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Results for “multiple exposures”

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At least 865 records · Page 48Linked to original sources
PubMed1997

Sequence analysis of hepatitis C virus variants producing discrepant results with two different genotyping assays.

Methods for identifying the genotype of hepatitis C virus (HCV) in clinical specimens are frequently based upon the direct characterisation of viral RNA sequences by polymerase chain reaction (PCR) amplification, or by serologically based methods, in which the infecting genotype is inferred from the pattern of antibody reactivity to type-specific peptides or recombinant proteins used as antigens in an Enzyme Linked Immunosorbent Assay (ELISA). Although genotyping by direct, PCR-based methods show generally highly concordant results with the genotype inferred from serological typing assays (> 95% agreement), there exist a small number of samples that produce discrepant results. To investigate the underlying reasons for the discrepancies, we obtained eleven samples from haemophiliacs and four samples from patients with chronic hepatitis C that produced discordant results between a PCR based assay (InnoLipa I and II) and a serotyping assay (Murex HC02). Nucleotide sequences in the 5'noncoding region (5'NCR), core, and NS4 region were used to identify the genotype of the circulating virus and to identify amino acid changes in NS4 that might alter antigenicity. In 14 samples, sequence analysis of all three regions was concordant with the results of the InnoLipa assay. There were few if any amino acid substitutions in NS4 that might have accounted for the discrepant serotyping results, which were found predominantly in samples from individuals with a history of multiple exposure to HCV. It remains unclear whether the detection of antibody in such discrepant samples corresponds to previous expression of a different genotype than detected by PCR, or whether the virus population in plasma is more restricted in genotype diversity than the population in the liver or at other sites of viral replication.

Amino Acid Sequence↗
PubMedDate not supplied

Reactive airways dysfunction syndrome: two case reports.

Reactive airways dysfunction syndrome (RADS) is a type of asthma that develops in subjects without prior pulmonary disease, following single or multiple exposure to high levels of nonimmunogenic irritants. The main difference from classic occupational asthma is the absence of a latency period. Non-specific bronchial hyperresponsiveness is characteristic of the disease and usually persists after cessation of exposure. We report the cases of two subjects in whom RADS developed after occupational exposure to irritants.

Adult↗
PubMed2003

Multiple sclerosis and exposure to organic solvents, investigated by genetic polymorphisms of the GSTM1 and CYP2D6 enzyme systems.

An association between multiple sclerosis (MS) and exposure to organic solvents has been discussed. Organic solvents are metabolised by enzyme systems like glutathione Stransferase M1 (GSTM1) and CYP2D6, which express polymorphisms in the general population. GSTM1 null genotype has been associated with solvent-induced chronic toxic encephalopathy. Our aim was to see if a defect in one of these enzyme systems could explain the association between MS and exposure to organic solvents. In our study, 50 patients with MS were investigated, including 24 who had been significantly exposed to organic solvents and 26 who were not exposed. Polymerase chain reaction-based methods were used for genotyping GSTM1 and CYP2D6 polymorphisms in leukocyte DNA. No differences in genetic predisposition were found between MS patients exposed and those not exposed to organic solvents regarding GSTM1 null or CYP2D6 poor metaboliser genotypes. The possible association between multiple sclerosis and solvents may not, as for chronic toxic encephalopathy, be explained by defects in these systems.

Adult↗
PubMed1993

Multiple sclerosis and exposure to solvents, ionizing radiation and animals.

Earlier studies have indicated an association between multiple sclerosis and environmental factors, especially occupational exposure to solvents. The present study examined such relationships further. From medical files of hospitals in Kalmar and Jönköping, 91 cases of multiple sclerosis, diagnosed in 1983-1988, were identified from population registers corresponding to the catchment areas of the hospitals, and 348 referents were randomly drawn. The cases and referents answered a questionnaire concerning occupational exposure and animal contacts. The men had significantly elevated risks, determined from logistic odds ratios, for solvent exposure, occupational contact with dogs or cats, and leisure-time contact with caged birds. X-ray treatment and previous diseases were risk indicators among the women. For the men and women together, solvent exposure, radiological work, and previous diseases were associated with clearly elevated risks. Although the study concerned rather few subjects, the findings indicate that several exogenous factors might contribute to the development of multiple sclerosis.

Adult↗
PubMed1993

Lymphoma, multiple myeloma and leukaemia among French farmers in relation to pesticide exposure.

Lymphoma, multiple myeloma and leukaemia mortality among French male farmers and farm laborers (1984-1986) has been studied geographically. In each geographical area (89 "départements") exposure to pesticides in arable land has been characterized by an index taking into account different practices in the treatment of various crops as well as an estimate of the time per farmer spent cultivating each crop in 1970. The farmers population as a whole presented an increased mortality for multiple myeloma (SMR = 1.59, 95% CI = 1.32-1.89) and leukaemia (SMR = 1.33, 95% CI = 1.19-1.49) but not for lymphoma (SMR = 1.09, 95%, CI = 0.94-1.26). Using Poisson regression, leukaemia mortality appeared significantly linked to the pesticide exposure index (P = 0.04), after adjustment of farmers' economic status and a linear geographical gradient, whereas no significant relationship was found for lymphoma or multiple myeloma. This result reinforces a similar link reported from a previous French geographical study conducted at a smaller scale within a region.

Adult↗
PubMed1994

Sunscreens with broad-spectrum absorption decrease the trans to cis photoisomerization of urocanic acid in the human stratum corneum after multiple UV light exposures.

The trans to cis photoisomerization of urocanic acid (UCA) in skin is considered to play an important role in the mechanism of immunosuppression. We have investigated the effects of skin type and various sunscreens with low sun protection factor (SPF) on the UV-induced cis-UCA formation in human skin after exposure to artificial UV light. The rate of cis-UCA formation depends little on the skin type and is reduced by topical application of sunscreens. The rate of cis-UCA formation decreases with increasing SPF and only broad-spectrum, highly protective sunscreens offer protection against the UV-induced formation of cis-UCA, which accumulates in the stratum corneum after multiple UV exposures. A theoretical approach to estimate the distribution of cis-UCA after irradiation indicates that this compound may diffuse into the deeper layers of the epidermis with D approximately 10(-17) m2/s, and that its elimination from the stratum corneum is mainly due to desquamation.

Camphanes↗
PubMed2004

Children's health and the environment: public health issues and challenges for risk assessment.

Infants and children are not little adults. They are uniquely vulnerable to environmental toxicants. To protect infants and children against toxicants, the National Research Council in 1993 called for development of an approach to risk assessment that considers children's unique patterns of exposure and their special vulnerabilities to pesticides. Many aspects of that call were codified into federal law in the Food Quality Protection Act (FQPA) of 1996. This report highlights the central elements needed for development of a child-protective approach to risk assessment: a) improved quantitative assessment of children's exposures at different life stages, from fetal life through adolescence, including acute and chronic exposures, exposures via multiple routes, and exposures to multiple agents; b) development of new approaches to toxicity testing of chemicals that can detect unanticipated and subtle outcomes and that evaluate experimental subjects over the entire life span from early exposure to natural death to replicate the human experience; c) development of new toxicodynamic and toxicokinetic models that account for the unique physiologic characteristics of infants and children; d) development of new approaches to assessment of outcomes, functional, organ, cellular and molecular, over the entire life span; these measures need to be incorporated into toxicity testing and into long-term prospective epidemiologic studies of children; and e) application of uncertainty and safety factors in risk assessment that specifically consider children's risks. Under FQPA, children are presumed more vulnerable to pesticides than adults unless evidence exists to the contrary. Uncertainty and safety factors that are protective of children must therefore be incorporated into risk assessment when data on developmental toxicity are lacking or when there is evidence of developmental toxicity. The adequate protection of children against toxic agents in the environment will require fundamental and far-reaching revisions of current approaches to toxicity testing and risk assessment.

Child↗
PubMed2000

Effects of multiple acute morphine exposures on feline immunodeficiency virus disease progression.

Drug abuse is a common method of human immunodeficiency virus type 1 transmission, but the role of opiates on lentivirus disease progression is not well understood. The feline immunodeficiency virus (FIV)/cat system was used to model the weekend opiate abuser: the nondependent, nonaddicted, and nontolerant person. Sixteen cats were placed into 4 groups: FIV only, morphine only, morphine/FIV, and controls. Multiple acute morphine exposure did not increase the severity of early lentivirus infection. On the contrary, it delayed or moderated the FIV-induced disease progression. Although the animals were exposed to only 1 injection of morphine per day for 2 consecutive days per week, the morphine-treated FIV-infected animals had a delayed onset of the FIV-induced lymphadenopathy, did not develop or had a significant delay in the FIV-induced effects on brain stem auditory evoked potentials, and demonstrated a trend toward decreased virus load.

Animals↗
PubMed2004

Hippocampal plasticity across multiple days of exposure to novel environments.

The hippocampus is essential for learning complex spatial relationships, but little is known about how hippocampal neural activity changes as animals learn about a novel environment. We studied the formation of new place representations in rats by examining the changes in place-specific firing of neurons in the CA1 region of the hippocampus and the relationship between these changes and behavioral change across multiple days of exposure to novel places. We found that many neurons showed very rapid changes on the first day of exposure to the novel place, including many cases in which a previously silent neuron developed a place field over the course of a single pass through the environment. Across the population, the largest changes in neural activity occurred on day 2 of exposure to a novel place, but only if the animal had little experience (<4 min) in that location on day 1. Longer exposures on day 1 were associated with smaller changes on day 2, suggesting that hippocampal neurons required 5-6 min of experience to form a stable spatial representation. Even after the representation stabilized, the animals' behavior remained different in the novel places, suggesting that other brain regions continued to distinguish novel from familiar locations. These results show that the hippocampus can form new spatial representations quickly but that stable hippocampal representations are not sufficient for a place to be treated as familiar.

Animals↗
PubMed2001

The development of a new method to estimate total daily dose of pesticides in professional turf applicators following multiple and varied exposures in occupational settings.

The evaluation of absorbed dose of pesticides in humans requires a knowledge of the kinetics and dynamics of the compound. In some circumstances, data that allow for the estimation of dose may be available from human volunteer studies, although often, it will be based on results from animal studies. If human metabolism data are available, estimates of dose may be more accurate, but it should be recognized that pesticide exposure in an occupational setting may differ from that in a controlled laboratory study. In this study, data from previously published studies are used to evaluate the urinary excretion of 2,4-dichlorophenoxyacetic acid (2,4-D), following single dermal applications to human volunteers. These studies are evaluated with the objective of determining the best method of predicting total absorbed dose following multiple and varied exposures in occupational settings. Further, an alternative to laboratory-controlled human volunteer studies is presented. Data from a third previously published biological monitoring study on six professional pesticide applicators over a 2-week period were used to generate estimates of the urinary excretion of the pesticide 2,4-D that would result from a single dose. The method used to estimate the urinary excretion parameters is a variation of an overlay technique used in pharmacology, and may provide information on the kinetics of other pesticides when it is not possible to conduct human studies. The generated estimates of 24-h urinary excretion of 2,4-D over a 6-day period were remarkably similar to those obtained in controlled studies. Finally, a method was developed to use the generated estimates to determine total absorbed dose of pesticides for an independent group of 95 professional pesticide applicators. This method requires information on the amount of pesticide used for 6 days prior to the collection of two, 24-h urine samples.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2004

Developmental neurotoxicity of ketamine: morphometric confirmation, exposure parameters, and multiple fluorescent labeling of apoptotic neurons.

Ketamine is a widely used pediatric anesthetic recently reported (C. Ikonomidou et al., 1999, Science 283, 70-74) to enhance neuronal death in neonatal rats. To confirm and extend these results, we treated four groups of PND 7 rats with seven sc doses, one every 90 min, of either saline, 10 mg/kg ketamine, 20 mg/kg ketamine, or a single dose of 20 mg/kg ketamine. The repeated doses of 20 mg/kg ketamine increased the number of silver-positive (degenerating) neurons in the dorsolateral thalamus to a degree comparable to previous results (Ikonomidou et al., 1999, Science 283, 70-74), i.e., 28-fold vs. 31-fold respectively. However, blood levels of ketamine immediately after the repeated 20 mg/kg doses were about 14 micrograms/ml, about seven-fold greater than anesthetic blood levels in humans (J. M. Malinovsky et al., 1996, Br. J. Anaesth. 77, 203-207; R. A. Mueller and R. Hunt, 1998, Pharmacol. Biochem. Behav. 60, 15-22). Levels of ketamine in blood following exposure to the multiple 10 mg/kg doses of ketamine or to a single 20 mg/kg dose ranged around 2-5 micrograms/ml; although these blood levels are close to an anesthetic level in humans, they failed to produce neurodegeneration. To investigate the mode of ketamine-induced neuronal death, coronal sections were stained with both Fluoro-Jade B (a green fluorescent stain selective for neurodegeneration) and DAPI (a blue DNA stain), as well as for caspase-3 (using an antisera labeled red with rhodamine). These histochemical results confirmed the developmental neurotoxicity of ketamine, demonstrated that Fluoro-Jade B (FJ-B), like silver methods, successfully stained degenerating neurons in neonatal rats, and indicated that ketamine acts by increasing the rate of neuronal apoptosis.

Animals↗
PubMedDate not supplied

Comparison of systemic and local immune responses after multiple pulmonary antigen exposures.

Both systemic and local immune responses were evaluated in five male cynomolgus monkeys after a primary and multiple secondary challenges of the lung with sheep red blood cell (SRBC) antigen. Comparisons of peripheral blood and pulmonary antibody-forming cell (AFC) responses were made after primary and multiple secondary intrapulmonary challenges with SRBC. The primary immune response to SRBC was characterized by a low lung to blood AFC ratio. This ratio, however, increased successively with each challenge, resulting in a 15-fold increase after the third exposure of the lung to SRBC. These data suggest a decreasing contribution of systemic AFC to the lung response with each successive challenge. Histopathologic and autoradiographic evaluation was done to compare a newly immunized lobe, a multiply challenged lobe, and a saline instilled lobe. Large localized perivascular lymphoid follicles appeared in the lung lobe challenged multiple times. About 17% of these large mononuclear cells had taken up 3H-thymidine compared to 5% in the newly immunized lobe and 3.8% in the control lobe. The number of proliferating cells appeared to reflect the degree of immune responsiveness within each lung lobe. Together these data support a hypothesis that after the primary immune response is established, the secondary immune response is generated by local clonal expansion of antigen-specific lymphocytes within the lung.

Analysis of Variance↗
PubMed1999

Interpreting research on prenatal substance exposure in the context of multiple confounding factors.

Fetal exposure to specific drugs often occurs in the context of polydrug use, medical complications, and social/environmental risks. Early reports of severe developmental consequences of fetal exposure to illicit drugs, for example, cocaine, have largely been unsupported by recent studies that take these factors into account. Using a database of published studies on cocaine exposure, this article examines how confounding factors are controlled by recruitment and statistical strategies. Rather than attempting to reduce the impact of these factors, it is suggested that multiple risks in children's lives should be included in models of developmental outcomes along with drug exposure. Understanding the complexity of multiple risks in the child's environment and the subtlety of drug exposure effects can guide the choice of clinical treatment and intervention.

Child↗
PubMed1997

Human drug discrimination and multiple chemical sensitivity: caffeine exposure as an experimental model.

Multiple chemical sensitivity is a controversial diagnosis. Rigorous, controlled, laboratory-based research can reduce this controversy and lead to potential clinical confirmatory tests. The literature on human caffeine discrimination provides a rigorous methodology that can address reports that patients who suffer multiple chemical sensitivity (MCS) are sensitive to usually well-tolerated chemical doses; the studies require patients to discriminate caffeine from placebo under double-blind conditions. Several issues relevant to the conduct of caffeine discrimination studies using MCS patients as subjects are addressed; these issues include study design, determination of safe and tolerable training doses, and discrimination training. Such research will benefit patients and clinicians dealing with a diagnosis of MCS.

Caffeine↗
PubMed2000

Polyreactivity as an acquired artefact, rather than a physiologic property, of antibodies: evidence that monoreactive antibodies may gain the ability to bind to multiple antigens after exposure to low pH.

Evidence is presented that monoreactive antibodies exposed to low pH may acquire the ability to bind to multiple antigens. M11, a murine, monoclonal, IgM(K) anti-goat IgG (GIgG) was purified from a hybridoma supernatant by elution at low pH from an anti-mu-Sepharose 4B affinity column. By measuring the specific antiGIgG activities and the affinity constants for the interactions of M11, pre- and post-affinity-purification, with GIgG, M11 was shown to be monoreactive before purification. Quite unexpectedly, however, the affinity-purified M11 reacted extensively with size-fractionated liver proteins when tested in an immunoblot, clearly indicating that it was polyreactive. It was concluded that the exposure to low pH had altered the M11 binding-site so as to allow it to bind to many different proteins. This phenomena provides an alternative basis for interpreting the polyreactivity observed following affinity-purification.

Animals↗
PubMedDate not supplied

A fatal case of sun exposure in a multiple sclerosis patient.

A 35-year-old woman with a long standing history of relapsing-remitting multiple sclerosis became physically incapacitated by heat-induced muscle weakness while sunbathing and suffered fatal sun exposure. These deleterious effects of increased core temperature on the neurological symptoms have been documented for a half century. Elevation of the patient's core temperature may lead to either transient or permanent neurologic symptoms and signs that predispose to considerable morbidity and mortality.

Adult↗