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Biomedical subjects

D Wakefield

Publications and source records attributed to D Wakefield.

179 records · Page 10Linked to original sources
PubMed1985

Ocular involvement in the acquired immune deficiency syndrome (AIDS).

The acquired immune deficiency syndrome (AIDS) has reached epidemic proportions in the USA and the incidence of this potentially fatal viral infection is increasing rapidly in Australia. The loss of normal cellular immunity in affected individuals predisposes them to severe opportunistic infections and neoplasms, especially Kaposi's sarcoma. Both of 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. We present here the first Australian report of a patient with AIDS presenting with ocular involvement. The case is discussed in relation to current concepts of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Methylprednisolone pulse therapy in severe anterior uveitis.

Six patients with severe, refractory anterior uveitis (AU) were treated with intermittent, intravenous pulses of methylprednisolone (MP). Five patients had bilateral AU and all had decreased visual acuities. AU was idiopathic in four subjects, one male had ankylosing spondylitis (HLA-B27 +) and one female had juvenile polyarthritis. All patients were initially treated with 1 g of MP intravenously (IV) on alternate days during the first week. Subsequently, patients received weekly injections of MP on a reducing dosage regime to a maintenance dose of 125 mg IV weekly. This therapy produced a rapid resolution of the signs of uveal inflammation and improved visual acuity. Two patients have been maintained on this treatment regime for over 12 months without evidence of disease relapse or serious drug side effect. Pulse MP is effective in the treatment of severe anterior uveitis and may be a useful adjunct in the management of patients with uveitis.

Adolescent↗
PubMed1985

Alpha 1 antitrypsin serum levels and phenotypes in patients with retinal vasculitis.

alpha 1 antitrypsin is an important immunoregulatory protein, the serum level of which is genetically determined. Deficient phenotypes of this ubiquitous protease inhibitor are associated with a variety of inflammatory diseases including anterior uveitis. In order to investigate the role of this protease inhibitor in the pathogenesis of retinal vasculitis (RV) 25 patients were investigated. Diseases associated with RV included Behcet's syndrome (8), SLE (2), and sarcoidosis (1). Deficient phenotypes of alpha 1 antitrypsin were not associated with RV. However, the serum alpha 1 antitrypsin level was significantly increased in patients with active RV and paralleled disease activity in patients studied prospectively.

Adolescent↗
PubMed1985

The chemiluminescence response of normal human leukocytes to chlamydia trachomatis.

The aim of the present study was to investigate the phagocytic response of normal human polymorphonuclear leukocytes (PMN) and monocytes (MN) to eight serotypes of C trachomatis (B,C,D,E,F,I,J, and L2) using a chemiluminescence (CL) assay, with luminal and lucigenin as amplifiers. The magnitude of the phagocytic cell CL response was proportional to the phagocyte-to-chlamydiae ratio, with a poor CL response detected at a ratio of 1:125 and progressively larger CL responses up to ratios of 1:50,000. The durations of the CL responses to all chlamydiae serotypes tested were considerably longer than that for zymosan. The PMN demonstrated a relatively greater CL response to all chlamydiae serotypes tested when compared with MN. The PMN and MN CL responses to "genital serotypes" (D,E,F,I, and J) (as well as lymphogranuloma venereum serotype L2) were greater than that for "ocular" serotypes (B and C). Inactivation of serum complement and specific chlamydial antibody absorption reduced the CL responses of both PMN and MN. This is the first study to characterize the CL responses of normal human PMN and MN cells to C trachomatis, and it indicates the important role of oxygen dependent antimicrobial systems in the phagocytosis of this common human pathogen.

Animals↗
PubMed1984

Chemiluminescent response to pathogenic organisms: normal human polymorphonuclear leukocytes.

Chemiluminescence (CL) is a sensitive indicator of phagocytosis and intracellular killing; however, little is known of the normal CL response by human polymorphonuclear leukocytes to different pathogenic microorganisms. We investigated the luminol-enhanced CL response of normal polymorphonuclear leukocytes to a number of common bacterial pathogens and two yeasts. We analyzed the CL response to viable and heat-killed microorganisms at 25 and 37 degrees C. The CL response to all microorganisms was greater and more rapid at 37 degrees C. Variable responses were observed with viable and heat-killed microorganisms; some were unaffected, whereas other demonstrated reduced CL. Each microorganism caused a reproducible response pattern, which could be placed into two general categories. In the first category were those which caused a rapid exponential rise and decay in CL: Enterobacter cloacae, Salmonella typhimurium, Shigella flexneri, Staphylococcus aureus, Candida albicans, and zymosan. In the second category were those which rose slowly over a longer time course to a poorly defined peak: Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, and Streptococcus pyogenes. The CL response also reflected serum opsonic activity. The effect of inactivated complement, factor B, and removal of specific antibody were investigated. Increasing the concentration of zymosan gave a proportional rise in peak CL; however, a strain of E. coli caused a variation in peak time rather than peak height. Different CL kinetics were shown for three strains of K. pneumoniae, possibly a result of each having different membrane or cell wall characteristics. This study defines the nature and factors affecting the normal CL response to a variety of common pathogenic microorganisms.

Adsorption↗
PubMed1984

The effect of purified alpha 1 antitrypsin on PWM driven IgG synthesis.

As part of a study investigating the mechanisms for the association of alpha 1 antitrypsin (alpha 1 AT) deficiency with immune disorders, the effect of purified alpha 1 AT on PWM driven IgG synthesis of peripheral blood lymphocytes was investigated. This demonstrated that alpha 1 AT in physiological doses enhanced IgG synthesis in stimulated but not resting cells. This effect is probably due to the known inhibition by alpha 1 AT of macrophage function. Increasing number of macrophages are known to inhibit IgG synthesis in the PWM system suggesting that this apparently paradoxical enhancement by alpha 1 AT is probably due to inhibition of these cells.

Animals↗
PubMed1983

HLA antigens in uveitis.

HLA antigens are associated with a number of inflammatory eye diseases, most notably HLA B2 with anterior uveitis (AU). This association varies between different populations and ethnic groups. The aim of this study was to investigate the relationship between uveitis and HLA A, B and DR locus antigens in an Australian population. Seventy-two consecutive patients with uveitis were studied (37 males and 35 females) over a 6 month period. Thirty-two percent of the AU patients were HLA B27+, as were 42% of males (19% females) with their first attack of AU compared with 60% of males (23% females) with recurrent AU. The only significant difference in etiology between males and females was the greatly increased incidence of rheumatic diseases in males, in whom 77% (10/13) had radiological evidence of sacroiliitis. Additional findings included a lack of association between the HLA B7 cross reactive group and DR locus antigens in AU as well as the lack of any HLA associations in the 13 patients with posterior uveitis (PU).

Acute Disease↗
PubMed1983

Immunological features of HLA-B27 anterior uveitis.

Analysis of the immunological features of anterior uveitis (AU) revealed a dichotomy of abnormalities defined in terms of the HLA-B27 status of the patient. HLA-B27-positive AU was characterised by the occurrence of iris autoantibodies and an absolute T cell lymphopenia during active disease which returned to normal with recovery. This phenomenon was not observed in HLA-B27-negative AU or in controls and could not be attributed to antilymphocyte antibodies as these were not detected. Furthermore, there were no changes in T-cell subsets (helper and suppressor T lymphocytes). Compared with HLA-B27-positive AU patients, the HLA-B27-negative group demonstrated elevated IgE levels and increased prevalence of smooth muscle autoantibodies.

Adolescent↗
PubMed1983

Cell-mediated immune response to chlamydia in anterior uveitis: role of HLA B27.

The relationship between HLA B27 anterior uveitis (AU) and evidence of chlamydia trachomatis infection was investigated in 35 consecutive patients attending a uveitis research clinic, using a complement fixation test and lymphocyte transformation test to chlamydia (ornithosis-psittacosis) group antigen. A significant stimulation index (SI greater than 2) was found in 73% (11/15) of the HLA B27 positive patients compared with the HLA B27 negative AU patients and controls (P less than 0.03). There was no difference between AU patients with and without associated rheumatic disease or in terms of antibody response. The results of the present study indicate a significant relationship between the cell-mediated immune response to chlamydia group antigen and the HLA B27 positive subgroup of patients with AU.

Adult↗
PubMed1982

Immunogenetic factors in inflammatory eye disease. Influence of HLA-B27 and alpha 1-antitrypsin phenotypes on disease expression.

The relationship between the nature and severity of inflammatory eye disease was analyzed with respect to HLA antigens and alpha 1-antitrypsin phenotypes. Using standard ophthalmologic criteria, we divided patients with anterior uveitis into acute, chronic (greater than 3-month duration), bilateral, or recurrent disease. There was a significantly increased incidence of alpha 1-antitrypsin-deficient phenotypes in anterior uveitis, especially in those patients with severe (chronic, bilateral, or recurrent) disease. HLA-B27 acts as an independent predisposing factor: it was present in 22% of patients with their first attack of acute uveitis compared with 51% of patients with recurrent disease. Together, these genetic factors are present in 63% of patients with severe anterior uveitis and represent the most significant predisposing and prognostic factors so far detected.

HLA Antigens↗
PubMed1982

Immunology of ocular toxoplasmosis.

Toxoplasma gondii, due to its ability to escape and modify the normal immune response, is able to survive within the retina indefinitely with the production of an occasional acute inflammatory response. The cellular immune system is mainly responsible for limiting infection. Diagnosis is based on clinical features coupled with measurements of antibody response (systemic and ocular) and cell mediated immunity. The treatment of toxoplasma chorioretinitis when indicated should be specific and immunosuppressive agents should only be used in conjunction with antibiotics to avoid dissemination of the organism.

Humans↗
PubMedDate not supplied

Acute anterior uveitis and HLA-B27.

Acute anterior uveitis is a common ocular disease characterized by inflammation of the iris and ciliary body. In the majority of patients presenting with an acute attack of anterior uveitis, the only clues to the pathogenesis of this disease are its close association with the genetic marker HLA-B27 and the likely triggering role of a variety of gram negative bacteria. HLA-B27 acute anterior uveitis appears to be a distinct clinical entity frequently associated with the seronegative arthropathies, such as ankylosing spondylitis and Reiter's syndrome. Recent advances in our understanding of the structure and function of class I HLA molecules have revealed their fundamental function in antigen presentation and this has led to a reevaluation of their role in disease predisposition.

Acute Disease↗
PubMedDate not supplied

Intravenous immunoglobulin therapy for autoimmune diabetes mellitus.

OBJECTIVE: A variety of immune therapies have been used in an attempt to reduce the immune destruction of the insulin secreting beta cells which results in insulin dependent diabetes mellitus (IDDM). This study investigated the use of intravenous gammaglobulin therapy (IVIG) in children and adults with IDDM who participated in a two-year randomised controlled trial which also examined the effect of transfer factor in altering the natural course of IDDM. METHODS: Treatment was administered every two months for the duration of the study. IVIG was given in a dose of 2 g/ kg body weight in divided doses over two days. The other two groups received an intramuscular injection-the control group received normal saline and the transfer factor group received 1 i.u. of transfer factor. Remission rates, beta cell function and treatment side effects were assessed. RESULTS: Compared with the control group, IVIG therapy given every 2 months for 2 years, did not result in an increased number of complete remissions or differences in insulin dose, diabetes control or endogenous insulin secretion assessed as fasting and stimulated C-peptide responses to glucagon and a meal. IVIG therapy was associated with significant side effects. CONCLUSION: It is unlikely that IVIG therapy will be a viable option for immunotherapy in IDDM.

Adolescent↗