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Biomedical subjects

D Wakefield

Publications and source records attributed to D Wakefield.

At least 145 records · Page 8Linked to original sources
PubMed1989

Seronegative arthritis associated with serological evidence of Yersinia infection in Australia.

Infection due to yersinia enterocolitica is a common antecedent illness in patients with reactive arthritis in Scandinavia, but appears to be less frequent in other countries. In order to examine the frequency of yersinia infection in patients with seronegative arthritis in Australia we examined 22 patients, 15 with ankylosing spondylitis (AS) and seven with Reiter's syndrome (RS). A sensitive ELISA assay was used to detect serum antibodies to the most common serotypes. Six patients (29%) had positive yersinia serology, all were HLA B27 and four had a history of diarrhea preceding the onset of their disease. Four patients with positive yersinia serology had AS and two had RS. Antibodies were directed against Y. enterocolitica biotype 0:3 in three cases, Y. enterocolitica 0:9 in two cases and Y. enterocolitica 0:8 in one subject. Twenty-nine control subjects (13 HLA B27) had no serum antibodies to yersinia. The results of this study indicate that preceding yersinia infection occurs in a significant (p less than 0.05; compared to controls) proportion of patients with HLA B27 related seronegative arthropathies.

Adult↗
PubMed1989

Hypercatabolism of C3 and C4 in active and inactive systemic lupus erythematosus.

The metabolism of the complement proteins C3 and C4 was studied in patients with active and inactive systemic lupus erythematosus (SLE) using highly purified, functionally active preparations. Nine patients with active and eight with inactive SLE were examined and 11 control subjects. There was a significant difference in the level of double stranded DNA antibodies, immune complexes, and serum C4 between the patients with active and inactive disease. Seven of 16 patients had detectable C4 null alleles and four had low serum concentrations of complement inhibitors. Each subject received approximately 370 kBq [125I]C4 and 93 kBq [131I]C3. Both patient groups showed significant C4 hypercatabolism compared with control subjects, but there was no difference between patients with active and inactive disease. The fractional catabolic rate (FCR) of C4 was comparable in subjects with and without detectable C4 null alleles. C4 production rate was significantly lower in patients with active SLE than in control subjects. There was significant C3 hypercatabolism for both patient groups, but C3 production was normal. An inverse correlation was observed between serum concentration and FCR. There was a highly significant correlation between C4 FCR and C3 FCR for control subjects + patients with inactive disease but not for those with active SLE combined with either controls or the inactive group. We conclude that complement hypercatabolism occurs in SLE irrespective of disease activity and that accelerated turnover does not account completely for the low C4 concentration observed in patients with active disease. This low concentration also results from impaired plasma production, which could reflect a high incidence of C4 null alleles or (inhibitory) factors associated with pathological complement activation, or both. Low C4 production could affect generation of the C3 converting enzyme C4b, 2b and thus influence proceeding complement activation.

Alleles↗
PubMed1989

Cyclosporin therapy for severe scleritis.

To ascertain the efficacy of systemic cyclosporin therapy in the management of scleritis we performed an open, uncontrolled study of the use of this drug in severe refractory disease. Five of seven patients whose disease had previously been poorly controlled with a combination of corticosteroids and immunosuppressive drugs responded to cyclosporin therapy (10 mg/kg/day). Systemic side effects occurred in all but one patient, with tremor, hirsutism, hypertension, and raised serum creatinine being common. Recurrence of disease activity on decreasing the dosage of cyclosporin was frequent. The results indicate that cyclosporin is a useful additional drug in the treatment of severe scleritis.

Adult↗
PubMed1989

HLA antigens in the iris and aqueous humor gamma interferon levels in anterior uveitis.

The induced expression of HLA antigens on a variety of tissues involved in autoimmune diseases has been reported by several groups. In this study, we have examined the expression of HLA antigens in iris biopsy specimens from patients with anterior uveitis and compared them to patients with noninflammatory senile cataracts. In addition, we measured the levels of gamma interferon in the aqueous humor of the same subjects. Our results show that there was induced expression of class I and class II HLA antigens in iris biopsies from patients with anterior uveitis and that the level of induced expression correlated with the concentration of gamma interferon found in the aqueous humor. These results suggest that induced expression of HLA antigens on iris cells may play a role in the pathogenesis of anterior uveitis and that gamma interferon may be one of the mediators for this induced expression.

Aged↗
PubMed1988

Association of complement allotype C4B2 with anterior uveitis.

We have studied allotypes of the fourth component of complement (C4) in 44 patients with inflammatory eye disease in order to define genetic susceptibility factors further. Twenty-six patients had uveitis (18 had anterior uveitis) and 18 patients had retinal vasculitis. There was an increased incidence of the C4B2 allotype in patients with anterior uveitis (pc less than 0.002), especially in HLA B27 positive males. In contrast, there was no increased incidence of specific allotypes in patients with posterior uveitis or retinal vasculitis. This genetic association may form part of a disease susceptibility supratype in patients with anterior uveitis.

Alleles↗
PubMed1988

Expression of HLA antigens on the human uvea.

We examined the expression of HLA antigens on post-mortem human uveal tissues and on cultured uveal cells. There was no in vivo expression of class I or class II antigens in these tissues, except for the blood vessel endothelium which expressed class I but not class II antigens. Tissue cultured uveal cells were found to express class I antigens. The effect of interferon-alpha and interferon-gamma on the in vitro expression of these antigens was examined. Class I HLA antigen expression was enhanced by both interferon-alpha and interferon-gamma, while class II HLA antigens were induced on up to 100% of cultured cells, but only by interferon-gamma. These findings are discussed in their relation to immune mechanisms occurring in ocular inflammatory disorders.

Cells, Cultured↗
PubMed1988

HLA antigens in ocular tissues. I. In vivo expression in human eyes.

The eye is a common site for autoimmune inflammatory diseases, many of which are linked to HLA antigens. The role of these HLA phenotypes in the disease process is presently unknown. In view of the importance of HLA antigens to immune responses, a knowledge of the distribution of HLA antigens in ocular tissues may aid in our understanding of the role of these antigens in disease production or susceptibility. Apart from the cornea, the expression of HLA antigens in human ocular tissues has not been thoroughly investigated. In this study we examined the in vivo expression of HLA antigens in postmortem human eyes using immunohistochemical techniques. The majority of ocular cells were found not to express class I or class II HLA antigens, with the exception of the blood vessel endothelium, which was uniformly class I-positive. The significance of these results is discussed in relation to ocular immunity.

Choroid↗
PubMed1988

Current concepts in the management of scleritis.

Scleritis is an important, severely destructive, chronic inflammatory disorder affecting the eye wall. It presents a difficult management problem, often requiring high-dose systemic corticosteroid therapy or other immunosuppressive regimens to control the inflammatory response. A quantitative scleritis scoring system has been developed and its application to the assessment and management of scleral disease is discussed. This paper reviews current concepts in the management of scleral disease with emphasis on newer treatment modalities, such as pulse therapy with intravenously administered methylprednisolone or cyclophosphamide, and the use of orally administered cyclosporin.

Adrenal Cortex Hormones↗
PubMed1988

Antibodies to HIV are produced within the central nervous system of all subjects with all categories of HIV infection.

Anti-HIV antibodies were found in the cerebrospinal fluid of all 41 subjects tested whose serum contained these antibodies. To ensure that locally produced antibody was being detected, a sensitive assay was used to demonstrate the integrity of the blood-brain barrier. Antibodies to ubiquitous adenovirus group antigens were sought, simultaneously, in CSF and serum. A lack of adenovirus antibodies in CSF of subjects seropositive for adenovirus was required before CSF anti-HIV antibodies could be considered to be produced within the central nervous system. Of the 41 subjects tested eight were asymptomatic, eight were clinically well but had persistent lymphadenopathy, 14 were immunodeficient and had constitutional symptoms (AIDS-related complex or ARC) and 11 had AIDS. Oligoclonal banding was detected in the CSF of 16 subjects and a pleocytosis was present in 24. Neither finding clustered with a particular stage of infection. It appears that HIV infection of T lymphocytes and the central nervous system occurs simultaneously, early in the course of the infection. All HIV infected subjects are at risk of developing primary neurological as well as immunological sequelae. Currently poorly understood resistance factors must protect both lymphocytes and nervous system tissue from damage by the HIV virus, as to date, the majority of infected subjects have not become immunodeficient or developed neurological disease.

AIDS-Related Complex↗
PubMed1988

Current perspectives on immunology and psychiatry.

We selectively review recent research findings in the field of psychoimmunology which test the hypotheses that immunological dysfunction may be aetiologically related to mental illnesses such as schizophrenia, and that certain morbid affective states such as depression and other forms of psychosocial distress may be the cause of immunosuppression and through this mechanism affect the outcome of illnesses such as cancer. Our examination of research implicating immunological or infective mechanisms in the aetiology of schizophrenia indicates that most studies have been unable to control for major methodological difficulties but the compatibility of these theories with the dopamine hypothesis suggests that further research attention is warranted. More clearly, there is growing evidence demonstrating a link between depression, other states of psychological distress and immunosuppression, but the clinical significance of these findings remains uncertain. The complex relationship between stress and the outcome of illnesses such as cancer is discussed and the possible implications of these findings for clinical psychiatry are suggested.

Animals↗
PubMed1988

Increased serum neopterin levels in patients with acute anterior uveitis.

We examined the sera of 50 patients with anterior uveitis (AU) for the presence of interferon and neopterin, an interferon induced pteridine derivative. Neopterin release is induced by gamma interferon and it is a more stable compound. Our results indicate that although there is no detectable differences in serum interferon levels between patients and controls, neopterin levels were elevated in patients with active disease, possibly indicating a localised activation of the interferon system.

Adolescent↗
PubMed1987

Intravenous pulse methylprednisolone in scleritis.

We treated 14 patients with scleritis with intermittent pulse doses of intravenous methylprednisolone. There was 13 patients with anterior scleritis and one patient with posterior scleritis. A grading system was developed to quantitate the degree of scleral inflammation and to follow up the response to treatment. A standard protocol of intravenous administration of methylprednisolone was followed, commencing with 1 g on three occasions in the first week. Additional immunosuppression was required in six patients. The therapy improved the patients' conditions, with a significant reduction in the severity of the scleritis in all patients. Side effects included psychological disturbances, hypertension, and elevated glucose levels, but no patient required cessation of treatment. Pulse methylprednisolone treatment alone or in combination with other immunosuppressive agents is an effective therapy in severe scleritis and has fewer potential side effects than more conventional regimens of corticosteroid administration.

Adolescent↗