Temporal association between serum prolactin concentration and exposure to styrene.

BACKGROUND: Previous studies have suggested that occupational exposure to styrene is associated with increased serum levels of the anterior pituitary hormone prolactin (PRL). AIMS: To test the hypotheses that: (1) the effect of styrene exposure on PRL secretion is an acute effect, not a subchronic or chronic effect; (2) blood styrene, as a measure of absorbed dose, is a stronger predictor of serum PRL level than personal breathing zone air styrene concentration. METHODS: Subjects were recruited from 17 workplaces in the reinforced plastics industry. Personal breathing zone air styrene, whole blood styrene, and serum PRL were measured during one to three sessions, approximately one year apart. Linear multiple regression was used to model the relations between acute (air styrene or blood styrene obtained at same time as PRL), subchronic (average air or blood styrene over two or three sessions), and chronic (years of work in industry or facility times average air styrene over all sessions) indices of styrene exposure and serum PRL. RESULTS: Acute blood styrene concentration was the strongest predictor of serum PRL concentration, with the model predicting a 2.06-fold increase in PRL (95% CI 1.11 to 3.84) for every 10-fold increase in blood styrene. Serum PRL tended to increase with increasing styrene exposure in both men and women; however, women tended to have higher PRL levels. For women, the change in blood styrene between sessions 1 and 2 was a significant predictor of the change in serum PRL between sessions. CONCLUSIONS: Results confirm that styrene exposure enhances serum PRL concentrations and support an acute effect of styrene on PRL secretion.

Development of a life events/icon calendar questionnaire to ascertain occupational histories and other characteristics of migrant farmworkers.

BACKGROUND: Specialized methods are necessary to collect data from migrant farmworkers for epidemiologic research. METHODS: We developed a questionnaire that collected lifetime occupational histories and other lifestyle risk factors via a life events/icon calendar, and administered the questionnaire to a convenience sample of 162 migrant farmworkers in nine areas of the U.S. RESULTS: The average duration of the interviews was about 1 h 30 min, with an average of 45 min for the work history section. The occupational histories covered a median of 27.6 years per person for men and 20.8 years per person for women. The median number of years spent in farm jobs was 11.3 for men and 5.8 for women. The median number of farm jobs (crop/task combination) per person was 59 among men and 27 among women. Many farmworkers performed the same crop/task combinations at multiple times throughout their lives, yielding a median of 13 unique farm jobs and 8 unique crops among men and 7 jobs and 5 crops among women. CONCLUSIONS: The project demonstrated that it is feasible to collect detailed work histories and other risk factor data from farmworkers, documented the complexity of work histories encountered among farmworkers, and yielded recommendations for refining a questionnaire that will facilitate future epidemiologic research on farmworkers.

Radiographic evidence of silicosis risk in the diatomaceous earth industry.

There is limited and conflicting evidence regarding the exposure-response relationship between exposure to crystalline silica and silicosis; the level of risk to current workers remains uncertain. We conducted an epidemiologic investigation of 1,809 workers in the diatomaceous earth industry, where exposures to crystalline silica are primarily to the cristobalite form. On the basis of the median of three independent readings, 81 (4.5%) workers were judged to have opacities on chest radiographs (small opacities, profusion >= 1/0, and/or large opacities). Age-adjusted relative risk of opacities increased significantly with cumulative exposure to crystalline silica. The concentration of respirable crystalline silica to which workers were exposed (highly correlated with period of hire) was an important determinant of risk after accounting for cumulative exposure. For workers with an average exposure to crystalline silica of <= 0.50 mg/m3 (or hired >= 1950), the cumulative risk of opacities for a cumulative exposure to crystalline silica of 2.0 mg/m3-yr was approximately 1.1%; for an average exposure > 0.50 mg/m3 (or hired < 1950), the corresponding cumulative risk was 3.7%. These findings indicate an exposure-response relationship between cumulative exposure to crystalline silica and radiographic opacities; moreover, the relationship was substantially steeper among workers exposed at the highest average concentrations of crystalline silica.

Behavioral effects of low-level exposure to Hg0 among dental professionals: a cross-study evaluation of psychomotor effects.

A Across-study design was used to evaluate the sensitivities of five psychomotor tasks previously used to assess preclinical effects of low-level Hg0 (urinary < or =55 microg/l). Pooling dental professional subject populations from six studies conducted over the last 6 years, a larger study population was obtained with a high degree of uniformity (N = 230). The five psychomotor tests were: Intentional Hand Steadiness Test (IHST); Finger Tapping: The One-Hole Test: NES Simple Reaction Time (SRT); and Hand Tremor. Multivariate analyses were conducted following the hierarchical analysis of multiple responses (HAMR) approach. First, multiple scores of each test were combined into a single-factor (or related summary) variable and its reliability was estimated. Second. multiple regression analyses were conducted including log-transformed [Hg0]U levels, age, gender, and alcohol consumption in each model. Computed were both B and bu, the magnitudes of the log-Hg0 standardized coefficient. respectively uncorrected and corrected for dependent variable attenuation due to unreliability. Results indicated remarkable differences in the effects of relative level of Hg0 on psychomotor performance. Significant associations were found for the IHST factor (B = 0.415, p < 10(-6)), followed by finger tapping, which was relatively meager and insignificant (B 0.141, p = 0.17). The IHST results hold the greatest occupational relevance for dental professionals who rely on manual dexterity in restorative dentistry. Further, this statistical approach is recommended in future studies for condensation of multiple scores into summary scores with enhanced reliabilities useful in correcting for attenuation relationships (B(u)s) with exposure levels.

Neurobehavioral effects from exposure to dental amalgam Hg(o): new distinctions between recent exposure and Hg body burden.

Potential toxicity from exposure to mercury vapor (Hg(o)) from dental amalgam fillings is the subject of current public health debate in many countries. We evaluated potential central nervous system (CNS) toxicity associated with handling Hg-containing amalgam materials among dental personnel with very low levels of Hg(o) exposure (i.e., urinary Hg <4 microg/l), applying a neurobehavioral test battery to evaluate CNS functions in relation to both recent exposure and Hg body burden. New distinctions between subtle preclinical effects on symptoms, mood, motor function, and cognition were found associated with Hg body burden as compared with those associated with recent exposure. The pattern of results, comparable to findings previously reported among subjects with urinary Hg >50 microg/l, presents convincing new evidence of adverse behavioral effects associated with low Hg(o) exposures within the range of that received by the general population.

Quantification of historical dust exposures in the diatomaceous earth industry.

Quantitative estimates of dust exposure in a diatomaceous earth (DE) mining and milling operation have been derived based on air sampling records for the period 1948-1988. A total of 6395 records was included in the analysis. Conversion of results obtained by particle counting, expressed as millions of particles per cubic feet (mppcf) of gravimetrically from a filter cassette and expressed as mg m-3 total, were converted to mg m-3 respirable dust using a conversion factor derived from data obtained during the same periods at the plant. Conversion factors were calculated as the average difference of means on the log scale in order to provide stable and consistent conversions and as a ratio of arithmetic means so that the results could be compared with similar studies. After converting the available data to mg m-3 respirable dust, geometric mean (geometric standard deviation) concentrations were 0.37 (2.43) during the 1950s and 0.17 (2.35) during later periods. Exposures were estimated using two linear models, one estimating the changes in concentration over time, and the other providing job-specific mean exposures during the more recent period. Extrapolation of the estimates to periods prior to the availability of any data was done using a subjectively-determined scaling factor. The average estimated respirable dust concentrations for 135 jobs were 3.55 (+/-1.25), 1.37 (+/-0.48), 0.47 (+/-0.16) and 0.29 (+/-0.10) mg m-3 prior to 1949, 1949-1953, 1954-1973 and 1974-1988, respectively. Despite the limitations of the available data, the estimation procedures used are expected to provide reasonable quantitative estimates of silica-containing dust exposure for subsequent exposure-response analyses.

Dose-response associations of silica with nonmalignant respiratory disease and lung cancer mortality in the diatomaceous earth industry.

The potential carcinogenicity of crystalline silica to humans remains a controversial issue. The authors conducted an historical cohort mortality study of 2,342 male workers exposed to crystalline silica, predominantly cristobalite, in a diatomaceous earth mining and processing facility in California. During the years 1942-1994, mortality excesses were detected for nonmalignant respiratory diseases (NMRD) (standardized mortality ratio = 2.01, 95% confidence interval (CI) 1.56-2.55) and lung cancer (standardized mortality ratio = 1.29, 95% CI 1.01-1.61). NMRD mortality rose sharply with cumulative exposure to respirable crystalline silica; allowing for a 15-year latency, the rate ratio for the highest exposure stratum (> or = 5.0 mg/m3-years) was 5.35 (95% CI 2.23-12.8). The rate ratio for lung cancer reached 2.15 (95% CI 1.08-4.28) in the highest exposure category. These associations were unlikely to have been confounded by smoking or asbestos exposure. The findings indicate a strong dose-response relation for crystalline silica and NMRD mortality. The lung cancer results, although less convincing, add further support to an etiologic role for crystalline silica.

Lung cancer in chromate-exposed aerospace workers.

A retrospective cohort study evaluated the risk of lung cancer in aerospace workers with minimum of 6 months' employment in jobs with chromium [VI] exposure (n = 2429). Standardized incidence ratios (SIR) estimated the risk of lung cancer by duration of employment in chromate-exposure jobs and cumulative exposure based on industrial hygiene and work-history data. The overall SIR for lung cancer was 0.8 (observed [Obs] = 15). Lung cancer risk was inversely related to estimates of cumulative chromate exposure and duration of employment as a painter. Although based on few cases, an elevated lung cancer risk was found in subjects who had worked for 5 or more years as a chrome plater or surface processor tank tender (Obs = 2, SIR = 1.9) and sander/masker or polisher (Obs = 3, SIR = 2.7). A clear association was not observed between chromate exposure and the risk of lung cancer in this population of workers.

An updated mortality follow-up study of Florida phosphate industry workers.

We have added 14 years of mortality follow-up to a previously studied cohort of 18,446 white and 4,546 nonwhite male workers in the Florida phosphate industry. Follow-up was performed for the years 1949-1992. Based on comparisons with national rates, lung cancer standardized mortality ratios (SMR) were slightly elevated among white (SMR = 1.19; 354 observed) and nonwhite males (SMR = 1.13; 105 observed). However, no lung cancer excesses were found relative to local county rates (SMR = 0.98 for whites, SMR = 0.94 for nonwhites). Based on internal analyses of lung cancer mortality, using Poisson regression modeling, there were no associations of lung cancer with cumulative exposures to total dust, silica, or acid mists. There were weak trends of lung cancer risk with alpha and gamma radiation among white males, but no associations with radiation in nonwhites. No relation was found between acid mist exposures and laryngeal cancer. We conclude that there have not been large excesses of lung cancer or other diseases related to workplace exposures in this cohort.

Reanalysis of mortality from lung cancer among diatomaceous earth industry workers, with consideration of potential confounding by asbestos exposure.

OBJECTIVE: To evaluate the potential for confounding from asbestos exposure, primarily chrysotile, on the relation between crystalline silica and mortality from lung cancer among diatomaceous earth (diatomite) workers. METHODS: A reanalysis of a cohort mortality study of diatomite workers was performed to take into account quantitative estimates of asbestos exposure. The reanalysis was limited to a subset of the original cohort, comprising 2266 white men for whom asbestos exposure could be reconstructed with greatest confidence. Comparisons between mortality from lung cancer (standardised mortality ratios (SMR)) were made between rates for 1942-87 for United States white men, and workers cross classified according to cumulative exposures to crystalline silica and asbestos. Comparisons of internal rates, involving Poisson regression modeling, were conducted for exposure to crystalline silica, with and without adjustment for asbestos exposure. Exposures were lagged by 15 years to take into account disease latency. RESULTS: There was an overall excess of lung cancer (SMR 1.41; 52 observed). The SMRs for four categories of increasing crystalline silica among the workers not exposed to asbestos were 1.13, 0.87, 2.14, 2.00. An SMR of 8.31 (three observed) was found for workers with the highest cumulative exposure to both dusts. Internal analysis, after adjustment for asbestos exposure, yielded rate ratios for categories of exposure to crystalline silica: 1.00 (reference), 1.37, 1.80, and 1.79. CONCLUSIONS: Asbestos exposure was not an important confounder of the association between crystalline silica and mortality from lung cancer in this cohort. Although based on a small number of deaths from lung cancer, the data suggest possible synergy between these exposures. An extended follow up of this cohort is in progress and should enable better assessments of independent and combined effects on risk of lung cancer.

Analyzing multivariate neurobehavioral outcomes in occupational studies: a comparison of approaches.

Neurobehavioral studies often employ test batteries and confront issues of multiple testing and comparability between batteries. We have organized our battery of 12 tests into areas of neurobehavioral function to reduce the number of reported results, provide greater statistical power, and improve interpretability of the results. We explored several different organizational and statistical methods of creating summary scores including a priori groupings based upon clinical experience and factor analysis. We compared the sensitivity of these summary scores to performance changes associated with exposure to styrene in the manufacture of reinforced plastics. Our results demonstrated dramatic increases in power to detect exposure related changes compared to using individual test scores. Furthermore, the various methods provided generally compatible and comparable results. We encourage other neurobehavioral investigators to pursue and refine this approach.

Behavioral effects of low-level exposure to elemental Hg among dentists.

Exposure thresholds for health effects associated with elemental mercury (Hg degree) exposure were examined by comparing behavioral test scores of 19 exposed (mean urinary Hg = 36 micrograms/l) with those of 20 unexposed dentists. Thirty-six micrograms Hg/l is 7 times greater than the 5 micrograms Hg/l mean level measured in a national sample of dentists. To improve the distinction between recent and cumulative effects, the study also evaluated porphyrin concentrations in urine, which are correlated with renal Hg content (a measure of cumulative body burden). Subjects provided an on-site spot urine sample, were administered a 1-h assessment consisting of a consent form, the Profile of Mood Scales, a symptom and medical questionnaire, and 6 behavioral tests: digit-span, symbol-digit substitution, simple reaction time, the ability to switch between tasks, vocabulary, and the One Hole Test. Multivariate regression techniques were used to evaluate dose-effects controlling for the effects of age, race, gender and alcohol consumption. A dose-effect was considered statistically significant below a p value of 0.05. Significant urinary Hg dose-effects were found for poor mental concentration, emotional lability, somatosensory irritation, and mood scores. Individual tests evaluating cognitive and motor function changed in the expected directions but were not significantly associated with urinary Hg. However, the pooled sum of rank scores for combinations of tests within domains were significantly associated with urinary Hg, providing evidence of subtle preclinical changes in behavior associated with Hg exposure. Coproporphyrin, one of three urinary porphyrins altered by mercury exposure, was significantly associated with deficits in digit span and simple reaction time.(ABSTRACT TRUNCATED AT 250 WORDS)

Outcome of lumbar fusion in Washington State workers' compensation.

STUDY DESIGN: This study covered a large, population-based cohort of workers in the Washington State workers' compensation system who received lumbar fusion between August 1, 1986 and July 31, 1987 to determine work disability status, reoperation rate, and patient satisfaction. OBJECTIVES: To use predictors of outcome of lumbar fusion to design clearer clinical guidelines for lumbar fusion in injured workers. METHODS: Logistic regression analysis was used to determine the predictors of work disability and risk of reoperation after fusion. RESULTS: The lumbar fusion incidence rate was 41.7/100,000 workers a year (n = 388 patients). Overall, 68% were work disabled and 23% required further lumbar spine surgery 2 years post-fusion. Five markers of severity predicted worse work disability outcome (older age at injury, longer time from injury to fusion, increased increased time on work disability before fusion, increased number of prior low back operations, and increased number of levels fused). Even after adjusting for these variables, receiving instrumentation with fusion doubled the risk of reoperation. Most patients reported that back pain (67.7%) was worse and overall quality of life (55.8%) was no better or worse than before surgery. CONCLUSIONS: Outcome of lumbar fusion performed on injured workers was worse than reported in published case series. Prospective studies should be conducted to determine the biologic indications that might lead to improved outcomes in this disabled population.

Work-related traumatic brain injury in Washington State, 1988 through 1990.

OBJECTIVES: Brain trauma is a major cause of disability in the United States, especially among young adults. Work-related brain trauma cases represent a subpopulation that may be amenable to intervention efforts, but largely because of unavailability of data, this group has not previously been studied. METHODS: Washington State workers' compensation data were used to identify brain trauma cases and to describe incidence rates with respect to age, gender, and industrial classification. Cause of injury was evaluated for industrial classifications with numerous cases. RESULTS: Washington State workers experienced 301 brain traumas over a 3-year period (9.4/100,000 full-time equivalent workers per year). One third of all traumatic brain injury claims were concentrated among seven industrial classifications. Cause of injury was highly correlated with specific industrial classifications. CONCLUSIONS: This study demonstrates the usefulness of diagnosis-related group codes to identify cases of traumatic brain injury. These injuries are concentrated among a few industries, with a dominant specific cause for each industry. This suggests that intervention methods may be efficiently introduced to reduce traumatic brain injuries in the workplace.

Cancer incidence among firefighters in Seattle and Tacoma, Washington (United States).

In order to determine if exposure to carcinogens in fire smoke increases the risk of cancer, we examined the incidence of cancer in a cohort of 2,447 male firefighters in Seattle and Tacoma, (Washington, USA). The study population was followed for 16 years (1974-89) and the incidence of cancer, ascertained using a population-based tumor registry, was compared with local rates and with the incidence among 1,878 policemen from the same cities. The risk of cancer among firefighters was found to be similar to both the police and the general male population for most common sites. An elevated risk of prostate cancer was observed relative to the general population (standardized incidence ratio [SIR] = 1.4, 95 percent confidence interval [CI] = 1.1-1.7) but was less elevated compared with rates in policemen (incidence density ratio [IDR] = 1.1, CI = 0.7-1.8) and was not related to duration of exposure. The risk of colon cancer, although only slightly elevated relative to the general population (SIR = 1.1, CI = 0.7-1.6) and the police (IDR = 1.3, CI = 0.6-3.0), appeared to increase with duration of employment. Although the relationship between firefighting and colon cancer is consistent with some previous studies, it is based on small numbers and may be due to chance. While this study did not find strong evidence for an excess risk of cancer, the presence of carcinogens in the firefighting environment warrants periodic re-evaluation of cancer incidence in this population and the continued use of protective equipment.

Platelet monoamine oxidase B activity in workers exposed to styrene.

A cross-sectional study was conducted to evaluate monoamine oxidase type B (MAO-B) activity in platelets as a biomarker of effect of styrene and perchloroethylene exposures. MAO-B is an enzyme system involved in dopamine catabolism, the impairment of which has been postulated as a mechanism of styrene-induced neurotoxicity. We previously observed an inverse association between blood styrene and MAO-B among reinforced plastics manufacturing workers. The present study included 59 male boat plant workers exposed to styrene (exposure range < 1-144 ppm, 8-h TWA). Two comparison groups comprised six male dry cleaning workers exposed to perchloroethylene (PCE; exposure range < 2-37 ppm) and 14 male laundry workers not exposed to either agent. Respiratory protection was not used by any of the styrene- or PCE-exposed workers; thus, air concentrations were regarded as valid exposure indicators. MAO-B activity (pmol/10(8) cells/h) was measured in peripheral blood platelets, using phenylethylamine as substrate. Only small overall mean differences in MAO-B were observed among the three groups; mean values were 4.21, 4.51, and 4.12 for the styrene-exposed, PCE-exposed, and laundry workers, respectively. Despite the absence of gross differences among the groups, styrene exposure was inversely related to MAO-B. Mean values for four increasing exposure group quartiles were: 5.60, 4.13, 3.69, and 3.44. The Spearman rank correlation coefficient for styrene with MAO-B was -0.41. Adjustment for age, medication use, smoking, and alcohol consumption had only a minimal effect on this trend.(ABSTRACT TRUNCATED AT 250 WORDS)

Mortality among workers in the diatomaceous earth industry.

A cohort mortality study was conducted among workers from two plants in the diatomaceous earth mining and processing industry in California. Diatomaceous earth consists of the skeletal remains of diatoms. Exposure to amorphous (non-crystalline) and crystalline silica in the form of quartz results from open pit mining and exposure to crystalline silica (principally cristobalite) occurs in the processing of the material. Lung cancer and non-malignant respiratory diseases have been the health outcomes of greatest concern. The main study cohort included 2570 white men (533 Hispanic and 2017 non-Hispanic workers) who were employed for at least 12 months cumulative service in the industry and who had worked for at least one day during the follow up period, 1942-87. Vital status was ascertained for 91% of the cohort and death certificate information was retrieved for 591 of 628 (94%) identified deaths. The all causes combined standardised mortality ratio (SMR) was slightly increased (SMR = 1.12; 628 observed) compared with rates among US white males. The principal contributors to this excess were increased risks from lung cancer (SMR = 1.43; 59 observed) and non-malignant respiratory disease (NMRD) excluding infectious diseases and pneumonia (SMR = 2.59; 56 observed). The excess of lung cancer persisted when local county rates were used for comparison (SMR = 1.59). Internal rate comparisons by Poisson regression analysis were conducted to assess potential dose-response relations for lung cancer and NMRDs. Mortality trends were examined in relation to duration of employment in dust exposed jobs and with respect to an index of cumulative exposure to crystalline silica. The crystalline silica index was a semiquantitative measure that combined information on duration of exposure, differences in exposure intensity between jobs and calendar periods, the crystalline content of the various product mixes, and the use of respiratory protection devices. Increasing gradients of risk were detected for lung cancer and NMRD with both exposure indices. The relative risk trends for lung cancer and NMRD with crystalline silica exposure lagged 15 years were respectively: 1.00, 1.19, 1.37, and 2.74, and 1.00, 1.13, 1.58, and 2.71. Based on a review of available but limited data on cigarette smoking in the cohort and from application of indirect methods for assessing confounding variables, it seems unlikely that smoking habits could account for all of the association between exposure to dust and lung cancer. The intense and poorly controlled dust exposures encountered before the 1950s were probably the most aetiologically significant contributors to risks from lung cancer and NMRDs. The absence of an excess of lung cancer among workers hired since 1960, and the finding of no deaths attributed to pneumoconiosis as an underlying cause of death among workers hired since 1950 indicate that exposure reductions in the industry during the past 40 years have been successful in reducing excess risks to workers. Further mortality follow up of the cohort and the analysis of radiographic data will be needed to determine conclusively the long term patterns of disease risks in this industry.

Cancer identification using a tumor registry versus death certificates in occupational cohort studies in the United States.

Studies of cancer incidences among occupational cohorts are rarely performed in the United States because of incomplete registration and a limited time period available for follow-up. This study used data from concurrent studies of cancer mortality and incidence among a cohort of 4,528 fire fighters and police officers employed by the cities of Seattle and Tacoma, Washington, between 1944 and 1979 to examine the relative advantages of tumor registry and death certificate information. As expected, an increased ability to study relatively common cancers with low fatality rates was demonstrated using incidence data. The most dramatic example was seen for bladder cancer. Twenty-four bladder cancers had been diagnosed among the study cohort between 1974 and 1989, whereas only two deaths were attributed to this malignancy. The standardized incidence ratio for bladder cancer was 1.05 (95% confidence interval 0.67-1.55), whereas the corresponding standardized mortality ratio was 0.46 (95% confidence interval 0.05-1.65). The observed relative risk estimates for rapidly fatal cancers were similar using the two sources of information, and no increase in precision was observed. Of 142 persons in the registry area who died of cancer during the study period, 20 (14%) had a different site listed on the death certificate than was identified by the registry. Approximately 7% of the potential person-years of follow-up were lost due to migration out of the registry area; loss to follow-up was greater among older and short-term workers, but did not exceed 13% of the person-years. Population-based tumor registries can be a useful resource in the investigation of occupational cancer in the United States, especially for the study of cancers with high survival rates.

The 10-year experience of an academically affiliated occupational and environmental medicine clinic.

Occupational and environmental diseases are underrecognized. Among the barriers to the successful diagnosis, treatment, and prevention of these conditions are inadequate consultative and information resources. We describe the 10-year clinical and training experiences of an academically affiliated referral center that has as its primary goal the identification of work-related and other environmental diseases. The University of Washington Occupational and Environmental Medicine Program has evaluated 6,048 patients in its diagnostic and screening clinics. Among the 2,841 seen in the diagnostic clinics, 1,553 (55%) had a work-related condition. The most prevalent diagnoses included asbestos-related lung disease (n = 603), toxic encephalopathy (n = 160), asthma (n = 119), other specific respiratory conditions (n = 197), carpal tunnel syndrome (n = 86), and dermatitis (n = 82). The clinics serve as a training site for fellows in the specialty training program, primary care internal medicine residents, residents from other medical specialties, and students in industrial hygiene, toxicology, and occupational health nursing. The program serves two additional important functions: providing consultative services to community physicians and training specialists and other physicians in this underserved area of medicine.