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102 records – page 1 of 11.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) poisoning in Victor Yushchenko: identification and measurement of TCDD metabolites.

https://arctichealth.org/en/permalink/ahliterature95137
Source
Lancet. 2009 Oct 3;374(9696):1179-85
Publication Type
Article
Date
Oct-3-2009
Author
Sorg O.
Zennegg M.
Schmid P.
Fedosyuk R.
Valikhnovskyi R.
Gaide O.
Kniazevych V.
Saurat J-H
Author Affiliation
Dermato-Toxicology, Swiss Centre for Applied Human Toxicology, and Department of Dermatology, University Hospital, Geneva, Switzerland.
Source
Lancet. 2009 Oct 3;374(9696):1179-85
Date
Oct-3-2009
Language
English
Publication Type
Article
Keywords
Adipose Tissue - chemistry
Biopsy
Drug Residues - analysis - metabolism
Fatal Outcome
Feces - chemistry
Forensic Medicine - methods
Half-Life
Homicide
Humans
Male
Middle Aged
Politics
Substance Abuse Detection - methods
Sweat - chemistry
Tetrachlorodibenzodioxin - analysis - chemistry - metabolism - poisoning
Time Factors
Ukraine
Abstract
BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a long half-life of 5-10 years in human beings as a result of its high lipophilicity, and little or no metabolism. We monitored TCDD, its form, distribution, and elimination in Victor Yushchenko after he presented with severe poisoning. METHODS: In late December, 2004, a patient presented with TCDD poisoning; the levels in his blood serum (108000 pg/g lipid weight) were more than 50 000-fold greater than those in the general population. We identified TCDD and its metabolites, and monitored their levels for 3 years using gas chromatography and high-resolution mass spectrometry in samples of blood serum, adipose tissue, faeces, skin, urine, and sweat, after they were extracted and cleaned with different organic solvents. FINDINGS: The amount of unmodified TCDD in the samples that were analysed accounted for about 60% of TCDD eliminated from the body during the same period. Two TCDD metabolites-2,3,7-trichloro-8-hydroxydibenzo-p-dioxin and 1,3,7,8-tetrachloro-2-hydroxydibenzo-p-dioxin-were identified in the faeces, blood serum, and urine. The faeces contained the highest concentration of TCDD metabolites, and were the main route of elimination. Altogether, the different routes of elimination of TCDD and its metabolites accounted for 98% of the loss of the toxin from the body. The half-life of TCDD in our patient was 15.4 months. INTERPRETATION: This case of poisoning with TCDD suggests that the design of methods for routine assessment of TCDD metabolites in human beings should be a main aim of TCDD research in the metabolomic era. FUNDING: University of Geneva Dermatology Fund, and Swiss Centre for Applied Human Toxicology.
Notes
Comment In: Lancet. 2009 Oct 3;374(9696):1131-219660808
PubMed ID
19660807 View in PubMed
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A 5-year prospective assessment of the risk associated with individual benzodiazepines and doses in new elderly users.

https://arctichealth.org/en/permalink/ahliterature176448
Source
J Am Geriatr Soc. 2005 Feb;53(2):233-41
Publication Type
Article
Date
Feb-2005
Author
Robyn Tamblyn
Michal Abrahamowicz
Roxane du Berger
Peter McLeod
Gillian Bartlett
Author Affiliation
Department of Medicine, McGill University, Montreal, Quebec, Canada. robyn.tamblyn@mcgill.ca
Source
J Am Geriatr Soc. 2005 Feb;53(2):233-41
Date
Feb-2005
Language
English
Publication Type
Article
Keywords
Aged
Benzodiazepines - administration & dosage - adverse effects - pharmacokinetics
Dose-Response Relationship, Drug
Female
Follow-Up Studies
Half-Life
Hospitalization
Humans
Male
Proportional Hazards Models
Prospective Studies
Quebec - epidemiology
Risk assessment
Risk factors
Wounds and Injuries - epidemiology
Abstract
To determine the risk of injury associated with the new use of individual benzodiazepines and dosage regimens in the elderly.
Prospective database cohort study with 5 years of follow-up.
Quebec, Canada.
Two hundred fifty-three thousand two hundred forty-four persons aged 65 and older who were nonusers of benzodiazepines in the year before follow-up.
Population-based hospitalization and prescription and medical services claims databases were used to compare the risk of injury during periods of benzodiazepine use with those of nonuse. Periods of use were measured for 10 insured benzodiazepines by drug and dose as time-dependent covariates. Injury was defined as the first occurrence of a nonvertebral fracture, soft-tissue injury, or accident-related hospital admission. Patient age, sex, previous injury history, concomitant medication use, and comorbidity were measured as fixed and time-dependent confounders. Cox proportional hazards models were used to estimate the risk of injury with benzodiazepine use and to determine the extent to which patient characteristics, differences in dosage, or in the effect of increasing dosage for individual drugs explained differences between drugs.
More than one-quarter (27.6%) of 253,244 elderly were dispensed at least one prescription for a benzodiazepine, and 17.7% of elderly were treated for at least one injury during follow-up, of which fractures were the most common. Patient characteristics, systematic differences in the risk of injury in elderly prescribed different benzodiazepines, and differences in dosage prescribed for individual drugs confounded the risk of injury with benzodiazepine use. The risk of injury with increasing dosage varied by drug from a hazard ratio of 0.92 (95% confidence interval (CI)=0.60, 1.42) for alprazolam to 2.20 (95% CI=1.39, 3.47) for flurazepam per 1 standardized adult dose increase.
The risk of injury varied by benzodiazepine, independent of half-life, as did the risk associated with increasing dosage for individual products. Higher doses of oxazepam, flurazepam, and chlordiazepoxide are associated with the greatest risk of injury in the elderly.
Notes
Comment In: ACP J Club. 2005 Jul-Aug;143(1):2415989312
PubMed ID
15673346 View in PubMed
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ABCB1 haplotypes differentially affect the pharmacokinetics of the acid and lactone forms of simvastatin and atorvastatin.

https://arctichealth.org/en/permalink/ahliterature152450
Source
Clin Pharmacol Ther. 2008 Oct;84(4):457-61
Publication Type
Article
Date
Oct-2008
Author
J E Keskitalo
K J Kurkinen
P J Neuvoneni
M. Niemi
Author Affiliation
Department of Clinical Pharmacology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Source
Clin Pharmacol Ther. 2008 Oct;84(4):457-61
Date
Oct-2008
Language
English
Publication Type
Article
Keywords
Area Under Curve
Cross-Over Studies
Female
Finland
Half-Life
Haplotypes
Heptanoic Acids - pharmacokinetics
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacokinetics
Lactones - pharmacokinetics
Male
P-Glycoprotein - genetics
Polymorphism, Single Nucleotide
Pyrroles - pharmacokinetics
Simvastatin - pharmacokinetics
Abstract
ABCB1 haplotypes were determined in 534 healthy Finnish volunteers, of whom 24 participated in a pharmacokinetic study on simvastatin and atorvastatin. The frequencies of occurrence of haplotypes c.1236T-c.2677T-c.3435T and c.1236C-c.2677G-c.3435C were 42.7 and 34.4%, respectively. The simvastatin acid AUC(0-12h) was 60% larger, the atorvastatin AUC(0-infinity) 55% larger, and the atorvastatin half-life 24% longer in subjects with the ABCB1 TTT/TTT genotype (n = 12) than in those with the CGC/CGC genotype (n = 12) (P
PubMed ID
19238649 View in PubMed
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The accumulation and retention of 95mTc by the Norway lobster, Nephrops norvegicus L.

https://arctichealth.org/en/permalink/ahliterature61729
Source
J Environ Radioact. 2001;57(2):139-49
Publication Type
Article
Date
2001
Author
D. Swift
Author Affiliation
Lowestoft Laboratory, Centre for Environment, Fisheries and Aquaculture Science, Suffolk, UK. d.j.swift@cefas.co.uk
Source
J Environ Radioact. 2001;57(2):139-49
Date
2001
Language
English
Publication Type
Article
Keywords
Animals
Diet
Environmental Exposure
Half-Life
Nephropidae - chemistry
Technetium - chemistry - pharmacokinetics
Tissue Distribution
Water Pollutants, Radioactive - pharmacokinetics
Abstract
Laboratory experiments were carried out to study bioaccumulation and determine a concentration factor (CF) for technetium (95mTc) in the homarid crustacean Nephrops norvegicus L. The steady state CF for accumulation from seawater was estimated to be about 2,000 and the biological half-time was about 50 days. The highest tissue Tc concentrations were found in the green gland and the digestive gland. Depuration following accumulation from water was slow with a half-time of about 165 days. Tc accumulation from labelled food followed a biphasic model with one compartment containing about 94 percent of the ingested activity and with a half-time of about 1 day and the second compartment containing about 6 percent of the ingested activity with a half-time of about 56 days. Most retained activity was found in the digestive gland.
PubMed ID
11545381 View in PubMed
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Alpha-particle carcinogenesis in Thorotrast patients: epidemiology, dosimetry, pathology, and molecular analysis.

https://arctichealth.org/en/permalink/ahliterature19345
Source
J Environ Pathol Toxicol Oncol. 2001;20(4):311-5
Publication Type
Article
Date
2001
Author
Y. Ishikawa
I. Wada
M. Fukumoto
Author Affiliation
Department of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo.
Source
J Environ Pathol Toxicol Oncol. 2001;20(4):311-5
Date
2001
Language
English
Publication Type
Article
Keywords
Adult
Aged
Alpha Particles - adverse effects
Carcinogens - adverse effects - pharmacokinetics
Carcinoma, Hepatocellular - epidemiology - etiology
Cause of Death
Cholangiocarcinoma - epidemiology - etiology
DNA Damage
DNA Mutational Analysis
Epidemiologic Studies
Europe - epidemiology
Female
Genes, p53
Half-Life
Hemangiosarcoma - epidemiology - etiology
Humans
Japan - epidemiology
Leukemia - epidemiology - etiology
Liver Cirrhosis - epidemiology - etiology
Liver Neoplasms - epidemiology - etiology
Loss of Heterozygosity
Male
Middle Aged
Radiation Injuries
Research Support, Non-U.S. Gov't
Risk assessment
Thorium Dioxide - adverse effects - pharmacokinetics
United States
Abstract
We studied the alpha-radiation risks in patients who received injections of Thorotrast, an X-ray contrast medium used in Europe, Japan, and the United States from 1930 to 1955. Thorotrast was composed of thorium dioxide (ThO2) and Th-232, a naturally occurring radionuclide. Because the physical half-life of ThO2 is 14 billion years and Thorotrast is hardly eliminated from the body, tissues in which it was deposited are irradiated by alpha-radiation for the entire lifetime of the subject. The dosimetry of Thorotrast patients is very complicated, but currently its reliability is quite high compared with other irradiated populations. The major causes of the death of Thorotrast patients are liver cancer, liver cirrhosis, leukemia, and other cancers. Three histologies of liver cancer are found: cholangiocarcinoma, hepatocellular carcinoma, and angiosarcoma. Although cholangiocarcinoma is the most frequent, angiosarcoma is characteristic of alpha-radiation. Among blood neoplasms with a higher incidence of increase than the general population, erythroleukemia and myelodysplastic syndrome were remarkable. Thorotrast patients exhaled a high concentration of radon (Rn-220), a progeny of Th-232, but no excesses of lung cancer in the patients of Japan, Germany, and Denmark were reported. Mutation analyses of p53 genes and loss of heterozygosity (LOH) studies at 17p locus were performed to characterize the genetic changes in Thorotrast-induced liver tumors. Interestingly, LOH, supposedly corresponding to large deletions was not frequent; most mutations were transitions, also seen in tumors of the general population, suggesting that genetic changes of Thorotrast-induced cancers are mainly delayed mutations, and not the result of the direct effects of radiation.
PubMed ID
11797840 View in PubMed
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Aluminum toxicokinetics in peritoneal dialysis patients.

https://arctichealth.org/en/permalink/ahliterature132420
Source
Clin Toxicol (Phila). 2011 Aug;49(7):659-63
Publication Type
Article
Date
Aug-2011
Author
Corinne Seng Yue
Megan Christie
Valery Lavergne
Tabo Sikaneta
Hulya Taskapan
Karine Mardini
Paul Tam
Robert Ting
Marc Ghannoum
Author Affiliation
Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
Source
Clin Toxicol (Phila). 2011 Aug;49(7):659-63
Date
Aug-2011
Language
English
Publication Type
Article
Keywords
Aged
Aluminum - blood - pharmacokinetics - toxicity
Body Burden
Dialysis Solutions - pharmacokinetics - toxicity
Drug Contamination
Female
Half-Life
Humans
Kidney Diseases - metabolism - therapy
Linear Models
Male
Middle Aged
Models, Biological
Ontario
Peritoneal dialysis
Prospective Studies
Quebec
Risk assessment
Risk factors
Tissue Distribution
Abstract
Despite the risk of aluminum (Al) toxicity in dialysis patients, little is known about its toxicokinetics (TK) in this population. A national contamination of dialysate solutions with Al provided the opportunity to study Al TK in peritoneal dialysis (PD) patients and to better understand the influence of covariates on its disposition.
Al levels in serum and dialysate as well as other laboratory values were collected prospectively from 83 PD patients after correction of Al contamination. Population TK analyses were conducted with NONMEM VI using standard model discrimination criteria. Covariate analyses were also performed using stepwise forward regression followed by backward deletion.
After correction of Al exposure, serum levels declined in a biphasic manner, which was captured by the TK model. The TK of Al were best described by a 2-compartment model with linear elimination. Total creatinine clearance was a significant covariate for total clearance (CL). Mean parameter estimates for volume of central compartment (V1), CL, volume of peripheral compartment (V2), volume of distribution at steady-state (Vss), and intercompartmental clearance (Q) were 168 L, 8.99 L/day, 12 000 L, 12 168 L, and 4.93 L/day, respectively. Inter-individual variability for CL and V2 were 22.6 and 51.1%, respectively. Al distributional half-life was 8.5 days, while the terminal elimination half-life was 7.2 years. This model confirms that the large Vss reflects the widespread distribution of Al in bone, lungs, liver, and other tissues.
This study describes the first population Al TK model in a large group of PD patients, which includes a covariate effect. The model confirms the extensive half-life and tissue distribution of Al in a dialysis-dependent population.
PubMed ID
21819285 View in PubMed
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Aminoglycoside pharmacokinetics in Alaskan natives.

https://arctichealth.org/en/permalink/ahliterature214307
Source
Am J Health Syst Pharm. 1995 Sep 15;52(18):2015-8
Publication Type
Article
Date
Sep-15-1995
Author
K L McAndrews
J E Murphy
Author Affiliation
Department of Veterans Affairs Pharmacy Service, San Diego, CA, USA.
Source
Am J Health Syst Pharm. 1995 Sep 15;52(18):2015-8
Date
Sep-15-1995
Language
English
Publication Type
Article
Keywords
Adult
Aged
Alaska
Aminoglycosides
Anti-Bacterial Agents - pharmacokinetics
Female
Half-Life
Humans
Inuits
Male
Metabolic Clearance Rate
Middle Aged
Retrospective Studies
United States
PubMed ID
8528870 View in PubMed
Less detail

An air pollution model for use in epidemiological studies: evaluation with measured levels of nitrogen dioxide and benzene.

https://arctichealth.org/en/permalink/ahliterature199269
Source
J Expo Anal Environ Epidemiol. 2000 Jan-Feb;10(1):4-14
Publication Type
Article
Author
O. Raaschou-Nielsen
O. Hertel
E. Vignati
R. Berkowicz
S S Jensen
V B Larsen
C. Lohse
J H Olsen
Author Affiliation
Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen O. ole@cancer.dk
Source
J Expo Anal Environ Epidemiol. 2000 Jan-Feb;10(1):4-14
Language
English
Publication Type
Article
Keywords
Air Pollution - analysis
Benzene - analysis - pharmacokinetics
Denmark
Environmental pollution - analysis
Epidemiologic Studies
Half-Life
Humans
Models, Theoretical
Nitrogen Dioxide - analysis - pharmacokinetics
Research Design
Vehicle Emissions
Abstract
The aim of the study was to evaluate the predictions derived from the Danish Operational Street Pollution Model (OSPM) when the input data are obtained by simple methods that could be used in large-scale epidemiological studies. The model calculations were thus compared with passive sampler measurements of nitrogen dioxide and benzene at 103 street locations in Copenhagen, Denmark, and at 101 locations in rural areas. Data on traffic and street configuration were collected by means of a simple registration scheme in which forms were filled out by local municipal authorities. Meteorological data were derived from routine measurements at Copenhagen airport, and data on background air pollution were based on a simple empirical model. Differences in air pollution levels between rural areas and Copenhagen and differences in nitrogen dioxide concentrations at various locations in Copenhagen were well reproduced by the OSPM. The correlation coefficients (r) between the measured and the predicted half-year average concentrations of nitrogen dioxide in Copenhagen were between 0.75 and 0.80 for various degrees of precision of the input data for the model. The results indicate that the OSPM used with the presented methods for generation of input data might be useful in assessing long-term exposure to air pollutants in epidemiological studies.
PubMed ID
10703843 View in PubMed
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Analysing half-lives for pesticide dissipation in plants.

https://arctichealth.org/en/permalink/ahliterature269814
Source
SAR QSAR Environ Res. 2015;26(4):325-42
Publication Type
Article
Date
2015
Author
R E Jacobsen
P. Fantke
S. Trapp
Source
SAR QSAR Environ Res. 2015;26(4):325-42
Date
2015
Language
English
Publication Type
Article
Keywords
Biodegradation, Environmental
China
Denmark
Half-Life
Lycopersicon esculentum - metabolism
Models, Biological
Pesticide Residues - chemistry - metabolism
Pesticides - chemistry - metabolism
Plants - metabolism
Triticum - metabolism
Volatilization
Abstract
Overall dissipation of pesticides from plants is frequently measured, but the contribution of individual loss processes is largely unknown. We use a pesticide fate model for the quantification of dissipation by processes other than degradation. The model was parameterised using field studies. Scenarios were established for Copenhagen/Denmark and Shanghai/PR China, and calibrated with measured results. The simulated dissipation rates of 42 pesticides were then compared with measured overall dissipation from field studies using tomato and wheat. The difference between measured overall dissipation and calculated dissipation by non-degradative processes should ideally be contributable to degradation in plants. In 11% of the cases, calculated dissipation was above the measured dissipation. For the remaining cases, the non-explained dissipation ranged from 30% to 83%, depending on crop type, plant part and scenario. Accordingly, degradation is the most relevant dissipation process for these 42 pesticides, followed by growth dilution. Volatilisation was less relevant, which can be explained by the design of plant protection agents. Uptake of active compound from soil into plants leads to a negative dissipation process (i.e. a gain) that is difficult to quantify because it depends largely on interception, precipitation and plant stage. This process is particularly relevant for soluble compounds.
PubMed ID
25948099 View in PubMed
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102 records – page 1 of 11.