Get Free USA Shipping Over $99.00. Flat-rate Shipping Fee $6.95 otherwise.
The following articles are presented as support for the findings of the role of minerals in the research of fibromyalgia.
Magazine: Southern Medical Journal, April, 1994
Our prospective, standardized cohort study was designed to assess the presence of alpha wave intrusions during non-rapid eye movement sleep (alpha-delta sleep) and its relationship to fibromyalgia, major depression, and chronic fatigue syndrome (CFS) in patients with a chief complaint of chronic fatigue. The study group comprised 30 consecutive patients seen at a university hospital referral clinic for evaluation of chronic fatigue. All patients had nocturnal polysomnography, dolorimetric tender point assessment for fibromyalgia, a comprehensive history, physical, and laboratory evaluation, and a structured psychiatric interview. Alpha-delta sleep was identified in 8 of the 30 patients (26%), major depression in 20 (67%), CFS in 15 (50%), and fibromyalgia in 4 (13%). Ten of the 30 patients (33%) had a primary sleep disorder (sleep apnea, periodic limb movements, or narcolepsy). Alpha-delta sleep was not significantly correlated with fibromyalgia, CFS, major depression, or primary sleep disorders, but was significantly more common among patients who had chronic fatigue without major depression. We conclude that primary sleep disorders are relatively common among patients with chronic fatigue and must be diligently sought and treated. Alpha-delta sleep is not a marker of fibromyalgia or CFS, but may contribute to the illness of nondepressed patients with these conditions.
ALPHA-DELTA SLEEP was first described in 1973 as an unexpected finding during studies of sleep in patients with various psychiatric disorders. The anomaly observed was an atypical electroencephalographic (EEG) pattern recorded during non-rapid eye movement (non-REM) sleep. The EEG appearance contained the expected delta waves (amplitude greater than 75 microvolts, frequency 0.5 to 2.0 cycles per second), intruded upon by prominent alpha activity (frequency 7 to 10 cycles per second). In normal individuals, alpha activity is characteristic of drowsy wakefulness, and delta activity indicates restorative non-REM sleep. The only clinical similarity among the patients with alpha-delta sleep was "a general feeling of chronic, somatic malaise and fatigue".(r1)
In a landmark study published in 1975, alpha delta sleep was noted to occur in a majority (70%) of patients with fibromyalgia, a common rheumatologic condition characterized by muscle pain, dysphoria, and fatigue, and among healthy subjects deprived of non-REM sleep.(r2) In the latter group, the alpha-delta sleep was correlated with objective evidence of increased muscle tenderness and the appearance of depression and irritability. Additional studies indicated that the experimental production of non-REM sleep deprivation induced alpha-delta sleep and muscle achiness and stiffness, overwhelming physical tiredness, heaviness, and sluggishness.(r3) Because mood disorders are often diagnosable in patients with fibromyalgial,(r4) the presence of alpha-delta sleep was assessed in patients with fibromyalgia and depressed patients of similar age and sex distribution.(r5) Alpha-delta sleep was present in 60% of patients with fibromyalgia and 42% of patients with major depression.
Alpha-delta sleep was also invoked as a mechanism for symptom production in patients with chronic fatigue syndrome (CFS), an entity characterized by disabling fatigue, myalgias, arthralgias, sleep disturbance, neuropsychologic abnormalities, fever, pharyngitis, and cervical adenopathy.(r6) CFS has been shown to overlap substantially with major depression(r7-r11) and to share many features of the syndrome of fibromyalgia.(r12) In the only study available to date, 14 patients with CFS were compared with 12 healthy controls. Prominent alpha intrusions during non-REM sleep were observed in all patients.(r13)
If consistently found, alpha-delta sleep could emerge as an important feature and perhaps as a biologic marker of many states characterized by chronic fatigue. Based on this premise, we undertook a prospective study to determine the frequency of alpha-delta sleep among patients with a chief complaint of chronic fatigue and to clarify the relationship of alpha-delta sleep with CFS fibromyalgia, and major depression as diagnosed in our study's patient population.
This prospective study was conducted in the Chronic Fatigue Clinic of the University of Connecticut Health Center, Farmington. The 30 consecutive patients in the study were 18 years of age or older (mean age 41 years, SD 7.9 years), had experienced persistent tiredness for at least 6 months, and had not been hospitalized during the 3 months before evaluation. All patients were non-Hispanic whites, and 21 (70%) were female. All patients agreed to the following study protocol: (1) a one-night sleep study; (2) a rheumatologic evaluation including dolorimetric testing for fibromyalgia; (3) a comprehensive laboratory evaluation including a general health panel, virologic and bacteriologic testing, and assessment of cellular and humoral immunity; (4) a complete history and physical examination; and (5) a psychiatric evaluation using a highly structured interview schedule. For patients with irresistible daytime somnolence, additional laboratory investigations included diurnal multiple sleep latency testing.
One-night sleep studies were done by accredited clinical polysomnographers. The recording montage included the EEG leads C[sub3]/A[sub2] and C[sub4]/A[sub1], electro-oculogram, and submental and anterior tibialis electromyograms. Nasal and oral airflow, respiratory effort (by inductance plethysmography), and arterial oxygen saturation were also continuously and simultaneously recorded. The sleep recordings were scored in 30-second epochs according to standard criteria.(r14) Alpha-delta sleep was diagnosed in the presence of prominent alpha frequency activity occurring tonically during non-rapid eye movement sleep (Figure). Arousals and awakenings were recorded and were designated as associated with limb movements or with apnea. Sleep apnea was diagnosed in patients whose oral-nasal airflow ceased for longer than 10 seconds at least five times per hour of sleep.(r15) For those patients having multiple sleep latency testing, narcolepsy was diagnosed if two or more sleep onset REM periods with a mean latency of less than 5 minutes occurred during five 20-minute nap opportunities spaced about 2 hours apart.(r15)
This portion of the study was done according to the American College of Rheumatology criteria. for the diagnosis of fibromyalgia.(r16) Patients were tested for 18 tender points by applying pressure with the index, third, and fourth fingers of the examiner's hand at the following nine bilateral surface sites: (1) the suboccipital muscle insertions, (2) the anterior aspects of the intertransverse spaces at C5-7, (3) the midpoint of the upper border of the trapezius, (4) the supraspinatus, at its origins above the scapular spine near the medial border, (5) the second costodhondral junctions, (6) 2 cm distal to the epicondyles, (7) in the upper outer quadrants of the buttocks, (8) posterior to the trodhanteric prominence, and (9) the knee, at the medial fat pad proximal to the joint line. Patients with 11 or more significantly tender points, generalized myalgias, and no other rheumatologic disease were classified as having fibromyalgia.
Comprehensive laboratory testing was done to identify medical disorders known to be associated with chronic fatigue. Data collected on all patients included complete blood cell count with differential white blood cell count, erythrocyte sedimentation rate, plasma glucose, creatinine, sodium, potassium, chloride, bicarbonate, calcium, phosphorus, magnesium, alanine aminotransferase, total protein, alkaline phosphatase, total bilirubin, iron, thyroid-stimulating hormone, thyroxine radioimmunoassay, triiodothyronine resin-uptake, cortisol, rheumatoid factor, antinuclear antibody, complement (CH[sub50]) levels, antithyroid microsomal antibody, antithyroglobulin antibody, total immunoglobulin (IgG) and IgG subclass levels, T4 and T8 surface marker cell counts, Lyme disease IgM and IgG antibodies by ELISA and Western immunoblot, and urinalysis.
The history-taking was semistructured and included explicit questions about the time of onset of fatigue, the degree of disability produced by the fatigue syndrome, and the presence and timing of the 11 CFS symptom criteria (feverishness, sore throat, tender or swollen cervical or axillary lymph nodes, myalgias, arthralgias, generalized headache, muscle weakness, postexercise fatigue, sleep disturbance, neuropsychologic abnormalities, and sudden onset). The physical-sign criteria of CFS (fever, nonexudative pharyngitis, and cervical or axillary lymphadenopathy) were assessed both by thorough review of previous medical evaluations and as part of the complete physical examination. The diagnosis of CFS was made in patients with (1) disabling fatigue (50% reduction in activity as compared with the premorbid activity level) of at least 6 months' duration and (2) at least eight of the symptom criteria or at least six symptom criteria and two physical-sign criteria.(r16)
Psychiatric diagnoses were based on the results of the Diagnostic Interview Schedule (DIS) of the National Institute of Mental Health, Version III-A, a highly structured diagnostic instrument.(r17) The questions 16-100 and 210-213 of this instrument were used to obtain diagnostic assessments for somatization disorder, panic disorder, generalized anxiety disorder, major depression, and dysthymia in current, previous 6 months, and lifetime time frames according to standard diagnostic criteria for mental disorders.(r18)
The study population was divided according to the presence of alpha intrusions during non-REM sleep. The statistical significance of differences was assessed by the chi-square test for proportions and the two-tailed t test for ordinal variables.
Medical and/or psychiatric conditions were diagnosed in 26 patients (87%) (Table 1). The most common diagnosis was that of major depression, active at the time of the examination in 20 patients (67%). Fibromyalgia was present in four (13%). All four patients with fibromyalgia were women, and all also met diagnostic criteria for both CFS and major depression, current at the time of examination. Two patients had medical conditions other than primary sleep disorders and fibromyalgia; Sjogren's syndrome and anemia were diagnosed in one patient and chronic Lyme disease in the other.
Fifteen (50%) of the 30 patients met the recently proposed research criteria for the diagnosis of CFS. The difference in the proportion of patients with active psychiatric disorders, sleep disorders, and alpha-delta sleep was statistically similar among the 15 patients with CFS and the 15 other patients with chronic fatigue (Table 2). Patients with CFS and the others with chronic fatigue also showed similar sleep architecture and sleep continuity (Table 3).
Eleven sleep disorders (5 cases of periodic limb movements with frequent awakenings, 3 cases of sleep apnea with oxygen desaturation, 1 case of both sleep apnea and periodic limb movements, and 1 case of narcolepsy) were found in 10 patients (33%). The age and sex distribution of the patients with sleep disorders were not statistically different from those of patients with normal sleep. Eight of the 10 patients with sleep disorders had a total of 12 psychiatric diagnoses likely to contribute to their chronic fatigue (7 cases of depression, 3 of panic disorder, and 2 of somatization disorder).
Alpha-delta sleep was recorded in 8 of the 30 patients with chronic fatigue (27%). Alpha-delta sleep was present in 4 of the 10 patients with sleep disorders: 2 patients had periodic limb movements and 1 each had sleep apnea and narcolepsy. None of the 4 cases of fibromyalgia showed evidence of alpha-delta sleep. Major depression was diagnosed in 3 of the 8 patients (37%) with alpha-delta sleep and in 17 of the 22 patients (77%) without this atypical sleep EEG pattern (Table 4). Patients with alpha-delta sleep and the other patients with chronic fatigue had similar architecture and continuity (Table 5).
This prospective study of sleep characteristics of patients with a chief complaint of chronic-fatigue has identified a relatively large number of treatable sleep disorders contributing to chronic fatigue and has demonstrated that alpha-delta sleep did not correlate with the presence of major depression, fibromyalgia, or CFS in this population The findings raise a number of clinically relevant issues with regard to the relationship between chronic fatigue and disordered sleep.
The first issue is the correlation between EEG sleep patterns and the presence of a depressive disorder. Mood disorders are commonly diagnosed among patients with chronic fatigue, the predominant diagnosis being that of major depression, either with recurrent episodes or as a prolonged single episode.(r18-r19)Electroencephalographic sleep research studies have identified REM sleep abnormalities as biologic markers for primary depression.(r20-r23) Our findings offer indirect support to this thesis, because we have identified a non-REM sleep event (ie, alpha intrusions during stage 4 of sleep) in a larger proportion of patients without a depressive disorder.
The second issue is the association between alpha-delta sleep and fibromyalgia. Alpha-delta sleep was not present on the polysomnograms of the patients with fibromyalgia diagnosed among our clinical sample. The discrepancy between our results and those of others(r2, r5) may be due to the small number of cases; because only 4 of the 30 patients with chronic fatigue had fibromyalgia, the possibility of a type I error cannot be excluded. The fact that our patients had a chief complaint of chronic fatigue, whereas "fibrositis" patients studied by other researchers reported muscle pain as their most bothersome symptom(r2) may also be a confounding factor.
The third issue is the association between alpha-delta sleep and chronic fatigue syndrome. In contrast to data contained in the only other study devoted to this problem,(r13) this atypical EEG pattern did not appear to characterize patients with CFS. However, the majority of our patients with CFS had nonpsychotic major depression, a psychiatric disorder that is no longer considered exclusionary for the case definition of CFS(r6) and one that, at least in our study, did not seem to be associated with alpha-delta sleep.
Last but not least, the fourth issue raised by our study is the identification of well-characterized sleep disorders as the most common physical disorders diagnosable among patients with chronic fatigue. Six of the 10 patients with sleep disorders reported significant daytime somnolence, but the specificity of this symptom appeared to be low, given the fact that most of the patients we have seen with chronic fatigue have disturbed sleep.(r24) Nevertheless, we believe the evaluation of patients with chronic fatigue should include a thorough inventory of sleep-related symptoms and an effort to distinguish fatigue and weakness from daytime somnolence.
Although the design of our prospective diagnostic study did not plan for a therapeutic component, treatment was offered to patients with alpha-delta sleep and sleep disorders, and substantial improvement was noted in some patients. For example, a 33-year-old machinist had a 7-year history of disabling fatigue and symptoms of feverishness, muscle weakness, and difficulty with concentration. The patient had no detectable medical or psychiatric disorder, and did not fulfill criteria for CFS. Alpha-delta sleep was recorded by nocturnal polysomnography. All symptoms improved considerably 1 month after initiation of treatment with a moderate dose of a serotonin-reuptake inhibitor. He had shown no improvement on successive therapeutic attempts with trazodone, amitriptyline, desipramine, bupropion, and alprazolam. Another case is that of a 39-year-old woman who had a previous diagnosis of CFS and who complained of excessive daytime sleepiness and difficulty with concentration. She was found to have obstructive sleep apnea, which was eliminated by treatment with nasal continuous positive airway pressure (CPAP). After several months of nasal CPAP therapy, she reported that she no longer had fatigue or other symptoms. A third example is a 44-year-old woman who had become so fatigued that she was barely able to carry out her household chores. She had impaired concentration, poor memory, and muscle pain, and she required frequent naps during the day because of fragmented sleep. In the sleep laboratory she was found to have periodic limb movements with frequent awakenings. After the initiation of treatment with low doses of clonazepam, she had no further symptoms of chronic fatigue or excessive daytime somnolence.
The results of our study should be interpreted with caution, because the sample size was relatively small and the results were not controlled by data obtained simultaneously from patients with major depression and fibromyalgia, but without chronic fatigue. Although a "first-night effect"(r25) was observed in only five of the 30 patients we studied, our data would have been stronger if confirmed by a second or third night evaluation in the sleep laboratory. Nevertheless, we believe it is reasonable to conclude that one-night EEG sleep studies, the current standard for the evaluation of sleep disorders, may contribute to the understanding of the pathophysiology of chronic fatigue by identifying two subgroups of patients. The first subgroup would include the individuals in whom a well-characterized and treatable sleep disorder could be wholly or partly responsible for the chronic fatigue state. Given the substantial proportion of treatable sleep disorders identified in this prospective study, clinicians may want to lower their threshold for using diagnostic sleep laboratories within the framework of a cost/benefit decision that will acknowledge the financial burden of such a referral. The second group would comprise patients with alpha-delta sleep, an atypical EEG pattern that seems to be prevalent among nondepressed chronic fatigue patients who do not have chronic fatigue syndrome or fibromyalgia. Continued research is clearly needed to understand the mechanisms of this nonrestorative sleep, to clarify the nature of its relationship with syndromes dominated by symptoms of fatigue and muscle pain, and to evaluate pharmacologic agents that could prevent the alpha intrusion anomaly.
TABLE 1. | ||
No. | % | |
Patients with attributable diagnoses | 26 | 87 |
Psychiatric disorders | 24 | 80 |
Chronic fatigue syndrome | 15 | 50 |
Sleep disorders | 10 | 33 |
Fibromyalgia | 4 | 13 |
Other physical disorders | 2 | 7 |
Patients without attributable diagnoses | 4 | 13 |
TABLE 2. | ||||
CFS (n=15) | Other (n=15) | |||
No. | % | No. | % | |
Fibromylagia | 4 | 27 | 0 | 0 |
Alpha-delta sleep | 2 | 13 | 6 | 40 |
Sleep disorders | 6 | 40 | 8 | 53 |
Periodic limb movements | 5 | 33 | 1 | 7 |
Obstructive sleep apnea | 1 | 7 | 3 | 20 |
Narcolepsy | 0 | 0 | 1 | 7 |
Psychiatric disorders | 12 | 80 | 12 | 80 |
Major depression | 11 | 73 | 9 | 60 |
class="mediumfont"Panic disorder | 4 | 26 | 3 | 20 |
Somatization disorder | 3 | 20 | 2 | 13 |
Generalized anxiety | 0 | 0 | 2 | 13 |
Some patients had more than one psychiatric diagnosis or sleep disorder.
TABLE 3. | ||||
CFS (n=15) | Other (n=15) | |||
Mean | SD | Mean | SD | |
Sleep continuity (minutes) | ||||
Sleep latency | 37 | 31 | 30 | 25 |
REM latency | 116 | 53 | 106 | 50 |
Total sleep time | 337 | 86 | 323 | 96 |
Sleep architecture (%) | ||||
Stage 1 | 6 | 4 | 10 | 14 |
Stage 2 | 56 | 10 | 53 | 11 |
Stage 3 | 7 | 8 | 5 | 2 |
Stage 4 | 11 | 7 | 14 | 9 |
REM sleep | 19 | 7 | 17 | 8 |
TABLE 4. | ||||
Patients with Alpha-Delta Sleep (n=8) | Other Patients with Chronic Fatigue (n=22) | |||
Age (mean and SD) | 44.1 | (10.2) | 39.9 | (6.6) |
Female sex | 6 | (75%) | 15 | (68%) |
Psychiatric disorders | 5 | (62%) | 19 | (86%) |
Major depression | 3 | (37%) | 17 | (77%)[*] |
Somatization disorder | 3 | (37%) | 2 | (9%) |
Panic disorder | 2 | (25%) | 5 | (22%) |
Sleep disorders | 4 | (50%) | 6 | (27%) |
Nocturnal myoclonus | 2 | (25%) | 4 | (18%) |
Sleep apnea | 1 | (12%) | 3 | (13%) |
Narcolepsy | 1 | (12%) | 0 | (0%) |
Chronic fatigue syndrome | 2 | (25%) | 13 | (59%) |
[*] P <.05.
TABLE 5. | ||||
Patients with Alpha-Delta Sleep (n=8) | Other Patients with Chronic Fatigue (n=22) | |||
Mean | SD | Mean | SD | |
Sleep continuity (minutes) | ||||
Sleep latency | 37 | 30 | 30 | 27 |
REM latency | 101 | 33 | 115 | 80 |
Total sleep time | 312 | 107 | 337 | 84 |
Sleep architecture (%) | ||||
Stage 1 | 6 | 5 | 9 | 12 |
Stage 2 | 49 | 7 | 56 | 11 |
Stage 3 | 7 | 3 | 7 | 2 |
Stage 4 | 4 | 19 | 10 | 7 |
REM sleep | 19 | 9 | 18 | 7 |
GRAPHS: Electroencephalographic deep recordings of 42-year-old woman with chronic fatigue. Clinical evaluation showed evidence of somatization disorder. Panel A-alpha sleep. Panel B-delta sleep. Panel C-alpha intrusion during delta sleep.
(r1.) Hauri P, Hawkins DR: Alpha-delta sleep. Electroencephalogr Clin Neurophysiol 1973; 34: 233-237
(r2.) Moldafsky H, Scarisbrick P, England R, et al: Musculoskeletal symptoms and nonREM sleep disturbance in patients with "fibrositis syndrome" and healthy subjects. Psychosom Med 1975; 37: 341-351
(r3.) Moldofsky H, Scarisbrick P: Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation. Psychosom Med 1976; 38: 35-44
(r4.) Hudson JI, Pope HG Jr: Fibromyalgia and psychopathology: is fibromyalgia a form of "affective spectrum disorder"? J Rheumatol 1989; 16 (suppl 19): 15-22
(r5.) Ware JC, Russell JJ, Campos E: Alpha intrusions into the sleep of depressed and fibromyalgia syndrome (fibrositis) patients. Sleep Res 1986; 15: 210
(r6.) Schluederberg A, Straus SE, Peterson P, et al: Chronic fatigue syndrome research: definition and medical outcome assessment. Ann Intern Med 1992; 117: 325-331
(r7.) Taerk GS, Toner BB, Salit IE, et al: Depression in patients with neuromyasthenia (benign myalgic encephalomyelitis). Int J Psychiatry Med 1987; 17: 49-56
(r8.) Kruesi MJP, Dale J, Straus SE: Psychiatric diagnoses in patients who have chronic fatigue syndrome. J Clin Psychiatry 1989; 50: 53-56
(r9.) Wessely S, Powell R: Fatigue syndromes: a comparison of chronic "post-viral" fatigue with neuromuscular and affective disorders. J Neurol Neurosurg Psychiatry 1989; 52: 940-948
(r10.) Hickie I, Lloyd A, Wakefield D, et al: The psychiatric status of patients with the chronic fatigue syndrome. Br J Psychiatry 1990; 156: 534-540
(r11.) Lane TJ, Manu P, Matthews DA: Depression and somatization in the chronic fatigue syndrome. Am J Med 1991; 91: 334-344
(r12.) Goldenberg DL, Simms RW, Geiger A, et al: High frequency of fibromyalgia in patients with chronic fatigue seen in a primary care practice. Arthritis Rheum 1990; 33: 381-387
(r13.) Whelton CL, Salit I, Moldofsky H: Sleep, Epstein-Barr virus infection, musculoskeletal pain, and depressive symptoms in chronic fatigue syndrome. J Rheumatol 1992; 19: 939-943
(r14.) Rechtschaffen A, Kales A: A ManuaI of Standardized Terminology, Techniques and Scoring System for Sleep Stages of Human Subjects. NIH publication 204, Washington, DC, US Government Printing Office, 1968
(r15.) Green I: Polysomnography and Sleep Disorders Centers. Agency for Health Care Policy and Research, Health Technology Assessment Reports, No. 4, 1991. US Department of Health and Human Services, AHCPR Publication No. 92-0027, Rockville, Md, May 1992
(r16.) Wolfe FW, Smythe HA, Yunus MB, et al: The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Arthritis Rheum 1990; 33: 160-172
(r17.) Robins LN, Helzer E Jr: Diagnostic Interview Schedule (DIS). Version III-A. St. Louis, Mo, Department of Psychiatry, Washington University School of Medicine, May 1985
(r18.) American Psychiatric Association Committee on Nomenclature and Statistics: Diagnostic and Statistical Manual of Mental Disorders. 3rd Ed revised. Washington, DC, American Psychiatric Association, 1987
(r19.) Manu P, Matthews DA, Lane TJ, et al: Depression among patients with a chief complaint of chronic fatigue. J Affect Dis 1989; 17: 165-172
(r20.) Katon WJ, Buchwald DS, Simon GE, et al: Psychiatric illness in patients with chronic fatigue and those with rheumatoid arthritis. J Gen Intern Med 1991; 6: 277-285
(r21.) Kupfer DJ: REM latency: a psychobiologic marker for primary depressive disease. Biol Psychiatry 1976; 11: 159-174
(r22.) Reynolds CF, Taska LS, Jarrett DB, et al: REM latency in depression: is there one best definition? Biol Psychiatry 1983; 18: 849-863
(r23.) Akiskal HS, Lemmi H, Yerevanian B, et al: The utility of the REM latency test in psychiatric diagnosis: a study of 81 depressed outpatients. Psychiatry Res 1982; 7: 101-110
(r24.) Manu P, Matthews DA, Lane TJ, et al: The mental health of patients with a chief complaint of chronic fatigue. Arch Intern Med 1988; 148: 2213-2217
(r25.) Agnew HW, Webb WB, Williams RL: The first night effect: an EEG study of sleep. Psychophysiology 1966; 2: 263-266
From the Departments of Medicine and Psychiatry, University of Connecticut School of Medicine, Farmington, the Sleep Disorders Laboratory, Mount Sinai Hospital, Hartford, and the New Haven Sleep Disorders Center and Yale School of Medicine, New Haven.
Dr. Matthews was the recipient of the George Morris Piersol Teaching and Research Scholarship of the American College of Physicians (1989 to 1992). Dr. Abeles is supported in part by the University of Connecticut-National Institutes of Health Multipurpose Arthritis Center Grant No. 20621.
Reprint requests to Peter Manu, MD, Medical Director, Hillside Hospital, Long Island Jewish Medical Center, 75-59 263rd St, Glen Oaks, NY 11004.
~~~~~~~~
PETER MANU, MD, THOMAS J. LANE, MD, DALE A. MATTHEWS, MD, RICHARD J. CASTRIOTTA, MD, ROBERT K. WATSON, PhD, and MICHA ABELES, MD, Farmington, Connecticut