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may be quite pronounced in a normal disc if thevessels perforate centrally.18,19 The presence of

myopia increases the probability of O.A.G.20 Contri-buting to suspicion, of course, is a history that aparent or a sibling had glaucoma or graduallybecame irremediably blind in later life. The oph-thalmoscopist can derive some comfort from know-ing that pathological cupping tends to be overdiag-nosed,21 while established O.A.G. and field loss areunlikely to be present without definite pathologicalcupping.22 If referral to a clinic is decided on, awise precaution is to prescribe pilocarpine 1% eye-drops, to be instilled three times daily until thenight before the appointment.The shallow anterior chamber, small-diameter

cornea, and rather small eyeball of C.A.G. are notusually noticed by the generalist. Two things in thepatient’s story may alert him-transient discom-fort in one or both eyes in the evenings, sometimeswith transient coloured rings round lights, andmention of an emergency eye operation in a parentor sibling after an eye became acutely red and pain-ful. Such a story dictates emergency referral for bi-lateral iridectomy, with pilocarpine 1% eye-dropsimmediately and then three or four times daily toboth eyes.

Application of existing knowledge would reducethe numbers blind from glaucoma; in the 60-64year age-group for the period 1963-68, 3 per’100 000 of the population were certified blind fromglaucoma-12.9% of all reported causes of blind-ness.23 .

Myasthenia GravisMYASTHENIA gravis affects only 2-4 people in

every 100 0001,2 yet it preoccupies many research-workers. When Dr MARY WALKER3 first treated

myasthenia with an anticholinesterase the effectswere so impressive that her discovery was called theMiracle of St. Alfege (she was house-physician atSt. Alfege’s Hospital at the time). The fatiguabilityof the muscles, the characteristic feature of myas-thenia gravis, is due to progressive failure of neuro-muscular transmission, and the cause of this failureis becoming clearer. Electrophysiological record-ings reveal that the miniature end-plate potentialsspontaneously occurring at the motor end-platesare smaller than normal.4 At first this was attri-buted to release of abnormally small quanta of

acetylcholine (ACh),4 but we now know that the re-

18. Armaly, M. F. Trans. Am. Acad. Ophth. Otolar. 1969, 73, 898.19. Tomlinson, A., Phillips, C. I. Br. J. Ophth. 1971, 55, 165.20. Milton, R. C., Ganley, J. P. Investig. Ophth. vis. Sci. 1977, 16, suppl. p. 85.21. Hollows, F. C., Graham, P. A. in Glaucoma (edited by L. B. Hunt); pp. 114,

115. Edinburgh, 1966.22. Armaly, M. F. Trans. Am. Acad. Ophth. Otolar. 1969, 73, 898.23. Sorsby, A. Hlth Trends, 1973, 5, 7.1. Hokkanen, E. J. neurol. Sci. 1969, 9, 463.2. Newsom Davis, J. Br. J. Hosp. Med. 1974, 11, 933.3. Walker, M. B. Lancet, 1934, i, 1200.4. Elmquist, D., Hofmann, W. W., Kugelberg, J., Quastel, D. M. J. J. Physiol.,

Lond. 1964, 174, 417.

sponsiveness of the postsynaptic ACh-receptor isdecreaseds and the amount of ACh released is prob-ably more or less normal. There are correspondingultrastructural changes-severe degeneration ofthe normal postsynaptic folds, loss of ACh-receptor’sites, and widening of the synaptic cleft with nor-mal vesicles in the motor-nerve ending, 6,7

Help in understanding the genesis of the phar-macology and pathology of myasthenia gravis hascome from two unlikely sources-the venom of asnake, Bungarus multicinctus, and the electricorgan of the eel, Electrophorus electricus. Thesnake venom, ot-bungarotoxin, binds specifically tothe ACh receptor and was used in an affinity-chro-matography system to isolate the receptor from theelectric organs of the eel or of the ray, Torpedocalifornica, which are homologous to motor end-plates. Repeated immunisation of rabbits with pur-ified receptor produced a myasthenia-like disease.8Myasthenia has now been produced by immunisa-tion with syngeneic muscle ACh-receptor protein inrats.9 The experimental disease is biphasic. Anearly acute period of weakness, when macrophagesinvade the end-plate region and the nerve terminalsretract, is followed by a chronic phase when thepostsynaptic clefts degenerate without cellular in-filtration.6 Pathologically and physiologically this

’

chronic phase is closely similar to the human dis-ease. 10 The experimental disease can be transferredfrom animal to animal with antibody,11 but it canalso be transferred with lymph-node cells and itdoes not occur in animals severely depleted of T Icells by thymectomy and irradiation. 12

In 1960, SIMPSON13 hypothesised an autoimmunebasis for myasthenia gravis on account of its associ-ation with disorders thought to have an autoim- B

mune aetiology-such as myxoedema, thyrotoxi-cosis, pernicious anæmia, pemphigus, rheumatoidarthritis, and systemic lupus erythematosus.2,14The presence of lymphocytic infiltration in themuscles of myasthenic patients, thymic hyper-plasia, and antibodies reacting with the A bands ofstriated muscle and identified by the immunofluor-escent technique 15 indicated that an immunologicalreaction was taking place. Now antibodies to the

5. Grob, D., Namba, T. Ann. N.Y. Acad. Sci. 1976, 274, 143.6. Engel, A. G., Tsujihata, M., Lindstrom, J. M., Lennon, V. A. ibid. 1976,

274, 60.7. Engel, A. G., Lindstrom, J. M., Lambert, E. H., Lennon, V. A. Neurology,

1977, 27, 307.8. Patrick, J., Lindstrom, J. M. Science, 1973, 180, 871.9. Lindstrom, J. M., Einarson, B. L., Lennon, V. A., Seybold, M. A. J exp.

Med. 1976, 144, 726.10. Seybold, M. E., Lambert, E. H., Lennon, V. A., Lindstrom, J. M. Ann. N.Y.

Acad. Sci. 1976, 274, 275.11. Lindstrom, J. M., Engel, A. G., Seybold, M. E., Lennon, V. A., Lambert,

E. H. J. exp. Med. 1976, 144, 739.12. Lennon, V. A., Lindstrom, J. M., Seybold, M. E. Ann. N.Y. Acad. Sci. 1976,

274, 283.13. Simpson, J. A. Scott. med. J. 1960, 5, 410.14. Simpson, J. A. ibid. 1977, 22, 201.15. Strauss, A. J. L., Seegal, B. C., Hsu, K. C., Burkholder, P. M., Nastuk,

W. L., Osserman, K. E. Proc. Soc. exp. Biol. Med. 1960, 105, 184.

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relevant antigen, ACh-receptor protein, have beendemonstrated clearly in the serum of as many as87% of patients with myasthenia gravis, and not inthe serum of normal subjects or patients with otherneuromuscular diseases.I6-19 The electrophysiologi-cal features of myasthenia have, according to onegroup,20 been reproduced in mice by repeated injec-tions of serum or IgG from myasthenic patients,whereas normal serum had no effect. Antibodymight produce myasthenia by permitting the accessof macrophages and possibly cytotoxic lympho-cytes, by a direct complement-mediated toxic effecton the motor end-plate, by fixation to and altera-tion of the remaining ACh receptors, or by non-complement-mediated acceleration of ACh-receptordegradation.21 Lymphocyte transformation in thepresence of acetycholine-receptor protein has alsobeen demonstrated.22,23 The role of cell-mediatedimmunity in human myasthenia has not yet beenfully explored, but the evidence so far, includingthe occurrence of neonatal myasthenia and the im-provement after plasmapheresis,24 suggests thathumoral immunity is the more important. Never-theless it would be surprising if there were no con-comitant cell-mediated immune response, and the

requirement for T cells in the induction of the

experimental disease should not be forgotten.Why does the body sometimes treat the ACh-

receptor as an autoantigen? The answer may lie inthe relationship with thymic disease; 75% of myas-thenia patients have thymic hyperplasia and10-15% have thymoma. The epithelial cells of thethymus, whether the thymus comes from a myas-thenic subject or not, possess ACh receptors25 and,according to some but not all authorities, certainthymic cells have the potential to develop into stria-ted-muscle-like cells in tissue culture.25,26 Accord-

ing to one hypothesis, liability to myastheniadepends on a genetically determined tendency forthymic cells to express neoantigens which give riseto an immune response. In some strains of mice the

tendency for thymic cells in tissue-culture to

acquire myoid characteristics is indeed under thecontrol of a gene linked to the major-histocompati-bility-complex locus and is a sex-dependent trait.27

16. Aharanov, A., Abramsky, O., Tarrab-Hazdai, R. Fuchs, S. Lancet, 1975, ii,340.

17. Bender, A. N., Ringel, S. P., Engel, W. K., Daniels, M. P., Vogel, Z. ibid.1975, i, 607.

18. Lindstrom, J. M., Seybold, M. E., Lennon, V. A., Whittingham, S., Duane,D. D. Neurology, 1976, 26, 1054.

19. Mittag, T., Kornfeld, P., Tormay, A. New Engl. J. Med. 1976, 294, 691.20. Tokya, K. V., Drachman, D. B., Griffin, D. E., Pestronk, A., Winkelstein,

J. A., Fishbeck, K. H., Kao, I. ibid. 296, 125.21. Kao, I., Drachman, D. B. Science, 1976, 196, 527.22. Abramsky, O., Aharanov, A., Webb, C., et al. Clin. exp. Immun. 1975, 19,

11.23. Richman, D. P., Patrick, J., Arnason, B. G. W. New Engl. Med. 1976,

294, 694.24. Pinching, A. J., Peters, D. K., Newsom Davis, J. Lancet, 1976, ii, 1373.25. Engel, W. K., Trotter, J. L., McFarlin, D. E., McIntosh, C. L. ibid. 1977,

i, 1319.26. Kao, I., Drachman, D. B. Science, 1977, 195, 74.27. Wekerle, H. W., Ketelsen, U-P. Lancet, 1977, i, 678.

This is reminiscent of the human disease, which ismore common in women than men, may be familialin 5% of cases, and is associated with HLA-B8 (anassociation which is particularly strong in femaleswho are young when the disease starts28). Alter-natively an infective agent, perhaps a virus, mightstimulate an immune response to the ACh receptorin the thymus, which would cross-react with recep-tor in the neuromuscular junctions. The immuneresponse to the thymic ACh receptor might alsotrigger thymic hyperplasia, and perhaps neoplasticchange into a thymoma. The favourable effect ofthymectomy on the course of the disease 29 couldwell be explained by the removal of an importantthymic antigen. Adult thymectomy may producesubtle changes in circulating lymphocyte popula-tions but substantial changes in T or B cell counts,or mitogen or antigen responsiveness, have not yetbeen satisfactorily demonstrated: on the otherhand, titres of antibody to ACh receptor are sub-stantially lower after thymectomy and do correlatemoderately well with the degree of clinical im-provement. 30

THE VIEWS OF THE PATIENT

IN 1969 King Edward’s Hospital Fund for Londonpublished a survey of patients’ views in 10 general hospi-tals. Patients and their Hospitalsl in its third edition,with a companion survey2 of psychiatric hospitals, pro-vides statistical information from 68 general hospitalsand 9 psychiatric hospitals based on answers from

nearly 11 000 general patients and over 2 000 psychiat-ric patients.

"But can you get useful information from mental pa-tients ?" This was the comment offered by many peopleon hearing of the survey in the psychiatric hospitals.One of the most striking findings, writes the compiler,Winifred Raphael, was that only 2% of the patients whoreturned questionnaires failed to give rational answersand only 3% handed in very incomplete questionnaires.From the general hospitals the current views of patientsare compared with those expressed during the earlierstudies, and the trend seems to be towards improvement.Is this, Mrs Raphael asks, because more attention is

being paid to the views of the patients?The most unpopular item in the general hospital is

the bathroom, with washbasins second and lavatoriesthird. They also led in the dissatisfaction stakes of theearlier editions of Patients and their Hospitals. There arenot enough bathrooms, said the patients, not enoughwashbasins, not enough lavatories. Sanitary annexesconstitute large blots on the hospital skyline. Theupgrading, rebuilding, or substitution of such a complexmass of pipes drains the resources of the regional health

28. Pirskanen, R. J. Neurol. Neurosurg. Psychiat. 1976, 39, 23.29. Papatestas, A. E., Genkins, G., Horowitz, S. H., Kornfeld, P. Ann. N.Y.

Acad. Sci. 1976, 274, 555.30. Scadding, G. K., Thomas, H. C., Havard, C. W. H. Br. med. J. 1977, i,

1512.

1. Patients and their Hospitals. King Edward’s Hospital Fund for London,1977.

2. Psychiatric Hospitals viewed by their Patients. King Edward’s HospitalFund for London, 1977.