grade 2 did not differ significantly between study treatments. Compared with standard paclitaxel, Genexol-PM demonstrated non-inferior and even superior clinical efficacy with a manageable safety profile in patients with metastatic breast cancer.

Comparison of high MRI T1 signals with manganese concentration in brains of cynomolgus monkeys after 8 months of stainless steel welding-fume exposure.

PubMed

Park, Jung Duck; Chung, Yong Hyun; Kim, Choong Yong; Ha, Chang Soo; Yang, Seoung Oh; Khang, Hyun Soo; Yu, In Kyu; Cheong, Hae Kwan; Lee, Jong Seong; Song, Chang-Woo; Kwon, Il Hoon; Han, Jeong Hee; Sung, Jae Hyuck; Heo, Jeong Doo; Choi, Byung Sun; Im, Ruth; Jeong, Jayoung; Yu, Il Je

2007-09-01

Several pharmacokinetic studies on inhalation exposure to manganese (Mn) have already demonstrated that Mn readily accumulates in the olfactory and brain regions. However, a shortening of the magnetic resonance imaging (MRI) T1 relaxation time or high T1 signal intensity in specific sites of the brain, including the globus pallidus and subcortical frontal white matter, as indicative of tissue manganese accumulation has not yet been clearly established for certain durations of known doses of welding-fume exposure in experimental animals. Accordingly, to investigate the movement of manganese after welding-fume exposure, six cynomolgus monkeys were acclimated and assigned to three dose groups: unexposed, low dose (31 mg/m(3) total suspended particulate [TSP], 0.9 mg/m(3) of Mn), and high dose (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of total suspended particulate. The primates were exposed to manual metal arc stainless steel (MMA-SS) welding fumes for 2 h per day in an inhalation chamber system equipped with an automatic fume generator. Magnetic resonance imaging (MRI) studies were conducted before the initiation of exposure and thereafter every month. The tissue Mn concentrations were then measured after a plateau was reached regarding the shortening of the MRI T1 relaxation time. A dose-dependent increase in the Mn concentration was found in the lungs, while noticeable increases in the Mn concentrations were found in certain tissues, such as the liver, kidneys, and testes. Slight increases in the Mn concentrations were found in the caudate, putamen, frontal lobe, and substantia nigra, while a dose-dependent noticeable increase was only found in the globus pallidus. Therefore, the present results indicated that a shortening of the MRI T1 relaxation time corresponded well with the Mn concentration in the globus pallidus after prolonged welding-fume exposure.

Capecitabine and Oxaliplatin in the Preoperative Multimodality Treatment of Rectal Cancer: Surgical End Points From National Surgical Adjuvant Breast and Bowel Project Trial R-04

PubMed Central

O'Connell, Michael J.; Colangelo, Linda H.; Beart, Robert W.; Petrelli, Nicholas J.; Allegra, Carmen J.; Sharif, Saima; Pitot, Henry C.; Shields, Anthony F.; Landry, Jerome C.; Ryan, David P.; Parda, David S.; Mohiuddin, Mohammed; Arora, Amit; Evans, Lisa S.; Bahary, Nathan; Soori, Gamini S.; Eakle, Janice; Robertson, John M.; Moore, Dennis F.; Mullane, Michael R.; Marchello, Benjamin T.; Ward, Patrick J.; Wozniak, Timothy F.; Roh, Mark S.; Yothers, Greg; Wolmark, Norman

2014-01-01

Purpose The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. Patients and Methods Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m2, 5 days per week), with or without intravenous oxaliplatin (50 mg/m2 once per week for 5 weeks) or oral capecitabine (825 mg/m2 twice per day, 5 days per week), with or without oxaliplatin (50 mg/m2 once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). Results From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). Conclusion Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred. PMID:24799484

Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04.

PubMed

O'Connell, Michael J; Colangelo, Linda H; Beart, Robert W; Petrelli, Nicholas J; Allegra, Carmen J; Sharif, Saima; Pitot, Henry C; Shields, Anthony F; Landry, Jerome C; Ryan, David P; Parda, David S; Mohiuddin, Mohammed; Arora, Amit; Evans, Lisa S; Bahary, Nathan; Soori, Gamini S; Eakle, Janice; Robertson, John M; Moore, Dennis F; Mullane, Michael R; Marchello, Benjamin T; Ward, Patrick J; Wozniak, Timothy F; Roh, Mark S; Yothers, Greg; Wolmark, Norman

2014-06-20

The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m(2), 5 days per week), with or without intravenous oxaliplatin (50 mg/m(2) once per week for 5 weeks) or oral capecitabine (825 mg/m(2) twice per day, 5 days per week), with or without oxaliplatin (50 mg/m(2) once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred. © 2014 by American Society of Clinical Oncology.

A phase I trial of intraperitoneal GEN-1, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer, administered with pegylated liposomal doxorubicin in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers: An NRG Oncology/Gynecologic Oncology Group study

PubMed Central

Thaker, Premal H.; Brady, William E.; Lankes, Heather A.; Odunsi, Kunle; Bradley, William H.; Moore, Kathleen N.; Muller, Carolyn Y.; Anwer, Khursheed; Schilder, Russell J.; Alvarez, Ronald D.; Fracasso, Paula M.

2017-01-01

Objective The study’s purpose was to assess safety and efficacy of escalating doses of weekly GEN-1 with pegylated liposomal doxorubicin (PLD) in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers (EOC). Methods Patients had persistent or recurrent platinum-resistant EOC. The trial was a standard 3 + 3 phase I dose escalation design with patients receiving intravenous PLD 40 mg/m2 (dose level 1 and 2) or 50 mg/m2 (dose level 3) every 28 days and intraperitoneal GEN-1 at 24 mg/m2 (dose level 1) or 36 mg/m2 (dose level 2 and 3) on days 1, 8, 15, and 22 of a 28 day cycle. Cycles were repeated every 28 days until disease progression. Patients were monitored for toxicity, clinical efficacy, and evidence of systemic and intraperitoneal immunologic effect. Results Sixteen evaluable patients received a median of 4 cycles (range 1–8). No dose limiting toxicities were found. The adverse side effects were 4 grade 3 anemia, 2 grade 3 abdominal pain, 7 grade 3 neutropenia, and 2 grade 4 neutropenia. A clinical benefit of 57.1% (PR = 21.4%; SD = 35.7%) was found in the 14 patients with measurable disease. The highest number of partial responses (28.6%) and stable disease (57.1%) were found at dose level 3. The maximum tolerated dose was not reached. Increases in IL-12, IFN-γ, and TNF-α levels were found in peritoneal fluid following GEN-1 treatment. Conclusions GEN-1 in combination with PLD has encouraging clinical benefit and biological activity in recurrent or persistent EOC and warrants further investigation with escalating doses of GEN-1. PMID:28802766

Risk-adapted treatment of acute promyelocytic leukemia: results from International Consortium for Childhood APL.

PubMed

Testi, Anna Maria; Pession, Andrea; Diverio, Daniela; Grimwade, David; Gibson, Brenda; de Azevedo, Amilcar Cardoso; Moran, Lorena; Leverger, Guy; Elitzur, Sarah; Hasle, Henrik; van der Werff Ten Bosch, Jutte; Smith, Owen; De Rosa, Marisa; Piciocchi, Alfonso; Lo Coco, Francesco; Foà, Robin; Locatelli, Franco; Kaspers, Gertjan J L

2018-05-22

Pediatric acute promyelocytic leukemia (APL), a rare childhood neoplasm, can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials to date have employed high cumulative doses of anthracyclines. Here, we report the outcome of patients with newly diagnosed APL enrolled into the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically-proven APL. Patients were stratified into standard-risk (SR) and high-risk (HR) according to the baseline WBC count (< or ≥10x10 9 /L); both groups received identical induction treatment with ATRA (25 mg/m 2 /day, for 30 consecutive days) and 3 doses of idarubicin (12 mg/m 2 /dose). Two or three blocks of consolidation therapy were administered to SR and HR patients, respectively, while maintenance therapy with low-dose chemotherapy and ATRA cycles was given to all patients for 2 years. The cumulative dose of daunorubicin-equivalent anthracyclines in SR and HR patients was lower than that of previous studies, being 355 mg/m 2 and 405 mg/m 2 in SR and HR patients, respectively. Hematologic remission was obtained in 97% of patients; 8 children died of intracranial hemorrhage in the first 2 weeks following diagnosis. The 5-year overall and event-free survival for the whole cohort were 94.6% and 79.9%, respectively; they were 98.4% and 89.4% in SR and 84.3% and 74.2% in HR patients (p=0.002 and p=0.043, respectively). These data demonstrate that extended use of ATRA coupled to a risk-adapted consolidation can achieve high cure rates in childhood APL and limit anthracycline exposure. The trial was registered at www.clinicaltrials.gov with the following identification number EudractCT 2008-002311-40. Copyright © 2018 American Society of Hematology.

Inflammatory response and endothelial dysfunction in the hearts of mice co-exposed to SO2 , NO2 , and PM2.5.

PubMed

Zhang, Yingying; Ji, Xiaotong; Ku, Tingting; Sang, Nan

2016-12-01

SO 2 , NO 2 , and PM 2.5 are typical air pollutants produced during the combustion of coal. Increasing evidence indicates that air pollution has contributed to the development and progression of heart-related diseases over the past decades. However, little experimental data and few studies of SO 2 , NO 2 , and PM 2.5 co-exposure in animals exist; therefore, the relevant mechanisms underlying this phenomenon are unclear. An important characteristic of air pollution is that co-exposure persists at a low concentration throughout a lifetime. In the present study, we treated adult mice with SO 2 , NO 2 , and PM 2.5 at various concentrations (0.5 mg/m 3 SO 2 , 0.2 mg/m 3 NO 2 6 h/d, with intranasal instillation of 1 mg/kg PM 2.5 every other day during these exposures; or 3.5 mg/m 3 SO 2 , 2 mg/m 3 NO 2 6 h/d, and 10 mg/kg PM 2.5 for 28 d). Blood pressure (BP), heart rate (HR), histopathological damage, and inflammatory and endothelial cytokines in the heart were assessed. The results indicate that co-exposure caused endothelial dysfunction by elevating endothelin-1 (ET-1) expression and repressing the endothelial nitric oxide synthase (eNOS) level as well as stimulating the inflammatory response by increasing the levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Additionally, these alterations were confirmed by histological staining. Furthermore, we observed decreased BP and increased HR after co-exposure. Our results indicate that co-exposure to SO 2 , NO 2 , and PM 2.5 may be a major risk factor for cardiac disease and may induce injury to the hearts of mammals and contribute to heart disease. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1996-2005, 2016. © 2015 Wiley Periodicals, Inc.

Deconvolution analysis of 24-h serum cortisol profiles informs the amount and distribution of hydrocortisone replacement therapy.

PubMed

Peters, Catherine J; Hill, Nathan; Dattani, Mehul T; Charmandari, Evangelia; Matthews, David R; Hindmarsh, Peter C

2013-03-01

Hydrocortisone therapy is based on a dosing regimen derived from estimates of cortisol secretion, but little is known of how the dose should be distributed throughout the 24 h. We have used deconvolution analysis of 24-h serum cortisol profiles to determine 24-h cortisol secretion and distribution to inform hydrocortisone dosing schedules in young children and older adults. Twenty four hour serum cortisol profiles from 80 adults (41 men, aged 60-74 years) and 29 children (24 boys, aged 5-9 years) were subject to deconvolution analysis using an 80-min half-life to ascertain total cortisol secretion and distribution throughout the 24-h period. Mean daily cortisol secretion was similar between adults (6.3 mg/m(2) body surface area/day, range 5.1-9.3) and children (8.0 mg/m(2) body surface area/day, range 5.3-12.0). Peak serum cortisol concentration was higher in children compared with adults, whereas nadir serum cortisol concentrations were similar. Timing of the peak serum cortisol concentration was similar (07.05-07.25), whereas that of the nadir concentration occurred later in adults (midnight) compared with children (22.48) (P = 0.003). Children had the highest percentage of cortisol secretion between 06.00 and 12.00 (38.4%), whereas in adults this took place between midnight and 06.00 (45.2%). These observations suggest that the daily hydrocortisone replacement dose should be equivalent on average to 6.3 mg/m(2) body surface area/day in adults and 8.0 mg/m(2) body surface area/day in children. Differences in distribution of the total daily dose between older adults and young children need to be taken into account when using a three or four times per day dosing regimen. © 2012 Blackwell Publishing Ltd.

Atazanavir and Atazanavir/Ritonavir Pharmacokinetics in HIV-Infected Infants, Children, and Adolescents

PubMed Central

Kiser, Jennifer J.; Rutstein, Richard M.; Samson, Pearl; Graham, Bobbie; Aldrovandi, Grace; Mofenson, Lynne M.; Smith, Elizabeth; Schnittman, Steven; Fenton, Terry; Brundage, Richard C.; Fletcher, Courtney V.

2011-01-01

Objective To describe the pharmacokinetics of atazanavir (ATV) and ritonavir-boosted ATV/r in children ages 91 days to 21 years. Design Phase I/II, open label, multicenter study of once daily ATV and ATV/r as part of combination antiretroviral treatment in HIV-infected treatment experienced and naïve children. Setting Sites in the United States and South Africa. Subjects 195 children enrolled; 172 had evaluable ATV pharmacokinetics on day seven. Intervention Children were entered in age, dose and formulation (powder or capsule) cohorts. Intensive pharmacokinetic sampling occurred seven days after starting ATV. ATV doses were increased or decreased if the 24-hour area under the concentration time curves (AUC0–24hr) were <30 or >90 mcg*hr/mL, respectively. Main outcomes Cohorts satisfied protocol-defined pharmacokinetic criteria if the median ATV AUC0–24hr ≤60 mcg*hr/mL, and AUC0–24hr and ATV concentrations 24 hours post-dose (C24) were >30 mcg*hr/mL and ≥60 ng/mL, respectively, in ≥ 80% of children, with no individual AUC0–24hr <15 mcg*hr/mL. Results Unboosted ATV capsules satisfied pharmacokinetic criteria at a dose of 520 mg/m2 for those >2 to ≤ 13 years and 620 mg/m2 for those >13 to ≤ 21 years. ATV/r capsules satisfied criteria at a dose of 205 mg/m2 for those >2 to ≤ 21 years. ATV/r powder satisfied criteria at a dose of 310 mg/m2 for those >2 to ≤ 13 years, but pharmacokinetics in those ≤ 2 years were highly variable. Conclusions Body surface area-determined doses of ATV capsules and ATV/r powder and capsules provide ATV exposures in children >2 years that approximate values in adults receiving ATV/r. PMID:21610486

A phase I and pharmacologic study of sequences of the proteasome inhibitor, bortezomib (PS-341, Velcade), in combination with paclitaxel and carboplatin in patients with advanced malignancies.

PubMed

Ma, Cynthia; Mandrekar, Sumithra J; Alberts, Steven R; Croghan, Gary A; Jatoi, Aminah; Reid, Joel M; Hanson, Lorelei J; Bruzek, Laura; Tan, Angelina D; Pitot, Henry C; Erlichman, Charles; Wright, John J; Adjei, Alex A

2007-02-01

Bortezomib, a selective inhibitor of the 20S proteasome with activity in a variety of cancers, exhibits sequence-dependent synergistic cytotoxicity with taxanes and platinum agents. Two different treatment schedules of bortezomib in combination with paclitaxel and carboplatin were tested in this phase I study to evaluate the effects of scheduling on toxicities, pharmacodynamics and clinical activity. Patients with advanced malignancies were alternately assigned to receive (schedule A) paclitaxel and carboplatin (IV d1) followed by bortezomib (IV d2, d5, d8) or (schedule B) bortezomib (IV d1, d4, d8) followed by paclitaxel and carboplatin (IV d2) on a 21-day cycle. Fifty-three patients (A 25, B 28) were treated with a median of 3 cycles (range 1-8) for schedule A and 3.5 cycles (range 1-10) for schedule B. Grade 3 or higher treatment related hematologic adverse events in all cycles of treatment included neutropenia (A 52%, B 50%), anemia (A 12%, B 7.1%) and thrombocytopenia (A 16%, B 17.9%). Non-hematologic treatment related adverse events were fairly mild (primarily grades 1 and 2). The maximum tolerated dose and the recommended doses for future phase II trials are bortezomib 1.2 mg/m2, paclitaxel 135 mg/m2 and carboplatin AUC = 6 for schedule A and bortezomib 1.2 mg/m2, paclitaxel 175 mg/m2 and carboplatin AUC = 6 for schedule B. Six (21.4%) partial responses (PR) were seen with schedule B. In contrast, only 1 (4%) PR was achieved with schedule A. Similar proteasome inhibition was achieved at MTD for both schedules. Administration of sequential bortezomib followed by chemotherapy (schedule B) was well tolerated and associated with an encouraging number of objective responses in this small group of patients. Further studies with this administration schedule are warranted.

Phase I Study of SU5416, a Small Molecule Inhibitor of the Vascular Endothelial Growth Factor Receptor (VEGFR) in Refractory Pediatric Central Nervous System Tumors

PubMed Central

Kieran, Mark W.; Supko, Jeffrey G.; Wallace, Dana; Fruscio, Robert; Poussaint, Tina Young; Phillips, Peter; Pollack, Ian; Packer, Roger; Boyett, James M.; Blaney, Susan; Prados, Michael; Geyer, Russ; Friedman, Henry; Goldman, Stewart; Kun, Larry E.; MacDonald, Tobey

2009-01-01

SU5416 is a novel small molecule tyrosine kinase inhibitor of the VEGF receptors 1 and 2. A phase I dose escalation study stratified by concurrent use (stratum II) or absence (Stratum I) of enzyme-inducing anticonvulsant drugs was undertaken to estimate the maximum-tolerated dose (MTD) and to describe the toxicity profile of SU5416 in pediatric patients with refractory brain tumors. Dose escalations were conducted independently for stratum I starting at 110mg/m2 while stratum II started at 48mg/m2. Thirty-three eligible patients were treated on stratum I (n=23) and stratum II (n=10). Tumor types included 23 glial tumors, 4 neural tumors, 4 ependymomas and 2 choroid plexus carcinomas. The MTD in Stratum I was initially estimated to be 110mg/m2. The protocol was amended to determine the MTD after excluding transient AST elevation. Re-estimation of the MTD began at the 145mg/m2 dose level but due to development of SU5416 being stopped by the sponsor, the trial was closed before completion. The most serious drug-related toxicities were grade 3 liver enzyme abnormalities, arthralgia and hallucinations. The plasma pharmacokinetics of SU5416 was not significantly affected by the concurrent administration of enzyme-inducing anticonvulsant drugs. Mean values of the total body clearance, apparent volume of distribution, and terminal phase half-life of SU5416 for the 19 patients in Stratum I were 26.1 ± 12.5 liter/h/m2, 41.9 ± 21.4 liter/m2, and 1.11 ± 0.41 h, respectively. The plasma pharmacokinetics of SU5416 in children was similar to previously reported findings in adult cancer patients. Prolonged disease stabilization was observed in 4 of 16 stratum 1 patients. PMID:19065567