Screening for glaucomatous visual field loss with frequency-doubling perimetry.

PURPOSE: To conduct a preliminary evaluation of the efficacy of the frequency-doubling contrast test as a means of screening for glaucomatous visual field loss. METHODS: Contrast thresholds for frequency-doubled stimuli were obtained under four test conditions: superior hemifield, inferior hemifield, and central (5 degrees radius) targets using a method of adjustment (MOA); superior hemifield, inferior hemifield, and central targets using a modified binary search (MOBS); four quadrant stimuli and the central target using MOBS; and 16 stimuli (four per quadrant) and the central target using MOBS. One eye each of 36 patients with early (12), moderate (12), and advanced (12) glaucomatous visual field loss was tested, as was one eye each of 36 age-matched normal control subjects. RESULTS: For hemifield stimuli, the MOBS test procedure had better test-retest reliability, lower individual variation, and greater separation of the normal population and the population with glaucoma than did the MOA procedure. The use of progressively smaller, more localized stimuli produced successively better separation of glaucomatous and age-matched normal control eyes. Area under the Receiver Operating Characteristic curve was 0.81 for hemifield stimuli (sensitivity and specificity, 70% to 75%), 0.91 for quadrant stimuli (sensitivity and specificity, 83% to 85%), and 0.965 for the 16 stimuli (sensitivity 93%, specificity 100%). Test time was approximately 1.3 minutes for hemifields, 1.5 minutes for quadrants, and 5 minutes for the 16 targets. CONCLUSIONS: Preliminary results indicate that the frequency-doubled contrast test provides a quick, efficient means of screening for glaucomatous visual field loss. Test time is relatively short, test-retest reliability is good, and sensitivity and specificity for detection of glaucomatous visual field loss is very good. The use of the MOBS staircase procedure and small, localized stimuli result in the best performance for screening purposes. An expanded normative database and the use of more rapid suprathreshold screening strategies should enhance further the efficacy of this test.

Smoking, respiratory symptoms, and pulmonary function among a population of Hispanic farmworkers.

We conducted a cross-sectional study in the agricultural Central Valley to evaluate the prevalence of respiratory symptoms, smoking status, and pulmonary function in Hispanic California farmworkers. Of 759 farmworkers completing questionnaires and spirometry, 747 were Hispanic. The prevalences of current, former, and never smokers (29, 17, and 54 percent, respectively) were comparable to rates in other studies of Hispanics, but daily cigarette consumption (median-five for men and three for women) was lower than in comparison populations. Prevalences of chronic cough, chronic phlegm, and persistent wheeze were low (1.6, 5.1, and 2.8 percent, respectively). Current smoking, increased age, female sex, and working greater than or equal to 8 months per year in agriculture were associated with increased prevalence of respiratory symptoms. Adjusted lung function was higher than for reference populations. Hispanic California farmworkers have a similar smoking prevalence to other Hispanic populations, but lower respiratory symptom prevalences and higher pulmonary function are consistent with lower daily cigarette consumption and the "healthy worker effect."

An assay using embryo aggregation chimeras for the detection of nonlethal changes in X-irradiated mouse preimplantation embryos.

We have developed a short-term in vitro assay for the detection of sublethal effects produced by very low levels of ionizing radiation. The assay utilizes mouse embryo aggregation chimeras consisting of one irradiated embryo paired with an unirradiated embryo whose blastomeres have been labeled with fluorescein isothiocyanate (FITC). X irradiation (from 0.05 to 2 Gy) and chimera construction were performed with four-cell stage embryos, and the chimeras were cultured for 40 h to the morula stage. The morulae were partially dissociated with calcium-free culture medium and viewed under phase contrast and epifluorescence microscopy to obtain total embryo cell number and the cellular contribution of irradiated (unlabeled) and control (FITC labeled) embryos per chimera. In chimeras where neither embryo was irradiated, the ratio of the unlabeled blastomeres to the total number of blastomeres per chimera embryo was 0.50 (17.8 +/- 5.6 cells per unlabeled embryo and 17.4 +/- 5.5 cells per FITC-labeled partner embryo). However, in chimeras formed after the unlabeled embryos were irradiated with as little as 0.05 Gy, the ratio of unlabeled blastomeres to the total number of blastomeres per chimera embryo was 0.43 (P less than 0.01). The apparent decreases in cell proliferation were not observed in irradiated embryos that were merely cocultured with control embryos, regardless of whether the embryos were zona enclosed or zona free. We conclude that very low levels of radiation induce sublethal changes in cleaving embryos that are expressed as a proliferative disadvantage within two cell cycles when irradiated embryos are in direct cell-to-cell contact with unirradiated embryos.

Bone sarcoma characteristics and distribution in beagles injected with radium-226.

A total of 155 primary bone sarcomas were found in 131 of the 246 beagles injected with 226Ra and 5 primary bone sarcomas were found in 4 of the 158 unexposed controls. Of these 155 bone sarcomas, 146 (94%) were osteosarcomas and 9 were non-osteosarcomas. An additional 31 primary bone sarcomas (28 osteosarcomas) developed in 44 dogs terminated from the main study because of limb amputation for bone sarcoma. Non-osteosarcomas predominated in both the controls and the second lowest of six logarithmically increasing dose levels (there were no bone sarcomas in the lowest dose group). Osteosarcomas predominated at the higher dose levels, and incidence tended to increase as dose increased. The 146 osteosarcomas were distributed quite evenly between males and females (72:74). Of the 9 non-osteosarcomas, 6 occurred in males and 3 in females. The ratio of bone sarcomas of the appendicular skeleton to those in the axial skeleton was 110:45, with osteosarcomas occurring more often in the appendicular skeleton (108:38). Cases of multiple primary bone sarcomas in dogs injected with 226Ra were found only in the four highest dose groups. Amputations were performed on 44 of the 96 dogs (94 injected and 2 unexposed) that developed appendicular bone sarcomas. A statistical study of the distribution of bone sarcomas among 16 separate bone groups showed a statistically significant correlation to cancellous skeletal surface, but the variability among bone groups was too large for this relationship to be of real predictive value. It is postulated that the distribution of bone sarcomas reflects primarily the relative cell division rates in the bone groups and secondarily the radiation dose distribution, with the highest occurrence of bone sarcoma in the humeri, pelvis, femora and tibiae/fibular tarsal, and no occurrence in the coccygeal vertebrae, sternum, forepaws or hindpaws.

Bone sarcoma characteristics and distribution in beagles fed strontium-90.

A total of 66 primary bone sarcomas were diagnosed in 47 beagles; 43 of these dogs were part of the 403 beagles fed 90Sr and 4 were part of the 162 controls. Multiple primary bone sarcomas were found in 15 of the 47 beagles (32%). The incidence of multiple primary bone sarcoma was restricted to the two highest dose groups, except for a single control dog which developed two bone sarcomas. A threshold-like radiation dose response was observed; no sarcomas were observed in the lowest three dose groups, but the number of primary bone sarcomas increased rapidly in the higher dose groups. Of the 66 primary sarcomas, 49 were osteosarcomas (74%). As the dose increased, the proportion of osteosarcomas increased sharply, 4/10 (40%), 26/29 (90%), and 16/18 (89%), in the three highest dose groups. Thirteen of the bone sarcomas of other types occurred in males, and 4 in females, whereas 21 osteosarcomas occurred in males, and 28 in females. The ratio of bone sarcomas of the appendicular skeleton to those in the axial skeleton was 40:26, with osteosarcomas occurring more often in the appendicular than the axial skeleton (32:17), whereas nonosteogenic tumors showed no predilection (8:9). A statistical study of the distribution of bone sarcomas among 16 separate bone groups showed a correlation only with the distribution of cancellous bone volume-to-surface ratio and not with either skeletal mass distribution or dose distribution. The highest occurrence of sarcomas was in the humeri, femora, and mandible, and no occurrence in the coccygeal vertebrae, paws, or sternum. It is postulated that the distribution of bone sarcomas reflects a critical combination of the osteosarcoma precursor cell population, their cell division rate, and the radiation dose absorbed by these cells.

Ethnic differences in adolescent substance initiation sequences.

OBJECTIVES: To evaluate ethnic differences in the initiation sequences of tobacco, alcohol, marijuana, and cocaine use among US high school students and to determine if ethnicity is a predictor of progression from licit to illicit substances or initiation of illicit substances before licit substances. DESIGN: Cross-sectional analyses of the Centers for Disease Control and Prevention's 1995 Youth Risk Behavior Survey. SETTING: US high schools. PARTICIPANTS: A total of 8550 high school students randomly selected by cluster design. MAIN OUTCOME MEASURES: Respondents were categorized based on self-reported sequence of initiating substances as follows: none, licit substances only, licit substances then illicit substances (typical), illicit substances first (reverse), and licit and illicit substances at the same time (concurrent). RESULTS: Adjusting for age, maternal education, and region, progression from licit to illicit substances was significantly associated with black ethnicity (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.04-2.1) and male sex (OR, 1.4; 95% CI, 1.2-1.6). Black male and Latino female students whose mothers completed at least high school were more likely than white students with similarly educated mothers to initiate illicit substances before licit substances (OR, 3.0; 95% CI, 1.7-5.3; and OR, 5.9; 95% CI, 1.7-20; respectively). Similar trends were noted for the concurrent sequence. CONCLUSIONS: The pattern of initiating tobacco, alcohol, marijuana, and cocaine use differs by ethnicity. Maternal education may be a proxy variable for other significant risk factors.

Mechanisms of filtration of morphologically abnormal human sperm by cervical mucus.

It is well known that cervical mucus restricts penetration of morphologically abnormal human sperm, both in vitro and in vivo. However, the mechanisms of such restriction are not well understood. Using videomicrography to simultaneously analyze the motions and morphology of individual human sperm, we analyzed differential penetration of normal and abnormal sperm into fresh human cervical mucus. Abnormal sperm swam slower in mucus than the normal sperm, but their flagellar beat parameters were not commensurately different. Multivariate statistical analysis of the relationship between individual sperm velocity and flagellar beat parameters indicated that the heads of the abnormal sperm experienced greater resistance from the mucus than did normal heads. Differential mucus resistance, more than altered motile vigor, appears to be responsible for the restriction of abnormal sperm during migration through mucus.

Semen quality in varicocele patients is characterized by tapered sperm cells.

We used a retrospective case-control study design to compare sperm morphology in 50 varicocele patients and 50 patients with idiopathic infertility. Cases and controls were matched for the percentage of motile sperm and total sperm number per ejaculate. Varicocele patients had significantly more tapered sperm (36% +/- 3% versus 15% +/- 2%) and significantly fewer oval sperm (41% +/- 3% versus 47% +/- 2%). There was no significant difference between cases and controls in any other morphological type.

A comparison of the usefulness of SpermMar and immunobead tests for the detection of antisperm antibodies.

We compared two testing protocols designed to detect immunoglobulin (Ig) G antibodies on sperm surfaces: (1) SpermMar (Ortho, Raritan, NJ) and (2) Immunobead Testing (Biorad, Richmond, CA). The standard SpermMar (SPMAR) protocol (direct test of unwashed semen) was performed with 47 ejaculates and found to be more sensitive than Immunobead Testing (IBT) on washed sperm, detecting five samples with greater than or equal to 30% bead binding, all of which by IBT had less than 20% bead binding. In contrast, when SPMAR was performed on washed sperm or with an indirect antibody transfer from serum or seminal plasma, SPMAR results gave mostly low values for bead binding in comparison with IBT. Our data suggest that SPMAR be used only in direct assays employing unwashed ejaculates, that it can be easily incorporated into routine semen analysis as a screening test, and that positive results should be confirmed by IBT (IgG and IgA).

Prospective assessment of early fetal loss using an immunoenzymometric screening assay for detection of urinary human chorionic gonadotropin.

OBJECTIVE: To develop an economical, nonradiometric immunoenzymometric assay (IEMA) for the detection of urinary human chorionic gonadotropin (hCG) in studies of early fetal loss. To be effective, the IEMA must have a sensitivity equal to the standard immunoradiometric assay (IRMA) and sufficient specificity to eliminate the need for screening most nonconceptive cycles with the expensive and labor-intensive IRMA. DESIGN: Two different assays were used to measure hCG in daily early morning urine samples from potential conceptive cycles. SETTING: Women undergoing donor artificial insemination (AI) were evaluated in a prospective study. PATIENTS, PARTICIPANTS: Ninety-two women volunteers were selected on the basis of apparent normal reproductive health. INTERVENTIONS: Artificial insemination with nonfrozen donor semen was performed by cervical cup twice each menstrual cycle at 48-hour intervals, and daily urine samples were self-collected throughout the menstrual cycle. MAIN OUTCOME MEASURES: An IEMA was developed to detect urinary hCG using the same antibodies as in the standard IRMA; a study was designed to determine whether this nonradiometric assay could successfully detect the early fetal loss that was detected by the IRMA. RESULTS: Of 224 menstrual cycles analyzed by both assays, a total of six early fetal losses were detected by the IRMA. When the tentative screening rule was set to allow all six of these losses and 95% of future losses to be detected by the IEMA, an additional 34 false-positive results were detected by the IEMA. The specificity of the IEMA with this rule was calculated to be 84%. CONCLUSION: An IEMA based on the same antibodies used for the standard IRMA can serve as an efficient screening assay for the detection of early fetal loss. When the IEMA is used in this manner, nearly 80% of screened menstrual cycles can be eliminated without further testing by the IRMA.

The relationship between the motility and morphology of spermatozoa in human semen.

High-speed videomicrography was used to assess simultaneously the morphology and motility of seminal spermatozoa from 10 fertile donors and 10 patients being evaluated for infertility. In both donors and patients, morphologically normal spermatozoa were more likely to be motile and had significantly higher straight line velocity, greater rolling frequency and flagellar beat frequency than abnormally shaped cells. For donors and patients there were highly significant, linear correlations (R = 0.7 to R = 0.98) between the movement characteristics of morphologically normal and abnormal spermatozoa within an ejaculate. A greater percentage of normal donor spermatozoa were motile than were the normal spermatozoa from patients (56% vs. 28%, respectively, P less than 0.005) and normal donor spermatozoa also swam faster than normal patient spermatozoa (49.1 +/- 3.2 microns/sec vs. 37.4 +/- 4.3 microns/sec, mean +/- sem, respectively, P less than 0.05). Overall, a multivariate analysis of variance, including straight line velocity, rolling frequency, beat frequency, and flagellar beat amplitude, demonstrated that these movement characteristics were significantly greater for the normal cells from donors than for the normal spermatozoa from patients. These biologic distinctions notwithstanding, the discrimination between semen from donors and patients was not improved when only morphologically normal cells were analyzed for motility.

Morphometric analysis of spermatozoa in the assessment of human male fertility.

A videomicrographic system was developed for measurement of morphometric parameters of human spermatozoa. Contours of the images of spermatozoa on a video monitor are digitized by manually tracing them with the cursor of an electromagnetic digitizer integrated to a microcomputer. The accuracy and precision of the methodology were evaluated. A comparison of human sperm heads in shallow wet preparations and in dried, stained preparations indicated that the latter were smaller in length, width, projected area, and circumference, but that the ratio length/width was not different. An analysis was made of 457 ejaculates from 16 fertile donors. The variation between ejaculates within donors was similar in magnitude to the variation between donors. A study was performed comparing seminal sperm morphometry in single specimens from 30 fertile and 30 infertile men. The sperm head length/width ratio was the parameter that differed the most between these two groups. Moreover, it was the per-ejaculate variability of this parameter, rather than the central tendency, that maximized the difference.

Lessons from a surveillance program of semen quality.

The discovery in 1977 that dibromochloropropane (DBCP) could induce male sterility led to an interest in the surveillance of semen quality in men working in a pesticide manufacturing plant. The program consisted of an initial questionnaire, physical examination, and serial semen analyses. The success of the surveillance was limited by economic considerations and protocol compliance problems. Based on the experience with this program, recommendations for future surveillance efforts are presented.

Reproductive effects of chlorpromazine exposure to female mice: cell proliferation disadvantage revealed by the Chimera Embryo Assay.

Administration of chlorpromazine-HCl at 5 to 15 mg/kg bodyweight to pregnant CD-1 mice at 24 h after human chorionic gonadotropin (hCG) (20-23 h after mating) inhibited blastocyst formation and reduced the cell number of embryos recovered at 95 h after hCG. When embryos are recovered at the two- to four-cell stage (48-50 h after hCG) and cultured for an additional 47 h (to 95 h after hCG) or 72 h (to 120 h after hCG), blastocyst formation and embryo cell number were similarly reduced. When the dose range was reduced to 0.5 to 2 mg/kg bodyweight, no significant effect of the drug was observed on blastocyst formation or on embryo cell number. However, when aggregation chimeras were formed between embryos recovered from drug-exposed females and from untreated females, a decrease in cell proliferation rate of the embryo from the drug-exposed female was observed at a dose of 2 mg/kg bodyweight. This result indicates that exposing pregnant mice to chlorpromazine-HCl at doses as low as 2 mg/kg bodyweight can induce a potential for decreased cleavage rate in their pre-implantation embryos that can be revealed by challenging those embryos by direct contact with embryos from nonexposed females. Finally, when four-cell stage embryos recovered from untreated females cultured in the presence of chlorpromazine (0.1-25 mM), blastocyst formation and embryo cell number were significantly reduced in a dose-dependent manner. This last result suggests that in vivo the drug may act directly on the embryo from the pronuclear stage to the early morula stage of development.

Reproductive health outcomes among female flight attendants: an exploratory study.

Recent studies have suggested that female flight attendants may experience increased rates of spontaneous abortion. We conducted a survey of female flight attendants who were pregnant at any time between January 1, 1990, and December 31, 1991 (n = 418) using a mailed self-administered interest survey (response rate, 60 %) and follow-up questionnaire regarding reproductive outcomes and potential risk factors for adverse outcomes (response rate, 64%). The cumulative hazard of spontaneous abortion was 17% when maternal age, smoking, alcohol use, and prior spontaneous abortions were control led for, using a Cox life-table regression model. Of the female flight attendants who worked outside the home, 47 of 321 (15%) experienced a spontaneous abortion, compared with 6 of 73 (8%) who did not work outside the home during the pregnancy period (odds ratio [OR] = 1.91, 95 % confidence interval [CI] = 0.78-4.66). Flight attendants who experienced a spontaneous abortion during their first pregnancy during the study period reported working significantly more flight hours per month during their pregnancy (74 hours per month) than did flight attendants who delivered a live birth (64 hours per month) (Student's t = -3.30, P = 0.002). We conclude that although the results of this study must be considered preliminary because of the relatively low overall response rate (38%), we did not find an overall increased risk for spontaneous abortion among flight attendants, compared with other working women (10%-20%). Women who continue working as flight attendants during pregnancy and those who work relatively higher numbers of flight hours during pregnancy may, however, be at increased risk for spontaneous abortion, compared with flight attendants who do not perform such work.

Repeatability of the glaucoma-scope measurements of optic nerve head topography.

The Glaucoma-Scope is designed to measure the topography of the optic nerve head. Depth measurements are reported as a grid of cells where each value represents the average depth of an area 55 +/- 100 mum in size. The Glaucoma-Scope was tested on 10 normal and 18 glaucomatous subjects, >40 years of age. Two separate visits were simulated for each patient. To estimate measurement variability, depth values were analyzed in groups of 25 cells, comprising "areas of interest." A components of variance analysis was used to compare the variability of the difference between the depth of an area measured at the first and second visits. The analysis yields within visit standard deviation of the difference between depth measurements taken within the same visit (Sw), the standard deviation of the difference between depth measurements taken at separate visits (Sb), and the total standard deviation of the difference between depth measurements (Sd). For flat areas outside the optic nerve head, Sd = 11.68 mum. For flat areas within the optic nerve head, Sd = 17.91 mum. For areas at the bottom of the cup, which includes sloped areas, Sd = 32.01 mum. For sloped areas within the optic nerve head, Sd = 20.78 mum. For areas over a vessel, Sd = 34.76 mum. The mean standard deviation of a single pixel in the Glaucoma-Scope measurement is 15.42 mum. The Glaucoma-Scope measurements are highly reproducible for both healthy and glaucomatous subjects. Local variability in depth measurements should be considered when evaluating change in optic nerve head topography.

Markers of exposure to diesel exhaust in railroad workers.

Diesel exhaust is a known mutagen and a potential human carcinogen. Recent epidemiological studies have demonstrated a small increase in the risk of lung cancer from diesel exhaust exposure. However, many epidemiological studies have used crude estimates of exposure, and even accurate measures of exposure may not be accurate estimates of the internal dose received. Measurement of diesel exhaust exposure also has been limited by the absence of a standard marker. This study was undertaken to evaluate the usefulness of urinary mutagenicity as a biological marker of diesel exhaust exposure in the workplace. We measured the exposure of individual railroad workers to diesel exhaust by using personal air samples taken over two consecutive work shifts. Nicotine in the samples was measured to adjust the respirable particle concentrations for active and passive cigarette smoking. Urine samples were collected at the end of the study work shifts and were analyzed for markers of cigarette smoking (nicotine, cotinine) and for mutagenicity, using a sensitive microsuspension assay (micro preincubation assay; Salmonella strain TA98 with or without S9 enzyme). The number of cigarettes smoked on the study shift was recorded, and subjects completed a questionnaire at the end of the second day on personal habits and exposures at home and work. Multiple regression analyses were used to analyze independent determinants of urinary mutagenicity, including a generalized least-squares analysis that divided residual variation into between- and within-person components. Eighty-seven subjects completed 151 two-day protocols; an additional four subjects provided usable data for a single day (n = 306 samples). Respirable particle concentration was not a good marker of diesel exhaust exposure when contamination by environmental tobacco smoke existed in the work location, but respirable particle concentration that was adjusted for environmental tobacco smoke correlated with a priori assessments of diesel exhaust exposure by job grouping. Phenanthrene concentration, as a potential marker, was measured in a subset of personal samples, and correlated with known diesel exhaust exposure by job grouping. A constant ratio of phenanthrene to respirable particles in area samples from diesel exhaust-exposed work locations suggested that phenanthrene is promising as a marker for diesel exhaust. Mutagenic activity was also measured from extracts of respirable particles in a few personal filter samples, and this technique may be useful for further investigation in epidemiological studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Creatine kinase and its MB isoenzyme in the third trimester and the peripartum period.

Forty-nine normal pregnant women were recruited late in the third trimester for serial determinations of creatine kinase (CK) and its MB isoenzyme fraction (CK-MB) at four different times: (1) on recruitment between 36 and 40 weeks' gestation, (2) on admission in active labor, (3) immediately after delivery, and (4) on the first postpartum day. In the patients with vaginal delivery (n = 43) total CK was significantly elevated at time 4 compared with times 1, 2 and 3 (P value < .0001). CK-MB fraction was also significantly elevated at time 4 compared with times 1, 2 and 3 (P value < .0001). In 35.7% of the patients at time 4, CK-MB was sufficiently elevated to give the laboratory interpretation of "borderline" or "consistent with a myocardial infarction," even though none of the patients had cardiac symptoms or complications. A review of the literature shows that CK-MB is found not only in myocardium but also in uterus and placenta. The implication of this study is that elevations in total CK and CK-MB should be used with caution during the peripartum period to diagnose myocardial ischemia or infarction.

Sustained and selective attention in children with learning disabilities.

Sustained and selective attention of 30 fourth-, fifth-, and sixth-grade students with learning disabilities (LD) and 20 controls were compared. A continuous performance test (CPT) yielded no differences for students with LD and controls, suggesting similar ability for both groups in sustaining attention and inhibiting impulsive responding. Subjects with LD made more errors than controls on a selective attention task when letter distractors were adjacent to the target letter but not when they were distant, and more correct responses than controls when facilitating letters were adjacent to the target, suggesting that students with LD are less able to narrow the focus of their attention. Longer response times by students with LD indicate that they have slower information-processing skills than controls. Regrouping students according to teacher ratings for attention deficit-hyperactivity disorder (ADHD) yielded the customary impulsive response set on the CPT and more errors on the selective attention task, but no differences on response times for students with ADHD. LD students with ADHD made more errors than LD students without ADHD when letter distractors were adjacent to the target letter.

Risk factors for occupational illnesses associated with the use of paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) in California.

This study was conducted to identify risk factors for paraquat-related occupational illnesses. Pesticide-related illness is a reportable disease in California. A total of 231 skin (26.0%), eye (32.0%), local respiratory (3.5%), and systemic (38.5%) paraquat-related cases were reported to the Worker Health and Safety Branch, California Department of Food and Agriculture, during 1971 through 1985. Following paraquat exposure, we found no cases of pulmonary fibrosis. Annual numbers of cases ranged between 1 and 33 (median = 14 cases/y). Information on illnesses reported during 1981 through 1985 (n = 62) was merged with detailed information on paraquat use in agricultural settings (111,716 applications) for the same years. We found that crop treated, method of application, and season of application all contributed independently to the risk of reported illness. Hand application was associated with a higher risk of illness, compared with air application (RR = 99.1, 95% CI = 22.16-443.47); summer application was associated with a higher risk of illness than was winter application (RR = 4.1, 95% CI = 1.91-8.61); and fruit trees were associated with higher risk of illness than were other crops (mainly cotton) (RR = 3.6, 95% CI = 1.18-11.21).