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Biomedical subjects

J Pepys

Publications and source records attributed to J Pepys.

At least 37 records · Page 2Linked to original sources

Action of cromoglycate in relation to mediators.

The inhalation of salts of platinum, isocyanate and pine resin are mentioned as examples of immediate asthma reaction type I, which often shows IgE antibodies. Long before the onset of occupational asthma, exercise-induced asthma can exist in a sensitized stadium. Histamine is less involved in immediate asthma type I and in exercise-induced asthma. Unlike antihistamines, cromoglycate (DSCG) protects against attacks of the immediate type. SRS inhibitors are also effective prophylactically. SRS has an asthmagenic effect after mast cell degranulation and probably also after neutrophil degranulation. It is interesting that DSCG also inhibits the late reaction (re-outbreak or outbreak of asthma some hours after exposure). The reason for this is unknown. As DSCG reacts against late asthma even if inhaled after exposure, this explains the effectiveness of DSCG inhaled 3-hourly. In cases where IgG4 attaches itself to IgE which is fixed to the mast cell, an intrinsic asthma which shows normal IgE in circulating blood may be induced. It is worthwhile using DSCG in this instance.

Asthma↗

Bronchial provocation studies in workers exposed to the fumes of electronic soldering fluxes.

Flux cored solder commonly used in the electronics industry is a metal alloy, based on tin and lead, and a flux consisting of colophony with a small concentration of an activator. Thirty-four electronics workers with occupational asthma and seventeen with respiratory symptoms, probably from other causes, have been investigated by occupational type bronchial provocation testing. All the sensitized workers had a significant fall in FEV1 after exposure to colophony fumes for 15 min or less. The non-sensitized workers had no significant reactivity to this test. There was little correlation between the reaction to colophony fumes and the non specific reactivity to histamine, suggesting that colophony fumes were causing specific sensitization. In sensitized workers Portuguese Y colophony was found to cause slightly larger reactions than similar exposures to American WW colophony. In the six workers tested reactions followed exposure to abietic acid alone, the principal resin acid in colophony. Methylation of the carboxyl group of colophony was associated with decreased reactivity. Workers with non-specific bronchial hyperreactivity also sometimes reacted after exposure to fumes from the flux activators alone, but even this reaction could show specificity for the specific activator to which the workers was exposed. Finally two non-colophony substitute materials were evaluated.

Abietanes↗

Occupational asthma in a research centre breeding locusts.

The prevalence of work-related asthma, rhinitis and urticaria was measured in a scientific establishment working with locusts. Twenty-six percent of those handling the locust in the research centre had work-related wheeze or breathlessness, and one-third had work-related rhinitis and urticaria. Work-related symptoms were uncommon in scientists exposed to locusts in the field, and in other employees at the centre. Antigens were prepared from the locusts, Schistocerca gregaria and Locusta migratoria, as well as the moth, Chilo partellus, which was also bred at the centre. Skin prick testing with the locust antigens showed positive reactions in 55% of the atopic workers at the centre, but were also present in 43% of unexposed atopic workers. In this latter group there was a correlation between positive reaction to locust and dermatophagoides antigens. Atopic workers handling the locusts developed occupational asthma more often and more quickly than similarly exposed non-atopic workers. IgG and IgE antibodies to the locust antigens were found to correlate significantly with both the degree of exposure and the presence of disease.

Antibody Specificity↗

Histamine release from blood of asthmatics.

A group of forty-two steroid-dependent perennial asthmatics was studied over a 13-week period incuding the 8 weeks of a double-blind controlled trial of oral sodium cromoglycate. Given at a dose of 200 mg four times per day the drug provided no significant benefit to the patients when compared with results for those on placebo. Blood from eleven patients consistently failed to release more than 25% of the total cellular histamine when challenged with a range of concentrations of antibody to IgE. All six of the cryptogenic (intrinsic) asthmatics in the trial fell within this group, together with 2/12 asthmatics with negative skin tests but suggestive clinical histories implicating common alergens, and 3/24 extrinsic asthmastics with positive skin prick tests. There was no correlation between drug usage and histamine release in response to challenge with antibody to IgE.

Adult↗

Clinical correlations between long-term (IgE) and short-term (IgG S-TS) anaphylactic antibodies in atopic and 'non-atopic' subjects with respiratory allergic disease.

The sera of atopic and non-atopic persons with allergic pulmonary disorders were examined for long-term sensitizing, IgE and short-term sensitizing heat-stable (S-TS) antibodies which were present separately or together in the sera of some patients sensitive to antigens such as budgerigar serum proteins and Aspergillus funigatus. In fourteen atopic patients with extrinsic asthma, six had both types of antibody to common allergens, and of nine non-atopic patients with crytogenic (intrinsic) asthma, four had only heat-stable short-term sensitizing antibodies. The sera of atopic subjects with type I prick test reactions and positive RAST's, showed specific IgE antibody by baboon PCA tests to budgerigar serum proteins, A. funigatus, Timothy grass pollen extract and hen egg extract, and not to Dermatophagoides farinae, possibly because of naturally occurring mite antibodies in the baboon. The sera of non-atopic asthmatics, who had given negative prick test but positive immediate, dual or late intracutaneous tests, and only late asthmatic reactions, contained precipitins in most cases and gave little or no RAST reaction. On baboon PCA these sera contained either, S-TS antibody alone, or S-TS plus long-term sensitizing antibody, or long-term sensitizing antibody alone. Some of the sera with long-term sensitizing antibody contained blocking antibody which could diffuse away in the 24 hr delay for the baboon PCA test and could also be responsible for the negative RAST. Tests with insoluble anti-IgE immuno-adsorbents on two sera from persons sensitive to aspergillus confirmed that the S-TS activity was not due to IgE, and on two sera with negative RAST and negative prick tests to budgerigar serum antigens confirmed that the 24 hr monkey PCA responses were due to IgE.

Allergens↗

Toluene di-isocyanate-induced asthma. I. Reactions to TDI, MDI, HDI and histamine.

A group of twenty four workers handling di-isocyanates and with respiratory disease were investigated by occupational-type bronchial provocation tests for sensitivity to toluene di-isocyanate (TDI), to which all were exposed, and to diphenylmethane di-isocyanate (MDI) and hexamethylene di-isocyanate (HDI). Sixteen gave asthmatic reactions to TDI and eight of these also reacted to MDI. Four of the eight TDI and MDI reactors had histories of exposure only to TDI, and of them two reacted also to HDI. Of nine subjects tested with HDI, three gave asthmatic reactions, and all three also reacted to TDI and MDI. Thus reactions to MDI and HDI were elicited only in the TDI reactors. The possibility of specific sensitivity to these and other di-isocyanates requires tests in subjects exposed to them and not to TDI.

Asthma↗

Toluene di-isocyanate-induced asthma. II. Inhalation challenge tests and bronchial reactivity studies.

In sixty-three workers exposed to toluene di-isocyanate (TDI), no overall differences in bronchial reactivity to histamine inhalation and to exercise testing were found between the total groups of positive and negative TDI reactors to provocation tests. A subgroup of TDI highly sensitive subjects reacting to very low concentrations (less than or equal to 0.001 p.p.m.) were more sensitive to both histamine and exercise than the group who were less sensitive to TDI, and who reacted to higher concentrations (0.002--0.02 p.p.m.) than the group of non-reactors. There were, however, in the last group a number of subjects with high degrees of histamine reactivity who did not react to the TDI. These findings suggest that, on the one hand, the asthmatic reactions to TDI cannot be attributed solely to non-specific mechanisms and, on the other, that in subjects with high degrees of specific sensitivity non-specific mechanisms may also be playing a part.

Adult↗

Passive transfer in man and the monkey of Type I allergy due to heat labile and heat stable antibody to complex salts of platinum.

Passive transfer (P-K) tests have been performed in man and monkeys with sera from a group of six refinery workers sensitive to ammonium hexachloroplatinate and tetrachloroplatinite. Positive (P-K) prick test reactions were elicited in three human recipients and in the monkey to three of the test sera. The other three sera gave inconsistent results in man and negative results in monkeys and these differences appeared to correspond with the duration of exposure of the workers. The passive transfer tests did not correlate with the intensity of the prick test reactions in the donors or with the RAST; there was partial correlation with total levels of IgE. Antigen mediated histamine release from whole blood and washed leucocytes from two of the six subjects correlated with the RAST and P-K levels. These findings confirm the presence of specific IgE antibody to the platinum salts, and also of heat stable, short-term sensitising antibodies, presumably STS-IgG.

Adult↗

Specific IgE antibodies to platinum salts in sensitized workers.

A RAST has been developed for the measurement of IgE antibodies specific to platinum chloride complexes in sensitized workers. Human serum albumin covalently linked to Sepharose beads by the cyanogen bromide method was reacted with ammonium tetrachloroplatinite (II) (NH4)2PtCl4. This conjugate was more suitable for the RAST, than conjugates of HSA and the platinum salt prepared in solution and then linked to the activated Sepharose, showing better sensitivity and giving lower levels of non-specific uptake of IgE from sera of non-exposed subjects with high total levels of IgE, e.g. allergic bronchopulmonary aspergillotics.

Antibody Specificity↗

Occupational asthma due to inhaled carmine.

Two patients are described with occupational asthma due to carmine, a natural dye extracted from the insect Coccus cactus. Both had dual asthmatic reactons after carmine inhalation. Oral challenge provoked gastrointestinal symptoms in one patient, and asthma in them both, perhaps accounting for their continuing symptoms. One patient worked extracting carmine from the insects and the other used carmine as a cosmetic colouring agent.

Adult↗

Enzyme linked immunosorbent assay (ELISA) for IgG and IgE antibodies to protein and polysaccharide antigens of Aspergillus fumigatus.

ELISA has emerged as a useful alternative to other more costly and complex tests. Polystyrene microhaemagglutination plates have been used as solid phase to absorb Aspergillus fumigatus protein and polysaccharide components for detection of specific antibodies in patients with various forms of pulmonary aspergillosis. IgG and IgE antibodies to the polysaccharide as well as the protein allergens have been found. For the IgE test a double antibody technique has been developed, which is more sensitive than the conventional indirect ELISA.

Antigens, Fungal↗