458

to single ascertainment through offspring with recessivedisease; the chance of ascertainment is in fact proportionalto the number of offspring in both cases. The incidence ofdiabetes among relatives of patients with Fanconi’s anaemia,therefore, could simply be compared to that among relativesof matched normal controls, rather than using general-population figures as was done by Swift et al.l

University Department ofHuman Genetics,

Wassenaarseweg 62, Leiden,The Netherlands. G. R. FRASER.

DUCHENNE MUSCULAR DYSTROPHY:RESERVATIONS TO THE NEUROGENIC

HYPOTHESIS

SIR,-Duchenne muscular dystrophy has long been con-sidered as a degenerative myopathic disease-i.e., a

diffuse process affecting muscle fibres randomly. Thistraditional concept has been challenged mainly byMcComas et al. 2,3, who attributed the disease to a primaryneuronal abnormality. This neurogenic hypothesis 4was based on data obtained by the above authors 2,3

using a new neurophysiological method.5 5 They reportedthat in patients with Duchenne dystrophy the number ofmotor units was decreased, while the size of the " surviving "individual motor units remained " relatively " normal. 3.6 sWe have been applying this method for the past year to

control subjects and to patients with various neuromusculardiseases. Our preliminary results showed that the methodis useful in evaluating denervation and compensating re-innervation of " classical " anterior-horn diseases. Thehigh amplitude of motor units and the significant differences

1. Swift, M., Sholman, L., Gilmour, D. Science, 1972, 178, 308.2. McComas, A. J., Sica, R. E. P. Lancet, 1970, 1, 1119.3. McComas, A. J., Sica, R. E. P., Currie, S. J. Neurol. Neurosurg.

Psychiat. 1971, 34, 461.4. McComas, A. J., Sica, R. E. P., Campbell, M. J. Lancet, 1971, 1,

321.5. McComas, A. J., Fawcett, P. R. W., Campbell, M. J., Sica, R. E. P.

J. Neurol. Neurosurg. Psychiat. 1971, 34, 121.6. McComas, A. J., Sica, E. R. P., Currie, S. Nature, 1970, 226, 1263.7. Panayiotopoulos, C. P., Scarpalezos, S., Papapetropoulos, Th.,

Michas, C. Minerva Med. Greca, 1973, 1, 195.

Incremental responses (1-14) in a 10-year-old boy withDuchenne muscular dystrophy.

The mean amplitude of the 14 first motor units was 5-43 tJ.Vand some of them were less than 3 !j.V—i.e.; at noise levels. Thenumber of motor units estimated dividing the amplitude (812 )j!.V)of the maximum response (lowest trace on the left, unnumbered)by the mean amplitude of the incremental responses is withinnormal limits (149 motor units).

Calibration: 20 fl. V per division for the incremental responsesand 200 fl. V per division for the maximum response. Sweeptime: 5 msec. per division. Upward deflections denote relativenegativity of stigmatic electrode.

between thresholds of the graded responses in thesediseases makes it relatively easy to calculate the numberand size of motor units.However, we have the following main reservations as

to the validity of the method for an accurate estimation ofthe size and number of motor units in diseases such asDuchenne muscular dystrophy:

(a) The algebrical summation required for an accurate

calculation of the mean motor-unit potential would be affectedeven by small latency differences resulting from differences indiameter and length of activated nerve-fibres. A small motorunit summated in that way may well not produce any visiblechange in the peak-to-peak amplitude of the incremental responses,and thus the whole population of motor units might be mis-calculated.

(b) There is no convincing evidence that the incrementalresponse evoked by graded stimulation corresponds to theactivation of single motor units in normal and dystrophic patients.The 2 mm. recording electrode used for the localisation of theendplate zones is very large and therefore two or more neigh-bouring motor units with similar thresholds could be mappedout as one. The calculation of two motor units as one wouldcertainly affect the mean amplitude estimated by the small

sample of the eleven first motor units.’’(c) The noise level of the recording system (4 V) is high

enough to obscure motor-unit potentials of small amplitude. Itwould, for example,.be extremely difficult, if not impossible, tocalculate two successive incremental responses which differ lessthan 4-8 µV by mere observation on the oscilloscope traces. Forthis reason, we are now photographing each response evoked bygraded stimulation and the responses are measured after ampli-fication through a microfilm reader printer. In this way we areable to see that many of the graded evoked responses obtained inpatients with Duchenne muscular dystrophy were very small andcould be missed as they were overlapping at the noise level (seeaccompanying figure). The number of motor units was withinnormal limits.

This is expected for diseases with diffuse muscle-fibredegeneration and indicated by the usual electromyographicfindings of small amplitude and short duration motor-unitaction potentials in myodystrophies.

Eginition Hospital,Athens National University,74 Vasilissis Sophias Avenue,

Athens.

S. SCARPALEZOSC. P. PANAYIOTOPOULOS.

MATERNAL DIET AND LIPID COMPOSITION OF

BREAST MILK

SIR,-Although there is considerable interest in the

possibility that coronary atheroma starts in the neonatalperiod, we are unable to find any report of a relationshipof maternal diet to the degree of polyunsaturation of humanbreast milk.

Breast milk was therefore collected at intervals from a

38-year-old primipara following a minimum of 2 weekson special diets. The polyunsaturated low-cholesterol dietwas that normally prescribed for Frederickson type-nhyperlipidxmia. The " iodine number " was used as anestimate of the degree of unsaturation of the milk fats.The results were:

Date Diet Iodine no. of breastmilk

Feb. 15, 1972 Mixed lipids (about 40% 45

polyunsaturated fat)April 8, 1972 Polyunsaturated lipids 98

May 27, 1972 High saturated lipids 21March 21, 1973 Polyunsaturated lipids 57

Iodine no.Lactogen .... 25Cow’s milk .... 19Olive-oil standard .. 71

1. Kwiterovich, P. O., Levy, R. I., Frederickson, D. S. Lancet, 1973,i, 118.

459

We therefore presume that lipid composition of humanbreast milk will vary considerably with change of lipidcomposition of the diet. This may relate to the later de-

velopment of coronary atheroma.

Department of Clinical Chemistry,The Queen Elizabeth Hospital,Woodville, South Australia 5011.

MARJORIE WELLBYM. W. O’HALLORANM. L. WELLBY.

ASTHMA AND ANTITRYPSIN DEFICIENCY

SIR,-It remains controversial whether a partial deficiencyot Kj-antitrypsin in the serum is associated with an increasedliability to obstructive airways disease. It has been sug-gested 1 that, if this is a valid association, the type of lungdisease may not be predominantly emphysematous, as insevere antitrypsin deficiency, but may take the form ofchronic bronchitis.

It also seems possible that there could be an associationbetween antitrypsin deficiency and the other common typeof obstructive airways disease-namely, asthma. Thus,Woolcock et al. found an increased venoarterial differencein antitrypsin levels common to all types of obstructiveairways disease including asthma as compared with normalcontrols. I myself 3 described a patient who had bothantitrypsin deficiency and intrinsic asthma, and recentlyVithayasai et al. found that 18% of 50 children with

atopic asthma had partial antitrypsin deficiency, and amongthose with severe asthma the frequency rose to 37%. Also,Lukjan et al. found decreased plasma-kininase levels inpatients with asthma.

It therefore seemed reasonable to investigate whetherthere was an increased incidence of antitrypsin denciencyamong adult patients with asthma in the U.K. Accordingly,antitrypsin levels were determined by the radial immuno-diffusion method in 25 consecutive patients with asthmaattending Northampton Chest Clinic. Because the patientswere in regular chest-clinic attendance, in most the asthmacould be classified as severe. The diagnosis had beenmade on clinical grounds, and all cases had shown greatvariability of airways obstruction spontaneously or in

response to bronchodilators or corticosteroids. Most ofthem had corroborative evidence such as a family historyof allergic disease and sputum eosinophilia. Of those (14)in whom skin-test results were available, 7 showed reac-tions to multiple allergens, 2 a strong response to housedust mite only, and 1 to grass pollen only, and in 4 skintests were completely negative. Most (18) were on main-tenance therapy with prednisolone, but none was in anacute exacerbation. Peak flow-rates at the time of studyvaried from 120 to 520.The lower limit of normal antitrypsin levels was taken

to be 180 mg. per 100 ml. by this method in conformitywith the study of Vithayasai et al. Initially 4 patients hadantitrypsin levels below this, though in 3 the deficiencywas very slight, their levels being 170, 155, and 155 mg.per 100 ml., and in each case on repeat testing rose to wellwithin the normal range (285, 308, and 225, respectively),this rise being unassociated with any alteration in theclinical state.Thus, of 25 patients with asthma attending a U.K. chest

clinic, none had significant antitrypsin deficiency, the

expected frequency of heterozygous deficiency in theU.S.A. being 5% of the general population, though nocomparable figures are available for this country. Hence

1. Smith, J. P., Falk, B. A., Siskind, G. W. Chest, 1971, 59, 175.2. Woolcock, A. J., Green, W., Crockett, A. Br. med. J. 1971, ii, 134.3. Ferguson, G. C. Br. J. Dis. Chest, 1973, 67, 71.4. Vithayasai, V., Hyde, J. S. Proc. Inst. Med. Chicago, 1972, 29, 135.5. Lukjan, H., Hofman, J., Kiernowska, B. Bull. Pol. med. Hist.

sci. 1971, 14, 132.

these findings lend no support to the hypothesis that thereis an association between asthma and antitrypsin deficiencyin adults.

General Hospital,Northampton NN1 5BD. G. C. FERGUSON.

Obituary

WALTER ERIC CHIESMAN

Kt., C.B., M.D.Cantab., F.R.C.P.

Sir Walter Chiesman, who died on Aug. 13, wasborn in 1900.

He went to Whitgift Schooland decided early on medicineas his career, against the adviceof his headmaster. He had anexcellent singing voice andwent to Cambridge as a choralscholar at Corpus Christi,where he began his medicalstudies. Being tall and heavilybuilt, he was a keen sportsmanand played rugby for his college(he had been captain of hisschool XV), but he got his half-blue for swimming and becamecaptain of the UniversitySwimming Club.From Cambridge he went to

St. Thomas’s, where he didwell, intending to pursue an academic career in medicine.He became resident assistant physician, took his member-ship, and was first assistant of the medical professorial unitfrom 1929 to 1933. He also acquired a reputation as one ofthe leading amateur actors of his hospital and as the joint-manager of a series of brilliant Christmas shows. To theend of his life he was an excellent raconteur, and hisconvivial nature was much aided by his flair for the culinaryarts: he was a cook of almost cordon bleu standard. He

enjoyed teaching and became interested in research onpeptic ulcer, but left St. Thomas’s when he did not get thestaff appointment he had hoped for.

Being an excellent and dedicated physician, he settledin general practice of a very high standard and did well.Part-time advisership to a large chemical company satisfiedhis bent for the scientific side of medicine.At the outbreak of war in 1939, he became full-time

medical officer to I.C.I.’s General Chemical Division andwas in charge of a section concerned with the study ofchemical warfare, which happily never materialised; butit was there that he acquired his reputation, not only as anorganiser of research, but as an administrator and as anexpert on problems of industrial medicine. His publicationsduring that time are witness of his clear thinking, wisdom,and capacity for organising practical research; at the sametime, he made friends because of his tact, kindness, andgenuine interest in people and their problems. It was not

entirely surprising, therefore, that he was chosen in 1945to succeed Sir Henry Bashford, the first medical adviser tothe Treasury, in those days the virtual head of the medicalservices to the whole Civil Service, including the PostOffice, covering the problems of nearly three-quarters of amillion people, a cross-section of all occupations, in theUnited Kingdom and overseas. In this position he re-mained until his retirement in 1965, and carried out anenormous amount of pioneering work and reforms whichhad a great influence on the development of industrialmedicine in this country.