Acute Effects of Thirty Minutes of Light-Intensity, Intermittent Exercise on Patients With Chronic Fatigue Syndrome.

Key Words: Blood lactate, Chronic fatigue syndrome, Exercise, Heart rate, Physical activity.

Chronic fatigue syndrome (CFS) is a condition of unknown etiology characterized by extreme fatigue that is exacerbated by minimal physical activity.[1-5] Diagnosis is made when the following criteria, taken from the Centers for Disease Control and Prevention's (CDC) modified case definition of CFS,[6] have been met: (1) clinically evaluated, unexplained, persistent, or relapsing chronic fatigue that is of new or definite onset (has not been lifelong), is not the result of ongoing exertion, is not substantially alleviated by rest, and results in substantial reduction in previous levels of occupational, educational, social, or personal activities; and (2) the concurrence of 4 or more of the following symptoms, all of which must have persisted or recurred during 6 or more consecutive months of illness and must have not predated the fatigue:

* self-reported impairment in short-term memory or concentration severe enough to cause substantial reduction in previous levels of occupational, educational, social, or personal activities,

* sore throat,

* tender cervical or axillary lymph nodes,

* muscle pain or multijoint pain without joint swelling or redness,

* headaches of a new type, pattern, or severity,

* unrefreshing sleep, and

* postexertional malaise lasting more than 24 hours.

Although clinical findings and self-reported symptoms vary among patients with CFS, a worsening of symptoms, especially of fatigue, after previously well-tolerated levels of exercise continues to be the hallmark of this incapacitating disorder.[2-5] As a result, patients with CFS tend to limit their physical activity in order to minimize symptoms.[2-5] The Surgeon General has suggested that moderate aerobic exercise (eg, brisk walking) performed for 30 minutes, 3 times each week, will convey considerable health benefits and subsequently improve quality of life in individuals without functional limitations.[7] Additional research has demonstrated that people do not have to perform 30 minutes of continuous exercise to receive such health benefits.[8] DeBusk et al[8] demonstrated that as little as 10 minutes of exercise performed 3 times throughout the day will provide some health benefits. There is no consensus regarding the appropriate exercise prescription for patients with CFS. Some investigators[2-5] have reported that continuous exercise of sufficient intensity and duration exacerbates symptoms in patients with CFS. Sisto et al,[9] however, demonstrated that a discontinuous graded exercise test did not greatly exacerbate the underlying illness of patients with CFS. Therefore, for many patients with CFS, it is improbable that they can exercise continuously for 30 minutes without exacerbating symptoms, but it may be possible that they can perform light-intensity physical activity intermittently throughout the day to accumulate 30 minutes of exercise without exacerbating symptoms.

The purposes of this investigation were to characterize the physiological responses of patients with CFS to light-intensity physical activity performed intermittently and to evaluate whether this dose of physical activity exacerbates symptoms. We hypothesized that this type of exercise would be less demanding and produce little or no exacerbation of symptoms. If so, this exercise protocol may be prescribed safely to patients with CFS in the endeavor to keep them physically fit despite their illness.

Method

Subjects

Subjects were 9 women (mean age=44.2 years, SD=8.4, range=29-56; mean weight=74.2 kg, SD=18.8, range=56.36-110.91; and mean height=l.63 m, SD=0.8, range=1.55-1.78) and 1 man (age=48 years, weight=97.1 kg, and height=1.98 m) meeting the CDC's criteria for CFS.[6] The subjects were volunteers recruited by letter from the Tuscaloosa, Ala, and Birmingham, Ala, CFS support groups. Written consent was obtained from all subjects after an explanation of the study protocol, including the benefits and potential risks involved.

Study Protocol

Before exercise. Approximately 1 month prior to the exercise session, several questionnaires were mailed to the subjects. These questionnaires were used to assess the subjects' medical health history, CFS history,[6] degree of disability (Karnofsky Rating Scale),[10] general health over the previous 3 months (the 20-item Medical Outcomes Study Short-Form Health Survey [MOS-20]),[11] and level of physical activity (Atherosclerosis Risk in Communities [ARIC]/Baecke Physical Activity Questionnaire).[12] Subjects were asked to complete and return the medical health history and CFS history questionnaires as soon as possible. The medical health history questionnaires were screened by a physician for any possible contraindications to exercise. Additionally, subjects were excluded if they felt that they could walk continuously for 30 minutes without exacerbating symptoms. The CFS history questionnaires were also reviewed by a physician to confirm that the subjects met the CDC's diagnostic criteria for CFS. The remaining questionnaires were completed at the subjects' convenience and returned on the day of the exercise session.

Subjects were instructed to abstain from caffeine and alcohol for at least 24 hours prior to the exercise session and were asked to abstain from all food, drink, and nicotine for 2 hours prior to the exercise session. During the visit to the laboratory, subjects were acquainted with the exercise protocol and were encouraged to ask questions. Subjects signed an informed consent statement and answered several questions that assessed their dietary intake, medicinal intake, sleep pattern, and physical activity 24 hours prior to the exercise session. Additionally, subjects completed questionnaires assessing their degree of disability (Karnofsky Rating Scale),[10] their current ability to engage in 7 activities (Activity Restriction Index),[13] certain symptoms and their severity (Radial Plot of Symptoms),[10] and their mood for the previous week (Profile of Mood States [POMS] scale).[14] The Karnofsky Rating Scale was administered on 2 separate occasions before the exercise session to evaluate the reliability of measurements obtained with the scale. Immediately before exercise, their general health was surveyed again using the MOS-20. This survey instrument, however, was modified from the original version to collect information regarding the week prior to the session instead of for the previous 3 months. Heart rate (HR) and blood pressure (BP) were measured following 5 minutes of supine rest, 1 minute of sitting, and 1 minute of standing. After the 1 minute of sitting, blood lactate levels were measured from blood samples taken from a finger prick.

Exercise session. The treadmill protocol involved 10 discontinuous, 3-minute exercise bouts with no incline at a comfortable walking pace (0.58 m [multiplied by] [s.sup.-1] [1.3 mph] to 1.11 m [multiplied by] [s.sup.-1] [2.5 mph] self-selected by the subject. During the first exercise period, the treadmill speed was begun at 0.58 m [multiplied by] [s.sup.-1] (1.3 mph), and speed was slowly increased until the subject achieved a comfortable walking pace. This self-selected speed was subsequently used for the remaining 9 bouts of exercise. There was a 3-minute recovery period between exercise bouts. The subjects were allowed to choose between seated and supine rest. This option was provided because some of the subjects felt that resting in a supine position would enhance recovery. Oxygen consumption ([VO.sub.2]), carbon dioxide production ([VCO.sub.2]), minute ventilation (VE), respiratory exchange ratio (RER), and HR were determined every minute; BP was assessed at the end of the third minute of each exercise bout. Rate of perceived exertion (RPE)[15] was obtained at the end of the third minute of each walking phase of the exercise challenge. Subjects also rated their current fatigue at the end of the third minute of each recovery period using a 5-point fatigue scale that ranged from "none at all" to "severe."[9]

After exercise. Recovery from the intermittent exercise consisted of the subjects sitting quietly for 5 minutes. Oxygen consumption, [VCO.sub.2], VE, RER, and HR were determined every minute. Blood pressure was assessed 3 minutes following exercise, and blood lactate was assessed 1, 3, and 5 minutes following exercise. Immediately following the 5-minute recovery period, subjects completed the Radial Plot of Symptoms and the POMS scale. Both of these questionnaires were modified to collect current information. The subjects were asked to complete the Radial Plot of Symptoms every day for 7 days following exercise; the POMS scale 1, 2, and 7 days following exercise; and the Activity Restriction Index and the MOS-20 7 days following exercise. The POMS scale was modified to collect information for the past 24 hours instead of the previous week, and the MOS-20 was modified to collect information for the last 7 days. The subjects were also asked to keep a symptom log for the entire week following exercise. They were instructed to describe each of their symptoms, including the time of onset, severity, and duration.

Psychological Instruments

Several questionnaires were administered to document the subjects' level of activity, disability, fatigue, and mood before, during, and after exercise.

Karnofsky Rating Scale. The Karnofsky Rating Scale was used to evaluate the subjects' degree of disability. The scale ranges from 0 to 100, with 0 representing "death" and 100 representing "normal with no complaints or evidence of disease."[10] Although its sensitivity and ability to detect change may be limited for patients with CFS due to a restricted range of scores for the majority of patients with CFS, the measure has been used in clinical settings to establish patients' level of disability.[10]

20-Item Medical Outcomes Study Short-Form Health Survey. The MOS-20 was used to document the subjects' general health over the previous 3 months.[11] It is a 20-item survey instrument that assesses physical functioning, social functioning, mental health, health perceptions, and pain. This instrument has been used to assess the general health of patients with CFS.[13] In the same study,[13] a Pearson product-moment correlation coefficient (r) of -.73 was demonstrated between the MOS-20 and Wood Mental Fatigue Inventory scores.

ARIC/Baecke Physical Activity Questionnaire. This instrument has been shown to be related to detailed physical activity records (r=.59 and r=.33 for men and women, respectively) and peak [VO.sub.2] (r =.57 and r =.46 for men and women, respectively) and demonstrated reliability coefficients (r) of .86 to .92 in people without functional limitations.[12] The questionnaire includes 4 items to determine a person's sport- and exercise-related leisure activity and 4 items to determine non-sport- and exercise-related leisure activity.

Activity Restriction Index. The Activity Restriction Index was used to determine the subjects' current ability to engage in 7 activities (exercise and sports; housework and family responsibilities; shopping; work, career, or school; social activities; outdoor work; and favorite recreational activities) on a 7-point scale (0, indicating "not applicable or do not normally engage in this activity," to 6, indicating "severely limited").[13] The Activity Restriction Index has been used to assess the ability of patients with CFS to engage in activities, and an intraclass correlation coefficient of .84 has been demonstrated for the measure.[13]

Radial Plot of Symptoms. The Radial Plot of Symptoms coordinates symptoms, their severity, and their pattern with CFS.[10] The scale consists of 12 symptoms that individuals rate according to their level of agreement measured on an 11-point scale (0, indicating "no pain or problem," to 10, indicating "very severe"). This instrument is designed to produce high scores only for a certain diagnostic pattern of symptoms that are characteristically seen in patients with CFS.[10] This design allows for the differentiation of CFS from other illnesses. Although we are unaware of any research that has examined the reliability and validity of data obtained with this instrument, this scale has been used extensively as a diagnostic tool for CFS.[10] This scale was used in our study to provide information regarding subjects' symptoms before and after exercise.

Profile of Mood States. The POMS is a well-known instrument that has been used to document mood states in many different populations. There are 65 questions representing 6 categories: tension, depression, anger, confusion, vigor, and fatigue.[14] The response phrases of each of question range from "not at all" to "extremely."[14] This instrument has been shown to be correlated with the Visual Analog Mood Scale (Pearson r=.54-.70) in adults ranging in age from 18 to 94 years.[16]

Laboratory Methods

Exercise took place on a Quinton motorized treadmill.(*) Subjects' HR was monitored by an HR telemetry system.([dagger]) Blood pressure was measured every 3 minutes by the standard sphygmomanometric method. The metabolic measurements ([VO.sub.2], [VCO.sub.2], VE, and RER) were determined using an Aerosport TEEM 100.([double dagger]) Plasma lactate samples were obtained by finger prick, collected in 25-[micro]L tubes, and immediately analyzed using a YSI model 23L lactate analyzer.([sections])

Data Analysis

A repeated-measures analysis of variance (ANOVA) was used to evaluate differences in the metabolic variables assessed at the end of the 10 exercise and recovery stages. We also used the ANOVA to determine differences in symptoms assessed before exercise, immediately following exercise, and over several days following exercise. Pearson product-moment correlations were used as an index of the reliability of the Karnofsky Rating Scale. Pearson product-moment correlation has frequently been used as an index of reliability when 2 measures are involved (ie, pretest and posttest). Pearson product-moment correlation and intraclass correlation are similar in principle and structure.[17] The Pearson product-moment correlation is a more conservative measure of a reliability index. All statistical analyses were performed utilizing SAS statistical software.[18]([parallel]) Statistical significance was accepted at the P [is less than] .05 level.

Results

Physiological Responses to the Exercise

Prior to the exercise session, all 10 subjects felt that they could not walk continuously for 30 minutes without exacerbating symptoms. All subjects completed the exercise protocol, except for 1 female subject who reported dyspnea and calf pain and elected to terminate the exercise session after the fifth stage of walking. This subject's data were not included in the analysis. Mean values of the metabolic variables for the average third minute of the 10 recovery and exercise stages are shown in the Table. On average, the subjects walked at a speed of 0.71 [m.s.sup.-1] (SD=0.20, range=0.54-1.21) [bar]X= 1.58 mph, SD=0.44) at a [VO.sub.2] of 8.27 mL [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1] (SD=3.58, range=3.33-16.39). Six subjects chose to lie down and 3 subjects chose to sit down during the recovery periods. The mean energy cost for completing the actual 30 minutes of walking was 398.6 kJ (SD=172.6, range= 163.8-768.0) ([bar]X=94.9 kcal, SD=41.1, range=39.0-192.0). The results of selected metabolic variables (HR, VE, RER, and [VO.sub.2]) measured at the end of each exercise stage are shown in Figure 1. Although metabolic measurements were recorded every minute for the purpose of monitoring the subjects, only data taken from the third minute of each stage were analyzed and are reported. As discussed in previous literature,[19] the third minute of an exercise stage represents a steady state; thus, it was the only minute from each rest and exercise period used for data analysis in this investigation.

[Figure 1 ILLUSTRATION OMITTED]

Table.

Heart Rate (HR), Oxygen Consumption ([VO.sub.2], Systolic Pressure (SBP), Diastolic Blood Pressure (DBP), Ventilation ([VE]), Rate of Perceived Exertion (RPE), and Fatigue Scale (FS) Scores for the Average Third Minute of the 10 Exercise and Rest Stages During the Intermittent Exercise Protocol

                                    Exercise        Recovery

                                    X      SD       X      SD

HR (bpm)                         101.94   14.48   78.21   10.40
[VO.sub.2] (mL [multiplied by]
 [kg.sup.-1] [multiplied by]
 [min.sup.-1])                     8.27    3.58    3.16    1.23

SBP (mm Hg)                      126.90   15.80
DBP (mm Hg)                       79.06    9.05
[VE] (L/min)                      13.60    6.05    6.76    2.95
RPE                               13.15    2.72
FS                                                 3.23    0.92

The RPE and fatigue scale scores taken at the end of each exercise and rest stage, respectively, are shown in Figure 2. To assess physiological changes over time, metabolic variables assessed in exercise stages 2 through 10 were compared with those assessed in the initial exercise stage. There were no differences in HR, [VO.sub.2], RER, and RPE over time. Minute ventilation, however, was higher for the second stage of rest. In addition, fatigue scale scores were higher for the 5th, 6th, 9th, and 10th rest periods compared with the 1st rest period. Because of equipment malfunction, 2 subjects' blood lactate measurements were not used. Mean peak blood lactate was 1.31 mmol (SD=0.8) for the other 7 subjects.

[Figure 2 ILLUSTRATION OMITTED]

Symptoms

Before exercise. The questionnaires administered before the exercise session demonstrated that the subjects were limited by their disease. The Karnofsky Rating Scale was administered on 2 separate occasions prior to the exercise session to evaluate the reliability of the scores. The concordance on the Karnofsky Rating Scale scores was high (r=.69, P [is less than] .05). The mean score for the. Karnofsky Rating Scale administered 1 month prior to the exercise session was 63.75 (SD=11.88). A score near 60 indicates that most of our subjects were able to care for most needs, but required occasional assistance.[10] The mean score for the MOS-20 administered 1 month prior to the exercise session was 41.8 (SD=9.64). For both of these questionnaires, a score of 100 would indicate excellent health.[10,11] The mean score for total leisure-time activity as assessed by the ARIC/Baecke Questionnaire was 1.81 (SD=0.53). This score is much lower than that reported for a sample of men and women without functional limitations (men: [bar]X=2.95, SD=0.61; women: [bar]X=2.84, SD=0.68).[12] The mean score for the Activity Restriction Index obtained immediately prior to exercise was 4.13 (SD-0.75). A score of 1 would indicate no limitation, whereas a score of 6 would indicate severe limitation in performing a variety of activities.[13]

After exercise. Based on information obtained from the symptoms log, all of the subjects felt that their symptoms did not worsen severely after exercise. Some subjects, however, reported experiencing headaches, leg pain, fatigue, or sore throats, all characteristic of CFS. Comparison of Karnofsky Rating Scale mean scores of 66.67 (SD=10.0) obtained immediately before exercise and 67.50 (SD=11.65) obtained 1 week after exercise revealed no change in degree of disability. A score near 70 indicates that most of our subjects felt that 1 week after exercise they were able to care for themselves, but were unable to work or carry on other normal activities.[10] Comparison of MOS-20 mean scores of 43.2 (SD=8.4) obtained immediately before exercise and 43.4 (SD=7.3) obtained 1 week after exercise revealed no change in general health. Activity Restriction Index mean scores showed a slight improvement from 4.13 (SD=0.75) immediately before exercise to 3.88 (SD=1.43) 1 week after exercise. As shown in Figure 3, Radial Plot of Symptoms scores improved slightly immediately after exercise and every day for 7 days after exercise.

[Figure 3 ILLUSTRATION OMITTED]

Standard scores for each of the POMS categories for tests done before exercise, immediately after exercise, and on days 1, 2, and 7 after exercise are illustrated in Figure 4. Tension scores improved immediately after exercise, depression scores improved immediately and I day after exercise, and anger scores improved 2 days after exercise. Figure 4 also indicates that confusion, fatigue, and vigor scores did not change after exercise.

[Figure 4 ILLUSTRATION OMITTED]

Discussion

The purposes of this study were to characterize the physiological and psychological responses of subjects with CFS to intermittent exercise and to determine whether this stimulus worsened or improved symptoms in these subjects. This study demonstrated that 30 minutes of light-intensity intermittent exercise did not appear to exacerbate symptoms. Follow-up revealed no difference in Karnofsky Rating Scale, MOS-20, and Activity Restriction Index scores obtained immediately before exercise and 7 days after exercise and no differences in fatigue, vigor, and confusion scores for the POMS from the pre-exercise measurement to the day 1, 2, and 7 post-exercise measurements. In addition, Radial Plot of Symptoms scores did not change from the pre-exercise measurement to the measurement done each day for 7 days after exercise. Although these scores did not improve after exercise, the fact that these subjects felt that their level of disability, general health, and ability to engage in a variety of activities did not decline after exercise is very important to the scope of this study.

Furthermore, some of the instruments indicated improvement in symptoms after exercise. For instance, the POMS indicated that there was a reduction in tension scores immediately following exercise, in depression scores immediately and on day 1 following exercise, and in anger scores on day 2 following exercise. This low level of exercise seemed to relieve stress and improve mood, as some studies have previously indicated for other populations.[20] Conversely, symptom logs indicated that some subjects experienced fatigue, headaches, leg pain, or sore throats. These symptoms may have been due to the underlying disease and not the exercise protocol, as none of the scores from the health and well-being instruments worsened from before exercise to following exercise. These results suggest that some patients with CFS may be able to perform low levels of activity intermittently throughout the day to achieve health benefits without worsening their symptoms.

Our primary goal was to establish a practical protocol that subjects could do at their leisure. The subjects walked at a relatively low speed with no grade. They were encouraged to choose the speed that would best represent the speed at which they would walk if they began an intermittent walking program at home. On average, the subjects walked at a mean speed of 0.71 m [multiplied by] [s.sup.-1] (SD=0.20) ([bar]X=1.58 [mph.sup.-1], SD=0.44) at a mean [VO.sub.2] of 8.27 mL [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1] (SD=3.58). At the same speed, it is predicted that subjects without functional limitations would consume 7.76 mL [multiplied by] [kg.sup.-1] [multiplied by] [min.sup.-1].21 Although these subjects walked at a relatively low [VO.sub.2] and expended only approximately 420 kJ (100 kcal) while walking, these results are encouraging. Some patients with CFS may be able to approach the Surgeon General's recommendation of performing physical activity that uses approximately 630 kJ (150 kcal) of energy per day.[7]

Our physiological data did not show any abnormal responses in the subjects to low-intensity intermittent exercise. At no time during the protocol did their HR, BP, RER, and RPE change to indicate physiological distress. The VE for the second rest stage was elevated, and there was a trend for the RER to decrease somewhat over time for both the exercise and recovery stages. These findings may have been due to initial discomfort and anxiety from walking on the treadmill. As the exercise continued, anticipation declined and VE eventually more closely matched [VO.sub.2]. In addition, we measured blood lactate to detect any abnormal lactate responses to the entire session. Abnormal lactate responses to low levels of exertion have previously been described.[22] Because peak blood lactate levels did not exceed 2 mmol and peak RER did not approach a value of 1, our data do not indicate a reliance on anaerobic energy metabolism during the low-intensity exercise protocol used in this study.[23,24] Although RPE did not change throughout the protocol, fatigue did change. Subjects felt that their fatigue worsened during the latter half of the exercise session, possibly indicating a duration threshold of about 15 minutes of actual exercise. Because their symptoms did not worsen following exercise, however, this increase in fatigue (approximately 1.2 units on a scale of 1 to 5) during exercise may not serve as a good marker for potential symptom exacerbation. That is, if a person's fatigue score changes within this range while using this protocol, it does not necessarily mean that he or she is going to feel worse following exercise.

Conclusion

Currently, there are no data suggesting that exercises are effective as a primary treatment for patients with CFS. Patients with CFS typically feel much worse after modest amounts of physical exercise. Some investigators have suggested the onset of severe symptoms to be 6 to 48 hours following exercise[25] and to last from 2 days to 2 weeks.[2,26] We demonstrated that low levels of intermittent aerobic exercise did not exacerbate symptoms in our 9 subjects with CFS. This protocol may be important not only for improving the fitness levels of patients with CFS, but also for patients with other illnesses in which the ability to exercise is hindered by fatigue (eg, multiple sclerosis).

We did not determine whether 30 minutes of continuous exercise would exacerbate symptoms in our sample of subjects with CFS. All 10 subjects, however, felt that they could not exercise for 30 minutes without experiencing exacerbation of symptoms. In addition, from review of the literature, it appears that patients with CFS cannot tolerate exercise of a duration and intensity tolerated by people without functional limitations.[2-5] This is a limitation of this study, however, and future investigation is warranted to determine whether 30 minutes of intermittent exercise is adequate to improve fitness without inducing exacerbation of symptoms in patients with CFS.

(*) Quinton Instrument Co, 2121 Terry Ave, Seattle, WA 98121.

([dagger]) Polar CIC Inc, 99 Seaview Blvd, Port Washington, NY 11050.

([double dagger]) Aerosport, 3518 West Liberty, Ann Arbor, MI 48103.

([sections]) Yellow Springs Instrument Co Inc, 1725 Brannum Ln, Yellow Springs, OH 45387.

([parallel]) SAS INstitute Inc, PO Box 8000, Cary, NC 27511.

References

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[2] Komaroff AL. Clinical presentation of chronic fatigue syndrome. In: Bock GR, Whalan J, eds. Chronic Fatigue Syndrome. Chichester, England: John Wiley & Sons Ltd; 1993:43-61. Ciba Foundation Symposium No. 173.

[3] Gibson H, Carroll N, Clague JE, Edwards RHT. Exercise performance and fatiguability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1993;56:993-998.

[4] Behan PO, Behan WHM, Bell EJ. The postviral fatigue syndrome: an analysis of the findings in 50 cases. J Infect. 1985;10:211-222.

[5] Sisto SA. Chronic fatigue syndrome: an overview and intervention guidelines. Neurol Rep. 1993; 17:30-40.

[6] Fukuda K, Straus S, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. Ann Intern Med. 1994; 121:953-959.

[7] Shalala DE. Physical Activity and Health: A Report of the Surgeon General. Atlanta, Ga: Centers for Disease Control and Prevention; 1996.

[8] DeBusk RF, Stenestrand U, Sheehan M, Haskell WL. Training effects of long versus short bouts of exercise in healthy subjects. Am J Cardiol. 1990;65:1010-1013.

[9] Sisto SA, LaManca J, Cordero DL, et al. Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome. Am J Med. 1996;100:634-640.

[10] Bell DS. The Doctor's Guide to Chronic Fatigue Syndrome: Understanding and Treating, and Living With CFIDS. Readling, Mass: Addison-Wesley Publishing Co; 1994;124:126-130.

[11] Stewart AL, Hays RD, Ware JE Jr. The MOS short-form general health survey: reliability and validity in a patient population. Med Care. 1988;26:724-735.

[12] Richardson MT, Ainsworth BE, Wu HC, et al. Ability of the Atherosclerosis Risk in Communities (ARIC)/Baecke Questionnaire to assess leisure-time physical activity. Int J Epidemiol. 1995;24:685-693.

[13] Bou-Holaigah I, Rowe PC, Kan J, Calkins H. The relationship between neurally mediated hypotension and the chronic fatigue syndrome. JAMA. 1995;274:961-967.

[14] McNair DM, Lorr M, Droppleman LF. Profile of Mood States: Manual. San Diego, Calif: Educational and Industrial Testing Service; 1971.

[15] Borg GAV. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14:377-381.

[16] Nyenhuis DL, Yamamoto C, Luchetta T, et al. Adult and geriatric normative data and validation of the profile of mood states. J Clin Psychol. 1999;55:79-86.

[17] Kerlinger FN. Foundations of Behavioral Research. Orlando, Fla: Holt, Rinehart and Winston Inc; 1973.

[18] SAS User's Guide: Statistics, Version V. Cary, NC: SAS Institute Inc; 1985.

[19] McArdle WD, Katch FI, Katch VI. Exercise Physiology: Energy, Nutrition, and Human Performance. 3rd ed. Philadelphia, Pa: Lea & Febiger; 1991:92-144.

[20] Brown DR. Exercise, fitness, and mental health. In: Bourchard C, Shepard RJ, Stephens T, et al, eds. Exercise Fitness and Health. Champaign, Ill: Human Kinetics Inc; 1990:607-626.

[21] Kenny WL, Humphrey RH, Bryant CX. American College of Sports Medicine's Guidelines for Exercise Testing and Prescription. 5th ed. Baltimore, Md: Williams & Wilkins; 1995:278-279.

[22] Lane RJM, Burgess AP, Flint J, et al. Exercise responses and psychiatric disorder in chronic fatigue syndrome. BMJ. 1995;311: 544-545.

[23] Wilmore JH, Costill DL. Physiology of Sport and Exercise. Champaign, Ill: Human Kinetics Inc; 1994:109.

[24] Howley ET, Franks BD. Health Fitness Instructor's Handbook. 2nd ed. Champaign, Ill: Human Kinetics Inc; 1992:37.

[25] McCully KK, Sisto SA, Natelson BH. Use of exercise for treatment of chronic fatigue syndrome. Sports Med. 1996;21:35-48.

[26] Kent-Braun JA, Sharma KR, Weiner MW, et al. Central basis of muscle fatigue in chronic fatigue syndrome. Neurology. 1993;43:125-131.

LL Clapp, PhD, is Instructor, Health, Physical Education, and Recreation Department, Southwest Texas State University, Jowers Center, 601 University Dr, San Marcos, TX 78666 (USA) ([e-mail]). She was a graduate student in Human Performance Studies, Department of Education, The University of Alabama, Tuscaloosa, Ala, at the time this study was conducted.

MT Richardson, PhD, is Associate Professor, Human Performance Studies, Department of Education, The University of Alabama, Tuscaloosa.

JF Smith, PhD, is Professor and Chair, Human Performance Studies, Department of Education, The University of Alabama, Tuscaloosa.

M Wang, PhD, is Professor, Health Studies, Department of Professional Studies, The University of Alabama, Tuscaloosa.

AJ Clapp, PhD, is Assistant Professor, Department of Health Sciences, Florida Atlantic University, Boca Raton, Fla. He was a graduate student in Human Performance Studies, Department of Education, The University of Alabama, Tuscaloosa, at the time this study was conducted.

RE Pieroni, MD, is Professor of Internal Medicine and Family Medicine, The University of Alabama, Tuscaloosa.

LL Clapp, Richardson, Smith, Wang, and Pieroni provided the concept and research design; LL Clapp and Richardson wrote the manuscript; LL Clapp and AJ Clapp collected the data; LL Clapp, Richardson, Wang, and AJ Clapp analyzed the data; LL Clapp and Richardson managed the project and provided the subjects; LL Clapp, Richardson, Smith, AJ Clapp, and Pieroni provided facilities and equipment; LL Clapp, Richardson, Smith, and Pieroni provided institutional liaisons; LL Clapp and AJ Clapp provided clerical/secretarial support; and LL Clapp, Richardson, and Pieroni provided consultation (including review of the manuscript before submission).

This study was approved by The University of Alabama's Committee for the Protection of Human Subjects in Research.

This article was submitted July 10, 1998, and was accepted April 26, 1999.3