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BRONCHOGRAPHY
657 Three such women have already been operated on and in each our presumed diagnosis of Stein-Leventhal syndrome was correct. All of them have had good results after wedge resection of the ovaries. Whenever it is impossible to perform more difficult and/or more complicated examinations, we therefore think that an increase of urinary 17-ketosteroids after injection of progesterone (" positive test) might be sufficient criterion for a diagnosis of Stein-Leventhal syndrome in those women with hirsutism, conspicuous menstrual disturbances, occasional sterility, and normal or slightly elevated urinary 17-ketosteroids. V. PATRONO "
Medical Clinic of the University of Rome.
G. NICOLOSI. BRONCHOGRAPHY
SIR,-Iagree with Dr. Smith and his colleagues (March 5) that a lot of heavy weather is made over bronchography, and their method is simple and effective. An equally simple and quick method is that with the Elaine Field needle, using the cricothyroid route.
This needle is, in effect, a small curved cannula with a short-bevel pointed end and a flush-fitting stylet which is mounted on a handle for ease of insertion. It was originally developed for children, but adult sizes are easily obtainable. After insertion, the cannula is tied in position with tapes, which obviates two snags of the ordinary cricothyroid method -i.e., having to hold the needle carefully so that it stays in the right place, and having to reinsert it if both sides are being done at one session. The proximal end of the cannula is ’Record ’-fitting to take the bronchogram syringe, which can be disconnected as soon as the right side has been done, and reconnected to do the left after the first lot of films have been taken. Premedication is not normally necessary and 1 ml. of
2% lignocaine through the cricothyroid membrane via a no. 12 needle should suffice to anxsthetise the skin and bronchial tree. (A second 1 ml. may be advisable in bronchitic patients with a good deal of sputum.) The method is very satisfactory for outpatients.
Central Lincolnshire Chest Mint Lane, Lincoln.
Unit,
J. B. WILKINSON.
AUTOIMMUNE HÆMOLYTIC ANÆMIA WITH ACUTE RENAL FAILURE DUE TO PHENACETIN AND P.A.S.
SIR,-Following the paper in your issue of Jan. 2 by Dr. Barbara MacGibbon and her colleagues, I should like to report another case 1 of sensitivity to P.A.S. A 50-year-old man had been treated for several years for pulmonary tuberculosis associated with renal diabetes. During 1956 he received 15 intravenous injections of P.A.S. (15 g. daily). The 14th and 15th injections were followed by fever. Two years later 12 injections were given. The last 3 injections were ill tolerated (general malaise, vomiting, and fever). Three months later another injection had to be stopped because of severe shock. At no time were signs of hxmolysis observed (no icterus, no dark urine, no anuria or even oliguria). No immediate haemorrhagic syndrome developed. The blood was examined 39 days after the last P.A.S. injection. The serum contained an allergic " antibody capable of agglutinating all compatible red cells, all leucocytes, and platelets of the same blood, but only in the presence of P.A.S. (0-05 g. per 100 ml. final concentration). The average titre was 1/12,1 for red cells, and 1/16 for leucocytes and platelets. The reaction was stronger at 37° C than at 15° C or 4° C. No haemolysis of normal or trypsinised red cells could be demonstrated with fresh serum or with inactivated serum samples to "
which fresh human serum had been added as a source of complement, in neutral or acid medium . This antibody was still active after heating at 56° C for 20 minutes, but was destroyed by heating at 70° C for 10 minutes. The reaction was inhibited by E.D.T.A. (disodium 1. Presented to the Société
française d’Allergie, Paris, Nov. 17,
1959.
sequestrene). The action on platelets could also be demonstrated by the inhibition of clot retraction. The antibody could be absorbed and eluted either on red cells and leucocytes or platelets. The reaction was equally positive with, instead of P.A.s., 3-aminosodium salicylate, 5-amino-sodium salicylate, p-amino sodium benzoate, sodium salicylate, sodium gentisate, methoxy-2-sodium benzoate, nitro-3-sodium salicylate, and nitro-5-sodium salicylate. It was negative with sodium benzoate, sodium phthalate, p-sulphosodium salicylate, sodium acetyl salicylate, sodium p-amino hippurate, m-amino-phenol, and phenacetin. The antibody was not neutralised by the addition of P.A.S. to the serum nor could it be removed by red cells alone. This
case is remarkable because this strong antibody did provoke clinical hxmolytic anxmia or a hxmorrhagic syndrome although it was active in both red cells and platelets. J. DAUSSET Centre National de Transfusion
not
Sanguine, Paris,
15e.
Y. BERGEROT-BLONDELL.
LUNG CANCER AND TOBACCO MOSAIC VIRUS
SIR,-In the search for carcinogens in tobacco smoke there appears to be little research activity in relation to the presence of active tobacco mosaic virus (T.M.V.) in the finished tobacco as found in cigarettes and pipe tobacco. This virus resists the processes of tobacco manufacture, remains infective for plants,’ and can be demonstrated serologically in tobacco offal.2 As a high-molecular-weight protein, it might not be expected that T.M.v. would be carried through in tobacco smoke, but it would be present for ingestion on contact with tobacco (a frequent occurrence in the cigarette-smoker but less common in the pipe-smoker). The induction of lung cancer by an ingested or not predominantly inhaled agent would also be an explanation of the apparent (but not universal) finding in lung-cancer/smoking statistics that inhalers are no worse off than non-inhalers.3 In these circumstances the cigarette would really function as a man-made vector, perhaps incorporating the correct chemical and temperature changes for the virus at the same time. The content of ribonucleic acid (R.N.A.) in T.M.v. is approximately 5%,4 and it is interesting that the other virus which has been suggested as a possible aetiologic agent in lung cancer (influenza virus) also has its nucleic acid in the R.N.A. form. The fundamental role of the nucleic-acid molecule in cell metabolism, which is the subject of so much current interest, is surely worth studying in relation to the R.N.A. of T.M.V. in tobacco. If T.M.V. is involved in the actiology of lung cancer, one might consider that, being a plant and not an animal virus, long exposure would be necessary for the incubation of lung cancer.
The fact that many types of plant virus must be eaten regularly without causing apparent ill-effect (from tomatoes, vegetables, &c.) would suggest that T.M.v. may have to be modified to attain pathogenicity for animals. The combustion processes in the cigarette might provide such a media for modifying the T.M.v. and it would be interesting to know whether the R.N.A. is liberated in this way from its protein or whether it is itself modified in the smoking process. T.M.V. must occupy a unique position in biology as the only virus likely to be brought into contact with man at a time when it is being subjected to a considerable temperature gradient 5near the burning cigarette end, as well as complex chemical processesgoing on around it or near to it in the burning of tobacco. Many possible changes could occur in the virus and the R.N.A. in the smoking process if one compares the changes in the influenza virus when exposed to heat.a 1. Smith, K. M. A Textbook of Plant Virus Diseases; p. 507. London, 1957. 2. Imperial Tobacco Co. Personal communication, 1959. 3. Doll, R., Hill, A. B. Brit. med. J. 1950. ii, 739. 4. Smith, K. M. Recent Advances in the Study of Plant Viruses; p. 144. 5. 6. 7. 8.
London, 1951. Harlow, E. S. Science, 1955, 123, 226. Greene, C. R. ibid. p. 227. Clemo, G. R. J. R. Soc. Hlth, 1959, 79, 74. Burnet, M. Enzyme Antigens and Virus. Cambridge,
1958.
Medical Clinic of the University of Rome.
G. NICOLOSI. BRONCHOGRAPHY
SIR,-Iagree with Dr. Smith and his colleagues (March 5) that a lot of heavy weather is made over bronchography, and their method is simple and effective. An equally simple and quick method is that with the Elaine Field needle, using the cricothyroid route.
This needle is, in effect, a small curved cannula with a short-bevel pointed end and a flush-fitting stylet which is mounted on a handle for ease of insertion. It was originally developed for children, but adult sizes are easily obtainable. After insertion, the cannula is tied in position with tapes, which obviates two snags of the ordinary cricothyroid method -i.e., having to hold the needle carefully so that it stays in the right place, and having to reinsert it if both sides are being done at one session. The proximal end of the cannula is ’Record ’-fitting to take the bronchogram syringe, which can be disconnected as soon as the right side has been done, and reconnected to do the left after the first lot of films have been taken. Premedication is not normally necessary and 1 ml. of
2% lignocaine through the cricothyroid membrane via a no. 12 needle should suffice to anxsthetise the skin and bronchial tree. (A second 1 ml. may be advisable in bronchitic patients with a good deal of sputum.) The method is very satisfactory for outpatients.
Central Lincolnshire Chest Mint Lane, Lincoln.
Unit,
J. B. WILKINSON.
AUTOIMMUNE HÆMOLYTIC ANÆMIA WITH ACUTE RENAL FAILURE DUE TO PHENACETIN AND P.A.S.
SIR,-Following the paper in your issue of Jan. 2 by Dr. Barbara MacGibbon and her colleagues, I should like to report another case 1 of sensitivity to P.A.S. A 50-year-old man had been treated for several years for pulmonary tuberculosis associated with renal diabetes. During 1956 he received 15 intravenous injections of P.A.S. (15 g. daily). The 14th and 15th injections were followed by fever. Two years later 12 injections were given. The last 3 injections were ill tolerated (general malaise, vomiting, and fever). Three months later another injection had to be stopped because of severe shock. At no time were signs of hxmolysis observed (no icterus, no dark urine, no anuria or even oliguria). No immediate haemorrhagic syndrome developed. The blood was examined 39 days after the last P.A.S. injection. The serum contained an allergic " antibody capable of agglutinating all compatible red cells, all leucocytes, and platelets of the same blood, but only in the presence of P.A.S. (0-05 g. per 100 ml. final concentration). The average titre was 1/12,1 for red cells, and 1/16 for leucocytes and platelets. The reaction was stronger at 37° C than at 15° C or 4° C. No haemolysis of normal or trypsinised red cells could be demonstrated with fresh serum or with inactivated serum samples to "
which fresh human serum had been added as a source of complement, in neutral or acid medium . This antibody was still active after heating at 56° C for 20 minutes, but was destroyed by heating at 70° C for 10 minutes. The reaction was inhibited by E.D.T.A. (disodium 1. Presented to the Société
française d’Allergie, Paris, Nov. 17,
1959.
sequestrene). The action on platelets could also be demonstrated by the inhibition of clot retraction. The antibody could be absorbed and eluted either on red cells and leucocytes or platelets. The reaction was equally positive with, instead of P.A.s., 3-aminosodium salicylate, 5-amino-sodium salicylate, p-amino sodium benzoate, sodium salicylate, sodium gentisate, methoxy-2-sodium benzoate, nitro-3-sodium salicylate, and nitro-5-sodium salicylate. It was negative with sodium benzoate, sodium phthalate, p-sulphosodium salicylate, sodium acetyl salicylate, sodium p-amino hippurate, m-amino-phenol, and phenacetin. The antibody was not neutralised by the addition of P.A.S. to the serum nor could it be removed by red cells alone. This
case is remarkable because this strong antibody did provoke clinical hxmolytic anxmia or a hxmorrhagic syndrome although it was active in both red cells and platelets. J. DAUSSET Centre National de Transfusion
not
Sanguine, Paris,
15e.
Y. BERGEROT-BLONDELL.
LUNG CANCER AND TOBACCO MOSAIC VIRUS
SIR,-In the search for carcinogens in tobacco smoke there appears to be little research activity in relation to the presence of active tobacco mosaic virus (T.M.V.) in the finished tobacco as found in cigarettes and pipe tobacco. This virus resists the processes of tobacco manufacture, remains infective for plants,’ and can be demonstrated serologically in tobacco offal.2 As a high-molecular-weight protein, it might not be expected that T.M.v. would be carried through in tobacco smoke, but it would be present for ingestion on contact with tobacco (a frequent occurrence in the cigarette-smoker but less common in the pipe-smoker). The induction of lung cancer by an ingested or not predominantly inhaled agent would also be an explanation of the apparent (but not universal) finding in lung-cancer/smoking statistics that inhalers are no worse off than non-inhalers.3 In these circumstances the cigarette would really function as a man-made vector, perhaps incorporating the correct chemical and temperature changes for the virus at the same time. The content of ribonucleic acid (R.N.A.) in T.M.v. is approximately 5%,4 and it is interesting that the other virus which has been suggested as a possible aetiologic agent in lung cancer (influenza virus) also has its nucleic acid in the R.N.A. form. The fundamental role of the nucleic-acid molecule in cell metabolism, which is the subject of so much current interest, is surely worth studying in relation to the R.N.A. of T.M.V. in tobacco. If T.M.V. is involved in the actiology of lung cancer, one might consider that, being a plant and not an animal virus, long exposure would be necessary for the incubation of lung cancer.
The fact that many types of plant virus must be eaten regularly without causing apparent ill-effect (from tomatoes, vegetables, &c.) would suggest that T.M.v. may have to be modified to attain pathogenicity for animals. The combustion processes in the cigarette might provide such a media for modifying the T.M.v. and it would be interesting to know whether the R.N.A. is liberated in this way from its protein or whether it is itself modified in the smoking process. T.M.V. must occupy a unique position in biology as the only virus likely to be brought into contact with man at a time when it is being subjected to a considerable temperature gradient 5near the burning cigarette end, as well as complex chemical processesgoing on around it or near to it in the burning of tobacco. Many possible changes could occur in the virus and the R.N.A. in the smoking process if one compares the changes in the influenza virus when exposed to heat.a 1. Smith, K. M. A Textbook of Plant Virus Diseases; p. 507. London, 1957. 2. Imperial Tobacco Co. Personal communication, 1959. 3. Doll, R., Hill, A. B. Brit. med. J. 1950. ii, 739. 4. Smith, K. M. Recent Advances in the Study of Plant Viruses; p. 144. 5. 6. 7. 8.
London, 1951. Harlow, E. S. Science, 1955, 123, 226. Greene, C. R. ibid. p. 227. Clemo, G. R. J. R. Soc. Hlth, 1959, 79, 74. Burnet, M. Enzyme Antigens and Virus. Cambridge,
1958.