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SALICYLATE AS AN ANTICOAGULANT

SIR,—I was interested to see that at a recent meetingof t4e. British Cardiac Society Dr. J. L. Lovibond,who had investigated the value of salicylate in the treat-ment . of coronary thrombosis, reported that this drugis an unpleasant but safe anticoagulant for domiciliaryuse. He found that few patients were able to toleratesodium salicylate or calcium aspirin (’Disprin ’) in themassive daily dosage of 200 grains for many days.This is not surprising ; for sodium salicylate is notoriouslymore prone to induce toxic symptoms than aspirin andhas the serious disadvantage of increasing the sodiumcontent of the body ; and calcium aspirin has nothingto recommend it in the treatment of thrombosis, as asubstitute for aspirin, except its solubility..

I am still using aspirin in suspension as a routinetreatment for phlebitis, pulmonary embolism, and

coronary thrombosis, in doses of 20 grains four-hourly-i.e., 160 grains daily. When the instruction to give themixture with milk or other food is strictly adhered to, thepatient seldom complains of any discomfort referable tothe drug. There is a big difference between giving20 grains of aspirin powder on an empty stomach and20 grains in suspension with food ; but it is surprisinghow many apparently intelligent people do not appreciatethis. It would be a great pity if a safe and simple remedyof proven value in the treatment of thrombotic diseaseswere to be discarded for the lack of a little common sense.

Torquay. PAUL GIBSON.

MYXŒDEMA FROM RESORCINOL OINTMENTAPPLIED TO LEG ULCERS

SIR,-In their article of May 6, Dr. Bull and Dr. Fraserreported myxoedema in three elderly women who hadfor a long time received applications of resorcinol ointmentfor varicose ulcers. In each case sections of the thyroidgland showed signs of hyperactivity characteristic of theaction of an antithyroid drug. In the same issue Dr.Doniach and Dr. Fraser confirmed the antithyroidactivity of resorcinol in animals and found that thiouracildoes not enhance this activity.We therefore thought it desirable to study the

histological response of the thyroid in animals afteradministration of resorcinol.

For this purpose seven rabbits (six bucks and one doe)were used, and five bucks served as controls. All of them

belonged to pure strains (Moravia Black, Silverblack, Chin-chinella), were 5-8 months old, and weighed 1220-2300 g.They were kept in the usual wire cages and were fed on hay,bread, and oats.

Resorcinol was administered subcutaneously as a 1%solution in 0-9% saline solution ; 50 mg. per kg. body-weightwas given for 4 days, and 75 mg. for 15 days. The totalamount of resorcinol administered was therefore 1325 mg.per kg. The absolute amount administered during the 3weeks of the experiment varied from 1596 mg. to 3096 mg.according to the weight of the animal. The drug was tol-erated fairly well; by the end of the experiment the animalshad lost about 5% of their weight. They were then killedby air embolism. The thyroids of these animals showed nosigns of enlargement (their weight averaged 95 mg.), nor anychange in their tender consistence or in their colour comparedwith those of the controls. Likewise the histological picturedid not differ from that in the control animals, apart fromchanges that were within normal limits.To observe the effect of’ methyl thiouracil and resorcinol

administered together, the former was given subcutaneouslyto seven rabbits in doses of 100 mg. per kg. body-weight in1V/10 solution of sodium hydroxide six times weekly for9 weeks (total amount 9040-11,105 mg.). From the 7th weekfour of the seven animals received resorcinol subcutaneouslyas in the previous experiment. All seven rabbits were

bucks, of pure strain, kept under the same conditions andkilled in the same way as in the previous series. The thyroidsof all seven animals were greatly enlarged; their weightaveraged 735 mg. and they had a fleshy red colour and firmerconsistence. Histological examination revealed in each case

the well-known effect of methyl-thiouracil, and this effectwas in no way modified by the resorcinol.Thus the administration of resorcinol does not change

the histological structure of the thyroid in rabbits,nor does it influence the effect of methyl-thiouraciladministered simultaneously.

Department of Pathology, SlovakUniversity, Bratislava, Czechoslovakia.

FR. KLEIN

V. OTTISJ. VELVART.

SIMPLE TEST FOR PREGNANCY

SiR,-For the past ten years I have been using asimple clinical test for pregnancy.

It consists in injecting 5 mg. progesterone on three alternatedays. The absence of withdrawal bleeding is a positive signof pregnancy. If the amenorrhcea is due to any other cause,bleeding occurs in about 5 days. Cases of obstruction-congenital or acquired-and of absence of the uterus can beeasily excluded by bimanual examination. I have had nochance to use the test in cases of hydatidiform mole ; butI expect that it would be positive.Suhag, Upper Egypt. M. EL MISHAD.

TUBERCLE BACILLI IN THE C.S.F.

SiR,-In your annotation of Aug. 19 you remark that"

many factors concerned in the pathogenesis of tuber-culous meningitis are still imperfectly understood."We have learnt that tubercle bacilli may be found in

the cerebrospinal fluid (C.S.F.) without clinical or patho-logical evidence of meningitis. We do not know whythe presence of tubercle bacilli in the c.s.F. is not alwaysfollowed by tuberculous meningitis, or why in some casesthe meningitis is only circumscribed. Rich suggestedthat very numerous bacilli are necessary to producemeningitis. Schwarz 2 has often seen cases where caseousmasses have broken down into the subarachnoid spacewithout a violent reaction, even in the presence ofnumerous acid-fast bacilli. It seems that the numberof tubercle bacilli is not the deciding factor in everycase. Koch 3 suggested that tubercle bacilli can multiplyin the c.s.F. It might be reasonable even to assume thatphagocytosis may take place when the organism getsinto the c.s.r., and the effectiveness of this could decidewhether or not tuberculous meningitis will develop.

During treatment of miliary tuberculosis with strepto-mycin tubercle bacilli may be found in the c.s.F. whiletuberculous meningitis is developing, without anyclinical evidence. For this reason diagnostic lumbar

puncture should be performed periodically on patientswith miliary tuberculosis. In diagnosis c.s.F. sugarestimation can help in distinguishing tuberculous menin-gitis from a tuberculoma in the meninges or the brain.With each the protein level and the number of the cellsis increased ; but whereas in tuberculous meningitis thecells usually exceed 20 per c.mm.-usually they number50--300, though they may exceed 1000-with tuberculomathe number remains under 20 per c.mm. In tuberculous

meningitis the sugar content is low and continues tofall,4 whereas in tuberculoma the sugar content is normal.Tuberculoma may or may not produce meningitis, so itis perhaps best to avoid the diagnosis of

" serous tubercu-

lous meningitis," suggested by Lincoln,5 because this

might give the patient or parents a false sense of security.It is no surprise that we can detect tubercle bacilli

in the of patients with tuberculous meningitis whohave received intrathecal streptomycin and have beenregarded as clinically cured. I have often found thatwhen a child seemed to be " clinically cured," the celland protein content of the c.s.F. decreased while the

1. Rich, A. R., McCordock, H. A. Bull. Johns Hopk. Hosp. 1933,52, 5.

2. Schwarz, J. Amer. Rev. Tuberc. 1948, 57, 63.3. Koch, O. Beitr. Klin. Tuberk. 1940, 94, 183.4. Steiner, B. J. Jb. Kinderheilk. 1923, 102, 173.5. Lincoln, E. M. Amer. Rev. Tuberc. 1947, 56, 95.