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lymphocyte response by linoleic acid was studied in 10 M.S.patients, 6 patients with other neurological diseases, and16 normal subjects. The results (see accompanying figure)fail to show statistically significant differences between themean inhibitions, but it is of interest that M.S. cases showeda preponderance of relatively high inhibition values. Thismay give further support to our suggestion that a defectin fatty-acid metabolism with a consequently alteredreaction to inhibition by polyunsaturated fatty acids mayinfluence lymphocyte response in M.S. On the basis ofthese pilot experiments a study under controlled blindconditions has been started and the results will be publishedelsewhere.

We thank Dr J. B. Foster for access to patients and Mrs J. M.Cobill for skilful technical assistance. J. M. is a fellow of theDeutsche Forschungsgemeinschaft.

Medical Research Council,Demyelinating Diseases Unit,

General Hospital,Newcastle upon Tyne NE4 6BE.

J. MERTIND. HUGHES.

Regional Neurological Centre,General Hospital,

Newcastle upon Tyne NE4 6BE. E. STEWART-WYNNE.

EFFECT OF MINOCYCLINE ON TETRACYCLINE-RESISTANT STAPHYLOCOCCUS AUREUS

SiR,—Resistance to the tetracyclines is not uncommonin strains of Staphylococcus aureus isolated from hospitalinfections. It has been reported that some of the neweranalogues of tetracycline have a greater antibacterialactivity, particularly against staphylococci resistant to

tetracycline.1, 2 Minocycline, 7-dimethylamino-6-demethyl-6-deoxytetracycline (’ Minocin’) is the newest analogueand has only lately become available in the U.K. In viewof the claim that minocycline is active against tetracycline-resistant strains of Staph. aureus, its antibacterial activitywas studied and compared with that of doxycycline(’Vibramycin’).

48 strains of Staph. aureus isolated from a variety ofinfections in hospital inpatients were examined. All strainshad been reported as resistant to tetracycline on routineantibiotic testing by the disc-sensitivity method. Theminimum inhibitory concentrations of minocycline, doxy-cycline, and tetracycline were determined by a tubedilution method, using an inoculum of 101i bacteria per ml.The results are shown in the table. 40% of the strains

were resistant to 25 vg. per ml. of tetracycline and 92%to 6.25 jjg. per ml. The distribution of minimum inhibitoryconcentrations (M.l.c.) for doxycycline was wide-27%were inhibited by 0-25 ptg. per ml., but 14% were resistantto levels of 6’25 jg. per ml. or more. Minocycline showeda greater activity, and 94% were sensitive to 0-25 µg. perml., and 61% to 0-06 µg. per ml. Two strains, however,were inhibited only by 12 5 tg. per ml. All the strainsexamined were more sensitive to minocycline than doxy-

1. Martell, M. J., Booth, J. H. J. med. Chem. 1967, 10, 44.2. Fedorkof, J., Katz, S. S., Allnoch, H. Am. J. med. Sci. 1968, 255,

252.

cycline-93 % by a factor of 4 and 21 % by 16. With onestrain the M.l.c.s were identical (12-5 µg. per ml.).The serum-concentration of minocycline on standard

dosage (approximately 2 µg. per ml.) would be effectiveagainst all strains studied apart from the two with M.I.C.Sof 12-5 µg. per ml. Although many of the strains wouldbe sensitive to blood-levels of doxycycline on standarddosage, the margin between the M.i.c. and serum-level isconsiderably less than for minocycline.

In the laboratory a single tetracycline disc has previouslydistinguished between sensitive and resistant strains ofbacteria. In view of the increased activity of minocycline,it is now necessary to use an additional disc when testingthe sensitivity of bacteria isolated from patients whereminocycline might be an effective therapy.

This study confirms the increased antibacterial activityof minocycline against tetracycline-resistant strains ofStaph. aureus. It will be a useful antibiotic in the treatmentof minor infections.

Wycombe General Hospital,High Wycombe,

Bucks. HP11 2TT.

DONALD A. LEIGHKATE SIMMONS.

S.I. UNITS: A REBUTTAL

SIR,—I have waited in vain for pens abler than mine toprotest against the imposition of these so-called " uniform "and " standard " units into the reporting of pathologicaldata. I should like to emphasise at the start that my objec-tion is against their use in laboratory reports for con-sideration by clinicians. Whatever units of measurementpathologists utilise for their tests in their laboratories is,of course, their own affair. New averages, new ranges, andunfamiliar units will lead only to bewilderment and con-fusion in those whose task it is to interpret the results. Afurther unnecessary burden is to be placed on the creakingmemories of the older clinicians who have more importantthings to do with their hippocampi.A solution is at hand which has been available for more

than 100 years-namely, truly standard units. For most

purposes clinicians need only know whether the result isabnormal and roughly how abnormal it is.4 The absoluteunits of measurement are quite irrelevant to this over-

riding principle. Real standard units (i.e., X—M, wheres

x=the raw value, m=the mean of the values, and s=standard deviation of the distribution) tell us immediatelywhat we require, irrespective of the original units. Theseneed not be memorised-nor need " the average ofnormal ", nor the " normal range ". Instead, we knowthat practically all normal results would be in the range+3 to -3, whatever the test. One does not need to be a

psychologist to realise that this simplification will save alot of effort and avoid confusion.

It is often said that this method should not be usedbecause most laboratory results are not normal in dis-

3. Bach, M. C., Zinner, S. H., Wilcox, C., Finland, M. J. Lab. chn.Med. 1972, 79, 316.

4. Hall, G. H. Lancet, 1967, i, 1329.

MINIMUM INHIBITORY CONCENTRATIONS OF MINOCYCLINE AND DOXYCYCLINE AGAINST 48 STRAINS OF TETRACYCLINE-RESISTANT

STAPH. AUREUS

1007

tribution. But, however skew the distribution, it can almostalways be normalised.What A. N. Whitehead called The Fallacy of Misplaced

Concreteness seems to have our pathological colleagues inits rigorous grip. Lip service only is paid to consumerconvenience: and it is interesting and revealing that theRoyal College of Physicians and the Royal College ofSurgeons were not consulted in the original discussionson this matter. It is almost certainly too late to prevent theintroduction of S.I. units and the predictable and unavoid-able confusion they will cause. But never let it be saidthat this was not foreseen and deplored and that an easierand more relevant alternative had not been proposed.

6 Friars Walk,Exeter EX2 4AY. G. H. HALL.

DIETARY CARBOHYDRATE AND SERUM-CHOLESTEROL

SIR,—I am sure that Dr Davis and his colleagues (April20, p. 750) realise that their brief report on the apparentrole of dietary carbohydrate in causing an increase inserum-cholesterol in obese mice is open to other inter-

pretations. The addition of large quantities of carbo-hydrate to a nutritionally complete basal diet must neces-sarily reduce the proportion of nutrients in the diet; fromtheir experiments alone, therefore, it cannot be decidedwhether the rise in cholesterol concentration was due to anincrease in dietary carbohydrate or to a reduction in dietaryprotein or in one or more of the mineral elements orvitamins.There is now, however, fairly substantial literature to

indicate that the cholesterol concentration may be alteredin diets that are identical in nutrient and caloric contentbut differ in type though not in the amount of carbo-hydrate. For example, substitution of sucrose for starchin such diets has been shown to increase the concentrationof cholesterol (and to produce many other changes) inrats 1, 2 and spiny mice 3 and in man. 4,5

Queen Elizabeth College,Atkins Building,

Campden Hill, London W8. JOHN YUDKIN.

ANENCEPHALY, SPINA BIFIDA,DIZYGOTIC TWINNING, AND HORMONES

SIR,—Spiers6 suggests that the epidemiology of anen-cephaly and spina bifida (A.s.B.) may be " opposite " to thatof dizygotic (D.z.) twinning in regard to: race in the U.S.;legitimacy; social class; fecundity; and geographical regionin the U.S. On the basis of this suggestion, he speculatesthat since D.Z. twinning seems to be associated with highlevels of gonadotrophin, A.S.B. may be associated with lowlevels of it.

It must be noted that Spiers’ line of reasoning is excep-tionally hazardous. This is because negative evidence isnot crucial: any failure of the epidemiologies to contrastcan (until evidence is forthcoming) be ascribed with someplausibility to other factors than hormone levels.So rather than rehearsing evidence for and against the

hypothesis, I should like to make an appeal.A proportion of pregnancies which eventuate in an A.S.B.

infant will have earlier undergone a form of testing toestablish pregnancy. I should be grateful if pathologists

1. Al-Nagdy, S., Miller, D. S., Yudkin, J. Nutr. Metabol. 1970, 12, 193.2. Qureshi, R. U., Akinyanju, P. A., Yudkin, J. ibid. p. 347.3. Bruckdorfer, K. R., Worcester, N. A., Yudkin, J. Proc. Nutr. Soc.

1974, 33, 3A.4. Naismith, D. J., Stock, A. L., Yudkin, J. ibid. 1971, 30, 73A.5. Szanto, S., Yudkin, J. Horm. metabol. Res. 1972, 4, 417.6. Spiers, P. S. Lancet, 1973, ii, 1149.

would forward to me details of these test hormone levels

(together with the levels of matched control subjects). If

Spiers’ hypothesis is correct, the test hormone levels of theA.S.B. pregnancies should be lower, on the average, thanthose of the normal control pregnancies.

Galton Laboratory,Department of Human Genetics and

Biometry,University College London,

4 Stephenson Way,London NW1 2HE. WILLIAM H. JAMES.

CHLORAMPHENICOL

SIR,-We are encouraged that our international survey 1on the indications and warnings issued with chlorampheni-col has prompted Dr Kimbel of the Arzneimittelkommissionder Deutschen Ärzteschaft 2 to examine the warnings givenwith all brands available in West Germany. We feel thatthe details of warnings and contraindications he lists tendto confirm, rather than negate, our concern.Dr Kimbel shows that 1 brand gave no contraindications

or warnings at all under any of ten heads-and that 14 of the18 brands gave one under only six or less of these ten heads.Presumably these findings reflect the lack of official guide-lines to manufacturers on the warnings required. We hopethat Dr Kimbel’s interest is a sign that such guidelineswill now be issued.

It would also be desirable for these guidelines to coverindications, since we found that many brands listedwider indications than is generally considered advisable.

Research Institute for Consomer

Affairs,43 Villiers Street,

London WC2N 6NE. MICHAEL DUNNE.

London Hospital Medical College. ANDREW HERXHEIMER.

Notes and News

MATERNAL DEATHS IN SCOTLAND

THE first report on the findings of the confidential

inquiry into maternal deaths in Scotland 3 shows that theactual number of deaths fell from 38 in 1965 to 14 in 1971.

During the same period the birth-rate fell from 193 to16-6 per thousand population, there was a definite trendtowards younger mothers and lower parities, and hospitalconfinements increased from 85% to 97%. All thesefactors would have influenced the change in maternal

mortality.Despite the fall in maternal-mortality rate per hundred

thousand total births from 37-1 in 1965 to 159 in 1971,there is little room for complacency, since about a third ofthe deaths were associated with avoidable factors, forwhich doctors were wholly or partly responsible in abouthalf the cases. In the remainder, responsibility was

attributed to the patient, because she either did not seekor she did not act on medical advice. The main faultascribed to general practitioners was failure to call in

specialist advice when complications arose, and thoseattributed to hospital medical staff were delays in diagnosisor in treatment and failure to call in help from a con-sultant. The report underlines the fact that older mothers,

1. Dunne, M., Herxheimer, A., Newman, M., Ridley, H. Lancet, 1973,ii, 781.

2. Kimbel, K. H. ibid. April 6, 1974, p. 623.3. A Report on an Enquiry into Maternal Deaths in Scotland 1965

1971. Available from H.M. Stationery Office. 65p.