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Biomedical subjects

G A Varigos

Publications and source records attributed to G A Varigos.

At least 19 recordsLinked to original sources

Epidermolysis bullosa acquisita in childhood.

This case report of an 11-year-old girl describes a juvenile form of epidermolysis bullosa acquisita, an autoimmune disease of IgG antibodies to basement membrane type 7 collagen. Our case illustrates an unusually severe, acute inflammatory presentation of this condition with prominent mucosal and constitutional features requiring admission to a paediatric burns unit. The treatment consisted of supportive topical and systemic agents, prednisolone and dapsone. She responded to dapsone alone and the course of the illness was uneventful.

Anti-Infective Agents

Auricular ossification.

A patient with extensive bilateral auricular ossification presented with chondrodermatitis nodularis helicis on one side. The condition was otherwise asymptomatic. Ossification was detected on radiological and histological examination. Underlying medical conditions were not found. We believe this developed as a consequence of cold injury. Auricular ossification is an unusual cause of the so-called petrified external ear, in which the subcutaneous tissue is stony hard. It is more commonly caused by dystrophic calcification. Calcification and ossification are clinically identical and histological examination is required to definitively differentiate them.

Aged

Fixed drug eruption to tartrazine.

An 11-year-old girl with a recurrent fixed drug eruption to tartrazine on the dorsum of the left hand is presented. Oral provocation tests to both the suspected food, an artificially coloured cheese crisp, and to tartrazine were positive. This case highlights fire need to consider artificial flavours, colours and preservatives as potential culprits in classic drug eruptions.

Child

Atopic eczema: its impact on the family and financial cost.

OBJECTIVE: To evaluate the impact of childhood atopic eczema on families and assess the personal financial cost of its management. DESIGN: Cross sectional survey. SETTING: Paediatric dermatology and paediatric diabetology outpatient clinics. PATIENTS: Parents of 48 randomly selected children with atopic eczema and 46 with insulin dependent diabetes mellitus. MAIN OUTCOME MEASURES: The impact on family score, the reported cost of relevant medical treatments, medical consultations, relevant hospitalisation, and income loss. RESULTS: Families of children with moderate or severe atopic eczema had a significantly higher impact on family score than families of diabetic children. A conservative estimate of the annual personal financial cost of managing mild, moderate, and severe eczema was Aus$330, 818, and 1255, respectively. The financial cost to the community for the management of atopic eczema in the study groups was greater. The personal financial cost of managing eczema was greater than for asthma. CONCLUSION: Childhood atopic eczema has a profound impact on the social, personal, emotional, and financial perspectives of families.

Adolescent

House dust mite immunotherapy results in a decrease in Der p 2-specific IFN-gamma and IL-4 expression by circulating T lymphocytes.

BACKGROUND: Allergen-specific immunotherapy (IT) can be an important adjunctive therapy in the treatment of allergic disorders. Although it has now been used for over 80 yr, the precise mechanism of action remains unclear. Recently a number of studies have shown that cytokine production may be modified by IT, but different protocols have been used and different results obtained. OBJECTIVES: The aims of the present study were: (1) to document the allergen-specific expression of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) by peripheral blood cells in both untreated house dust mite (HDM) allergic patients (non-IT) and following at least 10 months of HDM-specific IT (post-IT); and (2) to determine whether alterations in these critical regulatory cytokines correlated with the clinical outcome of IT. METHODS: IT was undertaken with nine fortnightly subcutaneous injections of increasing amounts of a Dermatophagoides pteronyssinus (Dpt) extract, reaching a final dose of 10,000 PNU. This was followed by 6- to 8-monthly maintenance injections of 5000 PNU. For cytokine measurement, mononuclear cells were separated from peripheral blood and stimulated with the major Dpt allergen, Der p 2, for 18 h, after which mRNA was isolated and IL-4 and IFN-gamma cDNA were amplified by polymerase chain reaction (PCR). The presence of the particular cytokine was determined by visualization following electrophoresis on an agarose gel. The study was observational in nature being open and without a placebo group. RESULTS: Fifteen Dpt-sensitive patients who had not received HDM IT (non-IT), and 16 who had, were studied. In the non-IT group, 80% expressed IL-4 and 75% expressed IFN-gamma. In those post-IT, only 12.5% expressed IL-4 and 19% IFN-gamma. The two patients still expressing IL-4 post-IT had had very little clinical response. Six patients were studied both pre- and post-IT. Prior to IT, three were positive for both cytokines, two positive for IL-4 alone and one for IFN-gamma. Post-IT, all six were negative for IL-4 and five were negative for IFN-gamma. CONCLUSION: Allergen-specific IT results in a reduction in expression of the critical cytokines IL-4 and IFN-gamma in circulating lymphocytes. It is possible that this is a contributary mechanism in the beneficial effect of IT.

Adolescent

Dermatophagoides pteronyssinus II-induced interleukin-4 and interferon-gamma expression by freshly isolated lymphocytes of atopic individuals.

Cytokines are known to play a major role in mediating many of the immunological and pathological features of allergic disease. Much of our understanding of cytokine production in response to allergens has come from studying allergen-specific T cell clones following long-term in vitro culture. This has largely been due to the lack of sufficiently sensitive assays to measure allergen-induced cytokine production by freshly isolated peripheral blood mononuclear cells (PBMCs). Here we have used the polymerase chain reaction to amplify reverse transcribed interleukin-4 (IL-4) and IFN gamma mRNA expressed by allergen-stimulated PBMCs from a variety atopic individuals. Using Der p II, a major allergen of the house dust mite (HDM) Dermatophagoides pteronyssinus, we have demonstrated that cells from HDM-sensitive atopic patients (n = 12), can be induced to express either IL-4 alone (three patients), IL-4 and IFN gamma (six patients), IFN gamma alone (two patients) or neither cytokine (one patient). Cells from 13 non-atopic control individuals were also stimulated with Der p II and cytokine mRNA production was studied. None expressed IL-4, while seven of 13 transcribed IFN gamma. Our results suggest that atopic individuals have allergen-reactive T cells at various stages of differentiation, with respect to the cytokines they produce. The use of this technique will aid in the further understanding of specific cellular hypersensitivity in allergic disease.

Animals

IL-4 production is increased in cigarette smokers.

Cigarette smoking has been associated with both increases in serum levels of total IgE and an increased risk of developing allergic-like symptoms. IL-4 and interferon-gamma (IFN-gamma) have reciprocal roles in the regulation of IgE synthesis, and as such prompted us to evaluate, in smokers, the production of these two cytokines. We demonstrate that phytohaemagglutinin (PHA)-induced IL-4 production by peripheral blood mononuclear cells (PBMC) of smokers (n = 19) is significantly higher than that of non-smokers (n = 10, P < 0.005). In addition, PBMC from heavy smokers, defined by the number of cigarettes smoked per day, produced significantly higher levels of IL-4 than those of light smokers. No difference between the groups was found for IFN-gamma production. Our data suggest an imbalance in cytokine production occurring in individuals who smoke. This imbalance, favouring IL-4 production, may be part of the mechanism responsible for the observed increases in serum IgE and allergic-like symptoms associated with cigarette smoking.

Adult

Interferon-gamma production in atopic dermatitis: a role for prostaglandins?

Peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis (AD) have a reduced capacity to produce interferon-gamma (IFN-gamma) in vitro, in response to phytohaemagglutinin (PHA) when compared to healthy non-atopic controls. This defect appears to correlate closely with the severity of AD at the time of sampling, with less IFN-gamma being produced by cells from patients with more severe disease. Enhanced production of IFN-gamma was observed as the patients clinical symptoms improved. In addition, IFN-gamma production could be increased by either pre-culturing the cells for 3 days prior to PHA stimulation or by addition of indomethacin to the culture medium. These observations suggest that the mechanism of reduced IFN-gamma production in AD is unlikely to be due to an intrinsic cellular defect. The possibility that prostaglandins mediate the suppressed production of IFN-gamma in AD was supported by demonstrating that exogenous prostaglandin E2 (PGE2) inhibited IFN-gamma production in PHA-stimulated PBMC. PGE2 at a physiological concentration (10(-9) M) was also shown to enhance interleukin 4 induction of IgE synthesis by PBMC cultures. Our data suggest that alterations in prostaglandin metabolism play a crucial role in the pathogenesis of AD by inhibiting the production of IFN-gamma.

Cells, Cultured

Monosodium glutamate-related orofacial granulomatosis. Review and case report.

A case is reported in a 15-year-old white girl who had a swollen lower face and lips; a diagnosis of orofacial granulomatosis was made. It was suspected that her condition had an allergic basis because an increase in clinical signs and symptoms was shown to be related to the food additive monosodium glutamate. Treatment with a restricted diet resulted in resolution of the facial swelling.

Adolescent

Recombinant interferon-gamma inhibits the expression of IL-4 receptors on human lymphocytes.

Interferon gamma (IFN-gamma) has been shown to inhibit many of the activities of IL-4, including the induction of IgE synthesis and the proliferation of T cell clones. Here we demonstrate that IFN-gamma is able to inhibit the expression of IL-4 receptors on peripheral blood lymphocytes from both normal healthy donors and from patients with chronic lymphocytic leukaemia. Inhibition was shown to be dose-dependent and did not affect the binding affinity of the receptor as shown by Scatchard analysis. IFN-gamma was unable to displace labelled IL-4 from its membrane receptor, which demonstrates that IFN-gamma and IL-4 do not compete for the same membrane binding protein. The ability of IFN-gamma to down-regulate IL-4 receptors may be important in controlling certain immune responses.

Cells, Cultured

Extracorporeal photochemotherapy in the treatment of cutaneous T-cell lymphoma. Complexity of objective evaluation.

The term cutaneous T-cell lymphoma (CTCL) encompasses the spectrum of diseases characterized by a monoclonal proliferation of malignant T lymphocytes predominantly of the mature T-helper cell type. These include mycosis fungoides, which is usually localized to the skin for many years, and the Sezary syndrome, the leukemic variant in which characteristic, bizarre lymphatic cells with deeply indented or cerebriform nuclei, the Sezary cells, infiltrate lymph glands and internal organs such as the spleen, liver, lungs, heart, and bone marrow. The condition is more common in men after their fourth decade. The treatment of CTCL varies depending on the stage of the disease. The skin of the patient is the primary index of effectiveness of therapy. Options range from topical steroids, topical nitrogen mustard, X-irradiation, electron beam irradiation, and 8-methoxypsoralen (8-MOP) combined with ultraviolet A photochemotherapy (PUVA), to leukapheresis and systemic chemotherapy. More recently, extracorporeal photochemotherapy (ECPC) has been introduced. The safety and efficacy of this modality is further investigated in six patients who fulfilled the criteria of diagnosis of CTCL. The problems encountered in objectively evaluating the clinical responses in the patients are outlined and improvements in the protocol to overcome these are suggested. The proposed mechanism of action is an immunostimulatory one and a procedure that is relatively free from side effects; it offers promise as a potential treatment for a difficult cancer.

Aged

A new treatment for acquired reactive perforating collagenosis.

Acquired reactive perforating collagenosis is reported in an insulin dependent diabetic patient with renal impairment, managed successfully with surgical debridement and split skin grafting. The literature on treatment of reactive perforating collagenosis is reviewed.

Adult

Psychological profile of the atopic eczema patient.

A survey of 40 patients with long-standing atopic eczema was carried out to test for the presence of certain psychological traits which had been reported in studies in earlier decades. A series of standardised personality tests was administered to these patients and the results compared with the findings for a normal group for each test. It was demonstrated that atopic eczema patients do have significantly high levels of anxiety and problems in dealing with anger and hostility. Whether such findings make any contribution to understanding the aetiology of this disorder is debatable, but they do have implications for treatment and management, and some of these are discussed.

Adolescent

A preliminary study of psychological therapy in the management of atopic eczema.

This paper presents a pilot study of the treatment of atopic eczema using a cognitive-behavioural approach involving self-monitoring of eczema severity, recording both internal (cognitive) and environmental antecedent trigger stimuli to flare-ups, and relaxation using imagery and habit reversal. Three patients are presented suffering from chronic atopic eczema. Although each differed in personality, complexity and severity of atopic eczema, all three showed a post-treatment reduction in symptom severity, an increase in their ability to control the disorder and a decrease in their reliance on medication. It is argued that although the cognitive-behavioural approach used did provide a useful conceptual framework for implementing the treatments described, certain aspects of these cases could also usefully be understood in more psychodynamic terms. A controlled trial is necessary to evaluate the relative importance of the different components of treatment reported in this pilot study.

Adult

Fluctuations in the expression of a glycolipid antigen associated with differentiation of melanoma cells monitored by a monoclonal antibody, Leo Mel 3.

A monoclonal antibody, Leo Mel 3, raised against a melanoma cell line (LiBr), binds to a carbohydrate determinant of cell surface gangliosides, the simplest of which is GD3. This monoclonal antibody was screened for by its capacity to block the recognition and lysis of the melanoma cells by cytotoxic T-lymphocytes with anomalous killer cell function, illustrating a novel approach for identifying monoclonal antibody to biologically relevant tumor-associated antigens. Leo Mel 3 reacted selectively with melanoma cells by indirect immunofluorescent and immunoperoxidase staining; it reacted with tissue from all primary and metastatic melanoma tested, and it bound to cells from all but one of six cultured melanoma cell lines. Leo Mel 3 did not react with a variety of carcinomas, lymphomas, leukemias, and other neuroectodermal tumors, nor with adult or fetal tissues, except fetal liver. Very weak staining of cutaneous basal melanocytes was noted in a minority of skin sections, and 50 to 80% of melanocytes in four of seven benign nevi showed weak to moderate reactivity. The antibody was relatively specific for human adherent melanoma cells, since it did not bind to the adherent murine B16 melanoma line nor to a nonadherent human melanoma cell line (PMC-22). Expression of the Leo Mel 3-defined antigen was unrelated to changes in cell cycle. When cells from an adherent melanoma cell line were detached and maintained briefly in suspension culture, the cells became markedly less reactive with Leo Mel 3 and, after readherence to plastic, they rapidly reexpressed higher levels of the ganglioside antigen; since Leo Mel 3 prevented attachment and growth of melanoma cells in vitro, a functional role for the ganglioside is suggested in cell adhesion and metastasis. Differentiation of melanoma cells with dimethyl sulfoxide, retinoic acid, and theophylline resulted in a marked and selective increase in the amount of Leo Mel 3-defined antigen, together with an increase in the target cell binding ability of these cells, assessed by cold target competition assays using anomalous killer cells.

Antibodies, Monoclonal