825

of 8 m.eq. a day there were no spontaneous attacks,nor could attacks be induced. The efficacy of a low-sodium diet may indeed be partly due to concurrentpotassium retention ; for BARTTER 15 has suggestedthat minimal excretion of sodium may depresspotassium secretion through lack of sodium ion

available for exchange. The diet used by CONN et al.in their studies is considerably more restricted thanthe conventional low-salt diet ; it would therefore beof great interest to find out whether an ordinarylow-salt diet would prevent spontaneous attacks, orwhether this would ’have to be supplemented bymercurial or other diuretic agents. In some patientssuch a regime might have advantages over regularpotassium supplements, which are not very palatable.We would certainly agree with CONN that adrenalec-tomy is not indicated in the management of periodicparalysis.

15. Bartter, F. C. Metabolism, 1956, 5, 369.16. Furtos, N. C., Doane, E. A. J. Amer. med. Ass. 1949, 140, 1274.17. Brennan, A.J., Wichelhausen, R. II. Ibid, p. 1275.18. Arany, L. S., Lewis, N. G. Amer. Rev. Tuberc. 1950, 61, 881.19. McCoy, H. I. Ibid, 1950, 62, 227.20. Brun, J., Kalb, J. C., Viallier, J., Pommateau, E. Lyon méd.

1950, 183, 381.21. Canetti, G., Saenz, A., Thibier, It., Chevassu-Perigny, J. Rev.

Tuberc., Paris, 1951, 15, 128.22. Meyer, A., Naveau, P., Naveau, M. Ibid, p. 258.23. Harold, J. T. Lancet, 1951, ii, 658.24. Thomas, O. F., Borthwick, W. M., Home, N. W., Crofton,

J. W. Ibid, 1954, i, 1308.25. Bruce, L. G., Cuthbert, J., Ritchie, J. A. Scot. med. J. 1957,

2, 83.26. Cummings, M. M., Livings, D. G. Amer. Rev. Tuberc. 1954, 70,

637.27. Chaves, A. D., Robins, A. B., Abeles, H., Petzer, L. R., Dangler,

G., Widelock, D. Ibid, 1955, 72, 143 : Ibid, 1956, 74, 293.28. Fox, F., Wiener, A., Mitchison, D. A., Selkon, J. B., Sutherland,

I. Tubercle, Lond. 1957, 38, 71.29. Mitchison, D. A., Selkon, J. B. Ibid, p. 85.

Resistant Tubercle BacilliTHE possibility that drug-resistant tubercle bacilli

might spread among the population was recognisedwhen streptomycin was first used more than tenyears ago. Instances of such spread have now beenreported in the U.S.A.16-’9 France,2o-22 and GreatBritain.23--25 Studies in the U.S.A. suggested thatresistant bacilli might account for about 1-2% ofnewly diagnosed infectious cases in that country 26 27but the information was incomplete. Accordingly,warnings about the dangers to the public health ofindiscriminate and irrational chemotherapy of tuber-culosis have been based on a-priori arguments.The tuberculosis research unit of the Medical ResearchCouncil, with the cooperation of many chest physicians,has now remedied this defect. Fox et al.28 describea survey of the drug-sensitivity of cultures of tuberclebacilli isolated from newly discovered patients inGreat Britain between June, 1955, and March, 1956.The bacteriological and statistical methods were

designed to detect all strains which were at all resistantand to distinguish these from strains that were actuallysensitive but were apparently resistant as a result ofexperimental variations in the sensitivity tests. MITCHI-SON and SELKON.29 in a separate report on the bacterio-logical aspects of the survey, show that their estimatesof the prevalence of strains resistant to streptomycin andp-aminosalicylic acid (P.A.-3.), if incorrect, were likelyto be too low, and that their estimate of isoniazidresistance may have been too high.

A representative sample of eighty chest clinicswas selected by a random process. 1404 sputumspecimens from the same number of newly diagnosedand untreated patients were cultured at a central

laboratory. From these specimens 974 positive cul-

tures were obtained ; and 50 (5 -1 %) were resistantto one or more of the three commonly used drugs,44 (4-5%) being cultures of Mycobacterium tuber-culosis and 6 (06%) cultures of atypical mycobacteria.Of the 44 resistant cultures of M. tuberculosis,22 (2-3%) were resistant to streptomycin, 21 (2-2%)to P.A.S., and 7 (0-7%) to isoniazid ; 5 were resistantto more than one drug. In many instances the cultureswere only slightly resistant, 19 of the 22 strainsresistant to streptomycin having resistance ratios ofno more than 16. But 3 strains were highly resistantto streptomycin, 11 to P.A.S., and 5 to isoniazid.3 of the 7 strains resistant to P.A.s. were ofbovine type and may, therefore, have been naturallyresistant. 30At present probably 1 in every 20 newly diagnosed

infectious patients in this country has resistant tuberclebacilli in the sputum. The prevalence varies withthe age of the patient. The highest proportion ofresistant cultures was obtained from young women ;nearly 10% of the women aged 15-34 were infectedwith resistant bacilli-an alarmingly high proportion.On the other hand, only 3 % of the men in this age-group had resistant cultures. The reasons for this

unexpected difference between the sexes is unknown.In those older than 34 there was little difference-4-9% in women, compared with 4-1% in men. The

prevalence also varied with the part of the countryin which the patients lived, the rate being 8-3%in Scotland and 8-2% in the Liverpool area but only2-5% in the Birmingham area and 1-6% in Wales.But the numbers of resistant strains from eacharea were small, and these differences may only havebeen chance fluctuations.Fox and his colleagues also investigated the possible

sources of infection of the 44 patients with primarilyresistant cultures and compared their contact historieswith those of 44 matched patients with sensitivestrains. 47 contacts of the patients with resistantbacilli had been diagnosed as tuberculous since 1945,compared with only 16 contacts of the group withsensitive bacilli. Moreover, for each drug separatelymore of the resistant than of the sensitive group wereknown to have been in contact with patients treatedwith that drug-13 against 6 for streptomycin, 12

against 3 for P.A.s., and 3 against 0 for isoniazid.Definite evidence of contact with organisms knownto be resistant was obtained from 10 of the 44 patientsinfected with resistant strains ; but no such contactwas found within the sensitive group. In at least halfthe patients infected with drug-resistant organismsthe searching inquiry for contacts revealed nothingto arouse the clinician’s suspicion that he might bedealing with a patient infected with resistant bacilli.Some of the implications of this important piece of

epidemiological research are clear. For the sake of the

patient and the community all chemotherapy shouldbe planned so that the risk of resistance is kept assmall as possible. Probably many of the primarilyresistant strains in this survey arose through treat-ment that would by present standards be judgedinadequate and unsafe. It should now be veryrare for a patient to remain infectious after

chemotherapy.31 32 It has been suggested that

30. Wallace, A. T., Webber, W. J. Ibid, 1956, 37, 358.31. Crofton, J. W. Brit. med. J. 1956, i, 345.32. Middlebrook, G. Bull. int. Un. Tuberc. 1956, 26, 179.

826

treatment is less effective in older people 33 butthis is unproved and it seems improbable. (Thecurrent M.R.C. trial of long-continued chemotherapyshould answer some of the questions about the

response to treatment of this important group ofpatients.) The fact that almost a quarter of thepatients infected with primarily resistant tuberclebacilli had been in contact with others known tobe expectorating resistant bacilli suggests that

preventive measures are not applied as efficiently asthey might be. The well-known, but not always well-applied, preventive measures that are necessary inall infectious cases should be imposed with particularvigour when a patient remains infectious after chemo-

33. Caplin, M., Griffiths, J. J., Silver, C. P. Tubercle, Lond. 1956,37, 233.

therapy. Sensitivity tests on all pre-treatmentcultures arc desirable, but not always practicable.In most cases in this country it is still possible to giveeffective treatment without such tests; but if thetests can be done the treatment can be more rational,more patients can be effectively treated, and theoccasional discovery of primary resistant cultureswill remind the physician of this danger. There ismuch to be said for starting treatment with all threedrugs simultaneously in newly diagnosed patientsif this is practicable and if the risk of vestibulardisturbance after daily injections of streptomycin inthe older patient is accepted ; and if pre-treatmentsensitivity tests can be done the results will indicatethe most suitable combination of two drugs for furthertreatment.

Annotations

THE BUDGET AND MEDICAL REMUNERATION

IN his Budget speech last week the Chancellor of theExchequer declared that one of his aims was to increasethe incentive to further effort by those earning overE2000 a year ; and his proposals provide substantialrelief for many in this group. Thus a man earning E3000a year who is married and is educating three childrenaged 11-16 will have his tax reduced from E906 to £732.The difference of f:174 represents a tax-free gain ofabout 6% of the gross income, which is almost comparableto the taxable 10% lately added to the salaries of juniorhospital staff as an interim measure.1The Economist 2 suggests that, with a view to ending

the dispute over doctor’s pay, the Government shouldfix the maximum sum that they are at the moment

prepared to offer by way of " interim adjustment

" andoffer to negotiate with the medical leaders on its distri-bution. We should greatly welcome such arrangement.If the profession’s negotiators found themselves at sucha meeting their first thought would no doubt he forthose who have not shared in the 10% increase for juniorhospital staff and will benefit little if at all by theBudget proposals. We have in mind particularly seniorhospital medical officers and family doctors with smallpractices.

1. See Lancet, April 6, 1957, p. 746.2. Economist, April 6, 1957, p. 24.3. Pletscher, A., Schuppli, R., Reipert, R. Z. Unfallmed. Berufskr.

1954, 47, 163.4. Grandjean, E. Brit. J. industr. Med. 1957, 14, 1.

HAZARDS OF EPOXIDE RESINS

IN the past few years a new group of syntlieticmaterials, the ethoxyline or epoxide resins, has come intoextensive use in industry, chiefly in the manufacture ofelectrical equipment, car bodies, and aircraft. Mostof these resins are aliphatic-aromatic polyethers contain-ing hydroxyl and terminal epoxy groups. When theyare mixed with highly reactive hardeners, which are

usually polyamines, they are transformed at room-

temperature into solid infusible substances. llanu-facturers of resins and hardeners are well aware of thehazards involved ; but the introduction of these suh-stances into works unfamiliar with chemical processeshas resulted in many instances of toxicity.

Pletscher et al.3 reported that, of 20 workmen handlingone of these resins, 6 had severe eczema and 8 temporaryskin irritation. On patch-testing, 4 of the affected 14were hypersensitive to the resin, 2 to the hardener, and3 to both substances. The 6 unaffected men were not

hypersensitive. According to (-,’i-a,iidjeaii,4 the eruption

associated with these resins has an initial phase, lastingfrom a week to several months, during which itchy ery.thematous patches appear on the face and upper limbs.In some people the reaction never proceeds beyond thisstage, which may he due to primary irritation by thealka.line hardener or he an early manifestation of sensitisationto the resin. In others, further contact leads to a veryirritating papulovesicular eruption ; and at this stagethe patient has to stop work.

Grandjean has formulated protective measures. Theworker should be taught to avoid spilling the resin orhardener or comtamimating door-handles or pencils.Good ventilation and local exhaust equipment are

desirable. Workers should wear gloves, plastic cuffs,and white overalls ; and their faces may be protectedbv barrier creams.

1. Hume, E. M., Krebs, H. A. Spec. Rep. Ser. med. Res. Coun.,Lond. 1949, no. 264.

2. Warkany, J. Advanc. Pediat. 1947, 2, 1.3. Mellanby, E. Proc. Roy. Soc. B. 1944, 132, 28.4. Wolbach, S. B., Hegsted, D. M. Arch. Path. (Lab. Med.), 1952,

54, 13.5. Millen, J. W., Woollam, D. H. M., Lamming, G. E. Lancet,

1953, ii, 1234.6. Millen, J. W., Woollam, D. H. M., Lamming, G. E. Ibid, 1954.

ii, 679.7. Moore, L. A., Sykes, J. F. Amer. J. Physiol. 1941, 134, 436.8. Woollam, D. H. M., Millen, J. W. Brit. J. Nutr. 1956, 10,

355.

VITAMIN A AND THE CEREBROSPINAL FLUID

DEFICIENCY of vitamin A is usually believed to giverise to nothing more severe than impairment of nightvision. This opinion springs largely from the observationsof llume and Krebs 1 on male conscientious objectors,and we have little information about the possible effectson pregnant women and their children. Experimentalstudies suggest that slight deficiency of vitamin A earlyin pregnancy is very harmful to the foetus. Warkany 2stated that gross maternal deficiency of this vitamin ledto abortion, and minor degrees of deficiency resulted inthe birth of deformed young ; the nervous system wasoften involved, and hydrocephalus was common. It was

thought that abnormality of bone growth was primarilyresponsible for the hydrocephalus 3 4 ; but recent evidenceruns counter to this opinion.

Millen et al. 5 6 found that young rabbits born to doesdeficient in vitamin A were constantly hydrocephalic.Although stenosis of the aqueduct was found, theseworkers thought that the hydrocephalus was caused byover-production of cerebrospinal fluid (C.S.F.) rather thanobstruction of its circulation or reabsorption. Vitamin Awas known to cause a fall in the C.s.F.pressure ofhydrocephalic vitamin-deficient calves.7Woollam and Millen 8 have now investigated the effects

of vitamin-A deficiency on the C.S.F. pressure in chicks.In fifty normal chicks, the average pressure did not