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Biomedical subjects

D Wakefield

Publications and source records attributed to D Wakefield.

At least 163 records · Page 9Linked to original sources
PubMed1987

Failure of Klebsiella pneumoniae antibodies to cross-react with peripheral blood mononuclear cells from patients with ankylosing spondylitis.

Cross-reactivity between antibodies to 2 strains of Klebsiella pneumoniae (K43 and F77) and the peripheral blood lymphocytes of patients with ankylosing spondylitis (AS) was examined in 3 separate antibody binding and cytotoxicity assays. Using K pneumoniae antisera in a chromium release cytotoxicity assay, we found no difference in the reactions of cells from AS patients and those from control subjects. This result contrasts with the results of previous studies. Similarly, using an enzyme-linked immunosorbent assay, we detected no significant increase in antibody binding to peripheral blood mononuclear cells (PBMC) in HLA-B27 positive patients with AS. Low levels of antibody binding were detected by a fluoresceinated antibody binding assay; however, normal rabbit serum, which was used as a control, was shown to have a binding affinity for PBMC that was significantly greater than that of specific K pneumoniae antisera. The results of our present study do not support the concept of a specific cross-reactivity between antibodies to K pneumoniae and the PBMC of patients with AS who are HLA-B27 positive.

Adult↗
PubMed1987

The complement system in type 1 (insulin-dependent) diabetes.

The complement proteins C1q, r, s, C2, C4, C3, factor B, C5, C6, and the inhibitors, C1 inhibitors, factors I and H were measured in 35 patients with recently diagnosed Type 1 (insulin-dependent) diabetes, 76 patients with longer-duration disease (30 with complications) and 43 first-degree healthy relatives. We found that C1q, C4 and C3 were reduced significantly in all groups of patients (p less than 0.001 for each protein in recent onset and uncomplicated patients; p less than 0.01, p less than 0.01 and p less than 0.05 respectively, for patients with complications) compared to 60 control subjects and that C4 was also reduced in healthy relatives (p less than 0.001). C4 allotypes were examined in 63 subjects (selected from the patient groups) in order to clarify the role of null alleles in the production of the C4 abnormality. These showed serum C4 to be reduced significantly in 50 patients without null alleles (patient mean 0.24 g/l; control subject mean 0.34 g/l) (p less than 0.0001), although levels were lowest in the 13 patients with one or more null alleles (mean 0.19 g/l). Finally, to examine the metabolic basis for the low concentrations of C4 and C3, the turnover of highly-purified, radiolabelled C4 and C3 was measured in seven recently diagnosed patients; four of these had low levels of C4. The data showed that three out of four of these patients had reduced synthesis of C3 and C4 and normal values for fractional catabolic rate. Two patients showed features of C4 hypercatabolism. We conclude that several early complement proteins are reduced in Type 1 diabetes, irrespective of duration or complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Topical fibronectin therapy in persistent corneal ulceration.

Fifteen patients with 20 episodes of persistent corneal ulceration, resistant to conventional therapy, were treated with topical autologous fibronectin. Thirteen corneal ulcers (eight patients) developed following penetrating keratoplasty, three patients had mucous membrane pemphigoid, two patients had herpetic keratitis and one each had Sjögren's syndrome and a trophic corneal ulcer. A standard protocol for fibronectin administration was followed. This therapy healed 16 of the 20 ulcers after a mean duration of treatment of 2.3 months. Corneal ulceration associated with mucous membrane pemphigoid failed to respond to fibronectin. Corneal ulcers which recurred after cessation of fibronectin responded to reintroduction of this therapy. Topical fibronectin is an effective therapy for refractory corneal ulceration and is free of major side effects.

Administration, Topical↗
PubMed1987

Chronic eosinophilic pneumonia in a patient with ataxia telangiectasia.

The first reported case of chronic eosinophilic pneumonia in a patient with ataxia telangiectasia is described. The patient displayed the immunoglobulin deficiencies and abnormalities of lymphocyte numbers characteristic of ataxia telangiectasia. Treatment with corticosteroids led to a dramatic recovery. The proposed pathogenetic mechanisms of chronic eosinophilic pneumonia are discussed in the light of the immunological abnormalities associated with ataxia telangiectasia.

Adult↗
PubMed1987

Cyclosporin therapy in Mooren's ulcer.

Mooren's ulcer is a rare disease of presumed autoimmune aetiology. Some cases run a chronic severe course and fail to respond to local and systemic therapy. We report here such a case with bilateral Mooren's ulcer that failed to respond to local therapy with topical corticosteroids, silver nitrate, and conjunctival resection, as well as systemic immunosuppression with corticosteroids, cyclophosphamide, and azathioprine. Systemic cyclosporin (10 mg/kg/day) resulted in resolution of the corneal ulceration within two weeks of beginning treatment, and the patient has remained in remission after 15 months of therapy. Cyclosporin side effects included hirsutism, hypertension, increased blood levels of urea and creatinine, and abnormalities in liver function tests. All these resolved on reducing the dosage of cyclosporin. The results in this case suggest that cyclosporin is an effective agent in patients with severe sight threatening Mooren's ulcer.

Adult↗
PubMed1986

Intravenous pulse methylprednisolone therapy in severe inflammatory eye disease.

Seventeen patients with severe ocular inflammatory disease were treated with intermittent pulse doses of intravenous methylprednisolone. There were five patients with chronic posterior uveitis, five with retinal vasculitis, three with scleritis, two with chronic anterior uveitis, one with pars planitis, and one with Mooren's ulcer. A standard protocol of intravenous administration of methylprednisolone was followed. In 15 of 17 patients receiving this therapy, visual acuity improved or stayed constant. Side effects included psychological disturbances, hypertension, and elevated glucose levels, but cessation of treatment was not necessary in any patient. Pulse methylprednisolone treatment appears to be an effective therapy for several forms of severe inflammatory eye disease and minimizes the potential side effects of more conventional regimens of corticosteroid administration.

Adolescent↗
PubMed1986

Uveitis: aetiology and disease associations in an Australian population.

Over a five-year period 245 patients with uveitis were investigated at the Uveitis Clinic, Sydney Eye Hospital, for possible aetiological and relevant disease associations. Uveitis was anterior in 75% of patients, posterior in 21% and generalized in 4%. Anterior uveitis (AU) was idiopathic in 52% of cases. In patients tested for the HLA-B27 antigen, 47% were HLA-B27 positive, including all cases of ankylosing spondylitis (8% of cases) and Reiter's syndrome (3% of cases). There was a marked male predominance in patients with AU, especially in HLA-B27 positive individuals. Posterior uveitis (PU) was most frequently unilateral, chronic and idiopathic (24% of cases), whilst recognizable aetiologies included toxoplasmosis (20%), Behcet's syndrome (14%), sarcoidosis (12%) and pars planitis (12%). The peak age of onset in patients presenting with AU was 30 to 40 years, whilst patients with PU presented a decade earlier. There were no major differences between males and females in the age of onset of their uveitis.

Adult↗
PubMed1986

The acquired immune deficiency syndrome: ocular findings and infection control guidelines.

The acquired immune deficiency syndrome (AIDS) is characterised by a loss of normal cellular immunity in affected individuals which predisposes them to severe opportunistic infections and neoplasms. These pathological processes may affect the eye, and ocular involvement with an opportunistic infection or malignancy may be the first clue to the presence of AIDS. This article reviews the ocular manifestations of AIDS and concludes with infection control guidelines for ophthalmologists treating patients with AIDS and related conditions.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Immunological abnormalities in patients with untreated retinal vasculitis.

Peripheral blood immunological features were assessed in 21 patients with clinical and angiographic evidence of retinal vasculitis (RV). Abnormalities of humoral and cellular immunity were frequent in this group of patients. Lymphopenia was the most common immunological abnormality, being present in 76% of patients at presentation (p less than 0.05). Peripheral blood T and B cells were decreased with a normal helper (OKT4) to suppressor (OKT8) T cell ratio in 11 patients tested (five with Behçet's syndrome and six with idiopathic RV). Significantly increased concentrations of serum immune complexes were present in 55% of patients (p less than 0.05). Results of the present study indicate the frequent association of peripheral blood immunological abnormalities in patients with active RV and indicate the possible role of immunological mechanisms in its pathogenesis.

Adolescent↗
PubMed1986

Chlamydial antibody crossreactivity with peripheral blood mononuclear cells of patients with ankylosing spondylitis: the role of HLA B27.

We have previously reported the association of Chlamydia trachomatis with HLA B27+ related diseases. To investigate the possibility that chlamydial antibodies serve to localize the immune response in such diseases, we examined the crossreactivity of chlamydial antibodies (rabbit anti-D and anti-L2 serotypes) with peripheral blood mononuclear cells of patients with ankylosing spondylitis (AS) and anterior uveitis (AU) and with human and bovine ocular tissue and cells in culture. Our results indicate a significantly increased percentage binding of chlamydial antibody (D serotype) to the mononuclear cells of HLA B27+ patients with AS when compared with HLA B27- patients with AS (12.9% +/- 2.2 versus 5.4% +/- 2.2), B27+ controls (5.5% +/- 1.5) and B27- controls (6.1% +/- 1.0). There was no significant difference between controls and HLA B27+ patients with AU (6.6% +/- 1.9) and B27- patients with AU (8.7% +/- 1.1). This crossreactivity could not be blocked by monoclonal HLA B27 antibody. Chlamydial antibodies (D and L2) crossreact with human and bovine conjunctiva but not uvea, tissue culture derived iris fibroblasts or smooth muscle cells. Our results provide additional support for the concept of crossreactivity between antibodies to microbial agents and peripheral blood mononuclear cells of patients with HLA B27+ AS.

Adolescent↗
PubMed1985

The role of alpha 1-antitrypsin deficiency in the pathogenesis of immune disorders.

The association between alpha 1-antitrypsin (alpha 1-AT) deficiency and a number of immune mediated diseases including rheumatoid arthritis, anterior uveitis, systemic lupus erythematosus, and asthma suggests that alpha 1-AT may be important not only as an anti-inflammatory protein but also as an immune regulator. That the relationship between decreased amounts of this inhibitor and these diseases is causal is suggested by both some of its physical properties and evidence indicating it is able to modulate immune function. alpha 1-Antitrypsin has a high plasma concentration, very broad range of inhibitory activity and is an acute phase reactant. Among other things, it is able to modulate lymphocyte proliferation and cytotoxicity, and monocyte and neutrophil function. Additionally, some of these changes are demonstrable in vivo in patients with severe alpha 1-antitrypsin deficiency. This paper reviews the important physicochemical characteristics of this protein, the association of its presence in decreased amounts with immune disorders, and finally the important mechanism that may underlie this disease association.

Connective Tissue Diseases↗
PubMed1985

Retinal vasculitis associated with HLA DR4. Brief definitive report.

Inflammation of retinal blood vessels may be associated with a variety of systemic immune diseases. Despite the fact that a number of immunological abnormalities have been reported in patients with retinal vasculitis (RV), previous studies have failed to demonstrate an immunogenetic predisposition to this disease. HLA A, B, and DR locus typing of 25 patients (14 females) with well-characterized RV revealed an increased incidence of HLA DR4 (corrected p value = 0.04, relative risk = 3.5). The HLA DR4 antigen was increased in patients with both central and peripheral RV as well as in patients with idiopathic disease (14 patients) and in those with Behcet's syndrome (8 patients). The results of this study indicate that immune response genes may be involved in the pathogenesis of RV.

Adolescent↗
PubMed1985

Decreased chemiluminescent associated phagocytic response of peripheral blood mononuclear cells to Chlamydia trachomatis in patients with HLA-B27+ anterior uveitis.

The chemiluminescent (CL) associated phagocytic response of peripheral blood monocytes to two serovars of Chlamydia trachomatis, Shigella flexneri and zymosan was assessed in a group of 26 patients with anterior uveitis (AU). HLA-B27+ patients with AU, when compared to HLA-B27- patients with AU and appropriate controls, had a significantly decreased CL response to C. trachomatis but no difference between groups in the response to S. flexneri and zymosan. The decreased chemiluminescent (phagocytic) response of mononuclear phagocytes to Chlamydiae may indicate an important abnormality in the pathogenesis of HLA-B27+ AU.

Adolescent↗
PubMed1985

Scleritis and the spectrum of external inflammatory eye disease.

Scleritis, episcleritis and Mooren's ulcer form a poorly understood spectrum of inflammatory syndromes involving the ocular surface. Their pathogenesis is thought to be a vasculitis and may be related to immune complex deposition, as these syndromes are often associated with systemic diseases which are assumed to be vasculitic in aetiology. Scleritis and Mooren's ulcer are amongst the most severe external inflammatory diseases, often causing extensive damage to the sclera and cornea. They require aggressive investigation and management, often including systemic anti-inflammatory therapy. Systemic immunosuppression may be necessary to control severe disease.

Anti-Inflammatory Agents↗