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Biomedical subjects

D Wakefield

Publications and source records attributed to D Wakefield.

At least 91 records · Page 5Linked to original sources
PubMed1995

Cell-mediated immune function and the outcome of chronic fatigue syndrome.

This study examined the importance of cell-mediated immunity in determining the long-term outcome of patients diagnosed with chronic fatigue syndrome (CSF). A total of 103 patients (74%) of 139 previously enrolled in one of two treatment trials conducted within a university hospital referral center was reviewed a mean of 3.2 yr after trial entry. Ongoing symptom severity, levels of disability and immunological function were assessed at follow-up. The relationship between immunological function at trial entry and measures of outcome was also evaluated. Sixty-five patients (63%) had improved, while only 6 (6%) reported no current symptoms. Thirty-one subjects (30%) were unable to perform any form of work and 26 (25%) were on a disability benefit directly attributable to CFS. Cell-mediated immune function, as measured at trial entry or follow-up, did not appear to affect outcome. Whilst improvement occurred in the majority of patients with CFS, a substantial proportion (37%) remained functionally impaired. Impairment of cell-mediated immunological function measured during the course of the illness may not be an important factor in determining long-term outcome.

Adult↗
PubMed1995

Lessons in cooperation: four hospital consortia relate their quality improvement experiences.

BACKGROUND: In 1989, The Robert Wood Johnson Foundation launched a demonstration project to test a consortium approach to quality improvement. As part of this project, four hospital consortia in various parts of the United States are currently sharing quality resources (for example, training) and collaborating on various improvement efforts. The purpose of the project is to demonstrate that hospitals can take on more difficult problems and accomplish more in cooperation with each other than on their own. CASE STUDIES: The Institute for Quality Healthcare (Iowa City, Iowa) has built a comparative database so that 40 member hospitals can make meaningful comparisons on various aspects of performance; The Vermont Program for Quality in Health Care has lowered the postoperative infection rate in Vermont by monitoring compliance with consensus guidelines; Interwest Quality of Care, Inc, which has member organizations in Utah, Wyoming, and Idaho, has adapted and disseminated guidelines for diabetic care; and The Public Hospital Institute, in Berkeley, California, has worked with the Joint Commission on Accreditation of Healthcare Organizations to develop a written guide to help surveyors understand the unique operational traits of public hospitals. LESSONS LEARNED: Projects such as those with champions in several member organizations and comparative data analysis lend themselves more easily to cooperative work than others. They also provide some strategies for collaboration, such as continually reinforcing the principles of collaboration, obtaining a fully informed commitment, beginning with initiatives that are likely successes, and being serious and vocal about the commitment to confidentiality. CONCLUSIONS: Collaborators in quality improvement gain important resources, such as better information, more relevant reference databases, colleagues and support for quality improvement specialists, and economies of scale in education programs, training materials, and interaction with vendors. However, the difficulties in collaboration are great. Hospitals must continually consider not only "What's in this for me," but also "What can we accomplish as a group that is greater than what each of us can do alone?"

California↗
PubMed1995

Can the chronic fatigue syndrome be defined by distinct clinical features?

To determine whether patients diagnosed as having chronic fatigue syndrome (CFS) constitute a clinically homogeneous class, multivariate statistical analyses were used to derive symptom patterns and potential patient subclasses in 565 patients. The notion that patients currently diagnosed as having CFS constitute a single homogeneous class was rejected. An alternative set of clinical subgroups was derived. The validity of these subgroups was assessed by sociodemographic, psychiatric, immunological and illness behaviour variables. A two-class statistical solution was considered most coherent, with patients from the smaller class (27% of the sample) having clinical characteristics suggestive of somatoform disorders. The larger class (73% of sample) presented a more limited combination of fatigue and neuropsychological symptoms, and only moderate disability but remained heterogeneous clinically. The two patient groups differed with regard to duration of illness, spontaneous recovery, severity of current psychological morbidity, utilization of medical services and CD8 T cell subset counts. The distribution of symptoms among patients was not unimodal, supporting the notion that differences between the proposed subclasses were not due simply to differences in symptom severity. This study demonstrated clinical heterogeneity among patients currently diagnosed as CFS, suggesting aetiological heterogeneity. In the absence of discriminative clinical features, current consensus criteria do not necessarily reduce the heterogeneity of patients recruited to CFS research studies.

Fatigue Syndrome, Chronic↗
PubMed1995

Iowa's National Laboratory for the study of Rural Telemedicine: a description of a work in progress.

As the federal administration advances the idea of the "information superhighway," many disciplines are being challenged to find ways to use advanced telecommunications to improve access to information, enhance learning opportunities, and achieve higher levels of international competitiveness. Telemedicine, the use of communications technology in the practice of medicine, may change the way rural health care is provided by improving access to medical information, diagnostic tools, and consultations. The information and health care services required by health care professionals are rapidly changing, and dissemination of this information to isolated practitioners has proven to be difficult. By providing support electronically from a central site, the most current information is more readily available. Using test-bed hospitals in rural and urban settings, the National Library of Medicine-funded National Laboratory for the Study of Rural Telemedicine at the University of Iowa is currently developing the necessary infrastructure to support targeted projects studying how telemedicine applications can be made more effective and readily available.

Clinical Laboratory Information Systems↗
PubMed1994

Longitudinal study of outcome of chronic fatigue syndrome.

OBJECTIVE: To examine the predictors of long term outcome for patients with the chronic fatigue syndrome. DESIGN: Cohort study. SUBJECTS: 139 subjects previously enrolled in two treatment trials; 103 (74%) were reassessed a mean of 3.2 years after start of the trials. SETTING: University hospital referral centre. MAIN OUTCOME MEASURES: Age at onset, duration of illness, psychological and immunological status at initial assessment. Ongoing symptom severity, levels of disability, and immunological function at follow up. RESULTS: 65 subjects had improved but only six reported no current symptoms. An alternative medical diagnosis had been made in two and psychiatric illness diagnosed in 20. The assignment of a primary psychiatric diagnosis at follow up and the strength of the belief that a physical disease process explained all symptoms at entry to the trials both predicted poor outcome. Age at onset of illness, duration of illness, neuroticism, premorbid psychiatric diagnoses, and cell mediated immune function did not predict outcome. CONCLUSION: Though most patients with the chronic fatigue syndrome improve, a substantial proportion remain functionally impaired. Psychological factors such as illness attitudes and coping style seem more important predictors of long term outcome than immunological or demographic variables.

Adaptation, Psychological↗
PubMed1994

Phenotypic and functional abnormalities in the peripheral blood T-cells of patients with primary Sjogren's syndrome.

Changes in regulatory T-cell subset (including the recently described CD4 helper inducers or suppressor inducers) balance in the peripheral blood may play a role in the pathogenesis of primary Sjogren's syndrome (SS). Direct immunofluorescence and flow cytometry were used to quantitate and analyse peripheral blood lymphocytes in 15 patients with primary SS and 15 control subjects. A reduction in the percentage of circulating CD4 lymphocytes was observed in patients with SS. There was no quantitative abnormality in the percentage of circulating CD4+ 2H4+ (suppressor inducer), CD4+ 4B4+ (helper inducer), CD2, CD3, CD8, CD8+ 2H4+, CD8+ 4B4+, CD25 (IL-2R), CD19, CD16, CD57 lymphocytes in the patients. Circulating CD8 lymphocytes expressing the activation marker HLA-DR were increased in the patients. The functional status of peripheral blood lymphocytes was assessed by PHA (phytohaemagglutinin) stimulation followed by monitoring their proliferative response by radiolabelled thymidine uptake and expression of CD25 (Interleukin-2 receptor). A reduction in the proliferative response of total, CD4-depleted, and CD8-depleted lymphocytes suspensions to PHA was demonstrated. The level of expression of CD25 (IL-2 receptor) was similar in patients and controls before and after 24 h stimulation with PHA. We conclude that there is a disturbance in the functional properties of peripheral blood T cells that can contribute to the immunopathogenesis of SS. Meanwhile, the quantitative reduction of suppressor/inducer lymphocytes as defined by the CD4 2H4 phenotype can be precluded from a role in the development of such an autoimmune condition.

Adult↗
PubMed1994

Cytokine-mediated induction of HLA antigen expression on human glomerular mesangial cells.

Well-characterized human glomerular mesangial cells were stimulated in vitro with interferon-gamma (IFN-gamma), interleukin-1, and tumor necrosis factor alpha (TNF-alpha) to determine the influence of these cytokines on the expression of class I and II HLA antigens. IFN-gamma induced a dose-dependent increase in expression of both class I and class II HLA antigens. TNF-alpha induced only class I antigens when used alone, but acted synergistically with IFN-gamma in the expression of class I and II antigens. Interleukin-1 had little effect on HLA antigen expression. These results raise the possibility that stimulated mesangial cells may act as antigen-presenting cells and may mediate local immune reactions in the glomerulus.

Antigen-Presenting Cells↗
PubMed1994

The treatment of chronic fatigue syndrome: science and speculation.

The chronic fatigue syndrome (CFS) is a heterogeneous disorder characterized by fatigue, neuropsychiatric symptoms, and various other somatic complaints. Treatment studies to date reflect both the diversity of medical disciplines involved in the management of patients with CFS and the multiple pathophysiologic mechanisms proposed. There have been few attempts to study integrated treatment programs, and although several controlled studies have been reported, no treatment has been shown clearly to result in long-term benefit in the majority of patients. Good clinical care integrating medical and psychologic concepts, together with symptomatic management, may prevent significant secondary impairment in the majority of patients. Future treatment studies should examine differential response rates for possible subtypes of the disorder (eg, documented viral onset, concurrent clinical depression), evaluate the extent of any synergistic effects between therapies (ie, medical and psychologic), and employ a wide range of biologic and psychologic parameters as markers of treatment response.

Combined Modality Therapy↗
PubMed1994

Cytokine production and fatigue in patients with chronic fatigue syndrome and healthy control subjects in response to exercise.

We have studied the relationship between the cytokine production induced in vivo by prolonged isometric exercise and the symptom complex marked by fatigue in patients with chronic fatigue syndrome (CFS). Twelve male patients and 13 matched male control subjects undertook an isometric hand-grip exercise protocol utilizing dynamometers. Subjects undertook 30 minutes of exercise, for which the target force was set at 40% of the maximal voluntary contraction and the duty cycle was 50%. Prior to, during, and for 24 hours following the exercise, blood samples were collected and assayed for the presence of cytokines, including interferon-gamma and interferon-alpha, interleukin-1 beta, and tumor necrosis factor-alpha. At those times subjects also completed the Profile of Mood States (POMS) questionnaire, which served as a measure of changes in subjective fatigue. No significant alteration in the level of any of the cytokines in the plasma of patients or control subjects was detected before, during, or after exercise. Surprisingly, the patients' levels of fatigue, depression, and confusion, as measured by the POMS, decreased in response to the exercise. These data do not confirm the presence of an immunologic process correlating with the exacerbation of fatigue after exercise experienced by patients with CFS. Limitations in the study design and in the sensitivity of the cytokine assays may have affected our results.

Adult↗
PubMed1994

Isolated bulbar conjunctival Kaposi's sarcoma.

We present a case of an isolated bulbar conjunctival Kaposi's sarcoma in a man with HIV infection. This is an unusual site for the initial presentation of Kaposi's sarcoma and in this site can be confused with a caroticocavernous fistula, cavernous haemangioma or chronic subconjunctival haemorrhage. Biopsy is required to confirm the diagnosis in isolated disease. Local radiotherapy is the preferred treatment for isolated Kaposi's sarcoma.

Adult↗
PubMed1994

Psychosocial needs of family caregivers of terminally ill patients.

The primary caregivers (mean age = 63 yr.) of 28 terminally ill veterans (mean age = 67 yr.) who were living at home were surveyed for their concrete and psychosocial needs. The caregivers also completed the Beck Depression Inventory, the Life Satisfaction Index, the Provision of Social Relations scale, and the Burden Inventory. The rank order of concrete and psychosocial needs is reported for these caregivers. Increased scores on depression were associated with decreased life satisfaction as was low social support. Not surprisingly, higher numbers of concrete and psychosocial needs were associated with increases in depression.

Adult↗
PubMed1993

Immunity and the pathophysiology of chronic fatigue syndrome.

The pathophysiology of chronic fatigue syndrome (CFS) remains unknown. The syndrome often follows a recognized or presumed infection and the disorder may therefore result from a disordered immune response to a precipitating infection or antigenic challenge. Abnormalities of both humoral and cellular immunity have been demonstrated in a substantial proportion of patients with CFS. The most consistent findings are of impaired lymphocyte responses to mitogen and reduced natural killer cell cytotoxicity. Cutaneous anergy and immunoglobulin G subclass deficiencies have also been found. Further studies are needed examining cytokine levels in serum and cerebrospinal fluid, and cytokine production in vitro in patients with CFS. Interpretation of the findings of published studies of immunity is limited by probable heterogeneity in the patient groups studied, and by the lack of standardization and reproducibility in the assays used. The pattern of abnormalities reported in immunological testing in patients with CFS is consistent with the changes seen during the resolving phases of acute viral infection. These data provide circumstantial support for the hypothesis that CFS results from a disordered immune response to an infection. Longitudinal studies of immunity in patients developing CFS after defined infectious illnesses will provide the best means of further examining this hypothesis.

Antibody Formation↗
PubMed1993

Immunologic and psychologic therapy for patients with chronic fatigue syndrome: a double-blind, placebo-controlled trial.

PURPOSE: To evaluate the potential benefit of immunologic therapy with dialyzable leukocyte extract and psychologic treatment in the form of cognitive-behavioral therapy (CBT) in patients with chronic fatigue syndrome (CFS). PATIENTS AND METHODS: Immunologic and psychologic treatments were administered to 90 adult patients who fulfilled diagnostic criteria for CFS in a double-blind, randomized, and placebo-controlled study. A four-cell trial design allowed the assessment of benefit from immunologic and psychologic treatment individually or in combination. Outcome was evaluated by measurement of global well-being (visual analogue scales), physical capacity (standardized diaries of daily activities), functional status (Karnofsky performance scale), and psychologic morbidity (Profile of Mood States questionnaire), and cell-mediated immunity was evaluated by peripheral blood T-cell subset analysis and delayed-type hypersensitivity skin testing. RESULTS: Neither dialyzable leukocyte extract nor CBT (alone or in combination) provided greater benefit than the nonspecific treatment regimens. CONCLUSIONS: In this study, patients with CFS did not demonstrate a specific response to immunologic and/or psychologic therapy. The improvement recorded in the group as a whole may reflect both nonspecific treatment effects and a propensity to remission in the natural history of this disorder.

Adolescent↗
PubMed1993

Primary tubulointerstitial nephritis and uveitis syndrome.

Primary acute tubulointerstitial nephritis and uveitis is an uncommon syndrome involving the kidney and eye. Although rare, to date 28 cases having been reported, it is important to recognise this entity to facilitate appropriate investigation and treatment. We report an unusual case of this syndrome in which the patient suffered a relapse of her nephritis concurrently with the onset of the first episode of uveitis. Both responded to treatment, although the uveitis subsequently recurred.

Adult↗
PubMed1993

Impaired in vivo immune responses in patients with melancholia.

Previous attempts to establish a relationship between impaired cell-mediated immunity (CMI) and major mood disorders have been limited by a failure to explore the relevance of depressive subcategories or to assess CMI by in vivo methods. In this case-control study CMI was assessed in 57 patients with major depression (31 with melancholic, 26 with non-melancholic disorders), and in age- and sex-matched controls by both in vitro and in vivo immunological techniques. Compared with control subjects and patients with non-melancholic depression, patients with melancholia demonstrated reduced in vivo CMI as assessed by delayed-type hypersensitivity (DTH) skin responses. Although increasing age, severity of depression, hospital admission for treatment, and reported weight loss are correlates of melancholia, none of these factors alone, or in combination, accounted for the differences in DTH responses observed between the two depressive subtypes. These data suggest that impaired CMI in vivo may be limited to those with melancholic disorders. At this stage the factors which account for this effect are unclear.

Age Factors↗