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R M Agius

Publications and source records attributed to R M Agius.

32 records · Page 2Linked to original sources

Occupational asthma and the chemical properties of low molecular weight organic substances.

Various low molecular weight substances cause occupational asthma, and there is scope for studying their chemical properties in relation to their propensity to cause this condition. Twenty-nine organic substances (molecular weight < 250), with or without oxygen or nitrogen atoms, were compared to control hazardous substances obtained from the list of occupational exposure limits. There were significantly more reactive groups in the active chemicals than in the controls. Carbon to nitrogen double bonds were also significantly over-represented in the active chemicals. If confirmed in a fuller study, these data could yield useful information on the causation of occupational asthma and on the hazard assessment of novel chemical entities.

Air Pollutants↗

An audit of occupational medicine consultation records.

There is a need to develop and test methods of audit of the consultation process in occupational medicine and to draw conclusions from the findings. An external audit was carried out on 313 randomly selected consultation records from the occupational health services of three health boards over a 26-month period. Additionally, nine months after the date of the first externally audited sample, a prospective internal audit was commenced within one board. In 58 of the consultations selected (19 per cent), audit was not possible mainly because records could not be found. In an appreciable proportion of the rest, there were shortcomings in the referral record or in the consultation record. The consultation records of 'career' occupational physicians were better than those of 'non-career' physicians, especially in recording specific diagnoses (91 per cent vs. 67 per cent; P < 0.0001) and in conclusions regarding occupational implications (86 per cent vs. 74 per cent; P < 0.0001). Multivariate regressions showed a highly significant improvement associated with prospective internal audit in one item, namely the record of occupational implications. However, the magnitude of this difference before and after audit was smaller than the independent difference arising from the career status of the physicians. The value of medical audit in improving quality of care and education in occupational medicine is discussed.

Adult↗

Questionnaire for the identification of back pain for epidemiological purposes.

OBJECTIVES: To design a questionnaire for the identification and assessment of severity of back pain for epidemiological purposes, and gain preliminary experience of its use. METHODS: A group of specialists, experienced in the epidemiology and clinical assessment of back pain, designed the questionnaire, and tested it individually. It was also given cross sectionally by interview to a population of male coal mine workers. RESULTS: The questionnaire comprised a maximum of 12 questions on the presence, radiation, frequency, and severity of back pain with reference to difficulty with specific activities, interference with normal work, and absence from work. 471 coal miners answered the questionnaire (66% of those invited). 56% (265 men) of the responders reported pain or ache in the back during the previous 12 months, and the incidence of first ever attacks during the same period was reported to be 34%. 69% reported having had back pain at some time. The responses to the questionnaire were partially validated by comparison with certified sickness absence for two days or more attributed to back pain. In men who were symptomatic in the previous 12 months, for the question relating to absence from work because of back pain, the sensitivity was 82% and specificity was 84%. CONCLUSION: The questionnaire is easy to administer and generates clear cut data that could be useful for epidemiological or screening purposes. Preliminary, limited, studies of its validity are reasonably encouraging, although further validation is required. It is hoped that researchers will find the questionnaire useful, will extend its validation, and continue to develop it.

Adult↗

Occupational asthma in salbutamol process workers.

Occupational asthma after exposure to salbutamol in the pharmaceutical industry has not been previously reported. The occurrence of occupational asthma is described in two pharmaceutical process workers who were likely to have inhaled doses appreciably in excess of the therapeutic dose range. The findings do not lead to an unequivocal conclusion on the mechanism of the asthma but it was probably a pharmacological consequence of high exposure.

Adult↗

Occupational physicians and their work: prospects for audit.

An anonymous postal questionnaire was sent to 200 occupational physicians in the UK to determine their activities, the nature of the organizations within which they work and their attitudes and practices with respect to audit. One hundred and sixty-six physicians responded to the questionnaire, of whom 119 (72 per cent) were currently practising occupational medicine. Fifty-seven (48 per cent) of these 119 were engaged in some form of audit but only 21 (18 per cent) were engaged in an audit of structure, process and outcome. Assessment of continuing fitness for work or sickness absence ranked first overall with respect to the proportion of the physician's time engaged. The study revealed a wide diversity in the organization of the practice of occupational medicine, in the qualifications of occupational physicians and in their participation in audit. Needs for the development and wider implementation of methods of audit in occupational medicine have been identified by the study.

Humans↗

Structure activity hypotheses in occupational asthma caused by low molecular weight substances.

Many substances with a low molecular weight (less than 1000 molecular weight) but of different chemical classes are recognized as causative agents of occupational asthma. Some of their major chemical properties are highlighted in relation to their putative interactions with human macromolecules. Thus, certain transition metals which form co-ordination complexes may chelate human proteins. Several organic substances have marked basic properties which are responsible for their chemical reactivity. Some of these, such as the bifunctional bases ethylene diamine, piperazine and para-phenylene diamine are known causative agents of asthma while their monofunctional counterparts, in spite of wide industrial application, are not similarly recognized causes. This suggests that the presence of multiple reactive groups is of importance in the molecular interactions with human macromolecules that eventually lead to occupational asthma. Reference is also made to other substances to exemplify hypothetical mechanisms of these interactions. Such generation of hypotheses is a prelude to quantitative studies of structure activity relationships (QSARs) where the hypotheses can be tested and revised. Structure activity hypotheses in isolation might not be adequate predictors of the risk of occupational asthma. However, if applied to novel chemical entities they might eventually prove useful in contributing to the development of policies for prospective health surveillance and in establishing priorities for epidemiological research.

Air Pollutants, Occupational↗

Peer review audit in occupational medicine.

There is an increasing awareness of the need for medical audit. A method for peer review medical audit that has been applied to two large industries is described. Occupational physicians act as auditors of randomly selected case notes from their colleagues' list of consultations using an agreed proforma as a guideline. Open discussion by the occupational physician of the auditor's comments identifies needs, such as for a change on policy or further education. Implementation of the agreed changes and subsequent review completes a cycle of audit.

Humans↗

The immunoglobulin E- and calcium-dependent release of histamine and eicosanoids from human dispersed mastocytosis spleen cells.

The clinical features of systemic mastocytosis have been ascribed to mast cell-dependent mediators, but there have been no studies of their release from isolated cells. We have investigated the release of histamine and eicosanoids from isolated spleen cells obtained from tissue of a mastocytosis patient undergoing therapeutic splenectomy. Dispersed cell preparations contained lymphocytes 65.9%, monocytes/macrophages 22.3%, neutrophils 9.9%, mast cells 1.1%, and eosinophils 0.8%; upon challenge with 0.1-3.0 microM A23187 they released histamine much greater than PGD2 greater than TXB2 greater than LTB4 greater than LTC4 approximately equal to LTD4 greater than LTE4. With immunological activation of passively sensitized cells, histamine and PGD2 release had similar dose-response characteristics, but TXB2, LTC4, LTD4, and LTE4 release differed in reaching maximum at 50 micrograms/ml and declining at 125 micrograms/ml anti-human IgE. Percoll centrifugation separated most of the histamine-containing cells to the middle of the gradient, but they were refractory to release with 0.3 microM A23187 or 50 micrograms/ml anti-IgE. Spontaneous release of histamine from these cells was not abnormally high (1.3%-4.5%). Electron microscopy of tissue sections revealed large numbers of mast cells with empty granules. It is possible that the refractory cells observed are such mast cells where intracellular histamine is no longer granule-associated. Most net histamine and PGD2 release was confined to cells at the bottom of the gradients (1.078-1.09 g/ml), although some release of PGD2 occurred near the top (1.05-1.058 g/ml). There was a significant correlation between the net release of histamine and PGD2 with both immunological (r = 0.92; n = 16) and A23187 (r = 0.97, n = 14) activation. These studies provide evidence for a link between PGD2 and histamine release in mastocytosis spleen cells.

Adult↗

Human pulmonary alveolar macrophages with smokers' inclusions: their relation to the cessation of cigarette smoking.

Bronchoalveolar lavage (BAL) was performed in 47 patients (24 smokers, 18 ex-smokers and 5 who never smoked). Cytocentrifuged preparations were stained with May-Grunwald-Giemsa (MGG) and differential counts of pulmonary alveolar macrophages (PAM) with smokers' inclusions were performed. The data supported an exponential reduction in this percentage and indicated that about 3 years elapsed before this percentage approximated to the values in patients who had never smoked. Electron microscopy was performed on eight BALs and the results supported those obtained by light microscopy.

Adult↗

Mast cell and histamine content of human bronchoalveolar lavage fluid.

Bronchoalveolar lavage was performed in 97 patients including control patients with bronchial carcinoma (24) and patients with sarcoidosis (20), cryptogenic fibrosing alveolitis (9), and asthma (4), and others. Cytocentrifuged slides were stained by two methods: May-Grünwald Giemsa and toluidine blue. In the last 32 subjects the bronchoalveolar lavage fluid was separated into supernatant and cell pellet for the subsequent assay of the performed mast cell mediator, histamine. Comparison of the two methods of staining showed a bias towards toluidine blue. Controls had a differential mean (SE) mast cell count of 0.07% (0.01%). Higher counts were noted in cryptogenic fibrosing alveolitis--0.61% (0.15%) (p less than 0.001)--and in sarcoidosis--0.14% (0.02%) (p less than 0.05). There was a strong correlation between absolute mast cell counts and cell lysate histamine concentration (r = 0.78, p less than 0.001). Less strong, significant, correlations between supernatant histamine concentration and absolute mast cell counts (r = 0.48, p less than 0.01) or cell lysate histamine concentration (r = 0.72, p less than 0.01) were also found. Derived mean values of histamine per mast cell ranged from 3.7 to 10.9 picograms. The mean histamine content of lavage fluid supernatant as a percentage of the total lavage fluid histamine was 24.9% (3.3%). The possible clinical significance of these findings is discussed.

Adult↗

Why are some low-molecular-weight agents asthmagenic.

The chemical structure of low-molecular-weight substances (LMW) that cause occupational asthma (OA) determines their reactivity and hence their OA hazard. LMW agents that can form at least two bonds with native human macromolecules carry a higher OA hazard. Thus bi- or polyfunctional LMW agents such as diisocyanates and aliphatic or cyclic amines, as well as dicarboxylic acid anhydrides and dialdehydes, rank highly among organic LMW substances, while some transition metal ions or their complexes also are OA hazards. More subtle effects arise from diverse reactive groups or unsaturation. Quantitative structure activity relationships show increasing promise in predicting the OA hazard of these LMW substances.

Asthma↗