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Background: There are few data on the natural history and prognosis of persons with chronic fatigue (CF) or CF syndrome (CFS). Therefore, we compared functional outcomes in patients with each condition and tested the validity of various prognostic indicators., Methods: Four hundred forty-five (89%) of 498 consecutive referral patients were surveyed an average of 1.5 years after an initial evaluation. Data from the initial evaluation were used to predict outcomes., Results: Sixty-four percent of all patients reported improvement, but only 2% reported complete resolution of symptoms. Patients initially diagnosed as having CFS reported greater symptom severity and lower level of functioning at follow-up than did patients with CF. Major depression predicted unemployment in the CF group. Older age, longer duration of illness, and a lifetime history of dysthymia predicted less improvement in the CF group. Current dysthymia predicted less improvement for the CFS group., Conclusions: The case definition of CFS according to the Centers for Disease Control and Prevention identifies chronically fatigued patients with poorer prognosis. In a tertiary care setting, recovery from CF or CFS is rare, but improvement is common. Prognostic indicators vary for the two groups, but the coexistence of dysthymia suggests poorer outcomes generally.

We prospectively evaluated 201 Southeast Asian refugees in a primary care clinic for intestinal parasites and their association with gastrointestinal symptoms. Patients completed a standardized screening questionnaire which elicited information on demographic factors and eight gastrointestinal symptoms, and stools were collected for ova and parasite examination. Although 89% had been living in the U.S.A. for more than 1 year, intestinal parasites were found in 37 (18%) patients and pathogenic parasites in 23 (11%). Among these 37 patients with intestinal parasites, seven (19%) had multiple parasites. Seven pathogenic and four nonpathogenic species were identified. Hookworm was most prevalent (4.5%), followed by Strongyloides stercoralis (2.5%) and Clonorchis sinensis (2%). Cambodians had the highest prevalence (11%) and Vietnamese and highland Laotians the lowest (0%). Intestinal parasitosis was not associated with gender or duration of residence in the U.S.A. Individual symptoms had a low positive predictive value for the presence of pathogenic parasites. This suggests that even years after immigration a substantial number of Southeast Asian refugees may benefit from screening and treatment for intestinal parasites.

A brief, culture-specific, self-report screening measure for depression, the Vietnamese Depression Scale, was used to determine the prevalence of depressive symptoms among 1,998 consecutive adult Vietnamese refugees who presented at 10 public health clinics within 2 months of their arrival in the United States. Of these patients, 6% met the criterion for a probable case of depression ("positive"). Being divorced, separated, or widowed and poorly educated were strongly associated with a greater likelihood of screening positive. Somatic complaints were common and induced considerable anxiety about physical health status. Nearly a third of the patients reported sadness and dysphoria; culture-specific symptoms of depression also were prevalent. Our findings document the feasibility of screening for depression using the Vietnamese Depression Scale among Vietnamese refugees, particularly in primary care settings where they are first likely to be seen by health professionals after arrival in their host country.

Objectives: To investigate the point prevalence of the chronic fatigue syndrome and unexplained debilitating chronic fatigue in a community-based sample of persons and to describe demographic, clinical, and psychosocial differences among those with the chronic fatigue syndrome, those with chronic fatigue, and healthy controls., Design: Prospective cohort study., Setting: A health maintenance organization in Seattle, Washington., Participants: A random sample of 4000 members of the health maintenance organization was surveyed by mail for the presence of chronic fatigue., Measurements: Persons with chronic fatigue were evaluated using a questionnaire that requested information about medical history and fatigue and related symptoms; validated measures of functional status and psychological distress; a physical examination; and standardized blood tests. A structured psychiatric interview was done in persons who appeared to meet the original Centers for Disease Control and Prevention (CDC) criteria for the chronic fatigue syndrome. Participants completed self-report measures at 12 and 24 months. Those with chronic fatigue were reevaluated in person 1 year after study enrollment., Results: 3066 (77%) of the 4000 members surveyed responded. Chronic fatigue was reported by 590 persons (19%). Of these, 388 (66%) had a medical or psychiatric condition that could account for the fatigue. Of the 74 persons (37%) with chronic fatigue who were enrolled in the study, only 3 met the CDC criteria for the chronic fatigue syndrome. The remaining 71 persons were designated as having chronic fatigue alone. Seventy-four healthy, age- and sex-matched controls who were drawn from the same sample but who denied having chronic fatigue were also studied. Demographic characteristics were similar in persons with the chronic fatigue syndrome, persons with chronic fatigue alone, and controls. Those with the chronic fatigue syndrome or chronic fatigue alone had more frequent cervical and axillary adenopathy, poorer functional status, and greater psychological distress than controls. Women and minorities were not overrepresented among cases with chronic fatigue., Conclusions: Using different assumptions about the likelihood that persons who did not participate in the study had the chronic fatigue syndrome, the estimated crude point prevalence of the syndrome in this community ranged from 75 to 267 cases per 100,000 persons. The point prevalence of chronic fatigue alone was strikingly higher; it ranged from 1775 to 6321 cases per 100,000 persons.

Background: Morning report is a time-honored tradition of most internal medicine residency programs. Despite its ubiquity, residents' attitudes regarding morning report have not been investigated., Methods: Using a 44-item questionnaire, we surveyed residents in an academic internal medicine training program working in five teaching hospitals on the processes of teaching and learning during morning report., Results: Among 74 residents completing the survey (100%), morning report was ranked as the most valuable of six educational activities. Residents preferred discussing new cases, with time equally divided between "great" cases and common problems, an interactive discussion with open-ended questions, and a Socratic teaching style. Seventy-two percent stated that attending physicians should be chosen from among the best teachers. General medical knowledge (90%), an ability to ask effective questions (86%), and good interpersonal skills (84%) were identified as the most important attending physicians' attributes. Discussions of basic science, use of anecdotes, and subspecialty knowledge were not considered highly desirable characteristics. Attending physicians with limited knowledge (41%) were viewed as the major obstacle to effective teaching while provocative attending physicians (52%) were considered as being most valuable to the learning experience., Conclusions: Residents believed that the morning report was a valuable educational experience. They preferred clinically based, open-ended interactive discussions led by attending physicians with a broad knowledge base. These findings underscore the importance of morning report in general, and the role of attending physicians in particular, in medical education.

Objective: To identify important determinants of noncompliance among Cambodian refugees., Design: Open-ended interviews., Setting: University-affiliated ambulatory care clinic in an inner-city hospital., Participants: Thirty adult Cambodian refugees (15 men and 15 women) who were regular utilizers of a refugee clinic., Measurements and Main Results: Sixty-seven percent of the participants described being noncompliant with at least one of their medications. Four common causes of noncompliance were identified: 1) misunderstanding the intent of the medication; 2) side effects; 3) concern about the effect of medication on "internal strength"; and 4) Cambodian ideas about pharmacokinetics., Conclusions: Noncompliance was commonly reported by the Cambodian respondents. Noncompliance was both intentional and unintentional; the unintended noncompliance derived from patients' attempting to comply with therapy according to Cambodian ideas about the body and Western medication. This article suggests clinical approaches to enhance compliance with prescribed regimens among recent Cambodian immigrants and refugees.

The National Cholesterol Education Program's guidelines for the detection, evaluation, and treatment of high serum cholesterol in adults were employed in screening 155 Southeast Asian refugees in a primary care clinic in Seattle, Washington. In order to determine the need for a therapeutic intervention, information also was collected on the presence of other coronary heart disease (CHD) risk factors. Male gender (39%), cigarette smoking (27%) and hypertension (26%) were the most common CHD risk factors; diabetes mellitus, obesity, a family or prior history of CHD or cerebral/peripheral vascular disease were each noted in less than 10%. The mean serum total cholesterol was 194 mg/dl. Thirty-seven (24%) patients required further lipoprotein analysis based on cholesterol level, history of CHD and risk factors for CHD. Twenty-one (66%) of 32 patients who underwent lipoprotein analysis (14% of all patients) were candidates for a therapeutic intervention for hypercholesterolaemia. Additionally, 14 (44%) patients undergoing lipoprotein analysis had depressed high-density lipoprotein levels (< 35 mg/dl). We conclude that CHD risk factors including hypercholesterolaemia are common in Southeast Asian refugee clinic patients and that in many, a therapeutic intervention may well be justified. Southeast Asian refugees should be routinely screened for hypercholesterolaemia and other CHD risk factors in accordance with the National Cholesterol Education Program's guidelines.

Background: The prolonged disability of patients suffering from chronic fatigue may be due to sustaining factors that are independent of the cause and subject to intervention. This study reexamined a cohort of patients with chronic fatigue to define medical and psychiatric predictors of persistent symptoms., Methods: Seventy-eight patients with chronic fatigue present for 6 months or more (not required to meet the Centers for Disease Control case definition for chronic fatigue syndrome [CFS]) completed a self-report, follow-up questionnaire to measure the overall improvement or worsening of their condition at a mean of 2.5 years after their initial examination. At the time of initial evaluation, patients underwent a structured psychiatric examination, physical examination, laboratory studies, and self-report measures of psychological distress and functional disability. The psychiatric examination queried the patient about 28 somatic symptoms that are separate from those associated with CFS. Discriminant analysis was used to determine which variables present at the initial examination were significant predictors of persistent symptoms and disability at 2.5 years., Results: The factors most important at the time of initial presentation in predicting persistent illness were: (1) more than eight medically unexplained physical symptoms separate from those associated with CFS case definition; (2) lifetime history of dysthymia; (3) duration of chronic fatigue symptoms greater than 1.5 years; (4) less than 16 years of formal education; and (5) age older than 38 years. None of the results of the initial physical examination, or immunologic, general laboratory, or viral antibody measurements were significant in predicting persistence of symptoms. Recovery rates for those who met the criteria for CFS by either of two case definitions were lower than the rate of noncases, but the differences were not statistically significant. The five aforementioned variables formed a significant discriminative function, correctly classifying 78% of those who recovered and 74% of those with persistent symptoms., Conclusions: At initial examination, patients with chronic fatigue, more than eight medically unexplained physical symptoms (excluding symptoms in the case criteria for CFS), a lifetime history of dysthymic disorder, longer than 1.5 years of chronic fatigue, less than 16 years of formal education, and who were older than 38 years were the most likely to have persistence of symptoms of chronic fatigue at the 2.5-year follow-up.

Background: Results of readily available clinical laboratory tests in patients with chronic fatigue syndrome were compared with results in healthy control subjects., Methods: Cases consisted of all 579 patients who met either the Centers for Disease Control and Prevention, Atlanta, Ga, British, or Australian case definition for chronic fatigue syndrome. They were from chronic fatigue clinics in Boston, Mass, and Seattle, Wash. Control subjects consisted of 147 blood donors who denied chronic fatigue. Outcome measures were the results of 18 clinical laboratory tests., Results: Age- and sex-adjusted odds ratios of abnormal results, comparing cases with control subjects, were as follows: circulating immune complexes, 26.5 (95% confidence interval [CI] 3.4-206), atypical lymphocytosis, 11.4 (95% CI, 1.4-94); elevated immunoglobulin G, 8.5 (95% CI, 2.0-37); elevated alkaline phosphatase, 4.2 (95% CI, 1.6-11); elevated total cholesterol, 2.1 (95% CI, 1.2-3.4); and elevated lactic dehydrogenase, 0.30 (95% CI, 0.16-0.56). Also, antinuclear antibodies were detected in 15% of cases vs 0% in the control subjects. The results of these tests were generally comparable for the cases from Seattle and Boston. Although these tests served to discriminate the population of patients from healthy control subjects, at the individual level they were not as useful., Conclusions: Patients with chronic fatigue syndrome who were located in two geographically distant areas had abnormalities in the results of several readily available clinical laboratory tests compared with healthy control subjects. The immunologic abnormalities are in accord with a growing body of evidence suggesting chronic, low-level activation of the immune system in chronic fatigue syndrome. While each of these laboratory findings supports the diagnosis of chronic fatigue syndrome, each lacks sufficient sensitivity to be a diagnostic test. Furthermore, the specificity of these findings relative to other organic and psychiatric conditions that can produce fatigue remains to be established.

Medical patients' (75 with chronic fatigue complaints, 61 with dizziness, and 88 with disabling tinnitus; N = 224) current and past psychiatric diagnoses and personality characteristics were assessed to determine if they could independently explain the number of medically unexplained physical symptoms that the patients had experienced. Cloninger's Tridimensional Personality Questionnaire (TPQ) and the Diagnostic Interview Schedule based on DSM-III-R were used to assess the personality and psychiatric diagnoses, respectively. The results revealed that the number of lifetime medically unexplained symptoms were significantly, independently, and positively related to increasing numbers of current and past anxiety and depressive disorders and to the harm avoidance dimension of the TPQ. In a second analysis, the "worry/pessimism" and "impulsiveness" subscales were positively related to the number of medically unexplained symptoms. The results suggest that somatization is associated with current and past history of psychiatric illnesses and harm avoidance in this sample of medical patients.

Background: Chronic fatigue syndrome (CFS), fibromyalgia (FM), and multiple chemical sensitivities (MCS) are conditions associated with fatigue and a variety of other symptoms that appear to share many clinical and demographic features. Our objectives were to describe the similarities and differences among patients with CFS, FM, and MCS. Additional objectives were to determine how frequently patients with MCS and FM met the criteria for CFS and if they differed in their health locus of control., Methods: Demographic, clinical, and psychosocial measures were prospectively collected in 90 patients, 30 each with CFS, FM, and MCS. Patients were recruited from a university-based referral clinic devoted to the evaluation and treatment of chronic fatigue and three private practices. Variables included demographic features, symptoms characteristic of each condition, psychological complaints, a measure of health locus of control, and information on health care use., Results: Overall, the three patient groups were remarkably similar in demographic characteristics and the presence of specific symptoms. Patients with CFS and FM frequently reported symptoms compatible with MCS. Likewise, 70% of patients with FM and 30% of those with MCS met the criteria for CFS. Health care use was substantial among patients with CFS, FM, and MCS, with an average of 22.1, 39.7, and 23.3 visits, respectively, to a medical provider during the prior year. Health locus of control did not differ among the three populations., Conclusions: In general, demographic and clinical factors and health locus of control do not clearly distinguish patients with CFS, FM, and MCS. Symptoms typical of each disorder are prevalent in the other two conditions.

Objective: To determine whether there are differences between men and women patients who have chronic fatigue syndrome (CFS) and, if so, to ascertain whether a gender-related pattern exists., Design: A descriptive study of demographic, clinical, and psychosocial measures, the results of which were prospectively collected for patients who had CFS., Setting: A university-based referral clinic devoted to the evaluation and management of chronic fatigue., Patients: 348 CFS patients who had undergone complete medical evaluations., Measures: Clinical variables included symptoms, physical examination findings, and laboratory results. Psychosocial assessment consisted of a structured psychiatric interview, the Medical Outcomes Study Short-form General Health Survey to assess functional status, the General Health Questionnaire to ascertain psychological distress, the Multidimensional Health Locus of Control, and measures of attribution, social support, and coping., Main Results: Overall, few gender-related differences were identified. Women had a higher frequency of tender or enlarged lymph nodes (60% versus 33%, p < or = 0.01) and fibromyalgia (36% versus 12%, p < or = 0.001) and lower scores on the physical functioning subscale of the Medical Outcomes Study Short-form General Health Survey (37.6 versus 52.2, p < 0.01); men more often had pharyngeal inflammation (42% versus 22%, p < or = 0.001) and reported a higher lifetime prevalence of alcoholism (20% versus 9%, p < or = 0.01)., Conclusions: In general, demographic, clinical, and psychosocial factors do not distinguish men from women CFS patients.

This prospective, cohort study examined the prevalence of sleep disorders among highly selected patients with chronic fatigue. On the basis of responses suggestive of sleep pathology on a screening questionnaire, 59 patients from a university-based clinic for chronic fatigue who had undergone a medical and psychiatric evaluation underwent polysomnography. Criteria for chronic fatigue syndrome (CFS) were met by 64% of patients and those for a current psychiatric disorder were met by 41%. Overall, 41% of patients had abnormal results for a multiple sleep latency test and 81% had at least one sleep disorder, most frequently sleep apnea (44%) and idiopathic hypersomnia (12%). In comparing patients who did and did not meet CFS criteria, no significant differences were found in individual sleep symptoms or sleep disorders. Likewise, symptoms and sleep disorders were unrelated to psychiatric diagnoses. In conclusion, chronically fatigued patients with suggestive symptoms may have potentially treatable coexisting sleep disorders that are not associated with meeting criteria for CFS or a current psychiatric disorder.

We compared three case definitions of chronic fatigue syndrome (CFS) applied to patients followed in CFS clinics at two institutions. All patients had debilitating fatigue without apparent etiology; patients with medical conditions associated with chronic fatigue and with major psychiatric disorders were stratified and presented separately. Patients were classified according to whether they met case definitions developed by a Centers for Disease Control and Prevention (CDC) Working Group, a British group, or an Australian group. When findings for 805 patients followed at the two clinics were combined, 61% met the CDC criteria, 55% met the British criteria, and 56% met the Australian criteria; these proportions were relatively similar at both sites. In addition, similar laboratory abnormalities were found for all case groups and for fatigued patients who met none of the three case definitions. These data suggest that more inclusive case definitions may be superior.

Background: Our goals were to determine the prevalence of unusual, debilitating fatigue and the frequency with which it was associated with the chronic fatigue syndrome (CFS) or other physical or psychological illness in an outpatient clinic population., Methods: We prospectively evaluated a cohort of 1000 consecutive patients in a primary care clinic in an urban, hospital-based general medicine practice. The study protocol included a detailed history, physical examination, and laboratory and psychiatric testing., Results: Five patients who came because of CFS studies were excluded. Of the remaining 995, 323 reported fatigue, and 271 (27%) complained of at least 6 months of unusual fatigue that interfered with their daily lives. Of the 271, self-report or record review revealed a medical or psychiatric condition that could have explained the fatigue in 186 (69%). Thus, 85 (8.5%) of 995 patients had a debilitating fatigue of at least 6 months' duration, without apparent cause. Of these patients, 48 refused further evaluation, and 11 were unavailable for follow-up; 26 completed the protocol. Three of the 26 were hypothyroid, and one had a major psychiatric disorder. Of the remaining 22 patients, three met Centers for Disease Control and Prevention criteria for CFS, four met British criteria, and 10 met the Australian case definition. The point prevalences of CFS were thus 0.3% (95% confidence interval [CI], 0% to 0.6%), 0.4% (95% CI, 0% to 0.8%), and 1.0% (95% CI, 0.4% to 1.6%) using the Centers for Disease Control and Prevention, British, and Australian case definitions, respectively. These estimates were conservative, because they assumed that none of the patients who refused evaluation or were unavailable for follow-up would meet criteria for CFS., Conclusions: While chronic, debilitating fatigue is common in medical outpatients, CFS is relatively uncommon. Prevalence depends substantially on the case definition used.

Objective: To describe the types and extent of psychiatric disorders found in a group of recently-arrived Eastern Europeans being treated by native-speaking mental health providers., Patients: Forty seven Hungarians, Romanians, Czechoslovakians, Poles and Gypsies referred by voluntary or government agencies, other organizations or community members to a refugee counseling service in Seattle, Washington. Over 90% were refugees and 68% maintained this status at the intake evaluation., Method: Clinical, descriptive study of data collected retrospectively by chart review., Results: The majority of clients had poor or fair English skills and less than half were employed. Twelve (26%) had a prior mental health problem and five (11%) a psychiatric hospitalization. The most common diagnoses were adjustment reaction in 21 (45%), marital/family problems in five (11%), and paranoid schizophrenia in five (11%)., Conclusions: Psychiatric disorders were frequent in this clinical population of Eastern Europeans presenting for outpatient mental health care and may be associated with previous mental health problems. Our findings emphasize the need for sensitivity to the special risks of emigration.

We evaluated knowledge about prescribed medications and compliance with taking those medications in 96 South East Asian refugees of different ethnic backgrounds seen in a primary care clinic. Two hundred and thirty (88%) of 262 prescribed medications were currently being taken by the patients. Although 97% of the medications were either named or described correctly, the correct rationale for taking the medication was known for only 79% and the correct dosage regimen for only 63%. Thirty-two (33%) of the 96 patients were not taking one or more of their prescribed medications, 17 (18%) were taking one or more medications not prescribed, 5 (5%) were taking duplicate forms of the same medication, and 4 (4%) were taking a medication that had been discontinued by the clinic provider. Seventy-two (75%) patients were taking one or more medications at an incorrect dose. Only 12 (12%) patients were fully compliant with all prescribed medications. We conclude that knowledge about and compliance with medications is a major problem among South East Asian patients attending a primary care refugee clinic.

Objective: To determine the prevalence of depressive symptoms among Vietnamese refugees who have lived in the United States for at least two months., Design: A prospective and descriptive study using the Vietnamese Depression Scale (VDS). Scores of > or = 13 on the VDS were considered indicative of depression., Setting: Ten public health clinics in four states., Patients/participants: Four hundred seventy-six consecutive adult Vietnamese refugees presenting for primary care., Interventions: The VDS, an 18-item culture-specific self-report measure, was used to screen for depressive symptoms., Measurements and Main Results: Twenty percent of these patients had scores of 13 or above. Although being female; being older; being divorced, separated, or widowed; and being poorly educated were significant univariate risk factors for screening positive, only the latter two were significant in a multivariate model. Physical complaints were common and induced considerable anxiety about health status, but psychological and emotional symptoms were even more prevalent. Patients scoring 13 or higher had a higher rate of endorsement for every item in the scale than did those scoring lower than 13., Conclusions: This study substantiates the feasibility and importance of screening for depressive symptoms among Vietnamese refugees, particularly in primary care settings where they are most likely to seek care for both medical and psychological problems.

Sera obtained for treponemal serology (VDRL) from 193 Southeast Asian refugees representing five ethnic groups seen in a primary care clinic were examined for antibodies to human T-lymphotropic virus type 1 (HTLV-1), human herpes-virus-6 (HHV-6), Epstein-Barr virus (EBV), and cytomegalovirus (CMV). The seroprevalence was highest for EBV (99%), followed in decreasing order by CMV (95%), HHV-6 (26%), and HTLV-1 (0.6%). The VDRL was positive in 15% of patients. The highest seroprevalence to HHV-6 was noted in the Chinese (33%) and the lowest in the Laotian hilltribes, the Mien and Hmong (14%). Antibody to HHV-6 was most prevalent among patients under 20 and those between 60 and 69 years of age. Differences were not found among ethnic groups in the seroprevalence of HTLV-1, EBV, or CMV.

A workshop was held 18 to 19 March 1991 at the National Institutes of Health to address critical issues in research concerning the chronic fatigue syndrome (CFS). Case definition, confounding diagnoses, and medical outcome assessment by laboratory and other means were considered from the perspectives of key medical specialties involved in CFS research. It was recommended that published Centers for Disease Control (CDC) case-definition criteria be modified to exclude fewer patients from analysis because of a history of psychiatric disorder. Specific recommendations were made concerning the inclusion or exclusion of other major confounding diagnoses, and a standard panel of laboratory tests was specified for initial patient evaluation. The workshop emphasized the importance of recognizing other conditions that could explain the patient's symptoms and that may be treatable. It was viewed as essential for the investigator to screen for psychiatric disorder using a combination of self-report instruments followed by at least one structured interview to identify patients who should be excluded from studies or considered as a separate subgroup in data analysis. Because CFS is not a homogeneous abnormality and because there is no single pathogenic mechanism, research progress may depend upon delineation of these and other patient subgroups for separate data analysis. Despite preliminary data, no physical finding or laboratory test was deemed confirmatory of the diagnosis of CFS. For assessment of clinical status, investigators must rely on the use of standardized instruments for patient self-reporting of fatigue, mood disturbance, functional status, sleep disorder, global well-being, and pain. Further research is needed to develop better instruments for quantifying these domains in patients with CFS.

To determine the prevalence of use of traditional health practices among different ethnic groups of Southeast Asian refugees after their arrival in the United States, we conducted a convenience sample of 80 Cambodian, Lao, Mien, and ethnic Chinese patients (20 each) attending the University of Washington Refugee Clinic for a new or follow-up visit. Interpreters administered a questionnaire that dealt with demographics, medical complaints, traditional health practices, health beliefs, and attitudes toward Western practitioners. In all, 46 (58%) patients had used one or more traditional health practices, but the prevalence varied by ethnic group. Coining and massage were used by all groups except the Mien, whereas moxibustion and healing ceremonies were performed almost exclusively by the Mien. Traditional health practices were used for a variety of symptoms and, in 78% of reported uses, patients reported alleviation of symptoms. The use of traditional health practices is common among Southeast Asian refugees. Clinicians who care for this population should be aware of these practices because they may supersede treatments prescribed by physicians or leave cutaneous stigmata that may be confused with disease or physical abuse. Good patient care may necessitate the use or tolerance of both Western and traditional modalities in many Southeast Asian refugees.

Objective: To conduct neurologic, immunologic, and virologic studies in patients with a chronic debilitating illness of acute onset., Design: Cohort study with comparison to matched, healthy control subjects., Patients: We studied 259 patients who sought care in one medical practice; 29% of the patients were regularly bedridden or shut-in., Main Outcome Measures: Detailed medical history, physical examination, conventional hematologic and chemistry testing, magnetic resonance imaging (MRI) studies, lymphocyte phenotyping studies, and assays for active infection of patients' lymphocytes with human herpesvirus type 6 (HHV-6)., Main Results: Patients had a higher mean (+/- SD) CD4/CD8 T-cell ratio than matched healthy controls (3.16 +/- 1.5 compared with 2.3 +/- 1.0, respectively; P less than 0.003). Magnetic resonance scans of the brain showed punctate, subcortical areas of high signal intensity consistent with edema or demyelination in 78% of patients (95% CI, 72% to 86%) and in 21% of controls (CI, 11% to 36%) (P less than 10(-9)). Primary cell culture of lymphocytes showed active replication of HHV-6 in 79 of 113 patients (70%; CI, 61% to 78%) and in 8 of 40 controls (20%; CI, 9% to 36%) (P less than 10(-8], a finding confirmed by assays using monoclonal antibodies specific for HHV-6 proteins and by polymerase chain reaction assays specific for HHV-6 DNA., Conclusions: Neurologic symptoms, MRI findings, and lymphocyte phenotyping studies suggest that the patients may have been experiencing a chronic, immunologically mediated inflammatory process of the central nervous system. The active replication of HHV-6 most likely represents reactivation of latent infection, perhaps due to immunologic dysfunction. Our study did not directly address whether HHV-6, a lymphotropic and gliotropic virus, plays a role in producing the symptoms or the immunologic and neurologic dysfunction seen in this illness. Whether the findings in our patients, who came from a relatively small geographic area, will be generalizable to other patients with a similar syndrome remains to be seen.

Objectives: To identify psychiatric differences between patients with chronic fatigue and those with rheumatoid arthritis and to investigate whether patients meeting Centers for Disease Control (CDC) criteria for chronic fatigue syndrome (CFS) can be differentiated from patients with chronic fatigue on measures of disability and psychosocial distress., Design: Cross-sectional study comparing 98 patients with chronic fatigue with 31 patients with rheumatoid arthritis on structured psychiatric interviews and patient questionnaires. Nineteen patients meeting CDC criteria for CFS were compared with 79 patients with chronic fatigue not meeting CDC criteria on questionnaires measuring disability and psychosocial distress., Setting: Consecutive patients with chronic fatigue were selected from a chronic fatigue clinic at the University of Washington, and 31 consecutive patients with rheumatoid arthritis were sampled from a private rheumatology practice., Main Results: Patients with chronic fatigue had a significantly higher prevalence of lifetime major depression and somatization disorder than did patients with rheumatoid arthritis. Patients with chronic fatigue also had a significantly higher prevalence of current and lifetime psychiatric diagnoses. Only 19 of 98 patients with chronic fatigue met CDC criteria for CFS. Patients meeting CDC criteria for CFS could not be differentiated from the larger group of patients with chronic fatigue on any study variable., Conclusions: Patients with chronic fatigue have a significantly higher burden of psychiatric illness than do patients with rheumatoid arthritis. The psychiatric illness preceded the development of chronic fatigue in over half the patients. Centers for Disease Control criteria for CFS did not select a subset of chronic fatigue patients who could be differentiated on disability or psychosocial parameters from patients with chronic fatigue who did not meet CDC criteria.

Various abnormalities revealed by laboratory studies have been reported in adults with chronic fatigue syndrome. Those most consistently reported include depressed natural killer cell function and reduced numbers of natural killer cells; low levels of circulating immune complexes; low levels of several autoantibodies, particularly antinuclear antibodies and antithyroid antibodies; altered levels of immunoglobulins; abnormalities in number and function of lymphocytes; and modestly elevated levels of two Epstein-Barr virus-related antibodies, immunoglobulin G to viral capsid antigen and to early antigen.

This review summarizes the symptoms and signs seen in patients with chronic fatigue syndrome (CFS). It is based on the authors' experience with two cohorts of approximately 510 patients with chronic debilitating fatigue and on the reported experience of other investigators with similar patients. The most characteristic symptoms of CFS are the sudden onset of an infectious-type illness, the subsequent chronic and debilitating fatigue, and postexertional malaise; many patients also have recurrent fevers, pharyngitis, adenopathy, myalgias, sleep disorders, and cognitive impairment.

A 17-year-old, previously healthy woman developed an acute "mononucleosis-like" illness with an associated "atypical" pneumonitis, followed by years of debilitating chronic fatigue, fevers, a 10-kg weight loss, night sweats, and neurocognitive symptoms. Thereafter, her sister developed a similar but less severe illness. The patient developed marked, chronic lymphadenopathy and splenomegaly, with associated persistent relative lymphocytosis and atypical lymphocytosis and with thrombocytopenia. After 3 years of illness, a splenectomy was performed, which resulted in some symptomatic improvement, prompt weight gain, and resolution of all hematologic abnormalities. Serial immunologic studies revealed a strikingly elevated number of activated B lymphocytes and a T lymphopenia, which improved but did not return to normal postsplenectomy. No causal association was found with any of several infectious agents that could produce such a lymphoproliferative illness. However, both the patient and her sister had evidence of active infection with the recently discovered human herpesvirus-6. Seven years after the onset of the illness, the patient and her sister remain chronically ill.

Twenty-three patients with polymyalgia rheumatica (PMR) followed in an academic rheumatology practice frequently reported symptoms commonly found in the recently described "chronic fatigue syndrome" or "chronic Epstein-Barr infection syndrome." These symptoms persisted for months after treatment had reduced the severity of the myalgias and lowered the sedimentation rate: periodically disabling fatigue (33%), recurrent pharyngitis (30%), sleep disorder (65%) and arthralgias (70%). However, antibody titers to Epstein-Barr virus in the patients with PMR were not significantly different from those in age and sex matched control subjects.

Twenty-one percent of 500 unselected patients, aged 17 to 50 years, seeking primary care for any reason were found to be suffering from a chronic fatigue syndrome consistent with "chronic active Epstein-Barr virus (EBV) infection," They had been experiencing "severe" fatigue, usually cyclic, for a median of 16 months (range, six to 458 months), associated with sore throat, myalgias, or headaches; 45% of the patients were periodically bedridden; and 25% to 73% reported recurrent cervical adenopathy, paresthesias, arthralgias, and difficulty in concentrating or sleeping. The patients had no recognized chronic "physical" illness and were not receiving psychiatric care. While antibody titers to several EBV-specific antigens were higher in patients than in age- and sex-matched controls subjects, the differences generally were not statistically significant. A chronic fatigue syndrome consistent with the chronic active EBV infection syndrome was prevalent in our primary care practice. However, our data offer no evidence that EBV is causally related to the syndrome. Indeed, we feel that among unselected patients seen in a general medical practice currently available EBV serologic test results must be interpreted with great caution.

Fifty patients with primary fibromyalgia who had been followed in an academic rheumatology practice frequently reported symptoms thought to be typical of "chronic Epstein-Barr virus infection," but not of fibromyalgia: recurrent sore throat (54%), recurrent rash (47%), chronic cough (40%), recurrent adenopathy (33%), and recurrent low-grade fevers (28%). In 55% of the patients, illness had begun suddenly, with what seemed to be a viral syndrome. Antibody titers to Epstein-Barr virus in the patients with fibromyalgia, however, were not significantly different from those in age- and sex-matched "healthy" and "unhealthy" control subjects.

We compared clinical outcomes of 65 hospitalized patients receiving clindamycin before and 59 after a sudden hospitalwide shift in dosing schedules for this drug from 600 mg every 6 hours to 600 mg every 8 hours. Outcomes studied included the efficacy of antibiotic treatment, length of febrile period, and frequency of adverse effects. We also compared and controlled for patient characteristics such as age, sex, presence of multiple diagnoses, length of therapy, and concurrent use of other antibiotics. There were no differences in measured clinical outcomes between the two groups. Treatment was successful in 87% of both groups. The average number of febrile days was 5.1 in the first group and 3.9 in the second (P less than .05). Patients on 6-hourly therapy experienced a 12% rate of antibiotic-related adverse effects vs. 5% for the 8-hourly group (P greater than .05). These data support the clinical rationale and safety of a hospitalwide reduction in the frequency of clindamycin dosing. In addition to considerable pharmacy and nursing time saved, this change also saved greater than $40,000 annually in antibiotic costs.

Natural killer (NK)3 cells are large granular lymphocytes that appear to play a significant role in the host's defense against viral infection. We performed an extensive phenotypic and functional characterization of NK cells on 41 patients with the chronic fatigue syndrome (CFS), or "chronic active Epstein-Barr virus infection" syndrome, and on 23 age- and sex-matched asymptomatic control subjects in an attempt to further characterize this illness. These studies demonstrated that a majority of patients with CFS have low numbers of NKH1+T3- lymphocytes, a population that represents the great majority of NK cells in normal individuals. CFS patients had normal numbers of NKH1+T3+ lymphocytes, a population that represents a relatively small fraction of NK cells in normal individuals. When tested for cytotoxicity against a variety of different target cells, patients with CFS consistently demonstrated low levels of killing. After activation of cytolytic activity with recombinant interleukin 2, patients were able to display increased killing against K562 but most patients remained unable to lyse Epstein-Barr virus-infected B cell targets. Additional cytotoxicity experiments were carried out utilizing anti-T3 monoclonal antibody to block killing by NKH1+T3+ cells. These experiments indicated that the NK cell that appears to be responsible for much of the functional activity remaining in patients with CFS belongs to the NKH1+T3+ subset, which under normal circumstances represents only approximately 20% of the NK cell population.

A variety of histologic changes have been observed in the kidneys of patients with light-chain deposition disease. We report 3 cases with kappa light chain deposition who presented with diverse clinical, histological, and ultrastructural features. All the cases were diagnosed by the presence of monoclonal kappa light chain deposits by immunohistochemical methods. Based on the present study and review of literature, four basic patterns of glomerular lesions are identified: (1) minimal glomerular changes without glomerular deposits, but with extensive tubular involvement; (2) mild glomerular changes with glomerular deposits; (3) focal or diffuse proliferative glomerulonephritis with or without crescents, and (4) nodular glomerulosclerosis resembling diabetic glomerulosclerosis. This pathological and clinical variability can cause diagnostic problems at initial presentation. A high index of suspicion is necessary along with appropriate laboratory data and routine staining for light chains.

Acquired cystic disease (ACD) is a recently described phenomenon occurring in the native kidneys of patients treated with long-term dialysis. Renal cell carcinoma is being diagnosed with increasing frequency in patients with chronic renal failure. In most, but not all, instances the cancers develop in association with ACD. Careful microscopic examination of end-stage kidneys undergoing dialysis discloses cysts lined with hyperplastic cells. Papillary hyperplasia of cyst epithelium is recorded in virtually every detailed pathology report of tumors arising in ACD and is the likely pathogenetic basis for the development of renal tumors in cystic kidneys undergoing dialysis. The pathology of ACD and its related neoplasms is reviewed. An estimate is made of the incidence of ACD and renal cell carcinoma in patients receiving dialysis by tabulating data from studies published in medical journals. Acquired cystic disease is found in approximately 35% of patients treated by long-term hemodialysis. Renal cell carcinoma occurs in approximately 5.8% of cases of ACD. Most of the cancers are found incidentally at autopsy or by examination of kidneys from bilateral nephrectomies and are of little clinical significance, but occasional cases present aggressive neoplasms that metastasize and cause the deaths of patients.

Medicare currently pays for "indirect costs" of medical education to support the higher costs of care in teaching hospitals. To investigate whether indirect costs are higher earlier in the training year when house officers might be less efficient--the "July phenomenon"--we compared utilization by 1251 patients hospitalized during July and August with 1338 patients hospitalized during April and May from 1982 through 1984 at Brigham and Women's Hospital, Boston, Mass. These included all patients in the 10 most prevalent medical and surgical diagnosis related groups. Using analysis of covariance to correct for age, sex, diagnosis related group, urgency of admission, temporal change, and mortality, we found no differences in length of stay, total charges, or categories of ancillary charges. These results suggest that there is no substantial increase in the cost of care early in the training year; there was no evidence of a "July phenomenon."

Convalescent excretion is a common sequel to salmonella infection, but in contrast to infections with Salmonella typhi, no clear picture of the natural history of nontyphi Salmonella excretion has emerged. The literature concerning frequency and site of chronic carriage, patterns of excretion, and relationship to bacteriologic methods used for enumeration of organisms was reviewed. An examination of 32 studies including 2,814 patients who were observed after salmonella infection showed that median duration of excretion was approximately five weeks. In univariant analyses, excretion was more prolonged in children less than five years of age, persons with symptomatic infections, persons infected with serotypes other than Salmonella typhimurium, and persons studied after first onset of symptoms. Persistent excretion beyond one year occurred in fewer than 1% of subjects. Despite the large number of convalescent excretors in the community at any one time, the paucity of outbreaks in which such food handlers or hospital personnel are implicated suggests that their role in transmission of salmonella infection is small. Because convalescent excretion is so common and persistent excretion and transmission so uncommon, follow-up fecal cultures after salmonella infections are rarely necessary.