Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “multiple exposures”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed2002

Oxidative stress associated DNA damage in testis of mice: induction of abnormal sperms and effects on fertility.

Our previous work has shown that prooxidant treatment has the propensity to induce male-mediated dominant lethal (DL) type mutations in mice. The present investigation is aimed to understand the effect of oxidative stress (OS) on DNA damage in testis, epididymal sperms and its propensity to induce sperm head abnormalities as well as its implications on male fertility in mice. Initially, employing two organic hydroperoxides, (t-butyl hydroperoxide, t-bHP and cumene hydroperoxide, cHP) as model prooxidants, induction of oxidative stress was ascertained following single/multiple sublethal doses. Further, the multiple exposure model was utilized to characterize effects on testicular weights, histoarchitecture, caudal sperm counts, lipid peroxidation, DNA damage and frequency of abnormal sperms. Single sublethal doses (1/20, 1/10 and 1/5 LD(50)) of t-bHP and cHP administered (i.p.) to adult mice resulted in only a marginal increase (20% at the highest dosage) in testicular MDA levels. However, multiple doses (1/10 and 1/5 LD(50) per day for 5 days) induced marked OS in testis and epididymal sperms as evidenced by a marked increase in lipid peroxidation at 24h after the last dose. This was associated with significant increase in the DNA damage (FADU assay) in the testicular tissue. While caudal sperm counts determined at all sampling weeks showed no treatment related alterations, analysis for head abnormalities revealed nearly 2-3-fold increase in the percent abnormal sperms among the hydroperoxide treated mice during the first 3 weeks. Furthermore, mating of prooxidant treated males sequentially for a period of 5 weeks with untreated females resulted in a significant reduction in average pup number per litter during the first 3 weeks. These results suggest that oxidative stress in testicular milieu is associated with DNA damage and produces higher frequency of abnormal sperms with significant effect on male fertility.

Animals↗
PubMedDate not supplied

1,2-Dibromo-3-chloropropane (DBCP)-induced nuclear atypia in rat kidney.

The reversibility of the nematocide 1,2-dibromo-3-chloropropane (DBCP)-induced renal injury was studied in adult male F344 rats. After a single dose of 200 mg DBCP/kg body weight, rats were sacrificed at 1, 3, 6, 9, 14, 28, and 196 days. Twenty-four hours after DBCP treatment, the animals showed signs of acute renal insufficiency, which, based on serum chemistry and urinalysis results, was reversed by the 14th day. Morphologic findings consisted of severe acute tubular necrosis, which was localized to the juxtamedullary cortex. The lesion was recognizable at 24 hrs and fully developed at 3 days post-exposure. The proximal convoluted tubuli were primarily affected, but there were also spotty necroses in distal convoluted tubuli and loops of Henle. Beginning regeneration was evident at 3 days post-exposure. Multiple mitoses, some of them abnormal, were seen. Four weeks after treatment some mitotic activity was still present, but the regeneration of the tubular epithelium was largely completed. There were several dilated, distorted tubuli lined with abnormal epithelial cells with large, hyperchromatic nuclei. Interstitial fibrosis was mild and there was no interstitial inflammation. Twenty-eight weeks post-exposure the nuclear atypia persisted in the tubular epithelium. Glomerular findings were minimal and consisted of focal hyperplasia of the epithelial cells of the parietal layer of Bowman's capsule and shrinking of the glomerular tufts at 4 weeks post-exposure. At 28 weeks post exposure only rare foci of glomerulosclerosis were seen. Epithelial cells of the renal pelvis showed minimal nuclear and cytoplasmic swelling 24 hrs after DBCP exposure. Urothelial atypia was not present. The results indicate that a single dose of DBCP is capable of producing nuclear atypia that persists in the renal tubuli beyond the regenerative phase. Follow-up of patients that have been chronically exposed to DBCP with periodic examination of urinary cytology is suggested.

Acute Kidney Injury↗
PubMed1996

Promotion of colorectal neoplasia in experimental murine ulcerative colitis.

BACKGROUND: The mechanisms underlying the frequent development of colorectal carcinomas in patients with ulcerative colitis are still unknown. AIMS: To evaluate whether mucosal necrosis and regeneration act as enhancing or promoting factors in colorectal tumorigenesis, development of multiple colorectal tumours was studied in a murine model of ulcerative colitis with azoxymethane pretreatment. METHODS: Periods of chronic ulcerative colitis in mice were induced by three repeated administrations of 3% dextran sulphate sodium subsequent to a single azoxymethane pretreatment, to give conditions similar to the clinically observed active and remission phases. RESULTS: In the chronic colitis group with carcinogen exposure, multiple mucosal tumours (10.5/mouse) developed in the colorectum. This occurred primarily on the left side of the large intestine or transverse colon, the sites of the most severe colitic injury. The observed lesions were high grade dysplasias and invasive adenocarcinomas. Increased cell proliferation was evidenced by high uptake of bromodeoxyuridine, and increased activities of thymidylate synthetase and thymidine kinase. No tumours were induced in the control groups with azoxymethane pretreatment or chronic colitis alone. CONCLUSIONS: Repeated mucosal erosion with necrosis and regeneration is critical for the development of colorectal tumours in this experimental colitis system.

Animals↗
PubMed1998

Anti-CD14 mAb treatment provides therapeutic benefit after in vivo exposure to endotoxin.

The presence of endotoxin from Gram-negative bacteria signals the innate immune system to up-regulate bacterial clearance and/or killing mechanisms. Paradoxically, such responses also contribute to septic shock, a clinical problem occurring with high frequency in Gram-negative septicemia. CD14 is a receptor for endotoxin (lipopolysaccharide, LPS) and is thought to have an essential role in innate immune responses to infection and thereby in the development of septic shock. Using a novel rabbit model of endotoxic shock produced by multiple exposures to endotoxin, we show that anti-rabbit CD14 mAb, which blocks LPS-CD14 binding, protects against organ injury and death even when the antibody is administered after initial exposures to LPS. In contrast, anti-rabbit tumor necrosis factor mAb treatment fails to protect when administered after LPS injections. These results support the concept that anti-CD14 treatment provides a new therapeutic window for the prevention of pathophysiologic changes that result from cumulative exposures to LPS during septic shock in man.

Animals↗
PubMed1985

Mortality of employees of the United Kingdom Atomic Energy Authority, 1946-1979.

An analysis was conducted of 3373 deaths among 39 546 people employed by the United Kingdom Atomic Energy Authority between 1946 and 1979, the population having been followed up for an average of 16 years. Overall the death rates were below those prevailing in England and Wales but consistent with those expected in a normal workforce. At ages 15-74 years the standardised mortality ratios (SMRs) were 74 for deaths from all causes and 79 for deaths from all cancers. Mortality from only four causes was above the national average--namely, testicular cancer (SMR 153; 10 deaths), leukaemia (SMR 123; 35 deaths), thyroid cancer (SMR 122; three deaths), non-Hodgkin's lymphoma (SMR 107; 20 deaths)--but in none was the increase significant at the 5% level. Half of the authority's employees were recorded as having been monitored for exposure to radiation, their collective recorded exposure being 660 Sv (65 954 rem). Among these prostatic cancer was the only condition with a clearly increased mortality in relation to exposure. Of the 19 men who had a radiation record and died from prostatic cancer at ages 15-74 years, nine had been monitored for several different sources of exposure to radiation. The standardised mortality ratios were 889 (six deaths) in employees monitored for contamination by tritium, 254 (nine deaths) in those monitored for contamination by other radionuclides, and 385 (nine deaths) in those with dosimeter readings totalling more than 50 mSv (5 rem); but the same nine subjects tended to account for each of these significantly raised ratios. Because multiple exposures were common and other relevant information was not available the reason for the increased mortality from prostatic cancer in this population could not be determined and requires further investigation. Excess mortality rates of 2.2 and 12.5 deaths per million person years per 10 mSv (1 rem) were estimated for leukaemia and all cancers, respectively. The confidence limits around these estimates were wide, included zero, and made it unlikely that the International Commission on Radiological Protection's cancer risk coefficients were underestimated by more than 15-fold. Thus despite this being the largest British workforce whose mortality has been reported in relation to low level ionising radiation exposure, even larger populations will need to be followed up over longer periods before narrower ranges of risk estimates can be derived.

Adolescent↗
PubMed2003

Definitions and types of work-related asthma: a nosological approach.

The workplace can trigger or induce asthma and cause the onset of different types of work-related asthma. Analysis of previous definitions of occupational asthma (OA) led to the conclusion that evidence of a direct causal relationship between workplace exposure and the development of asthma remains the key element for defining OA. Based on clinical features and pathophysiological mechanisms, the following conditions should be distinguished in the spectrum of work-related asthma: 1) immunological OA characterised by a latency period necessary to acquire immunologically induced sensitisation; 2) nonimmunological OA characterised by the rapid onset of asthma following single or multiple exposures to high concentrations of irritant compounds; 3) work-related asthma defined by exacerbation of symptoms in workers with pre-existing or coincident asthma; and 4) variant syndromes including eosinophilic bronchitis, potroom asthma, and asthma-like disorders caused by organic dusts. The issues and controversies relating to this approach are critically reviewed in order to stimulate the consensus development of operational definitions of work-related asthma.

Asthma↗
PubMed2005

Digital vibration threshold testing and ergonomic stressors in automobile manufacturing workers: a cross-sectional assessment.

Upper extremity musculoskeletal disorders (UEMSDs) comprise a large proportion of work-related illnesses in the USA. Physical risk factors including manual force and segmental vibration have been associated with UEMSDs. Reduced sensitivity to vibration in the fingertips (a function of nerve integrity) has been found in those exposed to segmental vibration, to hand force, and in office workers. The objective of this study was to determine whether an association exists between digital vibration thresholds (VTs) and exposure to ergonomic stressors in automobile manufacturing. Interviews and physical examinations were conducted in a cross-sectional survey of workers (n = 1174). In multivariable robust regression modelling, associations with workers' estimates of ergonomic stressors stratified on tool use were determined. VTs were separately associated with hand force, vibration as felt through the floor (whole body vibration), and with an index of multiple exposures in both tool users and non-tool users. Additional associations with contact stress and awkward upper extremity postures were found in tool users. Segmental vibration was not associated with VTs. Further epidemiologic and laboratory studies are needed to confirm the associations found. The association with self-reported whole body vibration exposure suggests a possible sympathetic nervous system effect, which remains to be explored.

Adult↗
PubMedDate not supplied

A proposal for the use of biomarkers for the assessment of chronic pollution and in regulatory toxicology.

Despite a wealth of information on biomarkers, they are not routinely used for regulatory purposes, even though the potential benefits of biomarkers to rationalise complex exposure-response relationships are clear. Biomarkers can be inappropriately applied or misinterpreted, because the fundamental assumptions in exposure-response relations have not been considered. Factors causing temporal and spatial variability in biomarker responses are reviewed. These include numerous geochemical and biotic variables. The variation can be minimised by appropriate study site selection, experimental replication, multivariate epidemiological approaches, normalised controls, and temporal calibration of responses; so that the regulatory use of biomarkers for biomonitoring and tracking pollution events, including chronic or multiple exposures to complex mixtures is possible. We propose and define the characteristics of biomarkers of chronic exposure or effect, which must measure changes in pollution/effect against long-term changes in other general stresses (disease, nutrition, environmental quality), relate to cumulative injury, and remain responsive over months or years. Neuroendocrine, immunological, and histological biomarkers are suggested for chronic pollution. We propose a regulatory framework for biomarkers based on a weight of evidence approach that can integrate biomarkers in risk assessment and long-term monitoring programmes.

Animals↗
PubMed2006

Pesticides and their metabolites in the homes and urine of farmworker children living in the Salinas Valley, CA.

In support of planning efforts for the National Children's Study, we conducted a study to test field methods for characterizing pesticide exposures to 20 farmworker children aged 5-27 months old living in the Salinas Valley of Monterey County, California. We tested methods for collecting house dust, indoor and outdoor air, dislodgeable residues from surfaces and toys, residues on clothing (sock and union suits), food, as well as spot and overnight diaper urine samples. We measured 29 common agricultural and home use pesticides in multiple exposure media samples. A subset of organophosphorus (OP), organochlorine (OC) and pyrethroid pesticides were measured in food. We also analyzed urine samples for OP pesticide metabolites. Finally, we administered four field-based exposure assessment instruments: a questionnaire; food diary; home inspection; and a self-administered child activity timeline. Pesticides were detected more frequently in house dust, surface wipes, and clothing than other media, with chlorpyrifos, diazinon, chlorthal-dimethyl, and cis- and trans-permethrin detected in 90% to 100% of samples. Levels of four of these five pesticides were positively correlated among the house dust, sock, and union suit samples (Spearman's rho=0.18-0.76). Pesticide loading on socks and union suits was higher for the group of 10 toddlers compared to the 10 younger crawling children. Several OP pesticides, as well as 4,4'-DDE, atrazine, and dieldrin were detected in the food samples. The child activity timeline, a novel, low-literacy instrument based on pictures, was successfully used by our participants. Future uses of these data include the development of pesticide exposure models and risk assessment.

Agriculture↗
PubMed2002

Enhancement of nasal inflammatory and epithelial responses after ozone and allergen coexposure in Brown Norway rats.

Repeated exposures to ozone cause inflammation and mucous cell metaplasia (MCM) in the nasal mucosa of laboratory animals. Similar cellular responses occur in humans during allergic rhinitis. We tested the hypothesis that exposure to ozone will enhance the inflammatory and epithelial responses associated with allergic rhinitis. Ovalbumin (OVA)-sensitized Brown Norway rats were exposed to ozone (0.5 ppm, 8 h/day) for 1 day or 3 consecutive days. Immediately after each ozone exposure, animals were challenged intranasally (IN) with either sterile saline or OVA dissolved in saline (1%, 50 microg/nasal passage). Twenty-four h after the last IN challenge rats were sacrificed; nasal tissues were removed and processed for light microscopic examination and morphometric analysis of numeric densities of inflammatory and epithelial cell populations and volume densities of intraepithelial mucosubstances. A single OVA challenge caused a significant influx of neutrophils and eosinophils into the submucosa of all nasal tissues. Ozone exposure further enhanced the appearance of eosinophils in the maxilloturbinates of OVA-challenged rats but did not increase inflammation in other nasal tissues. After 3 days of ozone/OVA coexposures, the nasal transitional epithelium lining the maxilloturbinates had increased numbers of epithelial cells as well as the appearance of mucus-containing cells in areas normally absent of these secretory cells (i.e., MCM). Multiple challenges with OVA caused increased epithelial mucosubstances in the respiratory epithelium lining the septum without increasing the number of epithelial cells. Multiple exposures to both ozone and OVA caused greater increases in intraepithelial mucosubstances in the septum than those elicited by OVA alone. These results demonstrate that exposure to ozone exacerbates epithelial and inflammatory responses associated with allergen challenge. In addition, coexposure of these agents enhanced the induced production of nasal mucosubstances caused by either agent alone.

Administration, Inhalation↗
PubMedDate not supplied

Lead poisoning from art restoration and pottery work: unusual exposure source and household risk.

Two cases of lead poisoning following exposures in the arts and crafts environment are presented. The first illustrates the impact of an unusual exposure source experienced by a female art conservator while restoring an antique Peruvian tapestry from the Chancay Period (A.D. 1000-1500). The second demonstrates the extension to the artist's family members of a lead hazard associated with pottery work. Noted were a wide spectrum of clinical and biochemical abnormalities, ranging from severe neurological and gastrointestinal symptoms to subtle alterations in the biosynthetic pathway of heme. Marked elevation of the blood lead level (up to 130 mcg/100 mL) was found in the most severe case of lead poisoning. The cases illustrate the need for industrial hygiene measures in this type of work in order to prevent lead intoxication, both in the adult artist and children in the household. However, in some instances of increased lead absorption in persons with lead-related hobbies, sources other than those associated with arts and crafts should be investigated. This alternative is illustrated by a third case, in which firearms training was the more likely source of excessive exposure. Multiple occupational factors must occasionally be considered in evaluating increased lead absorption.

Adult↗
PubMed2004

Short-term elemental mercury exposures at three Arizona schools: public health lessons learned.

Acute exposure of schoolchildren to elemental mercury continues to produce public health crises that drain available health and environmental resources. In this retrospective study, we report three incidents of limited exposure to elemental mercury in Arizona schoolchildren. Health workers screened 347 students, family, and staff by history and physical exam for exposure level and symptomatology. Urine and blood mercury testing further evaluated at-risk individuals. Environmental contamination was also assessed. Despite up to 28% of patients reporting symptoms, no individual was found to have elevated serum or urinary mercury levels requiring treatment. Elevated airborne mercury levels were demonstrated in the classrooms, dormitories, buses, and student homes and appropriate clean-up measures were instituted. Previous studies of multiple exposures to elemental mercury either focus on significant patient morbidity or lack biological data. In contrast, this study reports biological and environmental data demonstrating no clinical toxicity following acute exposure in a large sample. Confirmatory studies are necessary to develop cost-effective guidelines for the appropriate management of these public health crises.

Air Pollutants↗
PubMed1980

Effect of patulin on hepatic monooxygenase in male mice.

The in vivo effects of patulin on hepatic monooxygenase enzymes in male mice were examined after single and multiple exposures (i.p.) to the mycotoxin. The animals were exposed to a single dose of 1, 3 or 4.5 mg patulin/kg or daily doses of 1.0 mg/kg for 5 or 14 days. After single exposure no significant effect was observed on hexobarbital hydroxylation while aniline hydroxylase increased significantly at 3 mg/kg and at 48 hr. The demethylation of aminopyrine and ethylmorphine increased significantly 48 and 72 hr after 3.0 or 4.5 mg patulin/kg doses. A 12% increase was observed in cytochrome P-450 content 48 hr after exposure to 1 or 3 mg/kg. NADPH-cytochrome C reductase was enhanced significantly at all 3 dose levels at 48 hr. At 24 hr hepatic NADPH-dependent dehydrogenase activity increased 38 and 46% in animals exposed to a single dose of 3 mg patulin/kg, respectively. No effect of patulin was observed on the hepatic drug metabolizing enzymes examined except hexobarbital oxidation in mice exposed to multiple doses of patulin. Patulin at best was a weak inducer of the hepatic mixed function oxidase system.

Animals↗
PubMed2006

Risk assessment of endocrine disrupters: the role of toxicological studies.

Endocrine disrupters (ED) represent a good challenge for experimental toxicology. In order to deal with several critical points relevant to risk assessment: (a) ED may induce long-term effects upon exposure in susceptible developmental phases, including postnatal life up to puberty; thus, efforts are required to refine testing strategies, for example, by supporting the two-generation rodent study with a comprehensive in vitro/in vivo screening battery; (b) due to the regulatory role of endocrine homeostasis, mechanisms of endocrine disruption may impact on immune, neurobehavioral, and reproductive development, as well as on susceptibility to cancer; (c) the potential multiple exposure to ED with common targets through diet and/or living environment calls for the development of models to understand mechanisms of interactions and effects of mixtures; and (d) last but not least, ED may interact with a number of factors related to differential vulnerability of individuals or population subgroups, including the intake of nutrients or bioactive food components. Besides reducing the chance for noxious chemicals to enter our life, toxicological research on mechanisms may also lead to the definition of possible biomarkers of exposure, effect, and susceptibility that may be further exploited in human health surveillance.

Endocrine Disruptors↗
PubMed2000

Effects of concentrated ambient particles in rats and hamsters: an exploratory study.

Considerable controversy surrounds the biological plausibility of adverse effects from exposure to ambient particulate matter (PM)*, chiefly because these adverse effects have been observed at particle mass concentrations below those that have been shown to produce effects in healthy animals and human volunteers in the laboratory. To address this research gap, we examined the potential for concentrated ambient PM to produce pulmonary and cardiovascular changes in compromise rodent models. Normal healthy and monocrotaline-treated rats received single or multiple exposures to concentrated ambient PM, and their responses were tested using functional, cellular, biochemical, and histological endpoints. Analyses determined that no changes in pulmonary function or structure occurred after exposure to concentrated ambient PM. Cardiac arrhythmias did not increase after PM exposure in normal or monocrotaline-treated rats. Increased atrial conduction time, accompanied by a decrease in the duration of the T wave portion of the electrocardiogram (ECG) waveform, was observed in PM-exposed monocrotaline-treated rats in one experiment. In addition, on several but not all exposure days, small yet statistically significant increases in heart rate and peripheral blood cell differential counts were observed in normal and monocrotaline-treated rats within 6 hours after exposure to concentrated ambient PM. The observed changes in cardiovascular parameters in rats returned to control values by 24 hours after exposure. In a hamster cardiomyopathy model, no adverse cardiac or pulmonary changes were detected after exposure to concentrated ambient PM. Thus, these studies found that cardiopulmonary effects could be produced in rats, but not in hamsters with cardiomyopathy, exposed to concentrated ambient PM. None of the changes occurred on every exposure day and none appeared to be life threatening. Thus, the cardiac changes may reflect changes in homeostasis that could affect individuals who are critically ill, and these findings do not resolve the biological plausibility of adverse health effects associated with ambient PM in epidemiologic studies.

Age Factors↗
PubMed2001

Green tea polyphenol (-)-epigallocatechin-3-gallate treatment of human skin inhibits ultraviolet radiation-induced oxidative stress.

The use of naturally occurring botanicals with substantial antioxidant activity to afford protection to human skin against UV damage is receiving increasing attention. The green tea constituent (-)-epigallocatechin-3-gallate (EGCG) is a potent antioxidant and has shown remarkable preventive effects against photocarcinogenesis and phototoxicity in mouse models. In this study we have investigated the effects of topical application of EGCG, the major polyphenol present in green tea, to human skin before UV irradiation on UV-induced markers of oxidative stress and antioxidant enzymes. Using immunohistochemistry and analytical enzyme assays, we found that application of EGCG (mg/cm(2) skin) before a single UV exposure of 4x minimal erythema dose (MED) markedly decreases UV-induced production of hydrogen peroxide (68-90%, P < 0.025-0.005) and nitric oxide (30-100%, P < 0.025-0.005) in both epidermis and dermis in a time-dependent manner. EGCG pretreatment also inhibits UV-induced infiltration of inflammatory leukocytes, particularly CD11b(+) cells (a surface marker of monocytes/macrophages and neutrophils), into the skin, which are considered to be the major producers of reactive oxygen species. EGCG treatment was also found to inhibit UV-induced epidermal lipid peroxidation at each time point studied (41-84%, P < 0.05). A single UV exposure of 4x MED to human skin was found to increase catalase activity (109-145%) and decrease glutathione peroxidase (GPx) activity (36-54%) and total glutathione (GSH) level (13-36%) at different time points studied. Pretreatment with EGCG was found to restore the UV-induced decrease in GSH level and afforded protection to the antioxidant enzyme GPx. Further studies are warranted to study the preventive effects of EGCG against multiple exposures to UV light of human skin.

Adult↗
PubMed1985

Characterization of a photosensitive glucose derivative. A photoaffinity reagent for the erythrocyte hexose transporter.

The photosensitive reagent 6-N-(4-azido-2-hydroxy-3,5-diiodobenzoyl)-D-glucosamine has been assessed as a potential photoaffinity label for the hexose transporter. Under zero-trans conditions, transport experiments performed in the dark reveal that the reagent inhibits the uptake of D-glucose in resealed human erythrocyte ghosts. Increasing the concentration of glucose in the transport medium has a protective effect, reducing the inhibition. Kinetic analysis indicates that the probe acts as a competitive inhibitor with high affinity for the erythrocyte hexose transporter (Ki between 0.07 and 0.2 microM). Exposure to a 280 nm filtered high intensity mercury-vapor lamp results in a rapid and efficient photolysis. At low concentrations of the probe, specific labeling of membrane preparations was observed. Autoradiograms of 10% SDS gels revealed the specific labeling of bands 4.51 and 6. This labeling was concentration-dependent and protected by D-glucose (not the L-isomer) and phloretin in the medium. When subjected to multiple exposures of low concentration of the photoaffinity reagent, apparent saturation was achieved.

Affinity Labels↗
PubMed1994

A test for variations in individual sensitivity to hyperbaric oxygen toxicity.

It has been suggested that some individuals have above-average sensitivity to hyperbaric oxygen toxicity. An extensive human study completed at the Naval Experimental Diving Unit (NEDU) tested human tolerance to HBO and raised the possibility of assessing this hypothesis. In a group of 113 subjects given multiple exposures, some developed no symptoms of O2 toxicity while others developed symptoms on several occasions. The subjects in this study received unequal numbers of exposures of different depths and durations however, and it was not obvious how to determine unusual sensitivity. To assess the influences of chance vs. differences in sensitivity on the outcome of this experimental series, we performed a Monte Carlo simulation in which the experimental design was duplicated and the sensitivity hypothesis was evaluated statistically. The number of subjects giving rise to any symptoms and the distribution of individuals having symptoms on multiple occasions were evaluated. The simulation showed that the NEDU results were not unusual: nearly one quarter of the time the observed pattern of multiple symptoms could have been expected due to chance alone. The power of this simulation would have permitted detection of sensitivity factors 10 times (or greater) normal in 20% of the subjects at least half of the time.

Diving↗