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SERUM-IgA IN MYASTHENIA GRAVIS

SIR,-Two correspondents 1 have referred to decreased

serum-IgA concentrations in patients with myasthenia gravis,and suggest that these decreases reflect an immunodeficiencystate which may contribute to the pathogenesis of myastheniagravis. In both reports the IgA decrease was marginal.

In our patients with myasthenia gravis there is no signifi-cant decrease in mean IgA serum concentrations (2.42lil’28 [s.n.]; n=33) when compared with normal (2-46iO’77 g/1), although the scatter was considerable. We havepreviously reported that resting anti-Escherichia coli and isohae-magglutinin titres may often be decreased in myastheniagravis.1 We now report that decreased E. coli titres are foundmost frequently in patients of blood-group A. Moreover thefrequency of HLA-A2 in this group is increased. These obser-vations, together with a previous report4 that HLA-A2 mayoccur more frequently in myasthenia gravis patients with thy-moma, suggest the possibility that the association between thy-moma and myasthenia gravis is due to a humoral immunodefi-ciency.The nature of the humoral immunodeficiency in myasthenia

gravis is still not clear, but a genetically determined abnor-mality of immune response may be important in predisposingat least some individuals.

Department of Clinical Immunology,University and Hospital Services in Pathology,Perth Medical Centre,Nedlands, Western Australia 6009

J. D. WETHERALLJ. ROBINSONR. L. DAWKINS

HYPOCHOLESTEROLÆMIC EFFECT OF PECTIN

Sir,-Dr Durrington and his colleagues (Aug. 21, p. 394)report further evidence that pectin is a short-term hypocholes-terotsmic agent in man. The study from this unit6 was

reported in greater depth at the Medical Research Societymeeting in July,’ when it was shown that 36 g pectin dailytaken for 2 wk by 6 male volunteers (on ad-lib weighed diets)increased faecal fat output by 43% (P<0-05) and increasedfscca) bile-acid output by 34% (p<0.05). This observation isconsistent with the findings of Kay and Truswell8 that inges-tion of 15 g pectin daily by 4 male and 5 female subjects onmetabolically controlled diets caused a 44% increase of faecalfat output (p<0001) and a 35% increase of faecal bile-acidoutput (P<0’0.2) over 3 wk. In the latter study there was a 13%reduction of total serum-cholesterol, so the two studies

together support Dr Durrington’s suggestions that the effect ofpectin on serum-cholesterol may be related to bile-salt sequest-ration and increased stool-fat content.That dietary fibre (D.F.)-rich unrefined foods may be an

obstacle to excessive calorie intake was also mentioned. In thead-lib studies’ pectin did not cause a significant reduction ofcalorie or fat intake, but another form of D.F.-guar gum, agalactomannan-taken at a daily dose of 36 g by 7 volunteersreduced fat intake by 10%. Since several forms of D.F. havenow been shown to be hypocholesterolsemic, and since theseoccur in greater or lesser amounts in all vegetable foods, it

1. Behan, P. O., Simpson, J. A., Behan, W. M. H. Lancet, 1976, i, 593.2 Bramis, J., Sloane, C., Papatestas, A. E., Genkins, G., Augses, A. H., Jr.

ibid, p. 1243.3 Dawkins, R. L., O’Reilly, C., Grimsley, G., Zilko, P. J. Ann. N.Y. Acad. Sci.

1976, 274, 461.4 Feltkamp, T. E. W., van den Berg-Loonen, P. M., Nijenhuis, L. E.,

Engelfnet, C. P., van Rossum, A. L., van Loghem, J. J., Oosterhuis, H.J. G. H. Br. med. J. 1974, i, 131.

5 Dawkins, R. L., Robinson, J., Wetherall, J. D. Proc. 3rd int. Congr. MuscleDis 1975, p. 503.

6 Jenkins, D. J. A., Leeds, A. R., Newton, C., Cummings, J. H. Lancet, 1975,i, 1116.

7 Jenkins, D. J. A., Leeds, A. R., Gassull, M. A., Houston, H., Goff, D. V.,Hill. M. J. Clin. Sci. molec. Med. 1976, 51(4), 8P.

8 Kay, R M., Truswell, A. S. Am. J. clin. Nutr. (in the press).

seems not unreasonable to suppose that it is the eating of smallquantities of a variety of D.F. types rather than a large quan-tity of one specific D.F. type that may be one factor contribut-ing to the low serum-cholesterol levels of some populations.M.R.C. Gastroenterology Unit,Central Middlesex Hospital,Park Royal, London NW10 7NS

ANTHONY R. LEEDSMIGUEL A. GASSULL

SIGNIFICANCE IN MEDICAL STATISTICS

SiR,&mdash;Tomlin proposed that in studies of adverse reactions,the statistical significance probability should be 50% ratherthan the customary 5% or 1%. May advised that "10% oreven 20% may well be appropriate" if the purpose of rejectingthe null hypothesis is for giving warning or as a signal forfurther investigations. (I surmise that many medical investiga-tors, particularly those who are restricted to using small sam-ples, think the same. A colleague in Singapore showed me thedata from a small clinical trial. We both agreed the result wasstriking, but, since "statistical significance" was not quitereached at the 5% level, he refused to have the "negativeresults" published.) Although I accept the rationale of theserecommendations, I am not sure that altering the significanceprobability to suit specific investigations is part of the solution.Some writers (e.g., Bakan3) have pointed out that the null

hypothesis is seldom, if ever, true to begin with; it is unreason-able to expect the means or the rates from the respective popu-lations to be exactly the same. Therefore, statistical signifi-cance at any probability level can be obtained if the samplesize were sufficiently large (i.e., type-I error seldom exists). Andif the difference turned out to be "not statistically signifi-cant", it simply means that the sample used was not largeenough to detect the difference which is almost certain to existin the populations. Clearly, then, "statistical significance" isnot a basis for decision or for action. If it were, then therewould be no need to collect data in the first place-for weknow that "statistical significance" can be contrived, if we sochoose.The basis for decision or for action lies in the magnitude of

the difference (association) between the samples. And this mag-nitude is conditional to a set of factors relevant only to a par-ticular inquiry. In short, decision or action is based on no lessthan judicious judgment.

Perhaps the outcome of a significance test should not bedichotomised into "significant" and "not significant". (Thephrase, "approaching significance" also appears in some publi.-cations.) These phrases erroneously connote positive and nega-tive findings. Instead, why not just report the exact probabilityobtained from the test. This practice does not eliminate thebasic difficulty with the null hypothesis. But it does have cer-tain merits. Conventionally, negative findings (i.e., not statisti-cally significant results) are usually not published. Either theinvestigator is reluctant to disseminate such results or publica-tion may not be encouraged by editorial policy. This practice(malpractice) would be reduced if no "significance" were

attached to statistical findings. No one can deny the impor-tance of the accumulation of evidence, especially when suchevidence is obtained from inquiries that were properly de-signed, rigorously controlled, and conscientiously executed.Doing away with significance may also encourage the investi-gator to extract information from his data with greater pru-dence.

Some may argue that doing away with "statistical signifi-cance" will result in an increased demand on the alreadyvaluable journal space. But "not significant" results do notnecessarily imply a lack of scientific contribution; they are notnegative findings, though even negative findings can be useful

1. Tomlin, P. J. Lancet, 1976, i, 478.

2. May, D. ibid. p. 1025.3. Bakan, D. Psychol. Bull. 1966, 66, 423.

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information. In any case, statistical significance should not beconsidered an important acceptance criterion for publication.Some may feel that the 5%/1% convention is needed to

maintain objectivity in the evaluation of statistical data. Butthis is not so. Statistical significance at any probability level isa function of sample size. For example, a statistical signifi-cance at the 1% level may be medically quite meaningful inone study in view of the small sample size. A similar statisticalverdict from another study may make little or no differencemedically in view of the large sample used.4School of Public Health,University of Hawaii,Honolulu, Hawaii 96822, U.S.A. JAMES LEE

Q FEVER IN IRANSiR,&mdash;Reports on the prevention of animal diseases prompt

us to report on aspects of Q fever in Iran which are of specialsignificance for expatriates employed in the area.

Giroud and Yassemi5 found serological evidence of Q feverin cattle, horses, sheep, and camels in Iran, and Mofidi6 in awide serological survey of animals and man, found evidence ofthe disease over a large area. The first clinical cases were

reported by us from Shiraz,’ and between 1970 and 1973, test-ing with the Nine Mile strain of antigen at Abadan, we diag-nosed 49 acute cases. Our hospital provides services for oil

company personnel and their dependants-approximately87 500 Iranians and 200 expatriates.The complement-fixation test was carried out on 252

Iranians suspected of having Q fever; 21 (8.3%) were positive.The corresponding figures for expatriates were 64 cases and 28(44%) positive, indicating a higher incidence among expa-triates.

Most cases occurred in April, May, and June. The onset wasusually abrupt with headache, fever, fascial pains, and profusesweats. Cough and sometimes pleural pain developed on thethird or fourth day, and occasional hsemoptysis. Pneumonitisin one or more bronchopulmonary segments occurred in 50%of the cases. These lesions were slow to clear and resolutionwas often incomplete after six weeks. One patient presentedwith acute pericarditis with an effusion, which resolved com-pletely within three weeks. His complement-fixation test waspositive to 1/256++. An expatriate who had developed a com-parable pericarditis with effusion on retrospective study twoyears later, had a positive test to 1/16.

In an epidemiological survey to assess the level of immunityin Iranians, we tested 318 persons using antigen provided by theNational Institute of Allergy and Infectious Diseases, RockyMountain Laboratory, Montana. The antigen was freshlydiluted 1/100 in physiological saline so as to contain 0.1 com-plement-fixing unit/lml. The test dose was 01 ml (001 com-plement-fixing unit). After a cutaneous injection, arms were in-spected at 48 and 72 h. An induration of 5mm or more wasconsidered positive as indicating previous infection with theCoxiella burneti.The results of the skin tests were as follows:

In our area it appears there is a higher level of immunityamong Iranian males than females, and a lower level amongchildren under 7 as compared with adults.

4. Lee, J. Aust. N. Z. Jl Med. 1976, 6, 141.5. Giroud. P., Yassemi, H. Bull. Soc. Path. 1952, 45, 23.6. Mofidi, S. Personal communication.7. Eghtedari, A. A., Caughey, J. E., Kohout, E. Pahlavi med. J. 1970, 1, 66

We have no firm evidence as to the mode of infection in expatriates. Dust storms are common, and in a study of 14 expa-triates, 13 kept house dogs which were invariably tick infestedin the summer months.The study raises questions of the need for vaccination of ex-

patriates proceeding to the area and a probable risk inherentin keeping house dogs.National Iranian Oil Company Hospital,Abadan, Iran

J. E. CAUGHEYS. H. HAROOTUNIAN

FLAMMABILITY AND CONDUCTIVITY OFTRACHEAL TUBES

SIR The committee of the International StandardsOrganisation dealing with anaesthetic equipment and medicalbreathing machines (ISO/TC 121) has been concerned aboutthe flammability and conductivity of tracheal tubes and thepossible hazards arising from the use of laser beams in closeproximity to them.

I have been asked by that committee to inqure from organi-sations in the United Kingdom whether reports of any suchcomplications have been received and to summarise the repliesin the medical Press.The Department of Health and Social Security (Scientific &

Technical Branch), the Medical Defence Union, and the Medi-cal Protection Society have no record of any such complica-tions.

Hospital for Sick Children,London WC1N 3JH W. J. GLOVER

CIRCADIAN RHYTHM AND CHEMOTHERAPY FORCANCER

SIR,&mdash;I and my colleagues have demonstrated a circadianrhythm of proliferation in experimental murine sarcomas12

and in some human solid tumours ;3-’ the peak in cells engagedin D.N.A. synthesis was encountered during the morning inman. We suggested, in a non-randomised trial, the importanceof such a rhythm for choosing the hours and sequence of ad-ministration of antineoplastic drugs (more than 80% objectiveresponses in 69 treated patients6 7).

RESPONSES TO TWO CHEMOTHERAPY PROTOCOLS

This protocol A (including methotrexate 60 mg/m’ or

5-fluorouracil 15 mg/kg, according to histotogy, at day 1, in-fused from 10 A.M. to 8 P.M., followed on day 2 by combinedvinblastine 10 mg/m:Z and cyclophosphamide 300 mg/m2administered from 8 P.M. to 2 A.M.) has now been tested

against the opposite regimen B (beginning at 10 P.M.). Suchcourses were repeated every third week.

52 evaluable patients have so far been randomised (table’:in group A, 22/27(81%) responded objectively to chemo-

therapy, including 15 regressions to more than 50%(56%); ingroup B, 13/25(52%) patients responded including only ‘regressions to more than 50%(20%).The significant differences between the two groups (obiec-

1. Focan, C., Barbason, H., Betz, E. H. C. r. Acad. Sci. Paris, 1973, 276, 2229.2. Focan, C., Barbason, H., Betz, E. H. Biomedicine, 1975, 23, 2303. Focan, C. Rev. M&eacute;d. Li&egrave;ge, 1975, 31, 461.4. Focan, C., Pierard, G. Bull. Soc. fr. Derm. Syph. (in the press).5. Focan, C., Malaise, E. P., Richard, J. M., Tubiana, M. Unpublished6. Focan, C. Nouv. Presse m&eacute;d. 1975, 4, 2709.7. Focan, C. Eur. J. Cancer Monogr. (in the press).