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Minimal erythema dose after multiple UV exposures depends on pre-exposure skin pigmentation.

BACKGROUND/PURPOSE: Phototherapy consists of multiple ultraviolet (UV) exposures. Most previous studies have focused on erythema following a single UV exposure in fair-skinned persons. Although it is well known that phototherapy lowers the daily UV-threshold dose for erythema in clinical practice, this is insufficiently documented under controlled experimental conditions. The purpose of this study was to quantify the change in the daily threshold for a dose specific erythema grade after 1-4 consecutive daily UV exposures. METHODS: Forty-nine healthy volunteers (skin type II-V) with varying pigmentation quantified by skin reflectance. Two UV sources were used: a narrowband UVB (Philips TL01) and a Solar Simulator (Solar Light Co.). Just perceptible erythema after 24 h was chosen as the minimal erythema dose (+); besides + and ++ were assessed. RESULTS: We found a positive and significant exponential relationship between skin pigmentation and UV dose to elicit a specific erythema grade on the back after 1-4 UV exposures. After repetitive UV exposures the UV dose had to be lowered more in dark-skinned persons compared with fair-skinned persons to elicit a certain erythema grade. This applied to both UV sources and all erythema grades. CONCLUSION: In the dark-skinned persons the daily UV dose after the 4 days UV exposure should be lowered by 40-50% to avoid burns compared with the single UV exposure. For the most fair-skinned persons essentially no reduction in the daily UV dose was needed. Our results indicate that the pre-exposure pigmentation level can guide the UV dosage in phototherapy.

Adult↗

Depiction of pelvic fractures using 3D volumetric holography: comparison of plain X-ray and CT.

OBJECTIVE: The goal of this study was to demonstrate the feasibility and test the diagnostic performance of a new technology, 3D volumetric holography, for imaging pelvic fractures. The management of pelvic fractures may be complex, and advanced imaging studies such as CT are frequently indicated. Multiplanar CT reformations and 3D renderings provide clinically useful and complementary display of the directly acquired CT data. With the recent availability of volumetric multiple exposure holograms, produced from serial image data, it is now possible to produce true 3D images of the pelvis. In the hologram, one may view the CT data in 3D or as individual planar slices constituting the whole 3D pelvis. The diagnostic performance of the volumetric multiple exposure holograms was tested against routine radiography, CT, and 3D volumetric CT reconstructions. MATERIALS AND METHODS: Routine radiography and CT were performed in 15 patients with suspected pelvic fractures. Volumetric multiple exposure holograms and 3D volumetric CT reconstructions were created from the CT data. Axial and multiplanar reformation CT images were used as the standard for fracture, diastasis, and intraarticular fragment detection. RESULTS: Radiograms detected 39 of 50 of the fractures and diastases and no intraarticular fragments. The 3D CT reconstructions and the holograms viewed as 3D objects alone missed two small fractures of the anterior column and one hip with intraarticular bone fragments. When the volumetric multiple exposure holograms were viewed as a 3D object and as individual planar slices constituting the whole, their results were the same as the standard. CONCLUSION: Volumetric multiple exposure holograms were as sensitive and specific as axial CT and multiplanar reformations in detecting fracture pathology. By containing and making available, from one image, both planar and 3D information, volumetric multiple exposure holograms detected subtle anatomical features that were hidden by overlapping structures in the radiographs and the 3D CT images.

Fractures, Bone↗

Topical administration of low-dose tenofovir disoproxil fumarate to protect infant macaques against multiple oral exposures of low doses of simian immunodeficiency virus.

Simian immunodeficiency virus (SIV) infection of infant macaques is a useful animal model to determine whether topical (oral) administration of antiviral compounds to the nursing infant could reduce human immunodeficiency virus transmission through breast-feeding. The reverse-transcriptase inhibitor tenofovir was selected because of previous demonstrations that systemic drug levels are effective in preventing SIV infection. To mimic the multiple exposures to virus during breast-feeding, 14 infant macaques were fed 15 low doses of SIVmac251 without chemical restraint. Six animals were treated with placebo, and 2 groups of 4 animals received oral topical doses of tenofovir disoproxil fumarate (DF; equivalent to 0.037 mg of tenofovir/day). About half the animals of each group became infected. In a subsequent study, 2 oral inoculations of 4 juvenile macaques with a mixture of tenofovir DF and SIVmac251 induced persistent infection. Topical administration of low doses of tenofovir DF did not protect against oral SIV infection.

Adenine↗

The Italian Multiple Sclerosis Database Network (MSDN): the risk of worsening according to IFNbeta exposure in multiple sclerosis.

We evaluated the risk of worsening according to the length of exposure to interferon beta (IFNbeta) in a large cohort of 2090 multiple sclerosis patients collected by the Italian MS Database Network. Overall 44,140 patient-visits with a follow-up of 22,143 patient-years were evaluated. Forty-one per cent of patients were exposed to IFNbeta for up to 2 years, 39% for 2-4 years and 20% for more than 4 years. A Cox regression model was used to analyse two clinical outcomes: disability progression and worsening of relapse rate. The technique of propensity score was applied to reduce bias in the comparison of non-randomized groups. The risks of disability progression (HR =0.23; 95% CI: 0.17-0.30) and worsening of relapse rate (HR =0.19; 95% CI: 0.14-0.27) were reduced by about 4-5-fold in patients exposed to IFNbeta for more than four years, compared with patients exposed for up to two years. The propensity score technique confirmed the findings. The proportion of days covered by IFNbeta treatment was lower (P <0.0001) in patients exposed to IFNbeta for up to two years than in other groups. A clinical stabilization over two years of IFNbeta exposure may predict a subsequent good clinical response to treatment.

Adjuvants, Immunologic↗

Assessment of presystemic factors on the oral bioavailability of rifampicin following multiple dosing.

This study was carried out to elucidate the possible mechanism(s) responsible for reduced oral rifampicin bioavailability after multiple dosing. In addition to autoinduction, the relative contribution of the two possible controlling factors, e.g., intestinal metabolism and microbial degradation, was investigated using a rat model. Pharmacokinetic studies were carried out to assess the absolute rifampicin bioavailability by both oral and intravenous drug administration before and after 8 daily doses of 25 mg/kg. To estimate the possible involvement of microbial degradation, rifampicin kinetics were also assessed in rats on day 8 after receiving multiple oral dosing and concurrent administration of nonabsorbable triple antibiotics for gut sterilization 3 days prior to the study day. Pharmacokinetic parameters were generated by noncompartmental analysis. The results revealed a significant decrease in rifampicin levels for rats after multiple exposure, compared to single dosing; the mean clearance determined by intravenous dosing increased by 43% from 3.7 ml/min/kg and the half-life decreased by 24% from 238 min. However, the extent of decrease in rifampicin exposure following multiple dosing was substantially greater for rats dosed orally than intravenously; estimated absolute oral bioavailability decreased by 15% from 0.89 on day 1 to 0.76 on day 8. No apparent alterations in any of the pharmacokinetic parameters were observed after gut sterilization, suggesting minimal contribution of microbial degradation to the reduction in oral rifampicin absorption after multiple dosing. In addition to hepatic enzyme autoinduction, these results strongly suggest the involvement of enhanced intestinal metabolism as a contributing factor to the decrease in oral rifampicin bioavailability following prolonged exposure.

Absorption↗

The interpretation of occupational epidemiologic data in regulation and litigation: studies of auto mechanics and petroleum workers.

Epidemiologic data often serve as scientific basis for policies in regulation and opinions in litigation. The interpretation of epidemiologic data in both regulation and litigation is often challenged and debated. In this commentary, a wide range of issues concerning the interpretation of epidemiologic data in regulation and litigation are discussed. These issues include: case reports, study design, specificity of exposure, interview or recall bias, misclassification of occupation or exposure, confounding multiple exposures, confidence intervals and statistical power, selection of relevant studies, consistency of study results, study cohort definition, cohort membership misclassification, dilution effect, and subcohort or stratified analysis. Epidemiologic studies of auto mechanics and petroleum workers are used as examples to illustrate the importance of relying on sound epidemiologic principles in study interpretation. If these principles are not followed, the interpretation of epidemiologic studies will likely be erroneous and not useful to regulatory policy-makers or to those involved in litigation.

Automobiles↗

An overview of the vaccine adverse event reporting system (VAERS) as a surveillance system. VAERS Working Group.

We evaluated the Vaccine Adverse Event Reporting System (VAERS), the spontaneous reporting system for vaccine-associated adverse events in the United States, as a public health surveillance system, using evaluation guidelines from the Centers for Disease Control and Prevention. We found that VAERS is simple for reporters to use, flexible by design and its data are available in a timely fashion. The predictive value positive for one severe event is known to be high, but for most events is unknown. The acceptability, sensitivity and representativeness of VAERS are unknown. The study of vaccine safety is complicated by underreporting, erroneous reporting, frequent multiple exposures and multiple outcomes.

Adverse Drug Reaction Reporting Systems↗

Neoplastic transformation of mouse mammary epithelial cells by in vitro exposure to N-methyl-N-nitrosourea.

High-efficiency neoplastic transformation of mouse mammary epithelial cells in primary collagen gel culture was induced by N-methyl-N-nitrosourea (MNU). Mammary epithelial cells, isolated from virgin BALB/c mice, were embedded within collagen gels and grown in a serum-free medium containing prolactin, progesterone, and linoleic acid. The cells were then treated with MNU on day 3 of culture and subsequently at weekly intervals for up to 4 weeks. Eleven to 14 days after the final carcinogen treatment, the cells were removed from the collagen gels and injected into the cleared mammary fat pads of syngeneic hosts to assay for transformed cell populations. A single exposure or multiple exposures of these cells to MNU was effective in inducing tumorigenic cells that produced palpable tumors as early as 6 weeks after transplantation. Two treatments with MNU (100 micrograms/ml) were optimal for neoplastic transformation and produced tumors in 79% of the injected fat pads. All the tumors originated at the site of injection and had extensive central necroses. Histological examination indicated that the tumors were mammary carcinomas. Secondary transplantation of tumor pieces into intact mammary glands produced palpable carcinomas of the same histology within 1-8 weeks. Control cells cultured for the same periods of time as MNU-treated cells produced only ductal outgrowths that were morphologically similar to those found in the mammary glands of adult virgin hosts. This system provides a distinct means to study the mechanism of mammary neoplastic transformation at cellular and molecular levels.

Animals↗

Genital warts. Newly discovered consequences of an ancient disease.

Venereal warts are an ancient disease, but the relationship between certain human papillomavirus serotypes and genital neoplasia is just being recognized. Women are at higher risk for development of neoplasia from the infection and are more likely to be reinfected, because a male partner's lesions may be invisible without application of acetic acid or examination of a urethral smear. Other factors that favor progression to cancer are young age at first exposure, multiplicity of exposures, and immunosuppression. Colposcopy with cytology and biopsy allows definitive microscopic identification of the virus and serotyping. Aggressive management of both male and female partners will reduce the spread of the virus and reinfection. Successful treatment methods have included cryosurgery; electrocautery; carbon dioxide laser therapy; and use of a keratolytic, cauterizing agent, topical fluorouracil (Efudex), and interferon.

Colposcopy↗

Use of multiparameter analysis to quantitate hematological damage from exposure to a chemical (ethylene oxide).

This study was designed to test the value of a multiparameter approach in evaluating perturbations in bone marrow and peripheral blood elements of mice exposed to ethylene oxide (EtO). Mice exposed to 255 ppm EtO for 5 h/d were removed for analysis after 1, 2, 8, and 14 d (sequential exposure) and 4, 6, 8, and 10 wk (5 d/wk). Prior to sacrifice, blood was removed from the orbital sinus for blood cell counts, hemoglobin determination, and hematocrit. A blood film was made for differential leukocyte counts. Bone marrow was flushed from femurs and tibias and counted, and aliquot were used for stem-cell assay (CFU-S) or flow cytometry (FCM) analysis. One aliquot of marrow was stained with propidium iodide for cell-cycle analysis and another was reacted with fluorescein-conjugated monoclonal antibody for B-cell analysis. The preparations were analyzed for forward and 90 degrees scatter and fluorescence on an Ortho 50H cytofluorograph. Perturbations of peripheral leukocytes occurred after one exposure. After multiple exposures, hematocrit, red-cell number, and hemoglobin were generally depressed, with transient compensatory bursts, and bone marrow cellularity and CFU-S were below normal. However, white-cell numbers fluctuated dramatically during the exposure period. There was a shift in differential toward granulocytes, at times resulting in severely depressed numbers of lymphocytes in the peripheral blood. The FCM analysis showed an early depletion of granulocytes in the bone marrow followed by replacement and a relative lymphocyte deficit, especially pronounced at 10 wk. The B-cell changes reflected general lymphocyte perturbations. Shifts in numbers of cells in S and G/M were observed, consistent with a moderate bone marrow response to cell loss.

Animals↗

Environmental pollution and the global burden of disease.

Exposures to environmental pollution remain a major source of health risk throughout the world, though risks are generally higher in developing countries, where poverty, lack of investment in modern technology and weak environmental legislation combine to cause high pollution levels. Associations between environmental pollution and health outcome are, however, complex and often poorly characterized. Levels of exposure, for example, are often uncertain or unknown as a result of the lack of detailed monitoring and inevitable variations within any population group. Exposures may occur via a range of pathways and exposure processes. Individual pollutants may be implicated in a wide range of health effects, whereas few diseases are directly attributable to single pollutants. Long latency times, the effects of cumulative exposures, and multiple exposures to different pollutants which might act synergistically all create difficulties in unravelling associations between environmental pollution and health. Nevertheless, in recent years, several attempts have been made to assess the global burden of disease as a result of environmental pollution, either in terms of mortality or disability-adjusted life years (DALYs). About 8-9% of the total disease burden may be attributed to pollution, but considerably more in developing countries. Unsafe water, poor sanitation and poor hygiene are seen to be the major sources of exposure, along with indoor air pollution.

Air Pollutants↗

The Drosophila melanogaster seminal fluid protein Acp62F is a protease inhibitor that is toxic upon ectopic expression.

Drosophila melanogaster seminal fluid proteins stimulate sperm storage and egg laying in the mated female but also cause a reduction in her life span. We report here that of eight Drosophila seminal fluid proteins (Acps) and one non-Acp tested, only Acp62F is toxic when ectopically expressed. Toxicity to preadult male or female Drosophila occurs upon one exposure, whereas multiple exposures are needed for toxicity to adult female flies. Of the Acp62F received by females during mating, approximately 10% enters the circulatory system while approximately 90% remains in the reproductive tract. We show that in the reproductive tract, Acp62F localizes to the lumen of the uterus and the female's sperm storage organs. Analysis of Acp62F's sequence, and biochemical assays, reveals that it encodes a trypsin inhibitor with sequence and structural similarities to extracellular serine protease inhibitors from the nematode Ascaris. In light of previous results demonstrating entry of Acp62F into the mated female's hemolymph, we propose that Acp62F is a candidate for a molecule to contribute to the Acp-dependent decrease in female life span. We propose that Acp62F's protease inhibitor activity exerts positive protective functions in the mated female's reproductive tract but that entry of a small amount of this protein into the female's hemolymph could contribute to the cost of mating.

Amino Acid Sequence↗

Induction of a cytogenetic adaptive response in germ cells of irradiated mice with very low-dose rate of chronic gamma-irradiation and its biological influence on radiation-induced DNA or chromosomal damage and cell killing in their male offspring.

In earlier studies we have shown that either a single exposure or multiple exposures to a low dose of X-rays (0.05 Gy) induced a significant cytogenetic adaptive response in mouse germ cells. In this paper, a very low-dose rate (20 microGy/min) of chronic 60Co gamma-irradiation was used to pre-irradiate mice for 40 days. Then, another 40 days later, these mice were treated with a subsequent large dose of X-irradiation, followed 24 h later by cytogenetic analysis of their spermatocytes. Analysis for radiation-induced DNA and chromosomal damage was also carried out in splenocytes, bone marrow cells and spermatocytes of the offspring of mice adapted by the low-dose rate of chronic gamma-irradiation. Results demonstrated that (i) cumulative gamma-irradiation (1.10 Gy) at the dose rate 20 microGy/min induced a marked cytogenetic adaptive response in the mouse germ cells (stem spermatogonia); (ii) the sensitivity of offspring's bone marrow cells and spermatocytes to 1.5 Gy X-ray-induced chromosome aberrations was not influenced by the low-dose radiation delivered to paternal germ cells; (iii) either constitutive or post-irradiation DNA repair capacity (UV-induced unscheduled DNA synthesis, UDS) was not modified in the offspring's splenocytes; (iv) the sensitivity of the offspring's splenocytes to radiation-induced cell killing was also not altered. These results suggest that low-dose radiation delivered to the male parents with a significant induction of cytogenetic adaptive response in their germ cell does not likely cause any risk of damaging effects to the offspring of those irradiated male mice.

Adaptation, Physiological↗

Traumatic stress symptoms in women exposed to community and partner violence.

Prior research documents increased trauma symptoms associated with exposure to violence, primarily by examining types of violence separately. This study extends prior research by examining traumatic stress symptoms associated with two types of violence exposure, community violence and partner violence. A sample of 90 low-income African American women from an urban area completed measures assessing exposure to community violence, partner violence, and trauma symptoms. Exposure to community violence and partner violence were associated with increased reporting of trauma symptoms. Participants who experienced high levels of exposure to both types of violence reported more trauma symptoms than women who were exposed to only one type of violence or neither type of violence. The results suggest that the accumulation of exposures to violence is linked with greater distress. Thus, interventions with women exposed to violence should assess violence exposure in multiple domains and attend to the implications of multiple exposures to violence.

Adult↗

Localization of halothane-induced antigen in situ by specific anti-halothane metabolite antibodies.

Multiple or single halothane exposure of rabbits or guinea pigs induces an antibody reactive with trifluoroacetylated (TFA) proteins. The antigen that initiates this immune response was investigated in halothane-exposed rabbits and guinea pigs for its anatomical location in the liver, the chronology of its expression in situ and exposure conditions which would modulate its expression. Using an immuno-staining technique, binding by an anti-TFA antibody to the antigen was detected in liver tissue from all halothane-exposed rabbits and guinea pigs. Antigen could be detected only in the centrilobular area around the central vein where staining intensity was concentrated in an area seven to nine cells deep. In halothane-exposed rabbits, the appearance of TFA antigen was most predominant on the first and second days following a single exposure. Multiple exposures induced TFA antigen in a larger area around the central vein than did a single exposure. Though maximal expression of TFA antigen occurred following two or three exposures, subsequent exposures did not potentiate antigen expression. In halothane-exposed guinea pigs, exposure to deuterated halothane, which reduces the extent and metabolites of oxidative halothane metabolism, elicited the appearance of TFA antigen around the central veins, although to a lesser extent than during halothane exposure. Halothane-induced antigen was evident in guinea pigs as early as 6 h post-exposure and was still apparent 90 h later. Thus, halothane exposure by inhalation elicits the appearance of TFA protein conjugates which may, in turn, evoke the anti-TFA immune response.

Animals↗

Exposures to multiple air toxics in New York City.

Efforts to assess health risks associated with exposures to multiple urban air toxics have been hampered by the lack of exposure data for people living in urban areas. The TEACH (Toxic Exposure Assessment, a Columbia/Harvard) study was designed to characterize levels of and factors influencing personal exposures to urban air toxics among high school students living in inner-city neighborhoods of New York City and Los Angeles, California. This present article reports methods and data for the New York City phase of TEACH, focusing on the relationships between personal, indoor, and outdoor concentrations in winter and summer among a group of 46 high school students from the A. Philip Randolph Academy, a public high school located in the West Central Harlem section of New York City. Air pollutants monitored included a suite of 17 volatile organic compounds (VOCs) and aldehydes, particulate matter with a mass median aerodynamic diameter <or= 2.5 microm (PM2.5), black carbon, and a suite of 28 particle-associated trace elements. Sequential 48-hr ambient samples also were collected over 8 weeks in each season at an urban fixed site and an upwind, nonurban fixed site. Personal, indoor, and outdoor concentrations of particle elements were generally similar, suggesting that ambient sources may have driven indoor and personal exposures for most elements. More varied relationships among personal, home indoor, and home outdoor concentrations were observed for VOCs and aldehydes. For formaldehyde and acetaldehyde, and several VOCs, indoor concentrations far exceeded outdoor levels and appeared to dominate personal exposures. Strong seasonal differences in indoor to outdoor concentration ratios were observed for these compounds, reflecting the influence of home air exchange rates. For other VOCs, especially those related to motor vehicle exhaust, more consistent indoor, outdoor, and personal concentrations were observed, suggesting that ambient concentrations may have been the driving force for personal exposures to some VOCs. These results demonstrate exposures to a wide range of air toxic pollutants among young people attending school in inner-city New York.

Adolescent↗

Persistent hypertension after prenatal cocaine exposure.

Multiple blood pressure readings were obtained with time in 12 infants with documented in utero exposure to cocaine. Approximately half had hypertension or high-normal blood pressure with no evidence of renal, cardiovascular, or endocrinologic abnormalities.

Child, Preschool↗

Alteration of pulmonary macrophage intracellular pH regulation by sulfuric acid aerosol exposures.

In vivo exposure to sulfuric acid aerosols produces profound effects on pulmonary macrophage (PM phi) phagocytic function and cytokine release and perturbs intracellular pH (pHi) homeostasis. Because pHi influences a multitude of cellular processes, we sought to investigate the mechanism by which acid aerosol exposure affects its regulation. Guinea pigs underwent a single or 5 repeated 3-hr exposures to sulfuric acid aerosol (969 and 974 micrograms/m3 for single and repeated exposures, respectively). PM phi harvested immediately after exposure were incubated in HCO3-free media and their pHi recovery from an intracellular acid load was examined. The overall pHi recovery was depressed after single and multiple exposures to sulfuric acid aerosol. delta pHi (the difference between initial pHi and the one measured at 150 sec) decreased by 15.6 and 23.3% (p < 0.05) for single and repeated exposures, respectively. Initial dpHi/dt (maximum pHi recovery rate) after cytoplasmic acidification diminished by 20.3 and 32.2%, which were not statistically significant (p = 0.08 for repeated exposure). To determine whether the activity of the H(+)-ATPase pump the Na(+)-H+ exchanger was specifically altered by the acid exposures, PM phi were first incubated in Na+ and HCO3-free media with NBD-Cl (7-chloro-4-nitrobenz-2-oxa-1,3-diazol, blocking H(+)-ATPase and leaving only the Na(+)-H+ exchanger in effect) and then challenged with 30 mM NaCl. The pHi recovery of PM phi after Na challenge was significantly reduced in acid aerosol exposed guinea pigs (p < 0.05) compared to controls (for delta pHi, 18.2% lower in single exposure and 22.7% in multiple exposure groups; for initial dpHi/dt, 26.9% lower in single exposure and 22.4% in multiple exposure groups). In contrast, the H(+)-ATPase pump was inconsistently affected as indicated by delta pHi and initial dpHi/dt measured in the presence of MIA (amiloride-5-N-methylisobutyl, inhibiting the Na(+)-H+ exchanger and leaving only the H(+)-ATPase pump in effect). These results suggest that in vivo exposure to sulfuric acid aerosols induces alterations in pHi regulation in guinea pig PM phi attributable to changes in Na(+)-H+ exchanger activity.

Administration, Inhalation↗