Document nNRYKMmG3q45vVq0p23MRvZVX

1020 Special Report: Asbestos and Cancer u Canad. Med. Ann y.m May 8, 1966, vol. ggijj Summary Two methods of measuring the resistance or sensi tivity of Staph, pyogenes to mercury salts have been compared. Little difference was noted, but the agar plate method is preferred as it is technically easier to perform. Resistance to mercury appears to be associ ated with antibiotic resistance, but no difference in virulence between the two groups was demonstrated by means of intracerebral injection of mice. The mercury test may have a place as a screening procedure in view of the relationship between the resistance to mercury and to antibiotics. We are grateful to Miss Thibeaudeau and Mrs. J. SmalT'l for their technical assistance. References 1. Moore, B.: Lancet, 2i 453, I960. 2. Simpson, D. M.: Med. Serv. J. Canada, 201 120, 1964 3. Cadness-Graves, B. et al.: Lancet, 1i 736, 1943. ` 4. Fisk, A.: Brit. J. Exp. Path., 211 311, 1940. 5. Wecicman, B. G. and Catlin, B. W.: J. Bact., 73, 747 1957. ' 6. Reed, L. J. and Muench, H.: Amer. J. Byg., 27, 493 . 1938, 7. Barber, M., Hathoe, F. G. J. and Whitehead, J. e M Lancet, 2t 1120. 1949. '. 8. Blair, J. E. and Carr, M.: J. A. M. A., 166, 1192, 1958 9. Eleic, S. D.: Ann. N.Y. Acad. Sci., 65, 85. 1956. 1 10. Elek, S. D. and Conen, P. E.: Brit. J. Exp. Path 3a. 573, 1957. '. 11. Frappibr, A., Sonea, S. and Panisset, M.: Rev. CanaA Biol, 14, 162. 1955. Asbestos and Cancer The Report and Recommendations of a Working Group Convened Under the Auspices of the Geographical Pathology Committee of the . International Union Against Cancer Editor's Note--In October 1964, the New York The latent period between first exposure to the Academy of Sciences sponsored an international meet ing on the biological effects of asbestos. Following this meeting, some 40 delegates from Australia, Canada, Finland, France, Germany, Great Britain and Ireland, Italy, South Africa and the United States were invited to study the vast amount of information which had been presented with a view to the organization of an inter national study of asbestos and cancer. The terms of reference of this Working Group covered three major aspects of the problem: epidemiology, pathology and dust and detection of the related tumours is many years, usually 20 or more. Instances up to 60 years have been reported. For this reason, further cases of these associated tumours will be expected to occur for many years to come, even if dust exposures are now greatly reduced. Present evidence indicates that the associated carcinomas of the lung are not limited to exposure to any one type of asbestos fibre. However, further experimental pathology, and physics and chemistry. investigations are urgently needed to establish The findings of the Working Group and their recom whether the degree of risk is importantly related to mendations arising from these studies are recorded, in slightly abridged form, in the following report. the type of fibre inhaled. In the case of mesotheliomas evidence from The Association of Exposure to Asbestos Dust and Cancer several countries suggests that exposure to crocido lite (blue fibre) may be of particular importance, but it cannot be concluded that only this type of THE main types of asbestos of commercial interest are amosite, anthophyllite, chrysotile, fibre is concerned with these tumours, and further investigation of this problem is needed. crocidolite and tremolite. There is evidence of an Certain types of asbestos fibres in the virgin association between exposure to asbestos and state have been found to contain oils, waxes and malignant neoplasia. This has been established other organic matter. In addition, asbestos fibres mainly on information from Germany, Italy, South readily absorb hydrocarbons subsequent to mining. Africa, the United Kingdom and the United States Small or Pace amounts of various elements such as of America. nickel and chromium are also found associated The types of tumours which have been shown to with some types of fibre. The possible role of such be associated with exposure to asbestos dust are: associated materials in the development of tumours, 1. Carcinoma of the lung. following exposure to asbestos dust, is not yet clear. 2. Diffuse mesothelioma of the pleura and peri These findings, when considered in relation to toneum. the great increase in the use of asbestos for many There is some suggestion of an association also purposes in all countries, suggest that a more with gastrointestinal carcinoma, and possibly with serious and widespread hazard from exposure to ovarian tumours. asbestos dust may exist than is widely appreciated. SCF-FA-5680 Canad. Med. Ass. J. May 8,1965, vol. 92 . Special Report: Asbestos and Cancer 1021 Recommendations on Problems Requiring Epidemiological Study 1. That the relationship of fibre type to the risk of developing asbestosis, carcinoma of the lung, and mesothelial and other tumours be investigated. International and intranational comparative studies of mining and other populations exposed to only one type of fibre are recommended. Studies of the effect of exposure to different types of asbestos fibre within a country are likely to be of special value, but studies of groups exposed to apparently similar fibres in different parts of the same country are also likely to be informative. 2. That the relationship of dust dosage (includ ing concentration and duration of exposure), and the composition and physical state of the dust to the incidence of asbestosis, carcinoma of the lung, mesotheliomas, and other cancers be studied. Comparative studies in factory populations in the asbestos textile and other manufacturing processes using asbestos are likely to be useful, especially when there are records of past dust measurements. In any prospective studies of new entrants, the measurement of dust by a standardized method should be regarded as an essential part of the in vestigation. 3. That the effects of removal from further ex posure to asbestos dust be investigated. It is important to establish the subsequent morbidity and mortality from asbestosis, and the mortality from cancers associated with exposure to asbestos in population groups no longer exposed to the dust. 4. That further investigations be made of past and all future cases of diffuse mesothelial tumours of the pleura and peritoneum to establish any association with asbestos and other factors. These tumours should be diagnosed on the criteria suggested by the Panel on Pathology (see below) and the diagnoses should be reviewed by a panel of pathologists with experience of these rare tumours. The tumour and lungs should be investigated for the presence of asbestos by physi cal and chemical methods (see below). 5. That studies of morbidity and mortality be extended to asbestos-exposed populations that have not so far been widely investigated. (a) It is recommended that special attention be directed to surveys in the insulating, asbestos cement and asbestos products industries and other plants in which asbestos is regularly used. (b) It is also recommended that, since incidental exposure to asbestos dust may occur in certain trades and occupations, attention be directed to the handling and transporting of asbestos, pipe fitting, and the building and ship-building in dustries. (c) It is recommended that surveys be made to study environmental and community exposures, in cluding populations near mines and factories and elsewhere. (d) It is recommended that general population surveys be made nationally and internationally to establish by standardized methods, in areas of ,pre sumed high and low exposure to asbestos dust, the prevalence of asbestos bodies and fibres. (e) It is recommended that surveys of asbestosis in domestic and wild animals be extended to areas of high and low exposure. 6. Epidemiological Methods (a) General In addition to the usual information about the individual collected in such surveys, special atten tion should be directed to a detailed, social (in cluding smoking habits), occupational, environ mental, and medical history from early childhood to elucidate any possible exposure to or association with any type of asbestos or other dusts. A study of the family unit or household may be of interest in view of the occasional reports of significant neighbourhood and household exposures. In view of the association between exposure to asbestos dust and pulmonary fibrosis and its com plications, it is important to obtain as much in formation as possible about morbidity and mortality from all causes, with particular attention to: asbes tosis, chronic bronchitis and emphysema, bron chiectasis, diffuse interstitial fibrosis, pneumonia, tuberculosis, cor pulmonale, carcinoma of the lung, diffuse mesothelial tumours of the pleura and peri toneum, gastrointestinal tumours, and ovarian tu mours. (b) Clinical Criteria Symptoms It was agreed that in all surveys the presence or absence of cough, sputum, dyspnea, and chest pain should be recorded as a minimum. This should be recorded using a standardized questionnaire. Signs It was agreed that when physical examination was possible the minimal observations should in clude the presence or absence of clubbing of fingers, cyanosis, and basal rales in the chest. It was agreed that the measurement of sputum volume (first hour on rising) and degree of purulence recorded in a standard way1 was useful in association with the questionnaires for assessing ,1 -.-1 - ~;i k . :% i 1022 Special Report: Asbestos and Cancer ' Canad. Med. Asa J May 6, 1966, vol,*92^ the prevalence of bronchitis, and this may be rele vant to the disability caused by asbestosis. The epidemiological usefulness of examinations of sputum for asbestos bodies and fibres is at present uncertain but needs investigation. Mediastinal tissues should be examined for evi dence of neoplastic infiltration and for tuberculosis. Peritoneum: Parietal and visceral fibrosis in the peritoneum, such as parietal plaques and "sugar icing" of the spleen, should be recorded. (c) Classification of Chest Radiographs of Asbestos-exposed Individuals There is no international or national standardized classification of the radiological appearances of asbestosis. It is recommended that a scheme based if possible on an extension of the I.L.O. Classifica tion (1958)2 be developed. The aim should be to specify separately and record semiquantitatively the principal radiological features seen in asbestosexposed groups, but exposure to mixed types of dust is not uncommon and the appearances may, therefore, include those caused in part by other pneumoconioses. It is recommended that a working group be set up to develop and test a new international classifi cation. (d) Lung Function Assessment The preferred lists of lung functions to be used will vary according to the type of survey and the facilities available. A list"of'miiiimallihcl"a3flifibhar tests likely to be of use is as follows: Minimal Forced vital capacity (F.V.C.) Forced expiratory volume over 1 sec. (F.E.V.10) (b) Microscopic Examination It is recommended that at least six sections be . examined from the lungs before the degree of asbestosis is decided and these blocks should be taken from specific sites and identified in the follow ing standard manner: 1. Apex of right upper lobe, pleural surface. 2. Right middle lobe, lateral pleural surface. 3. Right lower lobe, middle of basal surface. 4. Left upper lobe, central section. 5. Lingula, central section. 6. Left lower lobe, central basal section. In addition, sections should be taken from the bronchi and peritracheal and peribronchial lymph glands, and from any suspicious or abnormal tissue. (c) Assessment of the Severity of Asbestosis It is recommended that this assessment should be based on the severity of interstitial fibrosis and the amount of :tiss.ueJn.voLved._The-proposed-scheme-is- as follows: Extent of Lunc Involvement Slight Degree of Asbestosis -> Slight <- Degree of Interstitial Fibrosis ^Slight Additional Transfer factor (diffusing capacity) of lung for carbon monoxide--single breath method Lung compliance Standard exercise test Peak expiratory flow Airways resistance Recommendations on Pathology and Experimental Pathology 1. Diagnosis of Asbestosis (a) Macroscopic Examination At necropsy the parietal pleura should be stripped if possible with the thoracic contents. It is desirable that at least one lung be inflated with fixative and whole lung sections be prepared. It is recommended that special note be made of the following: Pleura: for thickening and plaques (defined as localized areas of stiff hornlike material3). The site and size of all pleural lesions should be recorded. Lungs: The presence of interstitial fibrosis, bron chiectasis, cystic change, tuberculosis, pneumonic consolidation and tumours. The site of any tumour should be recorded as precisely as possible. Moderate -^-Moderate <- -Moderate Marked-- -> Marked <- -Marked A category of "minimal'' asbestosis is also pro posed to describe slight focal fibrosis in the region of the respiratory bronchioles associated with the presence of asbestos bodies; such changes are com monly confined to sections taken from the bases of the lower lobes. This scheme puts more emphasis on the extent of the lesions than the degree of fibrosis (which should be averaged for the six sections). Thus, a lung with moderately extensive disease but only slight severity of fibrosis is graded as "moderate asbestosis". The use of an average assessment of the six sections makes it impossible to have a grading of slight involvement and moderate or marked degree of fibrosis. . (d) The Detection and Significance of Asbestos Bodies and Fibres Sputum The presence of asbestos bodies and fibres is an indication of the exposure to asbestos dust and not evidence of asbestosis. It is therefore suggested that Canad. Med. Ass. J. May 8, 1965, vol. 92 Special Report: Asbestos and Cancer 1023 the bodies should be referred to as "asbestos bodies" and not by the previously used term, "asbestosis bodies". Because of their sporadic appear ance and, in the case of fibres, their relation to recent dust exposure, quantitative assessment of bodies and fibres in sputum is not, in the light of present knowledge, a very useful procedure but might become more useful when further investi gated. In sputum detection by direct examination under a coverglass and the use of phase contrast, oblique illumination or narrowed condenser diaphragms is proposed. If sputum concentration is used antiformin or "Eusol" treatment is recommended. Lungs From fresh lungs, the greatest number of positive results are obtained from smears from the base of a lower lobe (of the thickness of a thick blood smear as for malarial parasites), air-dried and mounted in balsam. A rough quantitative examina tion by low-power magnification is easy and practi cable. For fixed lungs the smear technique is of limited value, and unstained sections 30 microns thick are recommended. Fibres For investigation of asbestos fibres in lung sec tions, microincineration, acid treatment, and ex amination by phase-contrast are suggested. Mor phologically the fibres appear as straight rods of varying lengths and thickness, but with longitudinal shredding, and in the thicker fibres smaller fibrils may be recognized. While there are other structures described as pseudo-asbestos bodies, or curious bodies, little difficulty is found in distinguishing the genuine from the others. These other types usually have a carbon-black centre and a shape which is other than linear, but the body that can mimic an asbestos body completely is the small one found in talcosis, which may be trernolite, a form of asbestos. Chemical Analysis of Lung Tissue Where possible, blocks of tissue from the six areas chosen for histological study should be taken land the amount of collagen relative to total proteins estimated by the standard hydroxyproline methods. The results of collagen estimations should be ex pressed in absolute amounts and as percentages of defatted dried lung tissue.4 2. Diagnosis of Diffuse Mesothelial Tumours (a) Macroscopic The salient characteristic of the diffuse meso thelioma is its predilection to spread along the serosal membrane in which it occurs. In the pleural cavity, the entire surface may become re placed by a continuous layer of tumour, owing to symphysis of the pleural surfaces. This is uncom mon in the peritoneum where the surfaces often remain separate but covered by isolated plaques and nodules or diffuse infiltration. Only those meso thelial tumours in which serosal spread is unequi vocal should be termed "diffuse". A few benign diffuse mesotheliomas have been described. Almost all diffuse mesothelial tumours show evidence of malignancy by direct infiltration of adjacent tissues and organs and metastases to regional lymph nodes. The differentiation from metastatic tumour is the main problem in diagnosis and can only be made with complete certainty by the exclusion of all other sources of tumour at necropsy. Because of the tendency of the tumour to surround and infiltrate subserosal organs, these organs most commonly come under suspicion as points of origin. The possi bility that the primary growth may have been surgi cally removed must be borne in mind. (b) Microscopic Diagnosis is possible because the growth com monly shows histologic patterns which occur infre quently in other tumours and especially those which might metastasize to serosal membranes. Particu larly helpful is the presence in some diffuse meso theliomas of a mixed structure of malignant ele ments of both epithelial and mesenchymal charac ter, or other diverse combinations. Growths in which only one type of cytoarchitecture is present may also have a highly distinctive pattern; for ex ample, (1) a tubular or tubulo-papillary pattern in which the tumour cells show marked uniformity and are cubical or flattened; (2) masses of collagen in which there are either (a) cleft-like spaces lined or occupied by tumour cells, or (b) fine hyaline strands which form complex meshworks and laminated bundles. Other examples of these tumours may have an entirely non-specific structure presenting the appearance of a spindle cell sarcoma or of an anaplastic tumour. Because of the difficulty in clearly distinguishing on histologic grounds alone some of these growths from metastatic tumours, cases diagnosed from biopsy material should be called "probable meso theliomas". In epidemiological studies precise de tails of the pathological evidence on which the diagnosis was based should be stated. (c) Histochemistry Most of the mucoid material within mesothelio mas, although often intimately associated with the surfaces of the tumour cells, is extracellular. Intra cellular or intratubular mucin of an adenocarcinoma will usually take mucicarmine or PAS stains. The absence of these reactions in a tumour which con tains mucoid material can, when taken with the other features, be useful additional evidence of a mesothelial tumour. Hyaluronic acid is often present in mesothelial tumours. The demonstration of its removal from the tissue sections by specific hyaluronidase prepa- 1024 Special Report: Asbestos and Cancer W: May 8, 1jv9r6ca5.. Avossl..9J3'; I- rations is a useful histochemical test, but since the 3. The Contribution of Experimental Pathology acid is soluble in water, -the test requires that the It was agreed that various types of asbestos in tissues be fixed in a special precipitating fixative, such as forxnol alcohol acetic acid.8 It also appears duce in many species of animals lesions similar to those seen in human cases of asbestosis, meso likely that the quantitative measurement of hyalu thelioma, and carcinoma of the lung, but the need ronic acid in effusions, where this polysaccharide for more precisely planned experiments was em has been isolated and chemically characterized, phasized. may well become a reliable method for assisting in the diagnosis of mesodielioma, but it is empha sized that positive results for both the histochemical The desirability of using healthy animals of known response to asbestos under quantitative con ditions of exposure by inhalation, feeding, and and chemical tests for hyaluronic acid are found in only a proportion of cases of mesothelioma and they should not be used as sole diagnostic criteria. parenteral injection at several sites was accepted. Experiments in great variety are being undertaken in many parts of the world, particularly in Canada, (d) Exfoliative Cytology Great Britain, South Africa and the U.S.A. The prospect of providing standardized samples of tfl The contribution to the diagnosis of diffuse malig chrysotile, amosite, crocidolite, tremolite and anthoST nant mesothelioma by exfoliative cytology of serous phyllite asbestos for experimental work was wel fluids requires: (1) that the exfoliated neoplastic comed. mesothelial cells sufficiently resemble exfoliated It was agreed that there was a need for improv non-neoplastic mesothelial cells to allow them to be ing methods of identifying the type of asbestos in *?- recognized as having a mesothelial origin, and (2) submicroscopic fibres in tissues. Further studies of that they also possess the generally accepted the rate of formation and resistance to destruction features of malignancy. The latter are not often of asbestos bodies in different species of animals present, so a definite diagnosis of mesothelioma is may be useful. & then difficult. - It is recommended that there be closer collabora 1>y- Usually mesothelioma cells, while atypical, do tion between clinical and experimental pathologists Ife' not appear malignant but still show evidence of and other scientists in the field of experimental mesothelial origin. From cytology of the serous pathology, biochemistry, and biophysics, as applied fluid it is possible to be strongly suspicious and in to the problems of the biological action of asbestos. a few cases confident of the diagnosis of meso thelioma, but usually its presence can only be re ported as possible. The diagnosis of malignant mesothelioma by ex foliative cytology requires a familiarity with .the non-neoplastic mesothelial cell. Mesothelial hyper 4. Proposal for Pathology Reference Panels It is recommended that central consultation and reference panels be set up on regional, national and international levels. These panels will: plasia and hypertrophy can easily be mistaken for (a) Assist in establishing standards for patho malignant mesothelioma and vice versa. It may be logical classification of asbestosis. imprudent to do more than suggest malignant meso (b) Serve as consultation centres for diagnosis thelioma if there is not good supporting clinical, of mesotheliomas and other tumours associated with radiological or biochemical evidence. The exfoli exposure to asbestos. ated malignant mesothelioma cell must also be dis (c) Provide for general exchange of patho I tinguished from the adenocarcinoma cell, by far the commonest malignant cell recovered from serous logical material related to asbestosis and its associ ated tumours. fluids. This cell is well described in standard texts It is further suggested that a comprehensive atlas of exfoliative cytology. on the pathology of mesotheliomas should be pre (e) The Use of Tissue Culture in the Diagnosis pared. The various manifestations of mesotheliomas in s. some cases cause difficulty in distinguishing such & i . tumours from bronchogenic carcinoma, metastatic fe-- ovarian carcinoma, fibrosarcoma, etc. It is therefore recommended that where possible biopsy specimens Recommendations Relating to Physics and Chemistry 1. Reference Samples of Asbestos for Experimental Work of pleural and peritoneal neoplasms be studied after It is anticipated that there will be an expansion short-term passage, (a) in vivo, and (b) in vitro, of demand for asbestos of various types for bio to determine whether the rate of growth and/or logical and other studies. It is at present impossible morphology after transplantation can provide use to predict the biological effects of differences in ful criteria for a differential diagnosis of meso mineral composition, size distribution, associated theliomas. To achieve this it is recommended that organic matter and trace metals in different samples clinical pathologists seeing these tumours co-operate of asbestos. Also, fibres from a particular mine may with workers in experimental carcinogenesis who vary in composition and in the amount of absorbed are using tissue-culture methods. material. Canad. Med. Ass. J. May 8.1985, vol. 92 Special Report: Asbestos and Cancer 1025 It is therefore recommended that: (a) Standard reference samples, of respirable size, of amosite, chrysotile, crocidolite, tremolite and anthophyllite be prepared from as pure parent ma terial as possible and held at the Pneumoconiosis Research Unit (P.R.U.) in Johannesburg for distri bution to centres requiring them. (These standards should also serve as references for comparison with larger amounts of material--such as may be required for inhalation or chemical extraction.) It is pro posed that samples of chrysotile from different countries--for example, from Arizona, Havelock (Swaziland), Quebec and Shabani (Southern Rho desia)--be included in the reference collection. (b) The standard samples be analyzed and characterized quantitatively by: Chemical and spectrographic analysis. Optical and electron microscopy, for determina tion of shape, size distribution, and optical proper ties such as refractive indices, extinction angle, etc. X-ray diffraction analysis by the powder tech nique. Specific surface measurement by low tempera ture gas adsorption. Determination of amount and type of organic matter present. (c) Oils and waxes isolated from asbestos be prepared and also distributed through the P.R.U., Johannesburg. (d) When the standards have been collected and prepared, the P.R.U., Johannesburg, will notify workers of their existence through the U.I.C.C. Bulletin and any other appropriate channels. 1. Identification and Quantitative Assessment of Asbestos in Tissues In tissue sections- it may be only possible to identify the type of asbestos present. For quanti tative studies of the amount present in any organ such as the lung, it is necessary to analyze repre sentative samples of the organs. It is recommended that: Tissue sections should be treated to remove or ganic material, for instance, by ashing or treatment with active oxygen; but this will not remove the asbestos bodies completely, and chemical treatment may be necessary to free the fibres. The best method for this is not known, but treatment with acetic acid may be useful. Identification of the type of fibre can only be made on free asbestos fibres and not on fibres inside asbestos bodies. It is recom mended that methods of distinguishing asbestos from other fibres which may be present be further investigated. This can probably best be done by phase contrast or polarized light microscopy. It is also recommended that the treated sections be ex amined by electron microscopy for recognition of submicroscopic fibres. For large samples of tissue, acetic acid, hydrogen peroxide and formamide methods be tried as they appear to be superior to ashing, but the best method of extraction of mineral matter from tissue is not yet known and needs further study. However, the quantitative determination of asbestos in the residue obtained in this way is difficult but could be based, on chemical analysis, x-ray diffraction, or fibre counts. It is recommended that methods for concentrating such asbestos and separating different types of asbestos from each other be further investigated. Reprints may be obtained from the National Cancer Institute, 790 Bay St., Toronto, Ont. References T. Mn,LER, D. L.: Amer. Rev. Reap. Die.. 88t 473. 1963. 2. International Labor Office: Occup. Safety Hlth., 9t 63, 1959. 3. Gloyne, S. R.: Tubercle, 14i 445, 1933. 4. Harinoton, J. S. and Kilroe-Smith. T. A.: Arch. Environ. Health (Chicago), 9.- 395, 1964. 5. Wagner, J. C., Munday, D. E. and Harinoton, J. S.: J. Path. Bact., 84: 73. 1962. PAGES OUT OF THE PAST: FROM THE JOURNAL OF FIFTY YEARS ACO WHAT IS TO BE DONE? Nor is the death from asphyxiating gases a sudden and painless death, as hypocritical articles in German news papers will have us believe. In very small doses it first produces a temporary cessation of breathing reflexly through irritation of the nasal mucous membrane. Next, when this inhibition of necessity ceases, the gas is drawn into the other respiratory passages and, on account of its solubility in moisture, it attacks the respiratory mucous membranes, producing violent catarrh. The later sequelae are results of the disintegration of these membranes caused either by direct union of the chlorine with their proteins or by the formation of hypochlorous and hvdro-chloric acids and the evolution of nascent oxygen. There is fre quently a purulent discharge, with inflammation, bronchitis, haemorrhage, and broncho-pneumonia. All these symptoms have been observed in rescued soldiers. The sufferer may die before pneumonia ensues and, in the case of consider able concentration of the gas (over one in a thousand), dyspnoea, coma and death rapidly follow. But meanwhile what is to be done? Can we bring our selves to imitate the methods of the enemy? To blow steam or atomized water from a spray into the fumes may be effective but it is to be remembered that chlorine water blisters the skin and causes acute inflammation of the conjuctiva. A combination of wet respirators and water sprays would be useful and a means of creating a violent up draught of air some distance in front of the trenches, by means of burning gasoline or kerosene, would so dilute the cloud of vapour as to render it less noxious. Meanwhile we can take some comfort in the thought that it is but rarely that atmospheric conditions will render the use of this diabolic means of warfare possible. Already, if we can believe reports, our enemies have been caught in their own trap.--Editorial, Canad. Med. Ass. J., 5: 516, 1915.