777 nitrite test, despite its low cost, far from ideal even for screening programmes. Second Department of Pædiatrics, CONSTANTINOS A. SINANIOTIS Athens University School of Medicine, MILTIADES N. HARATSARIS "Aglaia Kyriakou" Children’s Hospital, CONSTANTINOS PAPADATOS J. Athens, Greece

ACETYLCHOLINE-RECEPTOR ANTIBODY IN CEREBROSPINAL FLUID

SiR,-Lefvert and Pirskanen’ proposed that the antibody against human acetylcholine receptor (AcChR) found in the cerebrospinal fluid (c.s.F.) of patients with myasthenia gravis

(M.G.) was synthesised locally within the central nervous sys(C.N.s.), and not the result of passive leakage through the blood-brain barrier. In six M.G. patients we also found antiAcChR antibody-an IgG2 in the c.s.F.-but in a ratio to that in serum which is no greater than that of total IgG (see table). Unfortunately, Lefvert and Pirskanen reported their findings in "arbitrary units," so it is difficult to compare their antibody values with our data, which are expressed as mol human

tem

receptor bound/I serum. The immunoprecipitation assay for anti-receptor antibody3 was done with either 5 1 serum or 100 1 c.s.F. albumin and IgG were measured immunochemically.4 The c.s.F./serum ratio for albumin was used as a test of blood-brain barrier function.s c.N.s. synthesis of total IgG was evaluated both by the "IgG index" (ratio of IgG in c.s.F. and serum divided by the ratio of albumin in c.s.F. and serum4) and as mg/day.6 By the latter method, only one patient (no. 2) had evidence of C.N.S. synthesis of total IgG greater than the normal mean + 2s.D. (3-3mg/day) as well as evidence of blood-brain barrier damage, and in no case of M.G. was the c.s.F./serum ratio for anti-receptor IgG antibody greater than that for total IgG. 1. Lefvert, A. K., Pirskanen, R. Lancet, 1977, ii, 351. 2. Lindstrom, J. M., Lennon, V. A., Seybold, M. E., Whittingham, S. Ann. N. Y. Acad. Sci. 1976, 274, 254. 3. Lindstrom, J. M. Clin. Immun. Immunopath. 1977, 7, 36. 4. Tourtellotte, W. W., Tavoloto, B., Parker, J. A., Comso, P. Archs Neurol. 1971, 25, 345. 5. Tibbling, G., Link, H., Ohman, S. Scand. J. clin. lab. Invest. 1977, 37, 385. 6. Tourtellotte, W. W. in Multiple Sclerosis Research (edited by A. N. Davidson, J. H. Humphrey, A. L. Liversedge, W. I. McDonald and J. S. Porterfield); p. 9. New York, 1975. 7. Fulpius, B. W., Fontana, A., Cuénoud, S. Lancet, 1977, ii, 350.

CONCENTRATION OF

IgG, ALBUMIN,

AND

ANTI-AcChR

to us that the measured anti-receptor antibody gained access to the c.s.F. by passive leakage from the serum. Fulpius et aJ.7 proposed that antibodies in the C.S.F. against AcChR produce central disturbances such as electroencephalographic abnormalities in M.G. and experimental M.G. The levels of Torpedo marmorata AcChR receptor antibody (in nmol/ml) in the c.s.F. of the two immunised rabbits upon which they based this conclusion were 1000 times greater than antibody titres to human receptor found by us in the c.s.F. of patients with M.G. but the rabbit c.s.F./serum ratios for anti-receptor antibody and for total IgG were similar. In the two immunised rabbits, the IgG ratios, which these authors used to assess barrier damage, were 1 -5 and 3 times greater than the control. The possibility exists, therefore, that barrier damage may have occurred--e.g., around the chronically implanted electrodesand electroencephalographic discharges could have been produced by substances other than anti-receptor antibodies. Even if in the future convincing evidence for c.N.s. distur-

This suggests

bance in M.G. accumulates, it remains to be determined whether the anti-skeletal muscle nicotinic acetylcholine receptor antibodies characteristic of M.G. can cross-react with C.N.S. acetylcholine receptors, and whether cross-reaction could alter transmission in the c.N.s., given the extremely low concentration of these antibodies present. Reed

Neurological Research Center, Department of Neurology, University of California, Los Angeles, California 90024, U.S.A. Salk Institute, LaJolla, California

significant.

W. W. TOURTELLOTTE C. HERRMANN, JR J. M. ANDREWS

J. LINDSTROM

WHY HAS CYANOCOBALAMIN NOT BEEN WITHDRAWN?

SIR,-In 1970, you published a letter from us under the heading Cyanocobalamin: a Case for Withdrawal,’ a copy of which we sent to the Committee on Safety of Drugs. Cyanocobalamin in the treatment of addisonian pernicious anaemia, with or without neurological involvement, is still being advocated.2 We are particularly concerned that patients 1.

Foulds, W. S., Freeman, A. G., Phillips, C. I., Wilson, J. Lancet, 1970, i,

35. 2. Data Sheet

Compendium; p. 311. Association of the British Pharmaceutical Industry, 1977.

ANTIBODIES IN SERUM AND C.S.F. OF CONTROLS AND PATIENTS WITH MYASTHENIA GRAVIS

N.s.=not

J. C. KEESEY

778 with tobacco amblyopia and optic neuropathy in pernicious anaemia are still being treated with cyanocobalamin. In some instances patients with tobacco amblyopia fail to respond to treatment

YEAST PHAGOCYTOSIS IN

C2-DEFICIENT

PLASMA

because, although hydroxocobalamin is prescribed,

is administered in its place. The diagnosis questioned, treatment stopped, and the patient consigned to a life of poor sight.

cyanocobalamin may then be

Because doctors are still confused about the differences between various forms of vitamin B12 commercially available and about their possible adverse effects, manufacturers should withdraw cyanocobalamin in favour of hydroxocobalamin for

therapeutic use. Princess

Margaret Hospital,

A. G. FREEMAN

Swindon, Wiltshire

Hospital for Sick Children, London WC1

J. WILSON

Tennent Institute of Ophthalmology, Western Infirmary, Glasgow

W. S. FOULDS

Eye Pavilion, Edinburgh

C. I. PHILLIPS

*Daily

SiR,-Phagocytosis is enhanced by products of the complesysteml and therefore might be expected to be impaired in patients who lack the second component of complement (C2). We have studied phagocytosis of yeast by blood neutrophils (P.M.N.) and monocytes from three patients with C2 deficiency (C2D) two of whom (patients 1 and 2) have systemic lupus erythematosus. Patient 1 takes oxycodone hydrochloride (4 tablets) and phenobarbitone (60 mg daily); patient 2 takes prednisone (10 mg) and hydroxychloroquine sulphate (400 mg daily).2·3 The third patient is a healthy twin of patient 2. The phagocytosis assay was adapted from Miller et awl.4 20x 106 Fleischman’s baker’s yeast organisms and buffy-coat P.M.N. and monocytes suspended in 2 ml 25% plasma in Hanks’ basic salt solution (H.B.S.S.) were incubated in an oscillating waterbath at 37 °C. After cytocentrifugation, Wright’s stains were made to assess yeast ingestion. After 15 min incubation in C2D plasma, the total number of C2D P.M.N. which ingested yeast and the total number of yeasts ingested per 100 P.M.N. were significantly lower than normal (P800 mosmol/kg H2O). Long-term lithium therapy thus impairs renal concentrating capacity, indicating irreversible kidney damage. The reduced =

1. Johnson, R., Stroud, R. J. Pediat. 1977, 90, 169. 2. Rynes, R., Urizar, R., Pickering, R. J. Am. J. Med. 1977, 63, 279. 3. Rynes, R., Urizar, R., Pickering, R. J. Clin. exp. Immun. (in the press). 4. Miller, M. E., Seals, J., Kaye, R., Levitsky, L. Lancet, 1968, ii, 60. 5. Coca, A. Z. Immunitätsforsch. 1914, 21, 604. 6. Pillemer, L., Ecker, E. J. biol. chem. 1941, 137, 139. 7. Gigli, I., Koethe, S., Austen, F. Clin. Immun. Immunopath. 1975, 8. Johnson, F., Agnello, V., Williams, F. J. Immun. 1972, 109, 141. 9. Repine, J., Clawson, C., Friend, R. J. clin. Invest. 1977, 59, 802.

experi-

the opsonisation process by using bacterial killing by the endpoint and have had contradictory results. We have now shown that bacterial killing by C2D P.M.N. must be studied independently of the phagocytic process since the killing abnormalities apparent in the presence of C2D plasma may very well be secondary to abnormal phagocytosis. of C2

DEFECTIVE PHAGOCYTOSIS IN C2 DEFICIENCY

treatment

ment.

1. 2.

Hestbech, J., and others. Kidney Int. 1977, 12, 205. Forrest, J. N. and others. J. clin. Invest. 1974, 53, 1115.

Why has cyanocobalamin not been withdrawn?

777 nitrite test, despite its low cost, far from ideal even for screening programmes. Second Department of Pædiatrics, CONSTANTINOS A. SINANIOTI...
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