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PubMed2001

Partitioning methods for multifactorial risk attribution.

The epidemiological problem of risk attribution in the framework of multiple exposures has been the subject of intensive research activities in the last decade. In particular, partitioning methods have been developed to define new multidimensional measures of attributable risk putting the task of quantifying a proportion of disease events in a population that can be ascribed to the adverse health effects of certain risk factors into a multifactorial perspective. The parameters generalize the concept of attributable risk to different multifactorial frameworks in which multiple exposures might be arranged in hierarchically ordered classes or in equally ranking groups. Partitioning methods are reviewed and differences between the multifactorial variants of attributable risk are illustrated by a component causes model.

Algorithms↗
PubMed1985

Local pulmonary immune responsiveness after multiple antigenic exposures in the cynomolgus monkey.

Two cynomolgus monkeys were immunized with sheep red blood cells in the right diaphragmatic lobe (RD) 4 times, 20 days apart. At the time of the fourth immunization, the left diaphragmatic lobe (LD) was also immunized. There were increases in both IgM anti-SRBC antibody-forming cells (AFC) and specific IgG in the RD lobe after each successive challenge. In the fourth challenge, the RD had an increase in anti-SRBC AFC 10-fold that of the LD lobe. The concentration of specific IgG was also higher in the RD lobe. With total protein as an indicator of vascular permeability, the LD had a greater increase in vascular permeability than did the RD. These data suggest that the increased immune responsiveness of the RD after multiple challenges was in part locally derived rather than entirely caused by increased recruitment of immune cells and antibody from the blood.

Animals↗
PubMed1990

T cell responses in a sporozoite-immunized human volunteer and a chimpanzee.

We have recently investigated the specificity of T cells induced in a human volunteer and a chimpanzee immunized by multiple exposures to the bites of large numbers of malaria-infected mosquitoes. T cell lines and clones have been obtained from a human volunteer immunized with Plasmodium falciparum sporozoites. These CD4+ T cell clones specifically recognize the native circumsporozoite (CS) protein expressed on sporozoites, as well as bacteria- and yeast-derived recombinant falciparum CS proteins. The epitope recognized by the sporozoite specific human T cells mapped to the 5' repeat region of the CS protein and was contained in the NANPNVDPNANP sequence. A T cell line has also been isolated from PBL obtained from a chimpanzee immunized by multiple exposures to the bits of P. vivax infected mosquitoes. The CS-specific chimpanzee T cells were used to identify a T cell epitope within a repeat region of the P. vivax CS protein.

Amino Acid Sequence↗
PubMed1993

The increased risk of hospitalizations for acute liver injury in a population with exposure to multiple drugs.

We conducted a nested case-control study to estimate and compare the relative risks for hospitalizations for newly diagnosed acute liver injury associated with the use of non-steroidal antiinflammatory drugs (NSAIDs) and other hepatotoxic drugs and their interaction. The source population comprised 228,392 members of the Saskatchewan Health Plan from 1982 to 1986. We used hospital records and the databases of the Department of Health. Thirty-four cases with confirmed liver injury were hospitalized. We randomly selected 500 controls from the source population. Crude risks ranged from 1 case per 100,000 prescriptions in current users of methyldopa, ampicillin, or NSAIDs to 14 cases per 100,000 prescriptions in current users of erythromycin estolate. The age-adjusted odds ratios for current users of NSAIDs was 1.8 [95% confidence interval (CI) = 0.8-3.7] and for other hepatotoxic drugs 5.9 (95% CI = 2.8-12.4). The adjusted relative excess risk due to the interaction between current exposure to both categories of drugs was 3.6, accounting for 31% of the cases of acute liver injury among those with exposure to both types of drugs. We conclude that the risk of hospitalization for acute noninfectious liver injury is different among users of various individual potentially hepatotoxic drugs. Concomitant current exposure to two or more drugs increases this risk above what would merely be expected from the sum of the individual risks.

Acute Disease↗
PubMedDate not supplied

Effects of triethyltin on responding of mice under a multiple schedule of reinforcement.

The lethality and behavioral effects of triethyltin (TET) were determined in adult, male BALB/c mice. Following a single IP dose of TET (10, 12.5 or 15 mg/kg), the lethality was determined at 24-hr intervals. By 144 hr after TET administration, lethality had risen to greater than 90% in the groups receiving the 12.5 and 15 mg/kg and 20% (6/30) in the group which received 10 mg/kg. No additional deaths were observed over the remainder of the two week observation period. The behavioral effects of 5, 7.5 or 10 mg/kg were determined in mice trained to respond under a multiple fixed-ratio 30, fixed-interval 600-sec schedule of milk presentation. At 3 hr after TET administration, the rate of responding was decreased at all three doses. However, by 27 hr after 5 or 7.5 mg/kg TET the rate of responding had returned to pre-injection control values while the responding of the mice in the 10 mg/kg group did not return to pre-injection control values until 51 hr after administration. In a separate group of mice, 7.5 mg/kg was administered at 2 week intervals for a total of 5 separate administrations. No evidence for a cumulative or diminished behavioral effect was observed. Neuropathological examination revealed a direct dose and time related pathology in the white matter of the CNS. Maximal edematous vacuolar change was observed 72 hr after TET administration. Such morphological changes, however, were totally absent 12 days after a single 10 mg/kg exposure. Multiple exposure to TET (7.5 mg/kg) at 2 week intervals for 10 weeks showed only minimal morphological alterations in the brain.

Animals↗
PubMed1990

Evaluation of occupational asthma from airborne egg protein exposure in multiple settings.

We previously reported IgE-mediated occupational asthma among workers exposed to airborne egg protein at a plant that produces liquid and dried powdered egg products. To demonstrate that our original observations are generalizable to other facilities that process eggs, and to estimate the prevalence of IgE-mediated occupational asthma among egg-exposed workers, we conducted surveys at two additional plants. We administered a questionnaire to 188 employees to identify workers with symptoms suggestive of occupational asthma. We further evaluated 88 workers with and without symptoms by a clinical examination by a physician blinded to results of other tests, serial peak expiratory flow rate (PEFR) determinations every three hours while awake for one week, and skin prick tests and serum specific IgE levels to extracts of factory egg products, commercial egg test reagents, and egg white protein fractions. Fourteen workers had work-related asthmalike symptoms by questionnaire, a physician diagnosis of occupational asthma, and evidence of IgE-mediated sensitization to one or more egg proteins. Workers exposed exclusively to liquid egg aerosol, as well as workers exposed primarily to dried airborne egg protein, developed occupational asthma. This study replicated our original observations and demonstrated that workers in all areas of liquid and powdered egg production are at risk of developing occupational asthma from exposure to airborne egg proteins.

Air Pollutants, Occupational↗
PubMed2004

Long-term health effects of repeated exposure to multiple vaccines.

The health of 155 former workers in a US military research program who had received multiple vaccines and 265 matched community controls was assessed. The study population was mostly male (83%) and elderly (median age, 69 years). Multiply immunized (MIP) subjects received vaccines and/or skin tests (median = 154) over a median of 17.3 years; interval from start of immunizations to survey completion was 15-55 years (mean = 43.1 years). MIP subjects characterized themselves as slightly less healthy than controls (P = 0.057). Fatigue (but no other symptom) was reported more frequently in the MIP group (P = 0.011), but was not associated with number of injections, number of vaccines, or time in program. No differences between MIP and control groups were seen for numerous self-reported medical conditions. Several statistically significant abnormalities were seen in clinical laboratory tests among MIP subjects, but none appeared to be clinically significant. A significant difference in frequency of monoclonal spikes and/or paraprotein peaks between MIP (12.5%) and control (4.5%) groups (RR = 2.7, P < 0.003) was observed; no associations with lifestyle, vaccine exposure, or medical conditions were found.

Aged↗
PubMed1995

Review of the multiple chemical exposure factors which may disturb human behavioral development.

Previous research both in humans and laboratory animals provides evidence that prenatal exposure to metals, pollutants and drugs may impair the neurobehavioral development of the offspring. This may induce mental and psychomotor disturbances as well as learning, behavioral and sensory disorders. However, proof for a strict causality between some low-level exposures to chemicals and behavioral developmental dysfunctions, is often considered still not to be established. The pertinent studies on neurobehavioral developmental toxicity of individual substances (lead, cadmium, organic solvents, PCBs, alcohol, nicotine, diazepam) are reviewed, and the methodologies and conclusions, the missing aspects and the existing problems which still need to be solved in further studies, are discussed. In addition, the necessity of undertaking a broad prospective cohort study on multifactorial influences on the behavioral development of children is emphasized.

Animals↗
PubMed1981

Multiple hyperbaric exposures during pregnancy in sheep.

Eleven sheep were subjected to hyperbaric comparable to 165 feet of sea water 31 times between the one hundred twelfth and one hundred thirty-seventh days of pregnancy. During 13 dives the maternal and fetal circulations were monitored for bubble formation during decompression. Bubbles were detected by external doppler probes in eight of 12 ewes, but in none of the fetuses. Nine ewes were delivered of normal lambs at term. In one, twin fetuses died during an abnormal labor. The pregnancy of another was terminated by cesarean section after decompression to look for bubbles in the fetal circulation.

Animals↗
PubMed1992

Patent infections of Ascaris suum in pigs: effect of previous exposure to multiple, high doses of eggs and various treatment regimes.

Fifty-four crossbred, 4-week-old pigs divided into nine equal groups were used to test whether multiple inoculations with high numbers of A. suum eggs with or without anthelmintic would result in patent infections. All pigs exposed to multiple prechallenge inoculations of 500, 1000, 2000, 5000, 10,000 and 20,000 and challenged orally 2 weeks later with 10,000 eggs harboured adult worms. When prechallenge infections were removed by pyrantel tartrate treatment the animals were more susceptible to challenge than controls not previously exposed to infections. The same drug used from 2 days before until 10 days after the last prechallenge infection eliminated that effect. Pigs subjected to the same multiple egg dosing regimen but given feed containing fenbendazole immediately before, during and for 10 days after multiple dosing developed significantly more adult intestinal worms after challenge than any other group. These worms were, however, significantly shorter than those that developed in any group of pigs. Adult worms from all these groups produced eggs that after embryonation were infective to mice.

Animals↗
PubMed1995

Susceptibility to herpes labialis following multiple experimental exposures to ultraviolet radiation.

We studied susceptibility to herpes labialis by exposing 20 volunteers to experimental ultraviolet radiation (UVR) on three occasions at 3- to 4-month intervals. The number of patients who developed lesions after each session was 9/20 (45%), 9/20 (45%) and 14/20 (70%). Herpes simplex virus (HSV) was isolated from 21/29 (72%) of lesions sampled. Three patients never developed a lesion, 13 developed lesions on one or two of the three occasions, and 4 patients had a lesion following all three sessions. Seven of 33 (21%) lesions were 'immediate' lesions (developed within 48 h) and the others developed 3-7 days after UVR exposure (delayed lesions). Development of lesions correlated with historical susceptibility to sun-induced herpes labialis, but not with age, sex, years with herpes labialis, frequency of herpes labialis from all causes, or concurrent serum levels of cortisol, dehydroepiandrosterone, estradiol, progesterone or alpha 1-antitrypsin. Among normally menstruating females, a significant association was identified between the development of herpes labialis and the luteal phase of the menstrual cycle (8 cases of herpes labialis/11 attempts, RR = 14, P = 0.005). The lack of correlation between episodes of natural herpes labialis and susceptibility to experimental UVR-induced disease suggests that these events are controlled differently. The results of serial attempts to induce experimental herpes in each patient was most commonly inconsistent, indicating that individual patient susceptibility to UVR varies over time. While the explanation for this variation remains unclear, stages of the menstrual cycle may be important among women.

Adult↗
PubMed1996

Response of sugar maple to multiple year exposures to ozone and simulated acidic precipitation.

Potted sugar maple seedlings were exposed to ozone and acidic precipitation in open-top chambers for three consecutive growing seasons. Periodic measurements of photosynthesis, dark respiration, through-fall and soil solution chemistry, and annual measurements of the weight of plant parts were made. Experimental treatments caused few and minor effects on above- or below-ground growth of the seedlings, even after three growing seasons. There were trends for reduced photosynthesis in trees exposed to elevated concentrations of ozone and increased photosynthesis in those exposed to the lowest pH simulated rain treatment. The chemistries of soil-solutions and through-fall were not altered significantly by treatment. Although major effects were not observed, sugar maple may respond to exposures that take place over a significant part of its life cycle.

Journal Article↗
PubMed1982

Reduced temporary and permanent hearing losses with multiple tone exposures.

Acoustic overstimulation of the guinea pig cochlea with a 16 kHz pure tone induces a loss in threshold sensitivity that can be either temporary or permanent depending on the duration of the trauma. When a second tone of lower frequency (10, 5 or 2 kHz) is presented to the same cochlea simultaneously with the first tone, then the resultant threshold loss produced by the 16 kHz tone is significantly less. This applies to both temporary and permanent threshold losses. The reduced threshold loss disappears as the intensity of the second tone decreases. This type of nonlinear cochlea behaviour is similar to other acoustically evoked nonlinearities generally grouped under the term, two-tone suppression or inhibition. The results disagree with the "equal energy hypothesis' as a method to establish damage risk criteria in noise-induced hearing loss.

Animals↗
PubMed1998

Missed diagnoses and misdiagnoses of environmental toxicant exposure. The psychiatry of toxic exposure and multiple chemical sensitivity.

Toxins such as carbon monoxide, lead, and mercury that present occasionally with primarily psychiatric symptoms can pose some of the most difficult diagnoses. This article reviews the clues that can allow the diagnostician to identify the role of one of these substances. Equally important, the article discusses the contentious issues that surround the phenomen known as multiple chemical sensitivity. Viewed primarily as a functional illness, often with legal overtones, this putative disorder is critically reviewed to see if it meets the same demanding standard of validity that is found in the psychiatric symptoms associated with other toxic disorders. Although questioning the strict medical origin of medical chemical sensitivity, the article outlines some treatment hints that may helpful in the management of this difficult group of patients.

Adult↗
PubMed2001

The effect of exposure to multiple lineups on face identification accuracy.

This study examines the conditions under which an intervening lineup affects identification accuracy on a subsequent lineup. One hundred and sixty adults observed a photograph of one target individual for 60 s. One week later, they viewed an intervening target-absent lineup and were asked to identify the target individual. Two days later, participants were shown one of three 6-person lineups that included a different photograph of the target face (present or absent), a foil face from the intervening lineup (present or absent), plus additional foil faces. The hit rate was higher when the foil face from the intervening lineup was absent from the test lineup and the false alarm rate was greater when the target face was absent from the test lineup. The results suggest that simply being exposed to an innocent suspect in an intervening lineup, whether that innocent suspect is identified by the witness or not, increases the probability of misidentifying the innocent suspect and decreases the probability of correctly identifying the true perpetrator in a subsequent test lineup. The implications of these findings both for police lineup procedures and for the interpretation of lineup results in the courtroom are discussed.

Adolescent↗