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local-authority doctors, and general practitioners with aparticular interest in children who, in the integratedN.H.S., will have both preventive and curative roles.

St. Charles’ Hospital,Exmoor Street,

London W10 6DZ.

KIM OATESDAVID HARVEY.

N.B.T.-TEST IN ACUTE APPENDICITIS

SIR,-We read with interest the letter by Dr. Drysdale(Sept. 16, p. 594), and we were somewhat surprised to seethe results he obtained with the nitroblue-tetrazolium(N.B.T.) test in acute appendicitis. Further inspection,however, reveals possible reasons for these findings.

Firstly, Dr. Drysdale does not state his technique. Wenote that he records results of up to 80%, and that he seemscontent to ascribe levels of 50% and 60% to streptococcalthroat infection. In our experience such levels will hardlybe reached in acute septicxmia with imminent death, letalone minor localised infection. We thus feel that Dr.

Drysdale’s method, or his reading of the result, mustdiffer from our own, and we would be grateful for someclarification.

Secondly, we must take exception to his grounds ofassessment. The N.B.T.-test is concerned with differentia-ting inflammation from infection, and to assess the test byhistological evidence of inflammation, without attemptingto assess the presence or absence of infection, is patentlywrong. Was there any correlation between acute suppura-tive appendicitis and positive tests, for instance ?

Finally, to pick acute appendicitis, in which the role ofinfection is far from certainly known, seems to us to be aproject fraught with dangers, and unwise as a means ofassessment of a new test.We must emphasise that in our hands, using those

criteria developed by ourselves and others, and using arecognised technique, this test will produce a correlationof over 90% in cases of bacterial infection.Department of Bacteriology,

School of Medicine,Leeds 2.

R. FREEMANB. KING.

** * We showed this letter to Dr. Drysdale and hisreply follows.-ED. L.

SiR.—The technique used in the N.B.T. test was that ofPark et al. as modified by Matula and Paterson—i.e.,using the 25-minute incubation and counting cells with

stippled cytoplasm as positive. The smears were made onslides rather than coverslips, and, to obtain a uniformdistribution with minimal clumping or disruption ofneutrophils, a little 30% bovine albumin was used to

resuspend the cells after the room-temperature stage ofincubation.

Samples were processed within two hours of taking;two slides were counted for each patient, and a subgroupwas double-counted by two observers with good con-cordance of results. All counting was done without know-ledge of the clinical outcome of the case.Whatever the initiating factor in acute appendicitis, by

the time of operation there is an infective element andcultural methods of defining this seem inappropriate. I was

unimpressed by any correlation between the severity ofthe histological changes and the height of the N.B.T.

positivity.My results are not so different from other reported

series,1-3 as is suggested (see accompanying table), especially

1. Matula, G., Paterson, P. Y. New Engl. J. Med. 1971, 285, 311.2. Feigin, R. D., Shackelford, P. G., Choi, S. C., Flake, K. K.,

Franklin, F. A., Eisenberg, C. S. J. Pediat. 1971, 78, 230.3. Humbert, J. R., Marks, M. I., Hathaway, W. E., Thoren, C. H.

ibid. p. 259.

RESULTS IN REPORTED SERIES

when it is remembered that our " normal " range almost

certainly included patients with occult infection. Inparticular, other workers have reported levels in the 60-70%range, and, as far as can be judged, these patients did nothave acute septicxmia with imminent death.The disappointment was the amount of overlap; pre-

dicting purely on the N.B.T. result and taking 10% as thedividing line, we would have been right in 72% of cases,and this reaches to about 80% if proven or probableinfections of other sites are excluded from the " false "

positives. Matula and Paterson reported 4/65 false

negative and Humbert et a1.3 10/53, but in both seriessome of these cases had complicating factors such as

immunosuppression or steroid or antibiotic treatment.

By using a common condition in a normal population I hadhoped to avoid these complications and improve the

figures.Some of my false negatives may have been because the

infection was too localised,4 but it is clear that otherworkers 5,6 have had false negatives in widely variablecircumstances. Even in Leeds, I note with interest, thereis up to 10% failure of correlation.

Department of Pathology,Princess Margaret Hospital,

Swindon, Wilts. H. C. DRYSDALE.

ABDOMINAL DISTRESS ANDERYTHROMYCIN ESTOLATE

Sir,- should like to support the observations ofProfessor Oliver and others (Nov. 4, p. 980) regardingabdominal distress associated with erythromycin estolateilosone ’).A 4-year-old boy had ilosone liquid 125 for acute otitis media.

Within 15 hours of the first dose (125 mg. by mouth every 6hours), nausea and severe cramping right-upper-abdominal paindeveloped. Examination revealed hypoactive bowel sounds,guarding, and rebound tenderness. Complete blood-count andurine analysis were normal. These findings dissipated over 8hours. The patient was not challenged with the drug becauseof the severity of the reaction.A year later, while she was living in a different part of the

United States, his 2-year-old sister was given ilosone chewabletablets 125 for acute otitis media. Within 6 hours she hadnausea, vomiting, and intermittent upper abdominal pain. Shewas given a second tablet 12 hours later, with the same results.Abdominal examination was normal on both occasions. This

patient tolerated erythromycin ethyl succinate (’ Erythrocin’) ’)(200 mg. by mouth every 6 hours for 2 days); then diarrhoeaensued, and the drug was discontinued in favour of penicillin.

4. Park, B. H. ibid. p. 376.5. Ng, R. P., Chan, T. K., Todd, D. Lancet, 1972, i, 1341.6. Esposito, R., De Lalla, F. ibid. p. 747.

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Neither patient is allergic to penicillin and neither had clinicalicterus.

These patients had two types of reaction to erythromycinestolate. The first had had the estolate salt before withoutintolerance. Upon readministration, abdominal distress

developed after 250 mg. and within 15 hours; the severityof the right-upper-quadrant abdominal pain and the

physical findings prompted surgical consultation andobservation in hospital for 8 hours. This presentation issimilar to that described by Professor Oliver and hiscolleagues. The second patient had the more commonlyencountered gastrointestinal disturbances which occur witheach dose and which are usually tolerated by most patientsduring a 10-day course. Since erythromycin is alleged tohave little effect on the gram-negative bacterial flora of thegut, the diarrhoea which ensued may also have been due tointolerance to the erythromycin.Mayo Clinic and Mayo Foundation,Rochester, Minnesota 55901, U.S.A. ROY S. ROGERS III.

LOWERING OF BLOOD-PRESSURE BYHYPERVENTILATION IN PRIMARY

ALDOSTERONISM

SIR,-We have observed a patient with primary aldo-steronism whose blood-pressure is strikingly lowered byhyperventilation.A 57-year-old man was admitted to our department

because of periodic paralysis, tetany, and hypertension.Physical examination was unremarkable except for severehypertension. Laboratory examination revealed hypo-kalasmia, metabolic alkalosis, undetectable plasma-reninactivity, and greatly increased urinary excretion of aldo-sterone.

Hyperventilation was performed for 4 minutes, while theblood-pressure was recorded through a cannula insertedin the right radial artery and blood was sampled from theleft dorsalis pedis artery. Neither paralysis nor tetany wasinduced, but remarkable changes of blood-gas and loweringof blood-pressure were observed (see accompanying table).No remarkable changes were found in the electrocardio-gram. The electroencephalogram showed slight slowing ofthe background activity.Mere inhalation of oxygen greatly increased P02, but

Pc02, pH, and blood-pressure were unchanged. Whenhe hyperventilated in a paper bag, the blood-pressure didnot fall. These results suggest that this patient’s hyper-tension may be due to hypercapnia which can be correctedby hyperventilation.Department of Neurology, HIDEKI IGISU.

Intensive Care Unit, KIYOMI IKEMOTO.

Department of Neurology,Kyushu University,Fukuoka, Japan. IKUO GOTO.

BLUE SCLERÆ

SiR,-The discussion on blue scleras 1-4 reminded meof a young girl with myasthenia gravis and strikingly bluesclerae whom I saw when I was a medical student at the

University of Virginia. She had no connective-tissue diseaseand was not iron deficient. She had been treated for a longtime with corticosteroids before I saw her, but her motherclaimed that the colour of her sclerx had not changed sincebirth.There are two reports from Japan of young girls with

myasthenia gravis and blue sclerae.6,6 A family study ofone of these patients 5 revealed that 6 of 24 family membershad blue sclerse and that 5 family members (3 with bluesclerae) had a history of bone fracture.These observations suggest that myasthenia gravis may

be another, although rare, cause of blue sclerae and theyalso suggest a relation between myasthenia gravis andosteogenesis imperfecta.

National Cancer Institute,Baltimore Cancer Research Center,

3100 Wyman Park Drive,Baltimore, Maryland 21211, U.S.A. PETER H. WIERNIK.

ARTERIAL-DISEASE RESEARCH

SIR,-I should like to congratulate Dr. Stanton (Nov. 18,p. 1081) on his hard-hitting and convincing letter. How-ever, I am a little surprised at his ignorance of the decision-making processes in medical science revealed by point 13.He seems to be under the impression that one has onlyto make a reasonable case in order to receive attention.I could write at length on this topic, but I could nevermake my point more cogently or more elegantly thanF. M. Cornford who, in his Microcosmographia Academica,first published by Bowes and Bowes in Cambridge in1908, wrote:

" You think (do you not ?) that you have only to state a

reasonable case, and people must listen to reason and act uponit at once. There is little hope of dissuading you; but has itoccurred to you that nothing is ever done until everyone isconvinced that it ought to be done, and has been convinced forso long that it is now time to do something else ? And are younot aware that conviction has never yet been produced by anappeal to reason, which only makes people uncomfortable ? Ifyou want to move them you must address your arguments toprejudice and the political motive. I should hesitate to writedown so elementary a principle, if I were not sure you need tobe told it. And you will not believe me, because you think yourcases are so much more reasonable than mine can have been,and you are ashamed to study men’s weaknesses and prejudices.

1. Hall, G. E. Lancet, 1971, ii, 935.2. Bennett, R. M. ibid. p. 1100.3. Agnoletto, A. ibid. p. 1160.4. Pope, F. M. ibid. p. 1160.5. Ogata, M., Eguchi, S., Fukuzaki, H. J. otorhinolar. Soc. Japan, 1964,

67, 279.6. Takaoka, Y. Naika, 1964, 14, 468.

LOWERING OF BLOOD-PRESSURE BY HYPERVENTILATION IN PRIMARY ALDOSTERONISM