Effects of hydrogen sulfide on neurobehavioral function. (Original Article).

Background: Nineteen hydrogen sulfide ([H.sub.2]S)-exposed patients were compared with 202 unexposed subjects. This 1997-to-2001 case-referent series was compared with 16 previous (1991-1996) case-referent patients.

Methods: New patients were bystanders of [H.sub.2]S exposure and none had been unconscious. In contrast, 13 members of the prior group were exposed at work and 7 had been unconscious. The three groups were compared on the basis of 8 physiologic and 12 psychological measurements. Observed measurements were compared with predicted ones after adjusting for age, sex, educational attainment (years), and other significant factors (observed/predicted X 100).

Results: The new group performed poorly compared with unexposed controls and were similar to the first group on balance, reaction time, color discrimination, visual performance, hearing, Culture Fair, digit symbol, vocabulary, verbal recall, peg placement, trail making A and B, and information.

Conclusion: [H.sub.2]S impairments associated with [H.sub.2]S were similar in 19 workers (44% had been unconscious) and in 16 bystanders who had not been unconscious.

Key Words: balance impairment, brain dysfunction, bystander, color discrimination errors, reaction time slowing

**********

Christison (1) described deaths attributable to hydrogen sulfide ([H.sub.2]S) inhalation in 1845. He stated that survivors recovered completely and this was believed for 150 years. But neuropsychological testing, a decade ago, showed persistent impairment in six "recovered" patients who had been unconscious after exposure to [H.sub.2]S (with one man being demented and bedfast) (2) and in other groups. (3,4) Unanswered questions include: 1) Do exposures without knockdown to unconsciousness have adverse neurobehavioral effects? 2) Does impairment follow protracted exposure to [H.sub.2]S levels between those detected by the human nose (approximately 30 parts per billion [ppb]) and 5 parts per million (ppm)? 3) Does exposure to a few breaths of 5 to 250 ppm of [H.sub.2]S cause impairment? Although the effects of brief human exposures to 2 to 10 ppm of [H.sub.2]S on pulmonary and cardiovascular function seem minimal, (5,6) they provided no data on neurobehavioral function.

Rats repeatedly exposed to [H.sub.2]S at 125 ppm showed impaired learning and performance speed in a maze task. (7) However, a precise ratio with which to predict human effects on the basis of the ratio of rat-to-human effects is lacking. In a rat model for [H.sub.2]S effects, artificial ventilation decreased the brain damage in rats that were administered sodium sulfide intraperitoneally while anesthetized with halothane. (8) Because [H.sub.2]S concentrations less than 25 ppm generally only stimulate or do not affect human ventilation, (5) however, damage as a result of hypoxia from apnea is not relevant. Impaired brain function in rats exposed to [H.sub.2]S (7,8) and in human testing (2-4,9) recommended systematic testing of additional subjects exposed to [H.sub.2]S in incidents, "experiments of nature." The likelihood of neurobehavioral ill effects from [H.sub.2]S, reviewed above, made the deliberate exposure of humans to this entity unthinkable and unethical.

Concentrations of [H.sub.2]S during human exposures vary momentarily without opportunities for measurements or even "grab" air sampling in unscheduled incidents; such ambient measurements usually lag actual conditions. Although blood sulfide is a biologic marker, it must be measured quickly after adding zinc acetate to the serum to trap [H.sub.2]S as zinc sulfide. (10) Animal studies for effects of sulfides administer sodium hyposulfide solutions rather than inhaling [H.sub.2]S. The [H.sub.2]S effect-to-dose ranges for human subjects are death at over 500 ppm, eye and respiratory irritation at 100 to 500 ppm, and variable discomfort of eyes and breathing between 5 and 50 ppm. Human subjects develop olfactory "fatigue" so they have no perception of exposure after seconds or minutes. (9)

Nineteen new patients were enlisted in the 4 years after the report of 16 patients in 1997. (9) Both exposed groups were compared with unexposed controls from whom prediction equations were developed (12) and consistency and pattern of response were examined.

Methods

Nineteen patients exposed to 1125 (10 at work and 9 at home) from nine states and Alberta were studied (Table 1). The 9 women and 10 men had a mean age of 45.1 years and a mean educational level of 12.7 years. Their exposures to [H.sub.2]S varied.

[H.sub.2]S Exposure

Four work exposures were in oil and natural gas sites; five were environmental (three from a natural gas storage site); two were from hog manure lagoons; two were from buildings' sewers; one in a paper mill; two from chemical explosions; two from working with granite and foam glass insulation; and one who lived across the road from a waste dump for gypsum board. Because these were transient, mainly outdoor exposures in unstable circumstances, there were no opportunities to measure concentrations. Durations of exposure varied from 20 minutes to 9 years with five durations less than 24 hours. Subjects were studied 1.7 to 22 years after their acute symptoms.

Community reference subjects were picked at random from voter registration rolls of Wickenburg, AZ, and were interviewed to exclude occupational exposure to neurotoxic chemicals and medical and neurologic diseases. All subjects gave informed consent and the protocol was approved by the Human Studies Research Committee of the Keck School of Medicine at the University of Southern Califomia. Referent subjects were reimbursed for their time.

Completed questionnaires were checked by computerguided reading so that subjects rectified omissions. Questionnaires included the frequencies of 35 conimon health complaints (13) rated from never to daily on an 11-point scale; the American Rheumatism Association 11 lupus erythematosus questions; (14) a standard respiratory questionnaire; (15) histories of occupational and other exposures to chemicals, pesticides, and herbicides; tobacco, alcohol, and drug use (prescription and illicit); history of unconsciousness; anesthesia; and head trauma and neurologic and medical historics. (13) The questionnaires and the neurophysiological and neuropsychological test battery had evolved through previous studies for formaldehyde effects (16) firemen exposed to thermolysis products of PCBs (17) and people exposed to toluene-rich chemical (13)--and included several groups of unexposed subjects. (12,13) Alcohol was measured in air expired after a 20-second breath-hold using a fuel cell analyzer.

Neurophysiological Tests

Simple reaction time (SRT) and visual two-choice reaction time (CRT) were measured from the appearance on the computer screen of a 10-cm block A to its cancellation by tapping a keypad A for simple and A or S for choice with a computerized instrument. (18) The lowest median score of the last seven in each of two trials of 20 was accepted for SRT and for CRT. Body balance was measured with the subject standing erect with feet together. The position of the head was tracked by two microphones from a sound-generating stylus on a headband, processed in a computer, and expressed as mean speed of sway in cm/s. (19) The minimal sway speed of three consecutive 20-second trials was the value used for sway with the eyes open and sway with the eyes closed.

The blink reflex was measured with surface electromyographic electrodes (EMG) from the lateral orbicularis oculi muscles bilaterally (20,21) after tapping the right and left supraorbital notches with a light hammer, which triggered a recording computer. Ten firings of R-1 were averaged to find the mean response for each side, and failures to respond were recorded. (21) Color confusion index was measured with the desaturated Lanthony 15 hue test under constant illumination and scored the method of Bowman. (23) Hearing (22) by was measured in the left and right ears with standard audiometers (Model ML-AM; Microaudiometrics, South Daytona, FL) at stepped frequencies of 500-8,000 Hz. The sum of deficits for each ear was the hearing score.

Threshold testing of visual fields used a computerized (Med Lab Technologies, North Wales, PA) automated perimeter that mapped the central 30 degrees of the right and left eyes individually. The performance value of each eye was the sum (in decibels) of the threshold values of 80 points within the central 30 degrees.

Neuropsychological Tests

Immediate memory or recall was measured with two stories from Wechsler's Memory Scale-Revised. (24) Culture Fair tested nonverbal nonarithmetic intelligence based on the selection of designs for similarity, difference, completion, and pattern recognition and transfer. (25,26) Culture Fair resembles Raven's progressive matrices. (27) The 46-word vocabulary test was from the multidimensional aptitude battery. (28) Digit symbol substitution from the Wechsler Adult Intelligence Scale-revised (WAIS-R) (29) tested attention and integrative capacity. Information, picture completion, and similarities, also from the WAIS-R, tested long-term (embedded) memory. Time needed to place 25 pegs in the Lafayette slotted pegboard was measured as were times to complete trail making A and B. These tests from the Halstead-Reitan battery (30,31) measured dexterity, coordination, and decision making. Peripheral sensation perception was measured with fingertip number writing errors. Subjects' moods were appraised by responses to 65 terms describing emotional status for the week using the profile of mood states (POMS). (32) Recall of the Rey 15 forms tested whether recall was appropriate or suggested malingering. (33)

Respiratory flows and vital capacities were measured from a full inspiration while subjects stood and blew forcefully into a volume displacement spirometer (Ohio 822; Sensor Medicis, Anaheim, CA) while using a nose clip. This maneuver was repeated until two forced expirations agreed within 5%. (34) Records of volume and flows were traced with a digitizer and were measured by a computer. Prediction equations adjusted for height, age, sex, and smoking status. (35)

Statistical Analysis

Scores and computed data were entered into an IBM-compatible microcomputer. Descriptive and analytical computations adjusted for differences in age, education, sex, height, and weight using stepwise linear regression modeling that used Stata statistical software (Stata Corp., College Station, TX). These prediction equations were based on measurements of the functions of 202 subjects. Each was symmetrically distributed (12) or was transformed mathematically for symmetry. The observed measurements and scores for each patient were compared with individual predicted values and were expressed as percent predicted. Then, the exposed group's percent predicted values were compared with the control group's by analysis of variance (ANOVA). (Other factors such as family income, hours of general anesthesia, POMS score, and depression score were tested for influence in equations but were excluded because their coefficients were not significant.) Statistical significance was defined as P < 0.05. Abnormalities for each pati ent were counted (Table 1) after assigning most bilateral tests a value of 0.5 per side (for example, hearing). Visual performance was scored 1 per side and balance was assigned 2 for the eyes open test and 2 for the eyes closed test. Two exposure variables, duration and latency from exposure to testing and profile of mode states score and depression score, were tested for influence on total abnormalities and specific measurements, ie, balance with eyes closed using regression analysis.

Results

New Subjects

The 19 exposed subjects were statistically significantly different from the unexposed (control) subjects for simple and two-choice visual reaction times (Table 2). Referent subjects had values near 100% of predicted (96.4-103.1) for all tests (Tables 2 and 3). Balance was affected as sway speed was increased with eyes open and with eyes closed. Blink reflex was slowed. Color error scores, a cone function, were abnormally elevated, and visual performance by visual fields, a rod function, was decreased. Grip strength and hearing were abnormal on the right.

Cognitive performance was decreased for Culture Fair, digit symbol substitution, and vocabulary. Immediate verbal recall for two stories was reduced and became more abnormal after 30 minutes (delayed). Peg placement and trail making A and B were abnormally slow. In contrast, fingertip number writing errors were not increased. The fund of information and picture completion (recognizing missing items) scores of the long-term memory tests were diminished but similarities (classifying two items, ie, dog and lion are animals) were not. After adjusting P values for the simultaneous inference, (36) all differences between the groups remained significant (Table 2).

Comparison of Groups

Test abnormalities in the 19 new subjects matched the 16 reported in 1997 (9) with minor variation (Table 3). Only hearing and grip strength varied; and the statistical significance of two long-term memory tests, picture completion and similarities tests, reversed. Perhaps having been unconscious slowed simple reaction time and decreased hearing in the members of the 1997 group, but the small differences did not suggest that unconsciousness was important.

The mean profile of mood states score was elevated almost fourfold (Table 2). Tension, depression, anger, fatigue, and confusion were all elevated significantly; and vigor was below unexposed control values (not detailed). However, neither total POMS score nor depression score influenced total abnormalities or specific measurements. The mean frequency of 35 symptoms was 5.8, more than double the mean of 2.6 in unexposed (control) subjects (Table 2).

Respiratory symptoms were significantly more prevalent in exposed subjects, particularly shortness of breath and wheezing (Table 4). Their mean pulmonary function values were slightly higher than unexposed subjects and midflow ([FEV.sub.[25-75]) and the ratio of 1-second forced expiratory volume to vital capacity ([FEV.sub.1]/FVC) were significantly better.

Neither duration of exposure nor the time between exposure and testing latency had significant coefficients for total abnormalities or specific measurements by regression analysis.

Discussion

The replication of observations in a second case-referent series of patients exposed to [H.sub.2]S added evidence for neurobehavioral abnormalities after [H.sub.2]S exposure and confirmed our earlier series. (9) These included both physiologic and psychological impairment. Long periods between exposure and testing suggest that these effects are permanent. The absence of unconsciousness after [H.sub.2]S exposure in the new group compared with 44% who had been unconsciousness in the 1997 group suggests that this is not a determinant of protracted impairment from [H.sub.2]S and fails to support the argument that hypoxia (37) is necessary for neurobehavioral damage. The twofold elevated symptom frequencies and elevated scores for depression, tension, and confusion shown on POMS suggest that adverse effects on the limbic brain sites of emotion and memory coincided with physiologic impairment. In addition, the frequency of 35 symptoms was elevated in all eight categories: irritation, indigestion, balance, mood, sle ep, memory, limbic, and respiratory. appears to damage three domains: the physiologic, the psychological, and the moods or limbic. In control subjects unexposed to neurotoxic chemicals, the three domains were independent, but damage from caused them to increase together. (13)

Extensive brain damage is deduced from the impairment of vision (second cranial nerve and occipital cortex); blink (cranial nerves V and VII); hearing and balance (Cranial Nerve VIII, cerebellum, proprioceptive and motor effector tracks); reaction time (visual perception and eye-hand coordination, parietal lobe); and associative and memory areas of the temporal occipital and parietal frontal lobes. Decreased memory and upset moods indicate impaired temporal lobe and limbic system function.

The five patients with minutes to hours of exposure averaged II abnormalities compared with 8.6 in others. This suggested that patients who were briefly exposed received higher doses of [H.sub.2]S and, thus, had greater effects than those who were exposed for longer periods of time. Neither duration of exposure nor latency to measurement was a factor in total abnormalities or specific measurements that cannot be considered surrogates for exposure to [H.sub.2]S.

Limitations

These observations were made as retrospective analyses of symptomatic people (this led to an inability to control all confounders). Collected people, environmentally exposed to [H.sub.2]S, are less homogenous than occupationally exposed groups. Of the workers, only two were in oil refineries. A dose-response analysis was not possible because [H.sub.2]S concentrations were rarely measured. Workplaces should be monitored; however, only 6 of these 19 patients were exposed at work and only 3 were in petroleum recovery and refining where air analysis is done. Other reduced sulfur gases such as carbon oxide sulfide, mercaptans, and thiophene should be measured simultaneously because they contribute to toxicity. (9,10)

The possibility that test results were altered consciously by patients to increase evidence of adverse effect (because they were contemplating lawsuits) seems unlikely because of the consistency and appropriateness of test results, the absence of effect of mood state scores on specific measurements and on total abnormalities, and the similarity to the earlier series (Table 3). (9) The 14 physiologic measurements, simple reaction time through grip strength (Tables 2 and 3), resist conscious interference that produces easily recognized inconsistencies in multiple trials and between tests in the same domain. This second group of exposed subjects essentially duplicated the results of the earlier series. (9)

Mechanism

It is not clear how the inhibiting effects of [H.sub.2]S on mitochondrial oxidation equate with enhanced metabolism of 1125 at this locus (10,11,38,39) but failure of neuronal respiration could account for the apparently enhanced damage from doses of [H.sub.2]S above 50 ppm acting briefly (as after a few breaths in human subjects).

As sulfide binds iron in cytochrome enzymes in mitochondria, hair cells in the semicircular canals and cochlea cease functioning--decreasing the hearing and balance function and probably damaging the balance-correcting pathways from the cerebellum and through vision. (38,39) Impaired balance leads to falls and is a serious impairment. The metabolic demand of the retina is high, especially the cones of the macula and the rods furthest from the optic disk. (38) Cognitive functions, thus intelligence, are reduced and attributed to overall brain slowing as cells are killed or damaged by 1125.

If catecholamine and 5-hydroxytryptamine levels in the brainstem are enhanced in human subjects (as was shown after sulfide administration in rats), respiration would be stimulated. (11) A possible mechanism was proposed when sulfide reversibly abolished [Na.sub.+] currents in a model system of neuroblastoma cells. (40) Such effects were previously found by others in synaptosomes. (41) Learning and memory in the rat, as measured in maze running, were adversely affected by repeated exposures to [H.sub.2]S at doses of 125 ppm for five 8-hour days. This impairment lasted for weeks after cessation of [H.sub.2]S exposure, (7) matching the permanence we observed in human subjects.

Irritation of the airways has been attributed (4-6) to the hydration of [H.sub.2]S, forming hydrosulfurous acid. The absence of airway obstruction suggests that airways are more resilient than the brain to [H.sub.2]S effects. Effects of [H.sub.2]S may extend to the heart as coronary disease mortality was more elevated in Finnish pulp mill workers exposed to [H.sub.2]S (standard mortality ratio [SMR] 1.50) than in those exposed to sulfur dioxide (S02) (SMR 1.23) after adjusting for smoking and common risk factors. (42)

Brain excitation followed by torpor and collapse was found in workers exposed to carbon disulfide (CS2) and resembled the effects from [H.sub.2]S. (43,44) Also, epileptiform seizures and psychosis have been described resulting from [H.sub.2]S (37) and CS2 exposure. (45) Because the effects of [H.sub.2]S and CS2 exposure are similar, central nervous system effects should be monitored in subjects after [H.sub.2]S exposures. (7,44,45)

The physiologic effects of [H.sub.2]S found in human subjects suggest additional animal experiments on mechanisms. Further human experimental studies (5,6) appear unethical in light of these findings. Meanwhile, physicians should advise their patients that the rotten egg odor promises harm and that avoidance of 1125 exposure is essential to preserve their brain function. Where human exposure from leaks, fires, and explosions are likely, monitoring [H.sub.2]S and reduced sulfur gases should be combined with an assessment of workers' neurobehavioral functions. Measurements of [H.sub.2]S concentrations in manure lagoons, landfills, sewers, and other nonpetroleum human exposures would help develop dose-response relationships.

Table 1

Demographic data, exposure: Duration, latency, symptoms, and
neurobehavioral abnormalities



Patient             Education
no.      Age   Sex    level    Occupation      State  Exposure

1        43    M       12      Driller         NM     Oil field



2        40    M       12      Granite sludge  VT     Cleaning tool
                                                      cutting granite
                                                      at work

3        38    M       12      Farmer/miner    UT     Hog lagoons


4        46    M       12      Crane operator  FL     Papermill



5        31    M       12      Pipe insulator  CA     Foam glass on
                                                       stream lines
                                                       (170 ppm
                                                       [H.sub.2]S)

6        34    F       14      Police          LA     Chemical
                                                       explosion


7        43    M       10      Oil driller     OK     Casing on oil
                                                       well

8        36    F       12      Unemployed      CA     Refinery
                                                       explosion

9        69    F       12      Housewife       NM     Natural gas
                                                       storage


10       32    F       12      Disabled/       NM     Natural gas
                                 unemployed            storage

11       37    F       10      Farming,        UT     Hog lagoons
                                gems

12       51    F       18      Teacher         CA     Refinery


13       49    F       12      Housewife       AL     Oil wells


14       72    M       12      Repairman       NM     Natural gas
                                                       storage

15       40    F       12      Clerk           TX     Building sewer



16       37    M       12      Pipefitter      CA     Refinery


17       52    F       17      Teacher         CA     Sewer gas



18       48    M       15      Electrician     MI     Natural gas wel


19       59    M       11      Mechanic        FL     Waste dump


Mean     45.1  9F     12.7

                     Months
                      from
Patient             exposure
no.      Duration  to testing          Symptoms          Abnormalities

1          6 hr        26       Impaired balance, loss       24.0
                               of recall, irritability,
                                       and anger

2          4 yr        36       Balance impaired, dec.       15.0
                                 libido, slow thinking


3          6 yr        60        Extreme fatigue, dec.       15.0
                                 appetite, prod. cough

4         20 min       6         Lightheaded, extreme        12.5
                                 fatigue, irritability
                                   and lack concent.

5          8 d         30       Balance, concent, dec.       12.0
                                    recent memory,
                                       headache


6         40 hr        32          Loss of concent.,         12.0
                                   dizziness, sleep
                                       disturbed

7          3 hr        5       Dizziness, eyes tearing,      11.0
                                       nauseated

8          2 d         45          Loss of concent.,         11.0
                                somnolence, memory loss

9          7 mo        60      Short of breath, loss of      10.5
                                   balance, loss of
                                       concent.

10         7 mo        60            Balance loss             7.5


11         6 yr        60          Throat irritation          7.5
                                       insomnia

12         7 d         6         Headache, dizziness,         7.0
                                      skin burns

13         7 mo        25       Seizures, memory loss,        6.0
                                    disturbed sleep

14         7 mo        60      Loss recent and long-term      6.0
                                memory, disturbed sleep

15         2 yr       120          Red itching skin,          4.0
                                 burning throat, sleep
                                       disturb.

16         9 yr       120          Cough, leukemia,           4.0
                                 fatigue, memory loss

17         2 hr        4            Loss of memory,           4.0
                                 shortness of breath,
                                        fatigue

18       1 1/2 hr      19          Headache, cough,           3.0
                                      disoriented

19         4 yr        24        Headache, dizziness,         3.0
                                  breathing distress

Mean                                                          9.2

Table 2

Hydrogen sulfide-exposed subjects (19) compared with 202 referent
subjects as percentage of predicted, means, and standard deviations
(SD), P values by analysis of variance

                                                 19 Exposed
                                              mean [+ or -] SD

Age (yr)                                     45.1 [+ or -] 11.6
Educational level (yr)                       12.7 [+ or -] 2.2
Simple reaction time (ms)                   108.1 [+ or -] 7.8
Choice reaction time (ms)                   106.4 [+ or -] 5.8
Balance sway speed (cm/s)      Eyes open    208.1 [+ or -] 166.4
                               Eyes closed  243.1 [+ or -] 141.9
Blink reflex latency R 1 (ms)  Right        113.3 [+ or -] 12.4
                               Left         111.4 [+ or -] 14.5
Hearing losses                 Right        118.3 [+ or -] 46.6
                               Left         109.7 [+ or -] 31.6
Color score                    Right         64.8 [+ or -] 57.7
                               Left          53.7 [+ or -] 40.2
Visual performance             Right         81.5 [+ or -] 21.4
                               Left          78.0 [+ or -] 29.4
Grip strength                  Right         89.5 [+ or -] 15.4
                               Left          93.8 [+ or -] 16.7
Culture Fair A                               89.7 [+ or -] 25.3
Digit symbol substitution                    90.0 [+ or -] 12.1
Vocabulary                                   77.3 [+ or -] 27.1
Verbal recall                  Immediate     78.3 [+ or -] 29.2
                               Delayed       62.3 [+ or -] 36.9
Pegboard                                     81.0 [+ or -] 19.3
Trails A                                    109.0 [+ or -] 12.6
Trails B                                    105.9 [+ or -] 9.3
Finger writing                 Right        103.4 [+ or -] 8.2
                               Left         103.3 [+ or -] 9.2
Information                                  71.5 [+ or -] 29.4
Picture completion                           75.8 [+ or -] 32.6
Similarities                                 79.1 [+ or -] 36.1
POMS score                                   77.1 [+ or -] 36.3
Frequency of symptoms mean     5.8 +/- 1.6      2.6 [+ or -] 1.2

                                     Referent
                                  mean [+ or -] SD  P value  Holm's P

Age (yr)                        46.6 [+ or -] 20.6  .757
Educational level (yr)          12.9 [+ or -] 2.3   .735
Simple reaction time (ms)       99.9 [+ or -] 3.7   .0001 *   .0017 *
Choice reaction time (ms)      100.0 [+ or -] 2.5   .0001 *   .0016 *
Balance sway speed (cm/s)      100.2 [+ or -] 20.0  .0001 *   .0015 *
                               103.1 [+ or -] 26.8  .0001 *   .0014 *
Blink reflex latency R 1 (ms)   99.4 [+ or -] 14.6  .0005 *   .0065 *
                                 6.4 [+ or -] 13.2  .0001 *   .0012 *
Hearing losses                 101.5 [+ or -] 24.6  .0310 *   .0310 *
                                99.3 [+ or -] 21.8  .0930
Color score                    102.6 [+ or -] 51.1  .0026 *   .0268 *
                               102.6 [+ or -] 51.1  .0001 *   .0010 *
Visual performance             100.0 [+ or -] 22.8  .0019 *   .0012 *
                               101.1 [+ or -] 21.7  .0002 *   .0120 *
Grip strength                   99.3 [+ or -] 17.5  .0200 *   .0200 *
                                99.1 [+ or -] 17.5  .2030
Culture Fair A                 101.2 [+ or -] 20.0  .0200 *   .0200 *
Digit symbol substitution      101.5 [+ or -] 9.2   .0001 *   .0009 *
Vocabulary                      99.1 [+ or -] 30.8  .0030 *   .0090 *
Verbal recall                   99.8 [+ or -] 31.1  .0040 *   .0080 *
                                99.9 [+ or -] 41.3  .0002 *   .0014 *
Pegboard                       101.8 [+ or -] 25.7  .0007 *   .0035 *
Trails A                       100.3 [+ or -] 8.3   .0010 *   .0008 *
Trails B                       100.4 [+ or -] 7.5   .0030 *   .006 *
Finger writing                 100.0 [+ or -] 7.5   .0850
                               100.0 [+ or -] 7.8   .1125
Information                    101.5 [+ or -] 39.4  .0014 *   .0056 *
Picture completion              99.3 [+ or -] 32.2  .0027 *   .0080 *
Similarities                    98.1 [+ or -] 41.2  .0530
POMS score                      21.0 [+ or -] 31.6  .0001 *
Frequency of symptoms mean       2.6 [+ or -] 1.2   .0001 *

* = Statistically significant.

Table 3.

Comparison of 16 (1997) patients and 19 (2001) patients as mean values
of percentage predicted

                                                  1997     2001
                                       Referent   (16)     (19)

Age (yr)                                 46.6     44.7     45.1
Education level (yr)                     12.7     10.0     12.9
Balance sway speed        Eyes open     100.0    159.0 *  208.0 *
                          Eyes closed   103.0    246.0 *  243.0 *
Simple reaction time                    100.0    151.0 *  108.0 *
Choice reaction time                    100.0    130.0 *  106.0 *
Blink reflex latency R-1  Right          99.0     87.0 *  113.0 *
                          Left           96.0     95.0    111.0 *
Visual performance        Right         100.0     72.0 *   81.5 *
                          Left          101.0     55.0 *   78.0 *
Color score               Right         103.0     75.0 *   65.0 *
                          Left          103.0     64.0 *   54.0 *
Hearing                   Right         100.0    160.0 *  118.0 *
                          Left          100.0    174.0 *  110.0
Grip strength             Right          99.0     94.0     90.0 *
                          Left           99.0     82.0 *   94.0
Culture Fair                            101.0     85.0 *   90.0 *
Digit symbol                            104.0     77.0 *   90.0 *
Vocabulary                               99.0     56.0 *   77.0 *
Verbal recall             Immediate      99.8     69.0 *   78.0 *
                          Delayed        99.9     60.0 *   62.0 *
Pegboard                                102.0     87.5 *   81.0 *
Trail making A                          100.0    178.0 *  109.0 *
Trail making B                          100.0    140.0 *  106.0 *
Fingertip number          Right         100.0    102.0    103.0
 writing errors
                          Left          100.0    104.0    103.0
Information                             100.0     69.0 *   72.0 *
Picture completion                       98.0     84.0     76.0 *
Similarities                             96.0     84.0 *   79.0
POMS score                               21.0     83.2     77.1
Symptom frequency                         2.6      4.0      5.8

* = Statistically significant.

Table 4

Respiratory symptoms exposed and control compared by ANOVA with P values

                                        Exposed (19) mean
                                           [+ or -] SD

Phlegm                                        36.8
Short of breath                Rest           63.2
                               Walking        84.2
                               Stairs        100.0
Wheezing                                      57.9
Short of breath with wheezing                 63.2

                               Unexposed (202) mean
                                   [+ or -] SD          P

Phlegm                                10.3            .002 *
Short of breath                        5.2           .0001 *
                                       8.6           .0001 *
                                      32.8           .0001 *
Wheezing                              10.3           .0001 *
Short of breath with wheezing         13.8           .0001 *

Pulmonary function for 19 hydrogen-sulfide exposed compared with 202
unexposed subjects

                    Exposed mean        Unexposed mean
                     [+ or -] SD          [+ or -] SD       P

FVC               98.0 [+ or -] 14.6  101.6 [+ or -] 15.1  .320
[FEV.sub.1]       93.7 [+ or -] 14.2   93.6 [+ or -] 15.8  .983
[FEF.sub.25-75]  105.9 [+ or -] 29.4   88.1 [+ or -] 35.0  .033 ** R
[FEF.sub.75-85]   86.0 [+ or -] 35.1   78.1 [+ or -] 52.7  .521
[FEV.sub.1]/FVC   77.7 [+ or -] 5.6    72.8 [+ or -] 9.5   .029 ** R

* statistically significant.

** R, statistically significantly better than controls.

Accepted March 26, 2003.

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RELATED ARTICLE: Key Points

* Central nervous system effects of hydrogen sulfide can be measured.

* Subjects exposed at home are impaired.

* Dose measurements are needed, but 1 ppm may be too much.

* Brief exposures above 25 ppm equate with months at 1 ppm.

From the Environmental Sciences Laboratory, Keck School of Medicine, University of Southern California, Los Angeles, CA.

The author developed the apparatus to measure balance, reaction time, and blink and has sold these devices for performance testing. All participants provided informed consent, and the study protocol was approved by the Human Studies Research Committee of the Keck School of Medicine, University of Southern California. Patients paid for their examinations.

Reprint requests to Kaye H. Kilburn, MD, Environmental Sciences Laboratory, Keck School of Medicine, University of Southern California, 2025 Zonal Avenue, CSC 201, Los Angeles, CA 90033. Email: [e-mail]

Copyright[C] 2003 by The Southern Medical Association

0038-4348/03/9607-0639