This project was designed with the primary goal of providing more information on the shape of the dose-response curve for hand repetition with respect to specific medical outcomes. A cross-sectional study was conducted in which workers' exposure to repetition and other physical stressors was quantified using a standardized observational method based on a 0 to 10 rating scale, and analyzed in conjunction with the prevalence of various upper limb disorders. Jobs were selected based on pre- determined levels of hand repetition. Standardized medical evaluations were performed on all participating, workers, and included a self-administered questionnaire, physical exam, and limited electrodiagnostic studies (EDS). A standardized observational method for rating ergonomic job exposures, specifically hand activity, was developed, field tested, and validated in this study. In addition, the inter-rater and intra-rater reliability of this new method was assessed. This rating system was found to be sensitive to the parameters of movement frequency and recovery time in hand intensive tasks. The method can be easily applied, requiring no instrumentation and a minimum amount of training, and thus may be useful in a wide range settings. Experienced raters are able to consistently apply this method at different points in time. Related studies show that the system can be easily learned by non-experts and consistently produce results that agree with the "experts". Analyses focused on evaluating exposure-response relationships with adjustment for pertinent covariates (e.g., age, gender, anthropometry, and psychosocial covariates). Repetitiveness of work was found to be significantly associated with prevalence of discomfort in the wrist, hand, or fingers, tendinitis, and symptoms consistent with carpal tunnel syndrome as indicated on a hand diagram. There was no statistically significant relationship between repetitiveness of work and electrophyiologically-determined median nerve impairment. There was a borderline significant positive trend between hand repetition and carpal tunnel syndrome defined by EDS and hand diagram scores. For example, a change in repetition from 'low' to 'high', representing 5.6 units on the 0 to 10 scale, would produce an odds ratio of 2.9 for risk of tendinitis in the dominant elbow, forearm, wrist, hand or fingers, after adjustment for age, gender, anthropometry, and pertinent medical history. Similarly, shifting exposure to hand repetition from 'low' to 'high' produced an odds ratio of 2.3 for risk of CTS-like symptoms in the dominant hand, based on hand diagram scores, again, after adjustment for age, gender and other pertinent covariates. The results of this study indicate there is a definite exposure-response relationship for certain measures ofUEMSDs and hand repetition, and that hand repetition can be a major contributing factor to these problems. Numerous screening procedures and devices have been proposed for measuring or detecting CTDs, and, in particular, carpal tunnel syndrome (CTS) among active workers. The present study provided an opportunity to evaluate many of these techniques in greater detail than ever before. Analyses involved comparing hand diagram scores and non localized wrist/hand/fin-er symptoms with electrodiagnostic test results. All configurations of hand diagram scores of the dominant hands had a statistically significant association with electrophysiologically determined median nerve dysfunction, but so did non localized symptom reports. The sensitivity, specificity, and positive predicted values of hand diagrams were poorer than those reported previously. While some test performance characteristics of hand diagrams were better than those for non localized distal extremity symptoms consistent with CTS, some were worse. Overall, our data suggest that hand diagrams are no better than using a questionnaire to determine if workers have experienced symptoms consistent with CTS in their wrists, hands or fingers without regard to localization. The choice of screening tool would depend on the goal of screening, in particular, whether it is more desirable to have slightly higher sensitivity or positive predictive value. While the overall test performance characteristics of hand diagrams were acceptable for epidemiological purposes, the relatively low positive predictive values for hand diagrams (relative to an electrodiagnostic 'gold standard') clearly point to the limitation of trying to use this screening device for identifying individual workers in need of further clinical evaluation (i.e., there would be too many false positive results). Results for both single-frequency and multiple-frequency vibrometry indicate that among randomly selected active workers both procedures have, at best, a weak association with traditional electro diagnostic measurements of median sensory nerve function at the wrist. Furthermore, the degree of association with electrodiagnostic measurements never exceeded that found for a symptom survey and/or hand diagram. Thus, one can achieve equivalent or better results (i.e., sensitivity, specificity, positive predictive value, and negative predictive value) using a self-administered questionnaire, rather than these psychophysical devices. Case reports and small case series have suggested that vitamin B6 deficiency is an important etiologic factor in carpal tunnel syndrome (CTS). To address this question we examined 125 randomly selected active workers from 2 industrial plants. Each worker completed a self-administered symptom questionnaire, and underwent electro diagnostic testing of the median and ulnar (sensory) nerves. Laboratory biochemical analyses of vitamin B6 status were also performed using the erythrocyte glutamic pyruvic transaminase (EGPT) assay, and quantification of plasma pyridoxal 5'-phosphate (PLP). Measurements of vitamin B6 status were unrelated to self-reported symptoms potentially consistent with CTS, or electrophysiologically-determined median or ulnar nerve function. These results suggest that CTS among active industrial workers is unrelated to vitamin B6 deficiency. Furthermore, empirical prescription of high doses of vitamin B6 to patients with CTS is unwarranted and potentially hazardous (i.e., vitamin B6 is a well known neurotoxin at pharmacological doses). Using traditional'cut-offs' for defining electrodiagnostic abnormalities for the median nerve at the wrist ('median mononeuropathy'), we have found that up to 25% of workers are 'abnormal', and that most such workers do not report symptoms consistent with CTS in the wrists, hands or fingers. In an effort to gain a better understanding of the implication of these findings, and their natural history, we conducted a prospective case- control study. Cases were workers with asymptomatic median mononeuropathy in one or both hands. Controls were asymptomatic workers without median mononeuropathy, and were matched to cases on age, gender, and place of employment. Cases and controls were followed for a mean of 17 months (minimum 10 months, maximum 24 months), at which point they were solicited to report whether they had experienced onset of symptoms potentially consistent with CTS since having the electrodiagnostic tests performed at 'baseline'. No electrodiagnostic testing was performed at follow-up. Approximately two-thirds of cases and controls responded to the follow-up symptom survey. The results demonstrated that there was no difference in the onset ofCTS-like symptoms among cases and controls. Furthermore, only 10% to 12% of cases and controls developed such symptoms during the follow-up period. Thus, the overwhelming majority of subjects with asymptomatic median mononeuropathy remained asymptomatic during the follow-up period. In a multivariate logistic model with symptoms at follow- up' as the dependent variable, and which included covariates for electrodiagnostic measurements, demographic parameters, duration of follow-up, and ergonomic exposures (specifically hand repetition), the only covariates which were significant, or approached significance, were ergonomic exposure and duration of follow-up. These results would suggest that a finding of asymptomatic median mononeuropathy is not a pre-clinical precursor of CTS. More practically, these results indicate that basing employment decisions on pre-placementJpost-offer electrodiagnostic screening test results for CTS are invalid and probably discriminatory. Another component of this study was to determine the relative influence of certain risk factors (work activity (industrial versus clerical), body mass index (BMI), and demographic factors) on the prevalence of median mononeuropathy at the wrist, and if there were interactions among these risk factors. This was a cross-sectional study of workers at five different work sites; four were industrial sites and one was clerical. Five hundred twenty-seven workers were recruited - 164 clerical and 363 industrial. The presence of median mononeuropathy in either hand was measured by electrodiagnostic techniques comparing median and ulnar sensory peak latencies. Thirty percent of workers in this study had an abnormality of the median sensory nerve at the wrist (34% of the industrial versus 21 % of the clerical workers). The adjusted risk for industrial workers was twice that of clerical workers. Obese workers (BMI > 29) were four times more likely to present with a median mononeuropathy than workers who were normal or slender (BMI < 25). There were no significant interactions between BMI and work site in relation to median mononeuropathy. Increasing age was also related to an increased risk of median mononeuropathy. Overall, obesity, industrial work, and age are independent risk factors that influence the prevalence of median mononeuropathy among active workers. A cross-sectional study of active workers at 6 different work sites (five sites involved manufacturing workers and 1 site represented clerical workers) was conducted to determine if symptomatic workers with an abnormal sensory nerve conduction consistent with carpal tunnel syndrome differed, in terms of electrophysiologic measures, psychosocial, demographic, anthropometric, or ergonomic variables, from workers with an asymptomatic median mononeuropathy. Cases were defined as workers with electrodiagnostic findings of a median mononeuropathy in either hand based upon a 0.5 msec prolongation of the median sensory evoked peak latency compared to the ulnar latency. This group was stratified on the basis of symptoms of numbness, tingling, burning or pain in the hand. The two groups were compared in terms of demographic, anthropomorphic, psychosocial, electrophysiologic and ergonomic risk factors. There were 184 active workers with a median mononeuropathy in one or both wrists documented on nerve conduction studies. These workers represented a subset of over 700 screened workers. The main outcome measure was each patient's report of symptoms of pain, numbness, tingling, or burning in the hand or fingers that lasted more than one week or occurred 3 or more times in the 12 months preceding the initial screening. Analyses suggest that workers with a median mononeuropathy who complained of hand symptoms were more likely to be female, have jobs with higher hand repetition levels, have higher ratings of job security, not have a history of diabetes, use more force in their job with more abnormal postures of their fingers and wrist, and have a trend toward a more prolonged median sensory distal latency. Most logistic regression models explained less than 15% of the variance (pseudo R2). Overall, women with jobs that have higher ergonomic risks and no history of diabetes were more likely to have reported symptoms associated with carpal tunnel syndrome compared to other workers with a documented median mononeuropathy. Psychosocial variables were not particularly discriminatory. None of the models allow enough precision to predict on an individual basis.