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Biomedical subjects

D Wakefield

Publications and source records attributed to D Wakefield.

At least 127 records · Page 7Linked to original sources

Eosinophilia-myalgia syndrome associated with L-tryptophan use.

A young, previously healthy woman presented with increasing muscle pain, lower limb swelling, fatigue and eosinophilia. She had consumed L-tryptophan tablets (one to two at night) over the preceding five months for management of her insomnia. Her condition slowly deteriorated and she developed generalised oedema and severe lethargy. A white blood cell count was 21.3 x 10(9)/L with 43% eosinophils (Normal range: 4.0-11.0 x 10(9)/L with 1-6% eosinophils. A biopsy specimen of the deep fascia and gastrocnemius muscle demonstrated fasciitis and myositis. The patient failed to recover after cessation of L-tryptophan use but her condition improved rapidly without significant sequelae after systemic treatment with corticosteroids.

Adult↗

Serologic evidence of Yersinia infection in patients with anterior uveitis.

Anterior uveitis is a common inflammatory eye disease associated with the HLA-B27 phenotype. Bacteriologic cofactors have been implicated in the pathogenesis of several diseases associated with HLA-B27. Using a sensitive enzyme-linked immunosorbent assay, we examined the incidence of previous Yersinia infection in a group of 28 consecutive patients with anterior uveitis. Twelve patients had a significantly increased antibody response to Yersinia, 8 of whom were HLA-B27 positive. Eight patients had IgM antibodies, possibly indicative of recent infection. There were no positive Yersinia serologic findings in our control group of 28 subjects, 13 of whom were HLA-B27 positive. A strong association was found between previous Yersinia infection and the development of anterior uveitis in HLA-B27-positive and HLA-B27-negative patients.

Adult↗

A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy in patients with chronic fatigue syndrome.

PURPOSE: The chronic fatigue syndrome (CFS) is characterized by profound fatigue, neuropsychiatric dysfunction, and frequent abnormalities in cell-mediated immunity. No effective therapy is known. PATIENTS AND METHODS: Forty-nine patients (40 with abnormal cell-mediated immunity) participated in a randomized, double-blind, placebo-controlled trial to determine the effectiveness of high-dose intravenously administered immunoglobulin G. The patients received three intravenous infusions of a placebo solution or immunoglobulin at a dose of 2 g/kg/month. Assessment of the severity of symptoms and associated disability, both before and after treatment, was completed at detailed interviews by a physician and psychiatrist, who were unaware of the treatment status. In addition, any change in physical symptoms and functional capacity was recorded using visual analogue scales, while changes in psychologic morbidity were assessed using patient-rated indices of depression. Cell-mediated immunity was evaluated by T-cell subset analysis, delayed-type hypersensitivity skin testing, and lymphocyte transformation with phytohemagglutinin. RESULTS: At the interview conducted by the physician 3 months after the final infusion, 10 of 23 (43%) immunoglobulin recipients and three of the 26 (12%) placebo recipients were assessed as having responded with a substantial reduction in their symptoms and recommencement of work, leisure, and social activities. The patients designated as having responded had improvement in physical, psychologic, and immunologic measures (p less than 0.01 for each). CONCLUSION: Immunomodulatory treatment with immunoglobulin is effective in a significant number of patients with CFS, a finding that supports the concept that an immunologic disturbance may be important in the pathogenesis of this disorder.

Adolescent↗

Differential enhancement of HLA-B27 by interferon.

To further examine the role of the HLA-B27 antigen in the pathogenesis of disorders such as anterior uveitis and ankylosing spondylitis, we have measured the level of enhancement of this antigen on peripheral blood lymphocytes and compared it with that of the class I HLA antigens HLA-A2 and HLA-B7 following interferon treatment. We found that the level of enhancement of HLA-B7 was greater than that of HLA-A2 or -B7 following treatment by alpha or gamma interferon (p less than 0.002). Similarly, the level of enhancement of HLA-B7 was greater than that of HLA-A2 (p less than 0.002) (Mann Whitney U-test). A differential enhancement of HLA-B27 by lymphokines may be important in the pathogenesis of HLA-B27-related disorders.

Genes, MHC Class I↗

Fibronectin: structure, function and significance in wound healing.

Several recent reports suggest a therapeutic role for topical application of autologous fibronectin in promoting healing of chronic skin and corneal ulcers. Fibronectin assists in wound healing by contributing to haemostasis, assisting in control of infection and debridement of wounds, and promoting re-epithelialisation, granulation tissue and ultimately a connective tissue of adequate tensile strength to repair the skin defect. The potential for fibronectin to be a therapeutic adjunct demands a close understanding of its structural and functional properties, and such knowledge, particularly emerging from research reported in the last five years, is reviewed.

Fibronectins↗

Behçet's syndrome: ocular features in an Australian population.

Inflammatory eye disease (IED) is often the most severe manifestation of Behçet's syndrome (BS). This disease is a common cause of uveitis in Mediterranean countries, the Middle East and Japan. In order to ascertain the prevalence of this disease in Australia, we reviewed the aetiology of patients attending our uveitis clinic over a five-year period. Twelve of 426 patients with inflammatory eye disease had definite Behçet's syndrome. Four patients had anterior uveitis, four had posterior uveitis, four had retinal vasculitis and one also had optic neuritis. Although inflammatory eye disease was the initial clinical feature of Behçet's syndrome in only three of our patients, it was the feature that led to a definite diagnosis in all but one patient. The inflammatory eye disease of Behçet's syndrome was characteristically recurrent and severe with significantly decreased vision in 10 eyes, cataracts in six eyes, macula oedema in four eyes and glaucoma in two eyes. We conclude that Behçet's syndrome is a rare cause of inflammatory eye disease in Australia and is unlikely to be recognised as a distinct clinical entity prior to the onset of ocular involvement. The visual prognosis of ocular inflammation in Behçet's syndrome remains guarded despite the use of a variety of immunosuppressive agents.

Adult↗

Cyclosporin therapy in Vogt Koyanagi Harada disease.

Vogt Koyanagi Harada Disease (VKHD) is a rare cause of uveitis and has not been previously reported in the Australian literature. The natural history of this severe inflammatory eye disease may be modified by the early use of high-dose immunosuppressive therapy, especially oral corticosteroids. We report three cases of VKHD who either failed to respond to high-dose corticosteroid (oral and intravenous) therapy alone or developed significant side effects, one of whom subsequently showed a beneficial response and another a transient beneficial response to cyclosporin therapy. Disease relapse or exacerbation of uveitis was the major problem encountered on attempted cyclosporin withdrawal. Further research is needed to define the optimum timing and indications for cyclosporin therapy in patients with VKHD.

Adrenal Cortex Hormones↗

Ocular cicatricial pemphigoid.

A series of 17 patients with ocular cicatricial pemphigoid (OCP) is described retrospectively. The importance of early recognition, especially of disease involving the medial canthus and caruncular region, diagnosis by biopsy, and adequate immunosuppressive and surgical therapy, are emphasised. A detailed grading scheme has been developed and this has enabled the authors to determine the success or failure of the therapy during the active treatment period. A combined ophthalmological and immunological approach to treatment can result in a successful visual outcome of this potentially blinding disease.

Aged↗

Cytomegalovirus retinopathy and the acquired immune deficiency syndrome: results of treatment with ganciclovir.

Cytomegalovirus (CMV) infection of the retina is the commonest potentially blinding ocular manifestation of AIDS. Recently the acyclic nucleoside dihydroxypropoxymethyl guanine (DHPG, ganciclovir) has become available to treat sight-threatening CMV retinopathy. This paper reports the clinical features and results of ganciclovir therapy in 48 patients seen over a four-year period. Seven patients were excluded from the study due to inadequate follow-up, leaving 41 patients as the study group. All patients responded clinically to this therapy. Patients were treated initially with high-dose ganciclovir (10 mg/kg/day) and then continued on lower dose treatment (5 mg/kg/day) indefinitely. Significant bone marrow toxicity developed in 12 patients (29.3%) requiring temporary cessation of therapy. Patients treated with ganciclovir retained vision and had increased survival times when compared to untreated patients. A poor visual outcome occurred when there was involvement of the macula or optic nerve head at presentation or when there was an interruption of ganciclovir therapy.

Acquired Immunodeficiency Syndrome↗

The psychiatric status of patients with the chronic fatigue syndrome.

The prevalence of psychiatric disorder in 48 patients with chronic fatigue syndrome (CFS) was determined. Twenty-two had had a major depressive (non-endogenous) episode during the course of their illness, while seven had a current major (non-endogenous) depression. The pre-morbid prevalence of major depression (12.5%) and of total psychiatric disorder (24.5%) was no higher than general community estimates. The pattern of psychiatric symptoms in the CFS patients was significantly different to that of 48 patients with non-endogenous depression, but was comparable with that observed in other medical disorders. Patients with CFS were not excessively hypochondriacal. We conclude that psychological disturbance is likely to be a consequence of, rather than an antecedent risk factor to the syndrome.

Adolescent↗

The role of mesangial cells in glomerular pathology.

The glomerular mesangial cell has become increasingly recognized as a multifunctional cell capable of mediating glomerular disease. This article reviews recent findings regarding the biology of these cells, and the relevance that these findings may have for our understanding of glomerular pathology.

Animals↗

Immunological privilege in the eye: a review.

The eye enjoys a privileged immunological status, in contrast to most sites in the body. Historically, it was thought that the eye, due to its lack of lymphatics, was not subject to the same immune surveillance as other tissues. In opposition to this, recent study has revealed that presenting foreign material via the eye produces marked effects on systemic immunity, leading to a state of tolerance when the same foreign antigen is presented systemically. The immunology of the eye is now known to consist of a myriad of local and systemic effects.

Animals↗

Immunological abnormalities in the chronic fatigue syndrome.

The chronic fatigue syndrome is a disorder of unknown aetiology which is characterized by debilitating fatigue. Recent evidence has suggested that viruses may persist in the tissues of patients with chronic fatigue syndrome. A concurrent immunological disturbance is likely to be associated with the persistence of viral antigens. Therefore, the humoral and cellular immunity of 100 patients who were suffering from chronic fatigue syndrome and that of 100 healthy, age- and sex-matched control subjects were compared. This study documents the frequent occurrence of abnormalities within the cellular and humoral immune systems of patients with well-defined chronic fatigue syndrome. Disordered immunity may be central to the pathogenesis of chronic fatigue syndrome. In patients with chronic fatigue syndrome, a significant (P less than 0.01) reduction was found in the absolute number of peripheral blood lymphocytes in the total T-cell (CD2), the helper/inducer T-cell (CD4) and the suppressor/cytotoxic T-cell (CD8) subsets. A significant (P less than 0.001) reduction also was found in T-cell function, which was measured: in vivo by delayed-type hypersensitivity skin-testing (reduced responses were recorded in 50 [88%] of 57 patients); and in vitro by phytohaemagglutinin stimulation. Reduced immunoglobulin (Ig) levels were common (56% of patients), with the levels of serum IgG3- and IgG1-subclasses particularly (P less than 0.05) affected.

Adolescent↗

HLA antigens in ocular tissues. III. Antigen presentation by gamma interferon-treated cultured uveal cells.

In previous studies we have shown that normal human uveal cells, with the exception of vascular endothelium, do not express class I or class II HLA antigens in vivo. Class I antigens are induced in vitro by a variety of cytokines, while class II antigens are only induced by gamma interferon. In this study we examine the capacity of cultured uveal cells, rendered class II HLA antigen positive by gamma interferon, to present antigen to T cells. Cultured uveal cells were found to present antigen (tetanus toxoid, PPD, and Candida albicans) to T cells, but only when they were pretreated with gamma interferon. This function of uveal cells was antigen specific and MHC restricted and was blocked by class II-specific monoclonal antibodies, indicating the crucial role of class II HLA antigens in antigen presentation.

Antibodies, Monoclonal↗

The metabolism of C3 and C4 in patients with immune complexes and normal complement levels.

The metabolism of the complement proteins, C3 and C4 was examined in two groups of patients with a high incidence of detectable immune complexes but normal levels of complement components. The specific aim was to ascertain whether significant ongoing complement activation occurred in these patients. Eleven patients with rheumatoid arthritis (RA), 11 with infection and 11 control subjects were studied. Each received approximately 10 microCi 125l.C4 and 2.5 microCi 131l.C3 by intravenous injection. Analysis of turnover data showed that there was significant hypercatabolism of both C3 and C4 in the two study groups compared to controls. Plasma production of C4 was normal for both groups (despite the presence of C4 null alleles in six out of 11 of the RA group), while C3 production was significantly elevated in both RA and infection (p less than 0.01 and p less than 0.001 respectively). Patients with infection showed a significant increase in extravascular/intravascular distribution of both proteins. The data show that immune complex formation is associated with accelerated turnover of complement proteins, irrespective of co-existing tissue damage or changes in the serum concentration of complement components. The findings suggest that both activation of complement and maintenance or enhancement of protein synthesis are important for the efficient processing of immune complexes in vivo.

Antigen-Antibody Complex↗