SENSITIVITY OF TUBERCLE BACILLUS

798 in a patient with sclerodermia, just as I find it difficult to think that sclerodactyly is due to the chance occurOne rence of Raynaud’s phenomenon in such a patient. case indeed has been published in which the oesophagus was calcified, and I doubt if Mr. Allison has had one of those in his series of peptic ulcers. If this one case must be admitted, then the immunity which Mr. Allision claims for the oesophagus from lesions which have been demonstrated in the heart and lung, and the rest of the intestinal tract, is not absolute. I said such lesions are rare, but they do occur, sometimes with remarkable rapidity, as in the case operated on by Prof. Grey Turner ; and they are worth remembering, because the prognosis is rather better than with cancer, which they can simulate, and sometimes because it is rather worse than with cardiospasm or peptic ulcer pure and simple. There seem to me to be three possibilities : (a) lesions due entirely to sclerodermia ; (b) lesions due to entirely fortuitous coincidental peptic lesions ; and (c) peptic lesions conditioned by regurgitation due in some way to sclerodermatous change. I think the third most likely, and then the first. And I think that one of these days Mr. Allison will think the same. W. A. BOURNE. Hove, Sussex.

Fig. 2-initial growth in medium containing img. P.A.S.

per 100 ml.

of horse plasma and 6 parts of physiological saline. This bacterial solution was allowed to stand for some hours before films were made from the supernatant fluid. When the slides had dried in air they were immersed in 6% sulphuric acid for 5-15 min.-fresh Dubos and Sauton cultures for at most 5 min., L6wenstein cultures for about 10 min., and sputum and glandular tissue for 12-15 min. depending on the thickness of the sections. The slides were rinsed twice under sterile conditions in two separate Petri dishes containing distilled SENSITIVITY OF TUBERCLE BACILLUS water. Then they were immersed in the medium (1part SiR,-Intensive treatment of tuberculosis with antidefibrinised horse blood plus 2 parts sterile distilled water) biotics and chemotherapeutic agents calls for in-vitro which was contained in 80 x 30 mm. culture tubes with resistance tests. Owing to the slow growth of the tubercle plugs made of cotton-wool wrapped in bandage gauze. The bacillus it has been impossible to obtain results quickly, medium was about the same as that used by Miiller.4 The but the introduction of Pryce’s1 slide-culture method P.A.S. concentrations were 15, 1-5, 0-15, 0-015, and 0-0015 mg. has significantly improved the position. I have used this per 100 ml. (corresponding to 10-3, 10-4, 10-5, 10-6, and 10-7mol.). method in studying the bacteriostatic effect of p-aminoThe P.A.s.-medium mixtures were prepared by adding 0-1 ml. of an 0-1 molar neutral P.A.S. solution to 10 ml. of the medium. salicylic acid (P.A.S.),2 and can confirm Lehmann’s3 Of this stock mixture (15 mg. per 100 ml.), 1 ml. was transfindings. I have found Pryce’s technique suitable as a routine ferred to 9 ml. of medium (=1-5 mg. per 100 ml.), and method of determining the effect of P.A.S. and of strepto-so on in decreasing concentrations. Naturally the various mycin on the growth of tubercle bacilli. One of the concentrations could also have been made up by successively advantages of this slide-culture method is that it diluting the 0-1 molar r..s. solution 10 times and adding enables one to determine resistance directly on the original 0-1 ml. of each dilution to 10 ml. of medium. The 0-1 molar material without previous culture, which means that P.A.S. solution was made up by dissolving 211 mg. sodium results may be obtained within a week. The only dihydroxy para-aminosalicylie acid in 10 ml. of water and requirement is that the material shall contain enough autoclaving the solution or, better, filtering it through a tubercle bacilli for all slides-usually 12-to get an Seitz filter. This stock solution is stable for at least one adequate number of viable bacilli. Should the quantity week when kept in a refrigerator. Double series were made of of bacilli be insufficient, the absence of growth might be each concentration as well as of the controls. After 7 days’ growth at 37’C one of the controls was stained and observed microscopically, and if it exhibited plentiful growth (myceliform, branched formations) all the slides were stained and examined. If the control exhibited no or little growth, the cultures were incubated for another 7 days. As a rule HaBberg’s 5 staining procedure was employed, but sometimes Ziehl-Neelsen’s. Decolorising must be performed very carefully and rapidly, for the young bacilli are not as resistant to acids as are bacilli which have grown for longer periods on other media. The after-staining with the contrast dye must be very brief, or, possibly, excluded. With the generally observed susceptibility to P.A.S. there may be seen plentiful formations of myceliform growthssuch as are described by Pryce-in the concentrations of 0-0015 and perhaps also of 0-015 mg. per 100 ml. (see fig. 1). Slides that have been submerged in media with higher P.A.S. concentrations exhibit no typical aecumulations of bacilli ; but these may be longer than usual, unevenly stained, and perhaps branched (branching forms according to Pryce). In my experience such microscopical pictures are common in with sputum or glandular tissue. In experiments Fig. I-Myceliform growths after 10 days’ cultivation in medium experiments containing 0-0015 mg. P.A.S. per !00 m!. with bacteria from Dubos’s, Sauton’s, or Lowenstein’s medium the same results will be obtained as regards the susceptibility to P.A.S. or to a effect. P.A.S., but slides from media with concentrations higher attributed streptomycin wrongly than 0-015 mg. per 100 ml. often exhibit another picture. This quick method may be applied to practically any In this case there may be seen small typical " colonies material. In addition to sputum, I have experimented similar to the forms observed by Pryceafter 6 days’ with cultures of tubercle bacilli from Lowenstein’s, cultivation of sputum slides (fig. 2). This typical accumulaDubos’s, and Sauton’s media, and from minced guineation of bacteria-which is never seen on non-incubated pig glands. The technique was as follows : slides-is apparently due to an initial growth of the bacilli. If the material consisted of sputum or glandular tissue I Thus Dubos cultures with their rapid growth often give rise prepared smears. If, on the other hand, it consisted of a to these forms. In estimating the susceptibility to p.A.s. bacterial culture, dispersed in a mixture of 1 part of a bacterial strain it is of great importance that the small 1. Pryce, D. M. J. Path. Bact. 1941, 53, 327. colonies discussed above do not continue growth during 2. Sievers, O. Svenska Läkartidn. 1946, 33, 2041. 4. Müller, H. J. Path. Bact. 1944, 56, 429. 3. Lehmann, J. Lancet, 1946, i, 14 ; Svenska Läkartidn. 1946, 33, 2039. 5. Hallberg, V. Acta med. scand. 1946, suppl. 180. "

this was

799 incubation when they have been subjected to P.A.S. concentrations higher than 0-015 mg. per 100 ml. so that the characteristic myceliform forms never arise. I have interpreted this phenomenon as a sign that there is an initial growth which ceases after some days owing to the bacteriostatic effect of P.A.S. The greater the growth-rate of the bacilli, the greater will be the initial growthbefore P.A.s. has time to exert its inhibiting effect. The fact that P.A.S. does not immediately affect the growth with Pryce’s slide-culture method agrees with the findings of Lehmann,3 who seldom obtained more than 90-95% inhibition in experiments with Sauton cultures despite high P.A.S. concentrations. So far I have not observed any consistent resistance to P.A.S. in my experiments with numerous samples from patients treated with this substance. In no case was there any growth in a concentration of 1-5 mg. P.A.S. per 100 ml., and consequently, since in ordinary P.A.S. therapy the blood concentration usually lies between 2 and 6 mg. per 100 ml., resistance of clinical importance has not been observed. OLOF SIEVERS. Bacteriological Laboratory, Sahlgren’s Hospital, Gothenburg, Sweden.

Should he have an operation ? It is in this type of case that I believe the residual-urine test to be of great value. Surely a prostate which prevents the bladder from emptying must be more dangerous than one which is less obstructive. I have been aware for a long time that a prostate might affect the upper urinary tract without producing residual urine, but have found little evidence of this in my own practice. I think that such cases must be exceptional and need not affect our general indications for operation. T. L. CHAPMAN. Glasgow.

prolonged

RISK FROM ASPIRIN PREPARATION

SiR,--In recent years an aspirin preparation has been introduced to the English market from across the Atlantic of which the novelty is that it can be eaten like a sweet." Have the makers carefully considered how easy it would be for an infant exploring the cupboards to eat these tablets " just like sweets " ? Who has not rescued his own children just in time from such a happening ? A warning on the package, and the wrapping of all tablets of this type in transparent paper of a distinctive colour never used for sweets, might help to "

e

counter the risk. Newcastle-on-Tyne.

A. FORSTER.

RETROPUBIC PROSTATECTOMY

surprised that Mr. Millin and Mr. Macalister (April 23) do not always advise operation for SiR,-I am not

with minimal symptoms. I am surprised indeed that they describe this view as "commonplace knowledge." Examination of the appropriate chapters of 8 standard textbooks of general surgery showed that 5 make no mention of expectant treatment, describe the condition as progressive, and give the impression that - the prostate which is enlarged should be removed if the patient’s condition is good enough. This is a matter of great importance and one which cannot be put aside lightly. An enormous proportion of men over fifty-five have some enlargement of the-

prostatic enlargement very

prostate, and of these a considerable number have mild urinary symptoms which continue to the end of their lives without any effect on their health. These symptoms often regarded as a natural result of age, and in the past such patients did not seek medical advice. I believe that this is the reason why so many writers describe as exceptional the non-progressive case of prostatic enlargement. With spreading knowledge, more and more patients with mild symptoms now consult surgeons. This is much to be encouraged and gives hope that a larger number of progressive cases will be treated at an earlier stage. It would be wrong if all of these mild cases were treated by operation, and I think that the article of March 5 by Mr. Millin and his colleagues might be interpreted as encouragement to do so. This impression could be corrected from Mr. Millin’s writings elsewhere, but there are many surgeons who remove prostates but who do not study the specialist literature of urology. My experience of the expectant treatment of prostatic cases has justified fully the continued use of the residualurine test, though my dependence on it has been exaggerated by your correspondents. No surgeon would refuse to help a distressed patient because his case did not ful.1 precise criteria. A more difficult decision must be made when a patient seeks advice about symptoms which are merely a minor inconvenience. Such a patient is concerned, not about the present, but about the future. He is fit ; his prostate is enlarged. are

’

THE MEDICAL ILLUSTRATOR

SiB,—I protest against education throughterror. as depicted in fig. 2 of the article by the senior medical illustrator of Guy’s Hospital in your issue of April 23.

.

This is wrong whether the education be general, health, or medical. It belongs to the time of Hieronymus Bosch and later of Heilige Breughel with. their representations of what may happen to us in Hell. It is not absent from the woodcuts of Albrecht Durer, who was contemporary with the former. It savours of nursemaid discipline with the frightening of her charges first with Boney, then with Bogy, and finally with a Bobby. All this is now a thing of the past. Rule by frightening the instructed is not in the spirit of our time and never was of England. Our artists have never used their powers to compel us to the will of those that would rule us ; nor will the illustrator to Guy’s find any evidence of it in the work of her predecessor, Joseph Towne, although he could depict emotion when he needed it, as may be seen in the first of the three wax models of the huge aortic aneurysm in which there is a depiction of agonising pain with the " drawn expression " of tense, halfcontracted muscles of the whole face that vies with any other example of the sculptor’s art. This wrong use of her art is of the greater moment because the illustrator to Guy’s has a great power of representing emotion in a few lines. Witness this picture with the variation in each of the four ages, although we may doubt whether the infant has yet an intelligence that will appreciate the meaning of death or its symbolism in a clothed skeleton. Give it a human femur and it will find it as excellent a drumstick as that of a Moa if there is a dustbin lid lying about ready for it to beat. Fig. i is in the right spirit. There is no doubt that that child has whoopers," and the calmness of the little nurse-mother is just what is needed under the circumstances. This is so truly England that the original might even be purchased by the Chantrey trustees, leaving the weeping Widow of the Cross-Roads, with its French influence, which public opinion compelled the Ministry of Transport to withdraw, to those of the Tate. Education by terror is a part of a trend that is but too evident today. Some years ago I gave a clinical lecture on Appointment with Fear, dealing with signatures for anaesthetics, for refusal to accept a doctor’s advice, and for leaving hospital, all of which I used to forbid I am glad therefore that my house-surgeon ever to use. it is one working at my own hospital that has enabled 111e to raise this point. To do so with reference to any other might savour of bad form. It was the late Dr. E. W. Goodall that first put this conception of criticism, without condemnation, into my head. He used to show to his D.P.H. class plans of the medical wards in Hunt’s house at Guy’s, with their four rows of beds between the crossventilation of the windows, as an example of* how not to build a hospital. He told me that he was glad they he would have some came from his own hospital ; diffidence in speaking about them with the emphasis, that was a part of his nature, had they been at any other. And so here. The last paragraph of this paper shows that it is a matter of Guy’s not of its senior illustrator. In the first It is a question of the Code of the Herd. instance of the little Herd of Guy’s ; but I much suspect, also of that larger Herd, of which this is but a small part, and which involves all the teaching schools at least in "

London.

Fifty years ago the direction of the code of the herd at a teaching hospital was in the hands of the individual members of the staff. This began to-change when the members increased to such an extent that no man had