Asthma mortality and morbidity.
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Biomedical subjects
Publications and source records attributed to R M Ford.
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Present traditional measures employed in the prevention of asthma are reviewed. It is recommended that in view of the extensive and possibly increasing prevalence of the disease together with continuing high death rates more attention in our treatment programs should be devoted to basic prevention in possibly susceptible people. High risk groups such as among small children, in certain industries and in developing counties make this approach especially desirable. An outline of suggested measures is presented.
A suggested basic approach to the diagnosis of allergic diseases, which involves the characteristics of allergic diseases themselves, is presented. Using these characteristics as basic guidelines in investigation, not only should the condition be diagnosed but main cause or causes and triggering factors should be demonstrated in individual patients. Investigational procedures ranging from history, and including simple skin tests and more sophisticated immunological investigations, are briefly analyzed and it is stressed that if a really adequate allergic investigation of all patients with suspect allergic disease is carried out in an effort to demonstrate and subsequently control all causes and triggering factors, then development of chronic disease, sometimes intractible to our standard methods of therapy, could well be prevented in many cases.
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Attention is drawn to the long wait in certain countries before new drugs and other therapies for the treatment of allergic diseases are approved by the local authorities, even when good trials with them have been carried out elsewhere. The main reasons for requiring repeat trials are poor original case selection and inadequate parameters of assessment, particularly environmental variations. The results of re-assessing patients who in the previous year had undergone a trial of a new chromoglycate-like drug (Doxantrazole) are used to illustrate the need to introduce standard basic requirements when new drugs and other agents are being tested in allergic diseases. A suggested format of such requirements is presented.
6,021 40-year-old and older chronic asthma suffers, seen during the past 20 years, were analyzed with regard to the development of primary lung cancer and their smoking habits. Over this period only two developed lung cancer, 0.032% as compared with 0.314% in the general population. Only 16.9% of chronic asthmatics had smoked over any significant period during the five years prior to assessment as compared with approximately 40% of the general population. Of those who did smoke, the tendency was to a lesser extent. This survey adds further evidence that cancer develops less frequently in patients suffering from an allergic disease such as asthma, perhaps because of (1) some enhanced immunological activity preventing the advent of new growth or (2) reduced smoking habits of chronic asthmatics.
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The present attitude in Australia towards the treatment of asthma is reviewed and attention is drawn to the need for employment of more basic methods of prevention. The disease is not just a chest condition but a manifestation, in many if not in most cases, of a generalized weakness of sensitivity- the bronchi are simply shock organs where much of the action takes place. A plea is also made for a reappraisal of teaching about asthma and related diseases at both undergraduate and postgraduate levels.
Tryptophan was measured in the ventricular CSE and serum and the neutral amino acids leucine, isoleucine, valine, phenylalanine, and tyrosine were measured in the serum of two cases with ventricular drains. Samples were taken every two hours for 24 hours in one case and for 16 hours in the other. The CSF tryptophan was correlated significantly with the free--that is, non-albumin-bound--serum tryptophan but not with the total serum tryptophan. CSF tryptophan was not correlated significantly with the ratio of free serum tryptophan to the sum of the neutral amino acids. These data suggest that, in man, brain tryptophan concentrations are influenced by the free and not the total serum tryptophan and that physiological variations of the neutral amino acids do not appreciably influence the concentration of brain trytophan.
Adenosine 3', 5'-monophosphate (cAMP) was measured in the CSF of 42 patients undergoing radiological investigation, neurosurgical procedures, or investigation of hepatic coma. The concentration of cAMP was significantly higher in ventricular CSF than in lumbar CSF. Premedication with pentobarbitone plus promethazine increased cAMP in lumbar CSF. There was no difference in cAMP concentration in lumbar CSF obtained before or after injection of air or after the administration of diazepam during lumbar pneumoencephalography. Lumbar CSF cAMP concentration was significantly increased in patients in hepatic coma. The concentration of cAMP in the lateral ventricle was not affected by general anaesthesia or by the presence of a complete block of the aqueduct of Sylvius. There was no decrease in lumbar CSF cAMP in patients with a complete stenosis of the aqueduct of Sylvius, partial blocks of CSF flow at the cervical level, or a complete block at the lower thoracic level. The concentration of cisternal CSF cAMP was similar to that of lumbar CSF. These results suggest that (1) there is a ventriculolumbar gradient in the concentration of cAMP but of insufficient magnitude to be detected by mixing of lumbar and ventricular CSF during pneumoencephalography, (2) lumbar CSF cAMP concentration is not dependent on brain as a source of this nucleotide; the source of this nucleotide may be largely derived from the spinal cord, (3) premedication may affect the concentration of cAMP in lumbar CSF cAMP, (4) the formation of cAMP is unimpaired in hepatic coma.
Parameters of humoral and cellular immunity have been measured in 91 asthmatic patients. Mean serum levels of IgG and IgE were raised. IgG levels were higher in those with a family history of asthma. IgE levels were higher in those with a past history of atopic eczema, but intrinsic and extrinsic asthma could not be differentiated on the basis of IgE levels. Thirteen of 74 patients failed to respond to tetanus immunization, while only 1 failed to respond to Salmonella typhi H antigen. Tetanus nonresponders had a raised mean serum IgA level, reduced spontaneous lymphocyte tritiated thymidine uptake, and reduced thymidine uptake in fetal calf serum. Eight of 87 patients failed to mount delayed hypersensitivity reactions to a battery of five intradermal antigens. The tritiated thymidine uptake of lymphocytes stimulated with phytohemagglutinin was normal in autologous serum, but reduced in fetal calf serum. The data support the hypothesis that asthma may be associated with immunodeficiency states.