Document 7OpK1Kn3e80wmzv2r2renMBgo

nJV-A-^ f U-> pic. i. 1937] PULMONARY ASBEBTOBIS. .Si) Ixssitudr. The physical *ljp>* in her chest were those of tbrotia of the right lung. Is July, 1922, signs of cavitation were noticed, the sputum became more profuse, with sweats and irregular temperature, and she died on March 14th, 1924. _Vn j-rar plate showed extensive fibrosis, more marked in the Tight lane', two calcareous glands at the root of the left lung, and {so small calcareous particle* in the base of the left lower lobe. appearances in the two lungs only may be summarized as follows: 1. There is well marked diffuse interstitial pneumonia with chronic bronchitis and some emphysema. 2. There is well marked anthracosis. 3. There is an extensive tuberculous condition with Staeroteopieal Appearance!. p'ujlt Lung.--The pleura is thickened over the entire surface of (he lung, and shows the remains of dense adhesions to the chest nil and pericardium. The luDg it firm and until. The glands the root of the lung are large, and on section are black, show a thickened capsule, and some calcareous particles. On section, the lung is seen to be fibrosed and to a large extent airless, the lung tissue being replaced by fibrous tissue. Dense strands of fibrous tissue from the pleura intersect the lung. In the apex there is a large cavity, the aise of a peeled tangonne orange. The middle and lower lobes show numerous small areas--varying in site from a hazel-nut to a pin's head--of caseation, some of which have proceeded to cavitation. The bronchi are dilated. Lf/t Lung.--The pleura is thickened and shows the remains of adhesions to the chest wall. The thickening and adhesions are not so marked as in the right lung. The lung is firmer than normal. At the root of the lung are two large calcareous masses, one she sise of a large hazel-nut, the other about half that sizecalcified tuberculous glands. The other glands are black and show periadenitis. .In the left apex there is an area of old scar tissue about the size of a sixpenny piece, and a cavity the size of a walnut. Scattered throughout the lung ere email areas of draper consistence than the rest of the lung, some of which rbow definite calcareous particles, others small areas of caseation. There is a considerable increase in the fibrous tissue. 'Throe outstanding features are presented by sections from this case. The first is the enormous amount of fine granular pigment in the peribronchial fibrous tissue, walls of alveoli, and in phagocytes scattered through the sections. S'.v particles of this dust are similar in size and shape to e black granules seen in the asbestos fibre, -The second unusual feature is the presence of large solid angular particles (Fig, 2). These are situated in areas of fibrosis and in caseating areas. They vary in size from 3 to 350 microns in length. The particles are so large-- masses of them are seen in certain areas--that they must have occluded small bronchi. Fibrosis of the "alveoli supplied has taken place and later necrosis, as seen in Fig. 3. We have never seen anything parallel to this in pneumonocaaiosis due to other dusts, nor have eve been able to find such occurrence in literature. On comparing these large particles with asbestos dust there is a striking resemblance in sizes, shapes, and colour. In fact, it is very easy to take each single particle found in the lung sections aud immediately find its brother in a slide made from the dust. chronic phthisis. 4. In the alveoli, bronchi, and bronchioles, and also in the interstitial fibrotic areas, are certain foreign bodies which will be described in detail later (Fig. 7). As this communication deals specially with the nature of the foreign bodies, the general histological features will bo dealt with very briefly. The interstitial fibrosis is such as might l.<e expected as a result of a combination of a pncumonocouiutic condition and a chronic tuberculous infection. The typical whorled formations seen in a more purely silicotic condition are not present. There is a marked endarteritis in the smaller branches of the pulmonary arteries; some are throm bosed and organized. Many of the smaller bronchi era obliterated; some have still casoons-lookiifg centres. Some of the alveoli show the usual metaplasia of their lining colls into cuboidul form. The .fibrosed and thickened walls of the bronchi in many places gradually merge into the areas of diffuse fibrous overgrowth. There arc numerous foci of lymphocytic cells among the fibroblasts. Some ef these seem obviously derived from lymphoid tissue in tho bronchial walls. XLe interstitial fibrosis Is progressive. The tuberculous condition is obvious histologically. Tubercle bacilli were not detected, but the histology is characteristic. The lesions are chronic in character, ami there is no special indication of an acute exacerbation. There is well marked caseous bronchitis with lymphatic spread and numerous fibro-cuseous deposits with giant cell systems (see Fig. 8). The bronchi, which are not specially the seat of tuberculous change, show catarrh with peribronchial thickening. There arc numerous emphysema tous areas. The alveoli show, in the majority of cases, tome thickening of their Avails, and contain many catarrhal cells, apparently derived from the lining cells; a similar catarrhal change is seen in the terminal bronchioles, some of Avliich are dilated. The Foreign Bodies. The larger black and irregularly fragmented bodies which have been described by Dr. Cooke were not very obvious in the material I examined,' but acre clearly seen in some microscopical preparations of his which I had the oppor tunity of examining. I shall not refer to them specially, ^ j We cannot think there ib any reasonable doubt that the particles in the lungs are the heavy, brittle, iron-containing fragments of asbestos fibre. The more extensive involve ment of the right lung is thus explained. The heavy par ticles would pass more easily down the more vertical* right bronchus than the horizontal left bronchus. but confine my attention to certain highly characteristic and much smaller*bodies which are abundant in all the sections examined. Some of these are free, hut many are phago- cytosed by the large mouonudear cells in the alveoli (Fig. 5). Some are easily included in comparatively small phagocytic cells, but the majority arc larger, varying in size from e. 20 p to 70 g, or even more in the case of certain elongated j ^HISTOLOGY OP PULMONARY ASBESTOSIS. formB. The smaller bodies are rounded and homogeneous, ' and all have a distinct yellowish-brown colour suggesting *T blood pigment. The longer forms have a highly character stuart McDonald, m.d., f.r.c.p.. Professor of Pathology, University of Durham. (WtfA Special Plate.) istic appearance, strongly suggestive of some argauic struc- ' ture. Most have an annular appearance, which on closer examination can be resolved into a closely set scries of rounded discoid bodies (Figs. 4, 5, 10, and 11). In Mr remarks are confined to the histological appearances in the lungs in this condition, with special reference to rertain foreign bodies of most unusual appearance which ere present both in the alveoli and interstitial substance some cases the globular forms are arranged along the more filamentous forms and occasionally are clustered at the ends of the rods, sinmlating sporangia of hyphomycetes (Figs. 5, 6, 10, and 11). Some hare club-like extremities at one or both ends of the filaments. of the lungs. The observations are based almost entirely Other*, again, suggest the appearance of minute crustacean on material supplied from the case described by Dr. Cooke. forms fFig. 10), but closer examination does not supiairt The investigation has been conducted in the pathological the' idea of either vegetable or animal origin. These department of the University of Durham College of bodies do not stain with the ordinary aniline stains, Medicine. but preserve'their original yellow-brown colour. They ore I may state, however, that the nppearances arc practically seen well in \jnstained sections. They give a charnctcVistir lentical with those observed in a second case of this con* prussian-blue reaction with potassium ferrocyanide and dition, sections of which I have had an opportunity cf dilute hydrochloric acid. Tbc reaction is not so obvious examining through the courtesy of Dr. 1. M. D. Grieve of unless the solutions arc slightly warmed. Where the bodies Arndey. Leeds. are too large to be phagocytosed by individual cells thRT , TIufology. tend to become surrounded bv plasmodial masses. Many Ufj Numerous sections have been made from both lungs. the phagocytes contain much carbon pigment in addition. The changes are more marked on the right side, but the Though these bodies are mainly found in the alveoli and M -..-j, ! `Dec. s. *9*7] AN ACTT7E CONSTITUENT 07 * GLUKHOBMENT." f 1027 debility, shortness of breath, and cough. At present she has no expectoration; her respiratory capacity is one inch. Although the apices of both lungs in front arc resonant, there is distinct flattening of the percussion note at the I ases. The respiratory murmur at the apices and mid* ,ung is coarser than usual, and*the expiratory murmur is prolonged. At the right base the respiratory murmur is feeble, and small dry friction sound is beard. Towards the base f the left lung and extending into the axilla are heard small moist tinkling sounds, suggestive of-cavitation haring taken place; here also email friction sounds can be beard. Similar physical signs prevail posteriorly. The apex beAt of the heart is displaced upwards and outwards; it is felt external to the nipple, a circumstance which, combined with marked accentuation of the second sound of the heart heard over the pulmonary artery, suggests that fibrotic changes hare already occurred in this lung. Although the patient states that she has no expectoration, this was present six weeks ago, and when examined was found to be free of tubercle bacilli. There is no enlarge ment of the external glands. 'Die other patient, aged 39, has been an asbestos worker for eighteen years. She had no illness until four years ago, when she developed cough and attacks resembling bronchial asthma. After remaining away from the factory for three months she returned to her employment, and .followed the occupation for three years, when she married, Vnd as' in the early . months of her pregnancy she %lost considerably in weight she retired from the factory. ^Although reduced considerably in weight, and the subject 'of cough all through her pregnancy, her infant daughter, ^who is 14 months old, is healthy and well developed. The patient complains of a dragging in the chest without actual pain. There is noticeable shortness of breath on slight exertion, and she complains of morning cough with expectoration. The sputum has been examined' and is negative a* regards tubercle bacilli. Her appetite is poor. She weighs 8 st., a drop of 3 st. having occurred within the lost two years. Her heart is healthy; the apex beat is not displaced, but the second sound over tho pulmonary artery is distinctly accentuated. The apices of her inngs are resonant.. Here the respiratory murmur is coarser than usual and the expiratory is prolonged, so that the inspira tory and expiratory murmurs approach each other in eqnality. Moist rales are heard in mid-axillae and snail friction with crepitation it heard at the bases. This woman's mother, who is aged 60, is still working in> the factory. From what I have seen clinically of pulmonary asbestesis it resembles silicosis of the lungs in the marked shortness of breath on slight exertion, deficient respiratory capacity, physical debility, and, in examination of the sputa of not too far advanced cases, absence of tubercle bacilli, but since fibrotic changes are developing in both of the patients to whom I have alluded, there is almost sure to develop, if such has not already taken place, pulmonary tuberculosis. The clinical picture of pulmonary asbestosis differs slightly from that presented by a patient the subject of ordinary tuberculosis of the lungs, m so far as there is a pronounced deadening of the skin varying from mild . bronzing to slight blueness, a degree of shortness of breath in excess of the physical Bigns, a greater amount of general disability, little expectoration, and comparative absence of night sweats. 1oj |Oj II AN ACTIVE CONSTITUENT OF THE PREPARATION CALLED "GLUKHORMENT." ........... w H. H. DALE, C.B.E., M.D., F.R.C.P., Eec. R.S., . . *x ' H. V. DUDLEY, O.B.E., M.So., Ph.D. (From Hi* Department, of Biochemistry and Pharmacology, National Institute (or Radical Bmearch, Hampatoad, London.) Ix May of this year Professor von Noorden published in the Klinische Wochemchrift an account of a new pancreatic preparation which had a controlling effect on carbohydrate metabolism, but, unlike insulin, wns effective when adminis tered by the mouth.1 To this preparation the name "glukhorment " had'been given, and the title of the paper made it clear that tbe substanoe was regarded by the author ax containing a new anti-glycosuria principle, naturally pre formed in the body. On information, evidently supplied to him by tbe chemist responsible for devising " glukhorment,'* . Professor von Noorden stated explicitly that, in spite of indications in the patent specification, which might suggest some connexion of the active principle with a guanidine derivative, no such derivative, and in particular no synthalin,* had been added; and, further, that the finished preparation contained no guanidine derivative of any kind in recognizable amount. Professor ron Noorden drew the cautious conclusion that, if the activity were due to a guanidine derivative, it would have to be one of extremely high activity. In July of this year one of ns (H. H. D.) received a communication front tlie Horment Company, who wore manufacturing glukhorment, stating that they were sending material in the hope that clinical trials of it could be arranged. In due course this and several subsequent consignments of glukhorment were sent by the Horment Company, with a request for their trial. A consideration of preliminary reports, on the mode of of this preparation on the human being and on animals, suggested a strong similarity between VPbffects and those with which we had become familiar, through experiments then for some time in progress, on the action of synthalin. Gome of the glukhorment , * " hyathalia " it Ui synthetic compound, deesaietlijlencdiiruinidine, *Wwucd b Flunk, Nathmsnn, and Wsyner, es an antidUbctlo (or dial administration, and already the subject ot numerous teporta was immediately placed in the hands of one physician,'who will presumably report his experience with it in due course. The physiological resemblance to synthalin was so pro nounced, however, that, before the question of wider clinical trials was considered, it was thought desirable to make a simple chemical examination, in order to confirm tlm OP fact that the preparation was free from synthalin and similar guanidine derivatives, ss stated in the paper by *_-_v_~- Professor von Noorden, of which copies hod been submitted t--. by the Horment Company in support of their request. The result of this first test showed clearly that a guanidine jJtJ derivative strongly resembling syntbalin was present in i m substantial amount in the glnkborment tablets as submitted for trial. The evidence thus early obtained was at once so dear and so surprising that it was considered desirable t - u. #3 to nse a further quantity of the material submitted, in order to obtain precise information as to the nature of the substance in question. . The isolation of tbe substance was made easy by tbe fact that the nitrate of synthalin is a remarkably Insoluble salt.. . . " Chemical Isolation from Glukhorment of a Guanidine Derivative closely resembling Synthalin. Two hundred glnkborment tablets were powdered; tbe powder, weighing 60 grams, was thrown into 1 litre of boiling water and the mixture was kept gently boiling for - fifteen minutes. Tbe liquid was then filtered, while still hot, from a large mass of insoluble protein. Tbe filtrate was evaporated in vacuo, with the addition of octyl alcohol to prevent frothing, ` to a volume of 120 c.cm. On standing, it set to a jelly; this was wanped to 40, when it became fluid, and concentrated nitric acid was added until tbe reaction of tbe. liquid was strongly acid to Congo red. A white crystalline, nitrate separated from the solution on standing, and the liquid no longer set to a jelly when cold. The crystalline material was collected by centrifuging, washed in the centrifuge with a small quantity SP-* ?IL of dilute nitric acid, and dissolved in about 25 can, of hot water. This solution was boiled with charcoal and filtered. To the hot filtrate 0.5 c.cm. of 6 per cent, nitric acid was added, and the nitrate crystallized on cooling. This was filtered off and dried; it weighed 1.135 grams. It was thenP P converted into the picrate by dissolving it in water ancM J adding a saturated solution of sodium picrate until no tyJC- further precipitate was produced. The picrate was filtered