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At least 235 records · Page 13Linked to original sources
PubMed1999

A likelihood-based method of identifying contaminated lots of blood product.

BACKGROUND: In 1994 a small cluster of hepatitis-C cases in Rhesus-negative women in Ireland prompted a nationwide screening programme for hepatitis-C antibodies in all anti-D recipients. A total of 55 386 women presented for screening and a history of exposure to anti-D was sought from all those testing positive and a sample of those testing negative. The resulting data comprised 620 antibody-positive and 1708 antibody-negative women with known exposure history, and interest was focused on using these data to estimate the infectivity of anti-D in the period 1970-1993. METHODS: Any exposure to anti-D provides an opportunity for infection, but the infection status at each exposure time is not observed. Instead, the available data from antibody testing only indicate whether at least one of the exposures resulted in infection. Using a simple Bernoulli model to describe the risk of infection in each year, the absence of information regarding which exposure(s) led to infection fits neatly into the framework of 'incomplete data'. Hence the expectation-maximization (EM) algorithm provides estimates of the infectiousness of anti-D in each of the 24 years studied. RESULTS: The analysis highlighted the 1977 anti-D as a source of infection, a fact which was confirmed by laboratory investigation. Other suspect batches were also identified, helping to direct the efforts of laboratory investigators. CONCLUSIONS: We have presented a method to estimate the risk of infection at each exposure time from multiple exposure data. The method can also be used to estimate transmission rates and the risk associated with different sources of infection in a range of infectious disease applications.

Algorithms↗
PubMed1986

The effects of nitrous oxide after exposure during middle and late gestation.

Recent evidence has indicated that the anesthetic gas nitrous oxide (N2O) is teratogenic to rats if exposed during the organogenesis phase of gestation. Little is known, however, of the anatomical or functional consequences of exposures occurring later in gestation when the brain is developing. Timed pregnant Sprague-Dawley rats were exposed to 75% N2O/25% O2 using one of the following protocols: 24 hr exposures on gestational days 11-15 or 16-20; or 8 hr exposures on gestational days 9-13, 11-15, 14-15 or day 15 only. Both 24 hr exposure protocols significantly reduced fetal and maternal body weight, an effect not observed after the 8 hr exposures. No N2O exposure resulted in gross morphological or skeletal changes. Likewise, no significant effects on total protein and DNA levels in fetal liver and brain tissues could be found subsequent to 24 hr exposures on days 16-20; or on one, three or six days following an 8 hr exposure on day 15. Evaluations of postnatal growth and neurological development in pups prenatally exposed for 8 hr on days 14 and 15 revealed two noteworthy effects. Their rate of growth in body weight was greater with respect to controls between the ages of 14 and 21 days, especially in the males. Also, reflex suspension was reduced, significantly so in the females. In conclusion, unlike 24 hr exposures, multiple 8 hr exposures to nitrous oxide during the middle to late stages of gestation did not produce effects detectable with standard teratological measures. Subtle differences in growth rate and reflex suspension, however, indicated that normal development had been interrupted, but its clear distinction as a lasting effect requires additional measures of function.

Animals↗
PubMed1991

Elementary methods of cohort analysis with several exposure levels.

This paper proposes an extension of the Mantel-Haenszel rate ratio for the dichotomous exposure to the multiple exposure levels. This extension is based on the unbiased estimating function approach and yields closed-form Mantel-Haenszel rate ratio estimators. Dually consistent variance and covariance estimators of the estimating functions are given and a quasi-score-based confidence interval for individual common rate ratio is provided. A similar extension to the common rate difference case is also given.

Arsenic Poisoning↗
PubMed1977

A simple device for testing the accuracy of x-ray timers.

A simple device for testing the accuracy of x-ray timers uses a portable record player whose turntable spins the film cassette beneath the lid on which lead shielding protects the film except for a tiny pin-hole through which the exposures are made. Multiple exposures of different times of the reproducibility of one time setting can all be made on one film.

Radiography↗
PubMed1993

Pesticide exposures and multiple myeloma in Iowa men.

A population-based case-control study of 173 White men with multiple myeloma (MM) and 650 controls was conducted in Iowa (United States), an area with a large farming population, to evaluate the association between MM, agricultural risk factors, and exposure to individual pesticides. A slight nonsignificantly elevated risk for MM was seen among farmers (odds ratio [OR] = 1.2, 95 percent confidence interval [CI] = 0.8-1.7). Although slight excesses were observed, there were no significant associations between MM and handling either classes of pesticides or specific pesticides. Thus, this study found little evidence to suggest an association between risk of MM and farming or pesticides.

Adult↗
PubMed1991

Estimating human exposure through multiple pathways from air, water, and soil.

This paper describes a set of multipathway, multimedia models for estimating potential human exposure to environmental contaminants. The models link concentrations of an environmental contaminant in air, water, and soil to human exposure through inhalation, ingestion, and dermal-contact routes. The relationship between concentration of a contaminant in an environmental medium and human exposure is determined with pathway exposure factors (PEFs). A PEF is an algebraic expression that incorporates information on human physiology and lifestyle together with models of environmental partitioning and translates a concentration (i.e., mg/m3 in air, mg/liter in water, or mg/kg in soil) into a lifetime-equivalent chronic daily intake (CDI) in mg/kg-day. Human, animal, and environmental data used in calculating PEFs are presented and discussed. Generalized PEFs are derived for air----inhalation, air----ingestion, water----inhalation, water----ingestion, water----dermal uptake, soil----inhalation, soil----ingestion, and soil----dermal uptake pathways. To illustrate the application of the PEF expressions, we apply them to soil-based contamination of multiple environmental media by arsenic, tetrachloroethylene (PCE), and trinitrotoluene (TNT).

Administration, Inhalation↗
PubMed2005

Dose-dependent allergic responses to an extract of Penicillium chrysogenum in BALB/c mice.

Indoor mold has been associated with the development of allergic asthma. Penicillium chrysogenum, a common indoor mold, is known to have several allergens and can induce allergic responses in a mouse model of allergic penicilliosis. Our hypothesis is that soluble components of P. chrysogenum (PCE) can dose-dependently induce responses typical of allergic asthma in BALB/c mice. Mice were exposed to 10, 20, 50, or 70 microg of PCE by involuntary aspiration four times over a 4-week period. Serum and bronchoalveolar lavage fluid (BALF) were collected before (day 0), and at days 1 and 3 following the final exposure. PCE-exposed mice demonstrated dose-dependent increases in: BALF total cell numbers including eosinophil, serum and BALF total IgE levels, BALF IL-5 levels, and increased severity of histopathologic lesions. A single exposure to the highest dose of PCE resulted in edema and cellular damage but not immune responses. Four exposures to Metarhizium anisopliae crude antigen (10 microg, positive control) resulted in equivalent or greater allergic asthma-like responses than those demonstrated by multiple exposures to 50 or 70 microg of PCE. Multiple exposures to 70 microg of PCE showed increased allergen-triggered immediate respiratory responses as well as non-specific airway hyperresponsiveness to methacholine as assessed by barometric whole-body plethysmography. Taken together, repeated pulmonary challenge with P. chrysogenum extract induced dose-dependent allergic asthma-like responses in mice.

Allergens↗
PubMed2003

Association of chromium exposure with multiple primary cancers in the nasal cavity.

A 56-year-old man who had worked at a chromate factory for 13 years developed squamous cell carcinoma of the left nasal cavity 11 years after retirement. He received intra-arterial chemotherapy, followed by surgery. Two years later, an adenocarcinoma was identified in the same nasal cavity just above the previous surgical region. He underwent medial maxillectomy in combination with postoperative irradiation. He has been disease free for 5 years after the second surgery. Microsatellite markers were examined in the second tumor specimen as a possible factor for carcinogenesis; however, replication errors were not observed in any of four loci (D2S123, D3S1067, TP53, D18S474) tested. The present case seems to have resulted from long-term exposure to chromium and, to our knowledge, is the first reported case with multiple primary cancers in the nasal cavity associated with chromium exposure.

Adrenal Gland Neoplasms↗
PubMed2002

Safety of aprotinin use and re-use in pediatric cardiothoracic surgery.

BACKGROUND: Hypersensitivity reactions to aprotinin have been reported in adult cardiac surgical patients undergoing initial and re-exposure to the medication. This study describes the incidence and impact of aprotinin hypersensitivity reactions in children undergoing cardiothoracic surgery. METHODS AND RESULTS: In this retrospective review of our entire experience with aprotinin (n=865), 681 first exposures, 150 second exposures, and 34 third or higher exposures were examined. Reactions were classified as mild (generalized cutaneous erythema, Type A) or severe (unexplained cardiopulmonary instability after aprotinin exposure, Type B). Records of patients sustaining a reaction were reviewed to assess the impact of the reaction on outcome and to survey reaction management strategies. Reactions occurred in 7 of 681 first exposures (1.0%), of which 2 were Type A and 5 were Type B. In second exposures, there were reactions in 2 of 150 (1.3%), of which both were Type B. In 34 third or higher exposures, there was only 1 reaction (2.9%), which was Type B. Reactions were no more likely on second, third, or higher exposure than on initial exposure. Skin testing had a negative predictive value of 98.9% and a positive predictive value of 20%. Anti-aprotinin IgE was undetectable in 7 of 8 reactor cases tested. No adverse sequelae were attributed to aprotinin reaction. CONCLUSIONS: The risk of hypersensitivity reactions to aprotinin is low in children undergoing cardiothoracic surgery, even with multiple exposures to the medication. Reactions are more likely with re-exposure, and risk increases with multiple exposures. Neither skin testing nor assays for IgE identified reactors.

Adolescent↗
PubMed2006

Benzene exposure and multiple myeloma: a detailed meta-analysis of benzene cohort studies.

Case reports and epidemiological studies of workers exposed to benzene have demonstrated associations with a number of lymphohematopoietic diseases, but the association with multiple myeloma (MM) has been less apparent. Data from all of the "benzene cohort studies" conducted to date have been selected and evaluated for inclusion in a meta-analysis. The analysis demonstrates a significant excess in the relative risk (RR) of MM in relation to benzene exposure. Pooling the data from seven cohort studies, a meta-analysis yields a statistically significant weighted RR estimate of 2.13 (95% CI = 1.31-3.46). In the analysis of cohort data, an understanding of the cohort follow-up period in relation to benzene exposure and RR of MM is important. Exposure-related RRs of disease decline after the median latency periods are exceeded, particularly when exposure has terminated decades earlier. The positive epidemiological evidence for benzene as a cause of MM is supported by biological plausibility for such an effect from benzene exposure. Studies of refinery workers are difficult to interpret in relation to benzene exposure and risk of MM, but are limited in the study design and analysis. Nonetheless, they provide some support for an association between refinery work and MM.

Benzene↗
PubMed2001

Simultaneous assessment of occupational exposures from multiple worker groups.

The methods developed by Rappaport et al. [Ann. Occup. Hyg. 39 (1995) 469] and Lyles et al. [J. Agri. Bio. Environ. Stat. 2 (1997a) 64; Ann. Occup. Hyg. 41 (1997b) 63]) for assessing workplace exposures on a group-by-group basis are extended to allow for the simultaneous assessment of data from multiple worker groups within the same industry. These extended methods allow models to be fit simultaneously to data on all groups in a study, even when some of the groups might not contribute adequate information to be modeled separately. We assume that the exposures are log-normally distributed, and that they can be adequately modeled by a mixed effects regression model with parameters for exposure levels and for between- and within-worker variance components. Simultaneously analyzing data from multiple groups is only advantageous when at least one of these variance components can be assumed to be homogeneous across the groups. Here, we advocate testing an assumption of homogeneous within-worker variance components, sigma(2)(w,h), using a likelihood ratio test to choose between a full model (distinct sigma(2)(w,h) for each group) and a reduced model (common sigma(2)(w) across groups). We then develop a procedure, which is conditional on the results of the likelihood ratio test, for testing whether or not each group of workers is overexposed to the contaminant of interest. This modeling and testing procedure was applied to 39 different data sets, each containing data for multiple groups, from a wide variety of industries. For these data, the testing procedure generally resulted in the same conclusion regarding overexposure under both models, even in those data sets where the within-worker variance components appeared to be quite heterogeneous. We also conducted a small simulation study to estimate the significance level of the proposed testing procedure, and found that the significance levels tended to be adequately close to the specified nominal level when a likelihood ratio test with significance level of at least 0.01 was used as a preliminary test. Additionally, we make specific recommendations for designing studies and suggest a method for determining whether engineering and administrative controls or individual-level interventions would be of most benefit to an overexposed group of workers.

Humans↗
PubMed2006

A novel method for biodosimetry.

Accurate methods for measuring the biological effects of radiation are critical for estimating an individual's health risk from radiation exposure. We investigated the feasibility of using radiation-induced mutations in repetitive DNA sequences to measure genetic damage caused by radiation exposure. Most repetitive sequences are in non-coding regions of the genome and alterations in these loci are usually not deleterious. Thus, mutations in non-coding repetitive sequences might accumulate, providing a stable molecular record of DNA damage caused by all past exposures. To test this hypothesis, we screened repetitive DNA sequences to identify the loci most sensitive to radiation-induced mutations and then investigated whether these mutations were stable in vivo over time and after multiple exposures. Microsatellite repeat markers were identified that exhibited a linear dose response up to 1 Gy of 1 GeV/nucleon 56Fe ions and 137Cs gamma rays in mouse and human cells. Short tandem repeats on the Y chromosome and mononucleotide repeats on autosomal chromosomes exhibited significant increases in mutations at >or= 0.5 Gy of 56Fe ions with frequencies averaging 4.3-10.3 x 10(-3) mutations/locus/Gy/cell, high enough for direct detection of mutations in irradiated cells. A significant increase in radiation-induced mutations in extended mononucleotide repeats was detectible in vivo in mouse blood and cheek samples 10 and 26 weeks after radiation exposure and these mutations were additive over multiple exposures. This study demonstrates the feasibility of a novel method for biodosimetry that is applicable to humans and other species. This new approach should complement existing methods of biodosimetry and might be useful for measuring radiation exposure in circumstances that are not amenable to current methods.

Biological Assay↗
PubMed2004

Potentiated startle and hyperalgesia during withdrawal from acute morphine: effects of multiple opiate exposures.

RATIONALE: Administration of an opiate antagonist following acute morphine exposure elevates the startle response in rodents, a phenomenon that may reflect the anxiogenic effects of withdrawal. Previous acute dependence studies have demonstrated escalated withdrawal severity following multiple withdrawal episodes. OBJECTIVES: To examine the effects of prior opiate exposure on the magnitude of withdrawal-potentiated startle and an additional measure of acute dependence, withdrawal-induced hyperalgesia. METHODS: The effects of repeated naloxone-precipitated morphine withdrawals on acoustic startle responding were evaluated in experiments that varied either the dose of the opiate antagonist (8-day, repeated measures procedure) or agonist (3-day procedure). Additional experiments examined withdrawal-induced hyperalgesia utilizing either a single-day dependence paradigm or the same 3-day procedure as in the startle experiment. RESULTS: Repeated naloxone-precipitated withdrawals from acute morphine exacerbated withdrawal severity in both startle procedures, although this effect varied biphasically (inverted-U function) with morphine dose in the 3-day dependence paradigm. Withdrawal from a single morphine exposure also induced hyperalgesia, and this effect was intensified by prior withdrawal episodes. CONCLUSIONS: These data demonstrate that repeated withdrawals from acute morphine exacerbate the severity of potentiated startle and hyperalgesia. These paradigms may be useful in examining the neural plasticity underlying the development of opiate dependence.

Acoustic Stimulation↗
PubMed2004

Micro-optic fabrication with subdomain masking.

An innovative fabrication technique is introduced that is based on multiple-exposure techniques for micro-optics fabrication. This approach is compatible with conventional lithography systems used in integrated circuit manufacturing and can be applied to thick and thin photoresists and is based on additive lithographic techniques introduced elsewhere [Appl. Opt. 41, 6176 (2002)]. We chose a simple subdomain basis set to transform the two-dimensional basis patterns into a family of various three-dimensional micro-optic elements using exposure control to modulate the third dimension. We demonstrate the capability to sculpt the photoresist into a variety of three-dimensional micro-optic elements by performing multiple exposures using elements from the subdomain basis set, without resorting to multiple etching steps.

Journal Article↗
PubMed1998

Differential effect of thyroid-stimulating hormone (TSH) on intracellular free calcium and cAMP in cells transfected with the human TSH receptor.

The thyroid-stimulating hormone (TSH) binds to a receptor which activates adenylate cyclase and elevates cAMP concentration. In addition, effects of TSH on intracellular calcium and inositol phosphate accumulation have been reported. However, the mechanism of TSH-stimulated accumulation of inositol phosphates and elevation of calcium levels is unresolved. Previous work from this laboratory has shown TSH to cause acute transient increases in intracellular calcium in pig, human and FR TL-5 rat thyroid cells as well as in cell transfected with the human TSH receptor (JPO9 cells) in some (but not all) experiments. The aim of this study was to investigate the variability of the calcium response to TSH in JPO9 cells to learn more about the nature of this calcium signal induction. Calcium responses to TSH were determined using the fluorochrome fura-2 in both monolayers of adherent cells and adherent single cells. The responses to a single addition and to repetitive additions of TSH were compared. We also determined the cAMP response to TSH using these two protocols of TSH addition. Our data show that, whereas the cAMP response to TSH is highly predictable and consistent and does not require multiple exposures to TSH, cells were unlikely to respond to TSH with an increase in calcium unless they received multiple challenges with the hormone. A single addition of 10 mU/ml TSH failed to increase calcium in any of 40 single cells examined and in only 4 of 15 monolayers of cells (27%) examined; in contrast, 10 of 12 monolayers eventually responded with an increase in calcium after multiple exposure to TSH and 18 of 67 single cells. Similar data were obtained whether calcium was measured in single cells or in populations of cells. We also demonstrated cooperativity between an adenosine derivative, N6-(L-2-phenylisopropyl)adenosine, and TSH such that their co-administration resulted in a consistent and marked elevation in calcium levels not achieved with either agonist alone. In summary, we suggest that the coupling between the TSH receptor and the intracellular signalling system that leads to activation of intracellular calcium in JPO9 cells requires repetitive stimulation or the influence of other agonists, in contrast with the coupling between the TSH receptor and activation of the adenylate cyclase enzyme.

Animals↗
PubMed1986

Toxic substance exposure and multiple myeloma: a case-control study.

By means of a population-based, multicenter case-control investigation, certain toxic substances were evaluated as risk factors for multiple myeloma. Interviews were completed on 698 subjects with newly diagnosed multiple myeloma, and 1,683 controls were selected from the same geographic areas as those of the cases. Respondents were asked if they had ever been "highly" exposed" to one or more of a list of toxic substances or to other substances not on the list. With the aid of a toxicologist, responses were then categorized into 20 exposure groups. Those who reported past exposure to pesticides had an estimated relative risk of 2.6 for multiple myeloma [95% confidence interval (CI) = 1.5-4.6]. Subjects exposed to a variety of compounds commonly used by painters had an estimated relative risk of 1.6 (95% CI = 1.1-2.4). An increased risk also was found for those who were exposed to sources of carbon monoxide (relative risk = 1.8, 95% CI = 1.0-3.2). Associations of borderline statistical significance were found for metals and organically high polymers (plastics and elastomers). No statistically significant associations were seen for exposure to fertilizers; dyes and inks; alkalies; acids; other caustic substances; chemical asphyxiants; aliphatic, chlorinated, or aromatic hydrocarbons; aldehydes and ketones; ethers; esters; oils; dusts; or asbestos.

Adult↗
PubMed1998

Risk and clinical significance of developing antibodies induced by topical thrombin preparations.

OBJECTIVE: TO determine the clinical relevance, prevalence, and risk of antibody development in patients exposed to topical bovine thrombin preparations. DESIGN: A prevalence study of individuals previously exposed to topical bovine thrombin was done by screening using Western blot assay to detect antibodies against bovine thrombin preparations. SETTING: A large tertiary care center. PATIENTS: A convenience sample of 120 stored blood specimens from patients previously exposed to topical bovine thrombin was identified from hospital records. A control sample of 114 stored blood specimens from nonexposed patients was used. Case reviews for 2 exposed patients with severe bleeding complications and difficult clinical management are presented. RESULTS: Twelve of the bovine thrombin-exposed patients were found to have antibodies directed against bovine thrombin and other coagulation factors (95% CI, 4.6%-15.4%). Patients receiving multiple exposures were 8 times more likely to develop antibodies than were patients with a single exposure (P < .001). CONCLUSIONS: (1) Topical bovine thrombin is associated with formation of antibodies to coagulation factors; (2) Patients receiving multiple exposures are more likely to develop antibodies to coagulation factors; and (3) Topical bovine thrombin use may cause severe bleeding problems and should be avoided if there has been previous exposure.

Administration, Topical↗