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Biomedical subjects

E F Krieg

Publications and source records attributed to E F Krieg.

At least 19 recordsLinked to original sources

Genetic basis for susceptibility to noise-induced hearing loss in mice.

The C57BL/6J (B6) and DBA/2J (D2) inbred strains of mice exhibit an age-related hearing loss (AHL) due to a recessive gene (Ahl) that maps to Chromosome 10. The Ahl gene is also implicated in the susceptibility to noise-induced hearing loss (NIHL). The B6 mice (Ahl/Ahl) are more susceptible to NIHL than the CBA/CaJ (CB) mice (+(Ahl)). The B6xD2.F(1) hybrid mice (Ahl/Ahl) are more susceptible to NIHL than the CBxB6.F(1) mice (+/Ahl) [Erway et al., 1996. Hear. Res. 93, 181-187]. These genetic effects implicate the Ahl gene as contributing to NIHL susceptibility. The present study demonstrates segregation for the putative Ahl gene and mapping of such a gene to Chromosome 10, consistent with other independent mapping of Ahl for AHL in 10 strains of mice [Johnson et al., 2000. Genomics 70, 171-180]. The present study was based on a conventional cross between two inbred strains, CBxB6.F(1) backcrossed to B6 with segregation for the putative +/Ahl:Ahl/Ahl. These backcross progeny were exposed to 110 dB SPL noise for 8 h. All of the progeny were tested for auditory evoked brainstem responses and analyzed for any significant permanent threshold shift of NIHL. Cluster analyses were used to distinguish the two putative genotypes, the least affected with NIHL (+/Ahl) and most affected with PTS (Ahl/Ahl). Approximately 1/2 of the backcross progeny exhibited PTS, particularly at 16 kHz. These mice were genotyped for two D10Mit markers. Quantitative trait loci analyses (log of the odds=15) indicated association of the genetic factor within a few centiMorgan of the best evidence for Ahl [Johnson et al., 2000. Genomics 70, 171-180]. All of the available evidence supports a role for the Ahl gene in both AHL and NIHL among these strains of mice.

Animals↗

Effects of environmental and organizational factors on the health of shiftworkers of a printing company.

This study explored the effects of environmental and organizational stressors on the health of shiftworkers in a printing company (n = 124). A questionnaire was used to gather data on work history, organizational factors, psychosocial characteristics, medical history, present health, occupational and non-occupational exposures, and lifestyle factors. The perception of environmental and organizational conditions was associated (P < 0.05) with chronic back pain (odds ratio [OR], 1.29), varicose veins (OR, 1.35), allergic rhinitis (OR, 1.27), depression (OR, 1.45), and gastritis (OR, 1.15). Anxiety scores were associated with allergic rhinitis (OR, 1.14) and skin allergy (OR, 1.09). Shiftwork was a significantly risk factor for conjunctivitis (OR, 3.68), depression (OR, 0.23), cardiac arrhythmia (OR, 7.13), and gastritis (OR, 4.38). Other associations included tenure and chronic back pain (OR, 4.89), toluene exposure and skin allergy (OR, 3.76), worksite and conjunctivitis (OR, 7.0), and worksite and dermatitis (OR, 1.24 to 4.95). The number of hours of exercise per week was associated with varicose veins (OR, 4.33), and alcohol intake was associated with cardiac arrhythmia (OR, 6.74).

Adult↗

Receiver operating characteristics analyses of Food and Drug Administration-cleared serological assays for natural rubber latex-specific immunoglobulin E antibody.

Receiver operating characteristics (ROC) analyses to evaluate and compare the diagnostic accuracy of Food and Drug Administration (510K)-cleared natural rubber latex (NRL)-specific immunoglobulin E (IgE) antibody immunoassays have not been performed using well-characterized skin-testing reagents. Sera were collected from 311 subjects (131 latex puncture skin test [PST] positive and 180 PST negative). All masked, coded sera were analyzed for latex-specific IgE antibodies in the Diagnostic Products Corporation microplate AlaSTAT, HYCOR HY-TEC RAST, and Pharmacia-Upjohn CAP System RAST FEIA (CAP). Diagnostic accuracy was evaluated using GraphRoc for Windows software to construct and analyze ROC curves in relation to the subjects' PST status and the results of the immunoassays. The ROC areas under the curve (AUCs) +/- standard error based on PST for the three diagnostic tests were 0.858 +/- 0.024, 0.869 +/- 0.024, and 0.924 +/- 0.017, respectively, for AlaSTAT, CAP, and HY-TEC. The HY-TEC system had a significantly greater AUC based on PST than those observed for AlaSTAT (P < 0.05) and CAP (P < 0.05) analyses. When the diagnostic tests were probed as to the cutoffs giving maximal diagnostic efficiency compared to PST, CAP and AlaSTAT yielded values of <0.35 kU of allergen IgE (kU(A))/liter and <0.35 kU/liter while the HY-TEC assay yielded 0.11 kU/liter. The diagnostic efficiencies based on PST in our cohort at these cutoffs were 87.1, 88.1, and 88.7%, respectively. The HY-TEC assay had a significantly greater AUC than CAP and AlaSTAT using PST as a diagnostic discriminator in our cohort. When the HY-TEC system was probed at its maximally efficient cutoff (0.11 kU/liter) versus HYCOR's recommended cutoff of 0.05 kU/liter, a loss of sensitivity of 8.4% was observed with a gain in specificity of 19.5%.

Antibodies, Anti-Idiotypic↗

Neurologic function among termiticide applicators exposed to chlorpyrifos.

Chlorpyrifos is a moderately toxic organophosphate pesticide. Houses and lawns in the United States receive a total of approximately 20 million annual chlorpyrifos treatments, and 82% of U.S. adults have detectable levels of a chlorpyrifos metabolite (3,5, 6-trichloro-2-pyridinol; TCP) in the urine. The U.S. Environmental Protection Agency has estimated that there are 5,000 yearly reported cases of accidental chlorpyrifos poisoning, and approximately one-fourth of these cases exhibit symptoms. Organophosphates affect the nervous system, but there are few epidemiologic data on chlorpyrifos neurotoxicity. We studied neurologic function in 191 current and former termiticide applicators who had an average of 2.4 years applying chlorpyrifos and 2.5 years applying other pesticides, and we compared them to 189 nonexposed controls. The average urinary TCP level for 65 recently exposed applicators was 629.5 microg/L, as compared to 4.5 microg/L for the general U.S. population. The exposed group did not differ significantly from the nonexposed group for any test in the clinical examination. Few significant differences were found in nerve conduction velocity, arm/hand tremor, vibrotactile sensitivity, vision, smell, visual/motor skills, or neurobehavioral skills. The exposed group did not perform as well as the nonexposed group in pegboard turning tests and some postural sway tests. The exposed subjects also reported significantly more symptoms, including memory problems, emotional states, fatigue, and loss of muscle strength; our more quantitative tests may not have been adequate to detect these symptoms. Eight men who reported past chlorpyrifos poisoning had a pattern of low performance on a number of tests, which is consistent with prior reports of chronic effects of organophosphate poisoning. Overall, the lack of exposure effects on the clinical examination was reassuring. The findings for self-reported symptoms raise some concern, as does the finding of low performance for those reporting prior poisoning. Although this was a relatively large study based on a well-defined target population, the workers we studied may not be representative of all exposed workers, and caution should be exercised in generalizing our results.

Adult↗

An algorithm for detecting features of the hormone profiles of the human menstrual cycle.

An algorithm for detecting features of the cycles of the gonadotropic and ovarian hormones in women is described. The algorithm can detect hormone peaks and normal cycles defined in terms of the peaks in sequences of measurements that have an arbitrary starting point in the menstrual cycle and are of arbitrary length. The algorithm makes use of fuzzy set theory and is optimized using signal detection theory.

Algorithms↗

Diagnostic performance of Food and Drug Administration-cleared serologic assays for natural rubber latex-specific IgE antibody. The Multi-Center Latex Skin Testing Study Task Force.

BACKGROUND: In the absence of Food and Drug Administration-approved natural rubber latex skin testing reagents, latex-specific IgE antibody immunoassays are used in the diagnosis of latex allergy. Comparative diagnostic performance of these tests has not been definitively determined. OBJECTIVE: We sought to study the predictive value of available Food and Drug Administration (510K)-cleared latex-specific IgE antibody immunoassays in the diagnosis of latex allergy. METHODS: Subjects (n = 312) were classified as having a positive (n = 117) or a negative (n = 195) latex allergy history (Hx) or having a positive (n = 131) or a negative (n = 181) puncture skin test (PST) response (Greer reagent). The 14 subjects with a negative Hx and a positive PST response had negative responses to glove provocation testing and thus were considered sensitized but asymptomatic. Sera from 22 subjects were split to evaluate intra-assay variation. All 334 coded sera were analyzed for latex-specific IgE antibodies in the Diagnostic Products Corporation microplate AlaSTAT, Hycor HY-TEC EIA System, and Pharmacia-UpJohn CAP System. Variance and diagnostic performance parameters of each test were computed with 95% confidence intervals in relation to the subjects' Hx and PST status. RESULTS: Intra-assay concordance of split sera results was 96.0% for all 3 assays, with coefficients of variation of less than 25% and between-assay coefficients of variation of less than 21%. The diagnostic performance of the CAP and AlaSTAT assays were equivalent in comparison with PST results: sensitivity, CAP 76.3% and ALASTAT 73. 3% and specificity, CAP 96.7% and AlaSTAT 97.2% (P = NS). The HY-TEC assay was more sensitive (91.6%) and less specific (73.3%) than the CAP and AlaSTAT assays (P <.001). From 9% to 25% of the sera were discordant, being positive in at least 1, but not all 3, assays. CONCLUSION: The CAP and AlaSTAT assays produce 24% and 27% of false-negative results, respectively, whereas the HY-TEC produces 27% of false-positive results when compared with the PST.

Antibodies, Anti-Idiotypic↗

Quantitative measure of genetic differences in susceptibility to noise-induced hearing loss in two strains of mice.

The CBA/CaJ (CB) and C57BL/6J (B6) inbred strains of mice were exposed for 1 h to noise intensities between 98 and 119 dB SPL. Previous studies indicated that the B6 mice exhibited permanent threshold shifts (PTS) after 1h exposure to 110 dB, whereas the CB mice did not exhibit any PTS. These differences in susceptibility to noise-induced hearing loss (NIHL) appear to be due to a gene for age-related hearing loss (AHL). The current study was designed to determine dose-response curves for NIHL over the ranges of intensities of noise that would characterize the B6 and CB inbred strains of mice. Because of the considerable differences in sensitivity to NIHL, the noise exposures for the two strains overlapped only at 110 and 113 dB. Nevertheless, the two strains exhibited two different dose-response curves, offset and with different slopes. We postulate that the B6 strain of mice exhibits a more linear increase for PTS from 98-113 dB, consistent with incremental effects on some metabolic physiological mechanism(s); the abrupt transition in NIHL between 113 and 116 dB for the CB mice is consistent with an ototraumatic structural injury.

Animals↗

Measuring endocrine profiles of women in field studies.

Improved methods are needed to evaluate the effects of occupational and environmental hazards on the reproductive health of human female populations. This communication describes highly specific, sensitive, and reliable time-resolved fluorescence immunoassays for measuring luteinizing hormone (LH) and follicle-stimulating hormone (FSH), estrone 3-glucuronide (E13G), and pregnanediol 3-glucuronide (Pd3G) in urine, a fluid that is convenient and painless to collect serially from large populations. Furthermore, some of the technical issues relevant to the successful application of these measurements to field studies are discussed.

Environmental Monitoring↗

Evaluation of postural stability in workers exposed to lead at a secondary lead smelter.

Postural sway testing was carried out on a group of 145 workers exposed to lead in a secondary lead smelter and 84 workers not exposed to lead in a hinge manufacturing plant. All workers were measured for blood lead levels (BLL) and erythrocyte zinc protoporphyrin (ZPP) concentrations at the time of testing and both a total cumulative and a time-weighted average BLL value was constructed for the lead exposed workers. The lead exposed workers mean BLL at the time of testing was 38.9 microg/dl and the non-exposed workers mean was 2.3 microg/dl. ZPP levels averaged 55.2 microg/dl for exposed workers and 18.9 microg/dl for non-exposed workers. Total cumulative BLL averaged 83476 microg/dl days for the exposed workers, with a mean time-weighted average BLL of 35.1 microg/dl. Six tests of postural stability, four two leg conditions and two single leg conditions were administered to all subjects using a force platform to produce measurements of sway for comparison purposes. The two leg conditions also manipulated the visual and proprioceptive systems. A statistically significant association was observed for sway measurements and the current BLL for all workers, but not with the current BLL of only the lead exposed workers. No statistically significant associations were present with the cumulative measures of long-term exposure. Of the six tests of sway, only the single leg conditions showed significant exposure effects. The results suggest effects of lead exposure among those with average BLL near 40.0 microg/dl, but only in the most challenging one leg conditions.

Enzyme Inhibitors↗

Effect of environmental temperature on the interactive developmental toxicity of radiofrequency radiation and 2-methoxyethanol in rats.

OBJECTIVE: This research was conducted to determine if altered environmental temperatures would affect the interactive developmental toxicity of radiofrequency (RF) radiation and the industrial solvent, 2-methoxyethanol (2ME). This is important because RF radiation is used in a variety of workplaces that have poorly controlled environmental temperatures, and many workers are concurrently exposed to various chemicals. Furthermore, we have previously demonstrated that combined exposure to RF radiation (10 MHz) and 2ME produces enhanced teratogenicity in rats. METHODS: RF radiation sufficient to maintain colonic temperatures at the control value (38degrees ), 39.0degrees or 40.0 degrees C for 2 or 4 h combined with either 0 or 100 mg/ kg 2ME at environmental temperatures of 18 degrees , 24 degrees and 30 degrees C (65 degrees , 75 degrees , and 85 degrees F) were given on gestation day 13 to Sprague-Dawley rats. Dams were killed on gestation day 20, and the fetuses were examined for external malformations. RESULTS AND CONCLUSIONS: Environmental temperature does affect the specific absorption rate (SAR) necessary to maintain a specific colonic temperature but does not affect the interactive developmental toxicity of RF radiation and 2ME in rats. These results, consistent with the literature, add to the evidence that the developmental toxicity of RF radiation (combined or alone) is associated with colonic temperature, not with SAR.

Abnormalities, Drug-Induced↗

Detecting pre-ovulatory luteinizing hormone surges in urine.

The study objectives were to determine (i) if pre-ovulatory luteinizing hormone (LH) surges, undetected in urine by two immunoradiometric assays (IRMA), were detectable by an ultrasensitive immunofluorometric assay (IFMA) and (ii) the influence of creatinine adjustment on the detection and timing of the urinary LH surges. Daily urine specimens were contributed by healthy 25-36 year old volunteers during 14 ovulatory menstrual cycles for an epidemiological study conducted in 1983-1985. Specimens were selected as having been previously assayed by two IRMA without consistently detecting LH surges. These urine specimens were remeasured using an IFMA and adjusted for creatinine concentration. IFMA measurements revealed unambiguous LH surges in all cycles. Adjusting IRMA urinary LH values for creatinine concentrations revealed previously undetected LH surges in four of eight cycles. Creatinine adjustment also altered the timing of IRMA and IFMA LH surges by 1-5 days. These results demonstrate an IFMA that detects pre-ovulatory LH surges in unpreserved, frozen urine from cycles where such surges were previously undetectable. Further, creatinine adjustment can markedly affect detection and timing of the onset and peak of the urinary LH surge. While our analysis suggests that this adjustment improves the validity of the LH measure, this requires further investigation.

Adult↗

Interactions of radiofrequency radiation-induced hyperthermia and 2-methoxyethanol teratogenicity in rats.

Radiofrequency (RF) radiation is used in a variety of workplaces. In addition to RF radiation, many workers are concurrently exposed to numerous chemicals; exposed workers include those involved with the microelectronics industry, plastic sealers, and electrosurgical units. The developmental toxicity of RF radiation is associated with the degree and duration of hyperthermia induced by the exposure. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), produces enhanced teratogenicity in rats. The purpose of the present research is to determine the effects of varying the degree and duration of hyperthermia induced by RF radiation (sufficient to maintain colonic temperatures at control [38.5], 39.0, 40.0, or 41.0 degrees C for up to 6 h) and 2ME (100 mg/kg) administered on gestation day 13 of rats. Focusing on characterizing the dose-response pattern of interactions, this research seeks to determine the lowest interactive effect level. Day 20 fetuses were examined for external and skeletal malformations. The results are consistent with previous observations. Significant interactions were observed between 2ME and RF radiation sufficient to maintain colonic temperatures at 41 degrees C for 1 h, but no consistent interactions were seen at lower temperatures even with longer durations. These data indicate that combined exposure effects should be considered when developing both RF radiation and chemical exposure guidelines and intervention strategies.

Abnormalities, Drug-Induced↗

Hearing loss from combined exposures among petroleum refinery workers.

Workers from a refinery (n = 438) were interviewed, had their hearing tested and had their exposures to noise and solvents assessed. Measurements suggested that most exposures to noise and solvents were within exposure limits recommended by international agencies; however, the prevalence for hearing loss within the exposed groups ranged from 42 to 50%, significantly exceeding the 15-30% prevalence observed for unexposed groups. The adjusted odds ratio estimates for hearing loss were 2.4 times greater for groups from aromatics and paraffins (95% CI 1.0-5.7), 3 times greater for the maintenance group (95% CI 1.3-6.9) and 1.8 times greater for the group from shipping (95% CI 0.6-4.9), when compared to unexposed workers from the warehouse and health clinic. The results of acoustic reflex decay tests suggest a retrocochlear or central auditory pathway involvement in the losses observed in certain job categories. These findings indicate that factors in addition to noise ought to be considered when investigating and preventing occupational hearing loss.

Adult↗

Toluene-induced hearing loss among rotogravure printing workers.

OBJECTIVES: This study explored the effects of occupational exposure to solvents and noise on the hearing of rotogravure printing workers from São Paulo, Brazil. METHODS: The study group comprised 124 workers exposed to various levels of noise and an organic solvent mixture of toluene, ethyl acetate, and ethanol. Data on work history, psychosocial aspects of the job, medical history, present health, stress, occupational and nonoccupational exposures to noise or chemicals, and life-style factors were collected through an interview. The participants underwent pure-tone audiometry and immittance audiometry testing. Their exposures to noise and solvents were assessed. RESULTS: Forty-nine percent of the workers had hearing loss. From the numerous variables that were analyzed for their contribution to the development of hearing loss (age, tenure, noise dose, solvent concentrations in air, biological marker for toluene, job category, work and medical history items, smoking, alcohol consumption, work perception scores, nonoccupational exposures), age and hippuric acid (the biologic marker for toluene in urine) were the only variables that met the significance level criterion in the final multiple logistic regression model. The odds ratio estimates for hearing loss were 1.07 times greater for each increment of 1 year of age [95% confidence interval (95% CI) 1.03-1.11] and 1.76 times greater for each gram of hippuric acid per gram of creatinine (95% CI 1.00-2.98). CONCLUSIONS: The findings suggest that exposure to toluene has a toxic effect on the auditory system. Further research is needed on the mechanisms underlying the effects of toluene and on the adequacy of current recommended exposure limits.

Adult↗

Genetics of age-related hearing loss in mice. III. Susceptibility of inbred and F1 hybrid strains to noise-induced hearing loss.

Some humans and mice are genetically predisposed to age-related hearing loss (AHL), and others are variously susceptible to noise-induced hearing loss (NIHL). The inbred C57BL/6J (B6) mice exhibit AHL at an early age, whereas the inbred CBA/CaJ (CB) mice do not. The B6 mice are much more susceptible to NIHL than are the CB mice (Shone et al., 1991; Li, 1992a). The B6 mice possess an Ahl gene which maps to chromosome 10 (Erway et al., 1995). This study was designed, using these two inbred strains plus two F1 hybrid strains of mice, to begin to test the hypothesis that the Ahl genotypes may influence the susceptibility to NIHL. These strains of mice (with putative genotypes) are: inbred CB (+/+) and B6 (Ahl/Ahl); hybrid CBB6F1 (+/Ahl) and B6D2F1 (Ahl/Ahl; D2 represents inbred DBA/2J). Twenty-four mice of each of these four strains were exposed to noise (110 dB for 0, 1 or 2 h) and tested for auditory-evoked brainstem response (ABR) thresholds. The CB and CBB6F1 strains of mice did not differ significantly from each other, exhibiting mostly temporary threshold shifts. The B6 and B6D2F1 strains of mice did not differ significantly from each other, but did exhibit permanent threshold shifts. These results support the hypothesis that genetic predisposition to AHL may be revealed at a younger age by NIHL. This suggests that it may be possible to use the NIHL to distinguish segregating genotypes (+/Ahl vs. Ahl/Ahl) among backcross progeny and thereby to identify and map single genes for AHL.

Acoustic Stimulation↗

Relaxation dynamics of spontaneous otoacoustic emissions perturbed by external tones. III. Response to a single tone at multiple suppression levels.

The relaxation dynamics of spontaneous otoacoustic emissions (SOAEs) interacting with an external tone have been successfully described using a van der Pol limit cycle oscillator model [Murphy et al., J. Acoust. Soc. Am. 97, 3702-3710 (1995) and Murphy et al., J. Acoust. Soc. Am. 97, 3711-3720 (1995)]. Data were collected for an SOAE interacting with a single-frequency ipsilateral suppressor. Transitions between different suppressed states were achieved by adding or removing signal at the suppressor frequency. The relaxation dynamics of the van der Pol model provided a good fit to the data.

Humans↗

Fibrogenic potentials of coal slags used as abrasive blasting substitutes.

This study was designed to examine the fibrogenic potentials of four coal slags that are being used as substitutes for silica sand in abrasive blasting. Six groups of 100 male Sprague-Dawley rats, including four coal slag groups, a vehicle control, and a positive control for fibrosis (Minusil quartz), were used. Each dust treatment group was given a single 40-mg dose of test agent via intratracheal instillation. Interim sacrifices of 15 animals per group were performed at 2 d, 3 mo, and 6 mo posttreatment, with the terminal sacrifice conducted at 12 mo. Hematoxylin and eosin stained histologic sections were prepared from designated formalin-fixed tissues collected at each necropsy and examined microscopically. Pulmonary silicon analyses were performed for each group at the 2-d and 12-mo sacrifices. Pulmonary function analyses were conducted for each group at the 3-, 6-, and 12-mo sacrifices. Lung hydroxyproline analyses were conducted for 15 animals in each group at the terminal sacrifice. The pulmonary fibrogenic potentials of the four coal slag groups were compared histologically with the Minusil and vehicle controls. A mild to moderate interstitial fibrosis, which was progressive with time, was noted in each of the coal slag groups. However, the coal slag-induced lung fibrosis was much less than that produced by Minusil. Differences in fibrosis among the individual coal slags were relatively minor and certainly not as striking as those between the slags and Minusil. Other data derived from this study, such as lung hydroxyproline content, pulmonary particulate burdens, pulmonary function, and animal body weights, provided further evidence of a reduced toxicity for the coal slags compared to Minusil.

Analysis of Variance↗

Validations of time-resolved fluoroimmunoassays for urinary estrone 3-glucuronide and pregnanediol 3-glucuronide.

Competitive time-resolved fluoroimmunoassays (FIAs) were developed for measuring 1,3,5(10)-estratrien-3-ol-17-one glucosiduronate (estrone 3-glucuronide, E(1)3G) and 5 beta-Pregnane-3 alpha,20 alpha-diol 3-glucosiduronate (pregnanediol 3-glucuronide, Pd3G) in unextracted urine. The assays are specific, detect 0.98 ng E(1)3G/mL and 0.035 microgram Pd3G/mL, measure 102.8 +/- 2.0% of E(1)3G and 93.6 +/- 2.9% of Pd3G added, and exhibit between and within assay coefficients of variation, respectively, of 5.3% and 7.1% for E(1)3G and 6.8% and 7.8% for Pd3G. The urine matrix does not interfere with the assay. Urinary steroid glucuronide profiles measured by these FIAs conform to those of urinary steroid glucuronides and serum estradiol and progesterone measured by other established immunoassays. These FIAs afford the advantages of non-radioisotopic procedures and urine sample collection (convenience, non-invasiveness, integration of pulsatile secretion) to evaluate menstrual function in epidemiological, medical, and athletic populations.

Antibodies, Monoclonal↗