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Biomedical subjects

R J Heddle

Publications and source records attributed to R J Heddle.

At least 19 recordsLinked to original sources
PubMed2004

In vitro testing to diagnose venom allergy and monitor immunotherapy: a placebo-controlled, crossover trial.

BACKGROUND: In people with a history of sting allergy, only prior reaction severity and older age are known to predict subsequent reaction risk. Furthermore, no diagnostic test other than a deliberate sting challenge has been found to identify people in whom venom immunotherapy (VIT) has been unsuccessful. OBJECTIVE: We aimed to assess the utility of a number of in vitro tests to diagnose venom allergy and to monitor immunotherapy. METHODS: During a double-blind randomized placebo-controlled crossover trial of Myrmecia pilosula ant VIT the following venom-specific tests were performed at enrolment, and at completion of treatment prior to a diagnostic sting challenge; leucocyte stimulation index (SI), IL-4 production, IgE RAST, histamine release test (HRT), leukotriene release test (LRT) and basophil activation test (BAT). Intradermal venom skin testing (VST) was also performed at trial entry. RESULTS: Only VST and HRT identified those at risk of sting anaphylaxis in the placebo group. Although IgE RAST, leucocyte SI and IL-4 production, LRT and BAT all correlated well with intradermal VSTs, they did not predict sting challenge outcome. After successful VIT, venom-induced leucocyte IL-4 production tended to fall, whereas IgE RAST increased and a natural decline in HRT reactivity was reversed. A confounding seasonal affect on laboratory results was suspected. CONCLUSION: The HRT warrants further assessment for diagnosis of venom allergy. Uninformative performance of the commercially available LRT and BAT tests may be due to pre-incubation with IL-3. None of the tests evaluated appear to be reliable markers of successful VIT.

Animals↗
PubMed2004

Insect sting anaphylaxis; prospective evaluation of treatment with intravenous adrenaline and volume resuscitation.

OBJECTIVES: To assess a protocol for treatment of sting anaphylaxis. DESIGN: Prospective assessment of treatment with oxygen, intravenous infusion of adrenaline (epinephrine), and volume resuscitation with normal saline. SETTING: Sub-study of a venom immunotherapy trial. PARTICIPANTS: 21 otherwise healthy adults with systemic allergic reactions to diagnostic sting challenge. MAIN OUTCOME MEASURES: Response to treatment, total adrenaline dose and infusion duration, recurrence of symptoms after stopping the infusion, and additional volume resuscitation. RESULTS: 19 participants required intervention according to the protocol. All received adrenaline, and five received volume resuscitation. In nine cases, physical signs of anaphylaxis recurred after initial attempts at stopping adrenaline but resolved after recommencing the infusion. The median total dose and infusion duration were 590 micro g and 115 minutes respectively, but were significantly higher for eight patients who had hypotensive reactions (762 micro g and 169 minutes respectively). Hypotension was always accompanied by a relative bradycardia, which was severe and treated with atropine in two patients. Widespread T wave inversion occurred, before starting treatment with adrenaline, in one person with an otherwise mild reaction. All patients fully recovered and were fit for same day discharge, apart from the person with ECG changes who was observed overnight and discharged the following day. CONCLUSIONS: Carefully titrated intravenous adrenaline combined with volume resuscitation is an effective strategy for treating sting anaphylaxis, however severe bradycardia may benefit from additional treatment with atropine. Cardiac effects of anaphylaxis, perhaps including neurocardiogenic mechanisms, may be an important factor in some lethal reactions.

Adult↗
PubMed1995

IgE+ cells in the peripheral blood of atopic, nonatopic, and bee venom-hypersensitive individuals exhibit the phenotype of highly differentiated B cells.

We have analyzed IgE+ cells in peripheral blood of atopic donors, donors hypersensitive to bee venom, and nonatopic control donors with two- and three-color flow cytometry. Although the percentage of IgE+ cells varied among these groups, the overall phenotypic patterns were similar. Most IgE+ cells do not display typical B-cell markers, such as CD19, CD20, and CD21. A significant proportion of these cells stain for CD38, indicating that they are more differentiated. IgE+ cells express Fc gamma RII and CD45RO, an isoform associated with an advanced level of differentiation. The majority of IgE+ cells do not coexpress other surface immunoglobulin isotypes. In the case of bee venom-hypersensitive donors, we have been able to identify a small population of IgE+ cells with a specificity for phospholipase A2, a major immunogenic component of bee venom. The phospholipase A2+ cells display a phenotype similar to that of the IgE+ cells.

Antibodies, Monoclonal↗
PubMed1995

Bee venom hypersensitivity and its management: patients perception of venom desensitisation.

The objectives of the study were to review bee venom immunotherapy from the patient's perspective: in particular its benefits and its problems, and to investigate any genetic tendency for bee venom hypersensitivity. A self administered, 9 item questionnaire was sent to 219 patients who had undergone either inpatient or outpatient bee venom immunotherapy at Flinders Medical Center. The clinic records of these patients were also reviewed. The controls for the genetic study were sought from patients, staff and students at Flinders University and Flinders Medical Centre. One hundred and forty-six questionnaires (some incomplete and anonymous) were received. The female to male ratio was 1:2.5. The age at the time of the initial anaphylactic reaction to a bee sting ranged between 2 to 59 years, with 67% of patients being less then 20 years old. Forty percent of patients underwent venom immunotherapy for a period less than 2 years with only 11% maintaining therapy for the recommended period of 5 years or more. Thirty three percent of patients stopped their therapy on their own accord. Bee stings occurring during bee venom immunotherapy (n = 56) were generally well tolerated except in 8 subjects, 7 of whom had not reached the maintenance dose. The reduction in systemic reactions to subsequent bee stings was significantly better in the study group receiving bee venom than in an historic control group treated with whole bee extract (p = 0.03). Fear of bee stings and restricted life styles were improved during or after venom immunotherapy. The frequency of a positive family history of systemic reactions to bee stings in the patient cohort was 31%, whereas in controls it was 15% (p = 0.013). Bee venom immunotherapy has dual benefits: patients are protected from subsequent sting anaphylaxis and there is reduced psychological morbidity. However, to be effective, venom immunotherapy requires a prolonged period of carefully supervised treatment and each venom injection can cause local and systemic side effects. Genetic factors appear to be present in those patients who develop immediate hypersensitivity to be stings.

Adolescent↗
PubMed1993

Common allergic skin conditions.

Skin conditions regarded as having an 'allergic' origin are extremely common. Immunologically specific hypersensitivities to food and aeroallergens and idiosyncratic reactions to food chemicals play a role in some of the individuals suffering from these conditions, but in others intrinsic or unknown factors dominate. Rashes are frequently seen in relation to food intolerance and adverse drug reactions that share common mechanisms.

Drug Hypersensitivity↗
PubMed1991

Immunoblot analysis of IgE and IgG antibodies to honey bee venom: cross sectional and sequential studies in bee sensitive subjects.

To investigate the specific IgE and IgG immune response to honey bee venom (bv), we performed immunoblot analysis of sera from 47 bee sensitive subjects and followed the response during and after venom immunotherapy in 15 of these subjects. Fifteen venom proteins varying in molecular size from 20 to 105 kDa were identified as being antigenic and consisted of a high molecular weight (HMW) group (5 to 105 kDa, containing the previously identified allergens B and C) and a low molecular weight group (LMW) containing hyaluronidase and phospholipase A. In general for a given individual the anti-venom IgE and IgG response was qualitatively similar although some variation between individuals was apparent. Reactivity with hyaluronidase and phospholipase A appeared only in those subjects showing reactivity with HMW components. During immunotherapy specific anti-venom IgG and IgE responses tended to be linked. Increased responses being seen against all components in 4 of 12 subjects, reductions in 3 and unchanged responses in the remainder. Following immunotherapy (mean 4.0 years), spontaneous reduction of IgE and IgG was seen in 5 of 5 subjects. Loss of reactivity with the LMW components was prominent in these sera.

Adult↗
PubMed1986

Increased intestinal permeability in atopic eczema.

We have investigated gastrointestinal permeability in children with atopic eczema by measuring the relative urinary excretion rates of the inert di- and monosaccharides lactulose and rhamnose following their oral administration. The median lactulose/rhamnose ratio was greater in 26 children with atopic eczema than in a control group of 29 children which included both healthy individuals and others with various noneczematous dermatoses. This increased permeability may be a primary abnormality of the gut or may reflect intestinal mucosal damage caused by local hypersensitivity reactions to food antigens.

Adolescent↗
PubMed1985

Bee sting anaphylaxis in an urban population of South Australia.

The clinical manifestations and circumstances of bee sting anaphylaxis have been studied retrospectively in 98 subjects. Most reactions occurred in children but the most severe reactions were seen in adult males, of whom 7 lost consciousness and 2 required cardiopulmonary resuscitation. Most stings causing anaphylaxis occurred on the unprotected feet whilst the subject was on lawn in the afternoons in December, January and February when the maximum daily temperature was between 20 and 30 degrees C. This is the temperature range when bees are particularly active in gathering pollen. However, a significantly greater frequency of anaphylactic reactions occurred at higher temperatures when bees are less active, suggesting that high environmental temperature may predispose the individual to greater exposure to bees or possibly to anaphylactic reactions per se. The presence of atopy did not appear to predispose subjects to bee venom hypersensitivity. Considerable anxiety and lifestyle alteration were identified in some subjects. The alleviation of this anxiety is considered an appropriate indication for bee venom immunotherapy.

Adolescent↗
PubMed1984

Combined oral and nasal beclomethasone diproprionate in children with atopic eczema: a randomised controlled trial.

In a double blind, placebo controlled, crossover trial in 26 children with severe atopic eczema those receiving four weeks' treatment with combined oral plus nasal beclomethasone diproprionate improved significantly more than those receiving placebo. No adverse effects were observed, but 24 hour urinary cortisol excretion was slightly reduced. This combination may provide effective treatment in refractory atopic eczema with relatively little of the danger associated with systemic administration of prednisolone and other traditional corticosteroids.

Administration, Intranasal↗
PubMed1984

Extrinsic factors in atopic eczema.

The debate over the role of extrinsic allergens in atopic eczema has been enlightened in recent years by some well-controlled studies and improvements in our understanding of conditions which lead to hypersensitivity. This paper reviews some of these findings, which have preventative and therapeutic implications. No attempt is made here to review other aspects of this multifactorial disease, nor to enter into detailed discussion of dietary or allergen avoidance regimens, which have been covered in several recent reviews. Such regimens are not without risk, and require expert supervision.

Allergens↗
PubMed1984

Urticaria and angio-oedema.

Urticaria and angio-oedema are a symptom complex covering a wide range of clinical disorders. Specific types are now well described, and it appears that many cases of idiopathic chronic urticaria which make up the vast majority of patients referred for assessment are due to intolerance to natural salicylates, preservatives and colouring agents. There is, therefore, an urgent need for legislation to enforce the clear identification of these chemicals in processed food and drugs.

Angioedema↗
PubMed1984

Bee-sting mortality in Australia.

Death as a result of a bee sting is uncommon in Australia. During the 22 years from 1960 to 1981, 25 individuals have been recorded by the Australian Bureau of Statistics as having died shortly after a bee sting. This gives a mortality incidence of 0.086/1 000 000 population per year, but may be an underestimate, as we report two additional fatalities that did not appear in the records of the Bureau of Statistics. South Australia has the highest mortality rate from bee stings of all the Australian States, with a recorded fatality rate of 0.26/1 000 000 population per year. As in other surveys, fatalities occur predominantly in men over 40 years of age, which suggests that there may be other contributory risk factors, for example, coronary atherosclerosis. No deaths were reported in individuals aged from six to 19 years, the age group in which bee-sting anaphylaxis is particularly common. It thus appears that the prevention of death per se is not a strong rationale for routine bee-venom immunotherapy in schoolchildren and young adults.

Adolescent↗
PubMed1983

Development of monoclonal mouse antibodies specific for allergenic components in ryegrass (Lolium perenne) pollen.

The development of monoclonal mouse antibodies against ryegrass (Lolium perenne) pollen allergens is described. Hybridoma colonies secreting antibodies specific for allergenic components were detected using an enzyme-linked immunosorbent assay. Positive colonies were cloned and expanded. The pollen components with which the monoclonal antibodies interact were identified and characterised following sodium dodecyl sulphate polyacrylamide gel electrophoresis and electrophoretic transfer to nitrocellulose. In this paper six monoclonal mouse antibodies are described. Three antibodies interact with a single molecule of between 30,000 and 35,000 daltons. One antibody interacts with a component of 16,000 daltons whereas the remaining two antibodies react with more than one component, one reacting with two components at 28,000 and 30,000, and the other with five components having molecular weights between 18,000 and 71,000 daltons.

Animals↗
PubMed1982

Escherichia coli antibody-secreting cells in the human intestine.

Mononuclear cells were isolated from the mucosa and submucosa of small intestine and colon of 22 subjects with localized, anatomically remote disease and four subjects with Crohn's disease (nine specimens) by sequential treatment with EDTA and collagenase. The effects of isolation techniques on cell yields and viability were examined. Secretion of specific IgA, IgM and IgG antibodies to common faecal Escherichia coli strains by individual mononuclear cells was studied using a haemolytic plaque assay. A majority of specific antibody secreting cells secreted IgA antibody. This response was greatest and most consistent in the distal colon but extended from stomach to rectum. There was no evidence of a primary defect in IgA antibody response in the few subjects with Crohn's disease available for study.

Antibodies, Bacterial↗