SERUM-IgE LEVELS AND COW'S-MILK AND EGG ANTIGENS

979 The concentration of C3 and C4 in serum from groups I-III combined was the same as in control serum. The groups did not differ from one another and there was no significant difference between the sexes. However the 95 confidence-limits of C4 in the combined groups were 007-0-60 mg/ml which

(0-125-0-49 mg/ml, mean=0-31). The serum-complement in group in (1082 units/ml) was significantly higher than in the control group (839 units/ml) is wider than normal mean

total

(P<0.01). HLA-B14 was associated with patients who had polyand other indications of altered immunological function. It is curious that these patients should have an abnormally high total serum-complement since complement consumption might be expected, at least while they have active disease. More detailed studies of immunological function in polymyositis may be well merited.

myositis

Muscular Dystrophy Group Research Laboratories, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE

Department of Microbiology, University of Newcastle upon Tyne

W. J. K. GUMMING P. HUDGSON D. LATTIMER M. SUSSMAN

M.R.C. Demyelinating Diseases Newcastle General Hospital

C. B. WILCOX

Unit,

PLASMA-MOTILIN IN CARCINOID TUMOURS

SIR,-The role of motilin in disease is unknown. With vasoactive intestinal polypeptide, glucagon, and gastrin much useful information has been obtained by identification of tumours producing these hormones, but no tumour or other disease has been identified in which motilin is found in excess. Furthermore, motilin has no clearly defined physiological role, though it may modulate bowel myoelectrical activity and gastric emptying.I.2 Plasma-motilin concentrations have a skew distribution (5-250 pMol/If)3 and fasting plasma-motilin values rise with age. We have shown that intravenous administration of isotonic fat emulsion (’Intralipid’, Vitrum) and rapid gastric distension with water raises plasma-motilin levels, whilst vagal stimulation (insulin hypoglycxmia) and intravenous pancreatic polypetide (PP) infusion suppress release of motilin. Whether these facts suggest a role in the control of gastric emptying is still open to speculation. Analysis of plasma samples from more than 1000 patients with a wide ranse of disease states-neoplastic, metabolic, degenerative, and vascular--of different organ systems revealed no disease with consistently raised plasma-motilin concentrations. General anxsthesia had no effect, but handling of the gut at surgery produced transient rises in systemic concentrations of the polypeptide. Carcinoid tumours are derived from the enterochromaffin cells which produce motilin, substance P, and 5-hydroxytryptamine,4 and since the causal agents of the carcinoid syndrome are ill understood we looked at motilin as a possible tumour marker or as a polypeptide component of the syndrome. In seven carcinoid patients with and without hepatic metastases fasting plasma-motilin levels were normal. The motilin response to a standard test meal was negligible and did not differ significantly from that found in healthy volunteers. However, there was a variable response to provocative agents used in testing for the carcinoid syndrome. In three carcinoid tumour patients (two foregut, one midgut) we used intravenous noradrenaline (1 ?g in 30 ml saline over 3 min) and bradykinin (2 :.tg in 30 ml saline over 3 min) on separate occasions as provocative agents. Noradrenaline produced a sharp rise of plasmamotilin in the mid-gut carcinoid only, whereas bradykinin produced a sharp rise in plasma-motilin in the two foregut

but not in the midgut tumour. Oral alcohol, although provoking the characteristic flushing and sweating in all three patients, did not alter the motilin levels. The two foregut tumours with hepatic metastases were treated by hepaticartery embolisation, but in only one did the systemic plasmamotilin increase after this procedure. No specific disease state is associated with abnormal plasmamotilin concentrations, and the variability of its release from neoplasms of the cell type (enterochromaffin) which produces motilin merely confirms the heterogeneity of carcinoid tumours. No clear role for this polypeptide has yet emerged. tumours

Departments of Surgery and Medicine, Roval Postgraduate Medical School and Hammersmith Hospital, London W12

*Present address: CURE, VA-Wadsworth, Bldg. 115, Rm 217, Wilshire and Sawtelle Blvd., Los Angeles, California 90073, U.S.A.

SERUM-IgE LEVELS AND COW’S-MILK AND EGG ANTIGENS

SIR,-Dr Jarrett’ drew attention to the role of IgE antibodies in "immediate" hypersensitivity and to the fact that foods can elicit acute atopic reactions mediated by IgE. It seems from recent findings (to be published presently) that IgE levels may also respond to reduction of oral antigen as a result of a change in diet over a long period. Serum-IgE levels were measured in 22 patients (group 1, generalised atherosclerosis) after a minimum of twenty-six weeks’ strict avoidance of all foods containing cow and egg protein. At the start of the trial, the patients were on the customary low-fat diet. Each patient was tested twice, and 12 other volunteers with a previous history of a myocardial infarct were tested twice as controls. These controls (group 2) were on a low-cholesterol diet; and the same tests were used in both groups. Of the 44 tests in group 1, only 8 gave serum-IgE levels over 30 i.u.; 30 gave levels below 10 LU. In group 2 (24 tests) only 2 gave levels below 140 (both being 92 !.u.). 8 patients in group 1 had been tested two-thirds of the way through the trial: 3 of these had levels below 10 i.u. It is thus clear that in patients the serum-IgE was reduced significantly (P<0.001) on the diet; and this finding raises several points. (1) The IgE reduction and clinical improvement during the triaF suggest that the cause of cardiac arterial disease has an immunological component-in this case associated with cow’smilk or egg antigens, or both. (2) A subsequent challenge with cow’s-milk, followed by serum-IgE estimations on the fifth and tenth days (in 22 patients), gave no significant evidence of immediate serum-IgE changes (group 1, after seven months’ cow’s-milk/egg-free diet). It seems therefore that the IgE response to this diet in atherosclerotic disease is a protracted process.

(3) Immunological changes during infancy

2 Ruppin, H., and others, ibid

Gastroent. 1976, 11, suppl. no. 39, p. 85.

3 Bloom, S. R, and others ibid p. 47. 4 Pearce, A., and others Virchows Arch. B. cell. Path.

frequently

mally high serum-IgE. (6) If the very low total IgE readings are representative of immunological peace specific to this regime, perhaps it might be useful in cardiovascular transplant surgery. following

made

possible

the work upon which this tetter

p. 93.

1974, 16, 111.

are

due to cow’s milk. Since atherosclerosis begins in these early years it is logical to propose that the cow’s-milk fraction would be more likely than the egg to contribute to the loss of IgE when the diet is changed. (4) It remains to be determined whether the IgE loss in group 1 reflects specific immunological response to the removal of cow’s-milk/egg antigens, or whether the exclusion of other foodstuffs (e.g., gluten, seafoods), would cause a similar fall in total serum-IgE. (5) The cow’s-milk/egg avoidance diet could conceivably be of benefit in pathological conditions characterised by an abnor-

The 1 Iioh, Z, and others, ScandJ.

I. M. MODLIN* S. R. BLOOM N. CHRISTOFIDES

1. Jarrett, E. Lancet, 1977, ii, 223 2. Crouch, T. H. N. Z. Jl Med. 1977,

85, 109.

s

980 based: the staff of the department of chemical pathology, Westminster Medical School, University of London (especially Prof. J. R. Hobbs, and Dr D. Hampton), Dr P. C. Elwood (M.R.C. Epidemiology Unit, Cardiff), Miss Gill Gough, and the staff of Newquay Health Centre, Cornwall. Standard Chartered Bank, 28 Northumberland Avenue, London WC2N 5AG

THORNTON H. CROUCH

operative polyneuritis and experimental and clinical models of acute polyneuritis, supports the view that surgery provokes a release of nerve antigens. This event, rather than co-trimoxazole treatment, may have initiated case described by Grossman et al. Division of Neurology, Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire, U.S.A.

acute

polyneuritis

in the

FREDERICK M. VINCENT

NEUROLOGICAL COMPLICATION OF LEVAMISOLE has been used to treat a variety of disSide-effects are uncommon, agranulocytosis being the most severe. We have seen a previously unreported neurological complication of levamisole treatment. An 18-year-old girl who had previously been in good health was given one tablet (150 mg) of levamisole because of an upper-respiratory-tract infection. At the end of the day she complained of a slight headache, but on the next day she felt completely well. A month later (Jan. 22, 1977) the same dose of levamisole was given when she had acute rhinitis. 6 h after taking the drug she had a severe headache, chest pain, fever, vomiting, and spastic contractions of muscles of the hands. These symptoms lasted for 8 h and were misinterpreted as manifestations of influenza. On the next day the patient made a full recovery; symptoms of the rhinitis disappeared. The same dose was given on Feb. 6 because of a small furuncle. 5 h later the girl suddenly became seriously ill with a severe headache, severe weakness, and incessant vomiting. In the next 3 h periodic breathing and frequent cramps of extremities developed; her temperature rose to 39°C; and for an hour she had motor aphasia. All these symptoms gradually disappeared over the next 15 h; slight asthenia remained. On Feb. 8 the girl returned to her studies at college. A neurologist could find nothing abnormal, and the girl is now symptom-free (5 months later). This reaction could reflect either a genetic defect of nervecell enzymes or an anaphylactoid response to levamisole (or a metabolite). Doctors should look out for neurological signs in patients on levamisole and withdraw the drug if such symp-

SIR,-Levamisole

PROPRANOLOL AND PEYRONIE’S DISEASE

eases.

toms

appear.

Institute of Rheumatism, Moscow, U.S.S.R.

J. A. SIGIDIN N. V. BUNCHUK

ACUTE POLYNEUROPATHY POSSIBLY ASSOCIATED WITH CO-TRIMOXAZOLE

SiR,—Dr Grossman and colleagues (Sept. 17, gest that co-trimoxazole may have caused

acute

616) sugpolyneuritis

p.

(Guillain-Barre syndrome) in a patient who had had cardiac surgery. They did not, however, consider the possibility that surgery itself was responsible. This has been reported.’-3 5-10% of the cases of acute polyneuritis in several large series1.2 followed surgical procedures which included intracranial, abdominal, orthopaedic, urological, and thoracic operations carried out with both spinal and general anaesthesia. The interval from the time of the operation to the development of the polyneuritis was 1-4 weeks, most cases developing after the second week. Surgery may either release nerve antigen, triggering an autoallergic response which culminates in polyneuritis, or alter-

natively may stimulate, through stress, an underlying process. Experimental allergic neuritis in animals develops approximately 2 weeks after immunisation with peripheral nerve fractions in Freund’s complete adjuvant. Rabies-vaccine-induced polyneuritis, which resembles both experimental allergic neuritis and classical acute polyneuritis, also takes 2 weeks to develop after challenge.2 The similarity of time interval in post1.

Wiederholt, W. C., Mulder, D. W., Lambert, E. H. Mayo Clin. Proc. 1964,

39, 427. 2. Arnason, B. G., Asbury, A. K. Archs Neurol. 1968, 18, 500. 3. Asbury, A. K., Arnason, B. G., Adams, R. D. Medicine, 1969,

48,

173.

SIR,—Osborne1 has described two patients on propranolol in whom Peyronie’s disease developed. We would like to report a further case. A 48-year-old truck driver had been treated for 20 months with propranolol for hypertension and ischxmic heart-disease. He presented with 8 months of pain on erection and progressive deviation of penis to the left. There was an easily palpable fibrous plaque at the base of the shaft of the penis on the left side associated with a fixed and fibrous band extending distally. With increasing use of propranolol as a first-line drug in the treatment of hypertension we may expect to see further cases. Medical Unit 1, Royal Melbourne Hospital, Victoria 3050, Australia

A. A. WALLIS R. BELL P. W. SUTHERLAND

HIGH URINE SPECIFIC GRAVITY INDUCED BY CARBENICILLIN

SIR,-A 20-year-old patient with severe burns had a sustained high urine specific gravity (sp. gr.) of 1042, daily urine output averaging .800 ml. Dehydration being moderate, we looked for another explanation. Three other conditions are known to increase urine sp. gr.-namely, heavy proteinuria, mellituria (glucose, mannitol), and excretion of contrast media. None applied to our patient. He was being given carbenicillin (’Pyopen’) 5 g intravenously every 4 h (30 g/day); if renal function is normal, 80% of the administered dose is found unchanged in the urine,2 so he was thus theoretically excreting 24 g each day (he had a normal serum-creatinine). To assess the influence of such amounts of carbenicillin on urine sp.gr. pyopen powder was dissolved in distilled water to a 3 g/dl concentration, reflecting the patient’s urine carbenicillin concentration: the sp. gr. of the solution was 1018. Thus, as a bedside rule, when a patient with normal kidney function is receiving carbenicillin, his real urine sp.gr. should be calculated by subtracting from the measured sp. gr. a factor equal to 6 times the urine carbenicillin concentration, the concentration being obtained by dividing 80% of the daily carbenicillin load by the 24 h urine volume. We also studied benzylpenicillin, about 80% of which is normally found unchanged in the urine.’ A 3 g/dl concentration of sodium penicillin G (50 megaunits/1) yielded a sp. gr. of 1014: the correction factor here becomes 4.7. Fluid management of severely burned patients relies partly on monitoring of urine sp. gr. Overhydration may ensue if the sp. gr. is misinterpreted.

Hôpital du Sacre-Coeur Montréal, Quebec, Canada

1. 2.

Osborne,

CLEMENT DEZIEL BERNARD DAIGNEAULT JULIEN MARC-AURELE GUY ALBERT ANDRE BRODEUR

D. R. Lancet, 1977, i, 1111. Goodman, L. S., Gilman, A. The Pharmacological Basis of Therapeutics,

p. 1146. New York, 1975.