2 BRITISH MEDICAL JOURNAL 5 APRIL 1975 several reasons such investigations have thrown little light on is gross it is difficult to test without recourse to esoteric the pathogenesis of these diseases. Firstly, the results have instruments. Every now and then, however, a colour distur- been remarkably divergent-mostly owing to the technical bance can be a valuable pointer to specific lesions of the factors already discussed. Secondly, it is not yet clear to what cerebrum as well as of the eye. Thus in certain patients with extent abnormal patterns in lymphocyte subpopulations are bilateral damage to the inferoposterior cerebral region altered Br Med J: first published as 10.1136/bmj.2.5961.2 on 5 April 1975. Downloaded from entirely and non-specifically secondary to disease activity; in colour vision may well be a presenting symptom'; overall hue particular, the sequestration of lymphocytes in diseased discrimination is impaired (hence the Ishihara test helps tissues may well distort the picture in the peripheral blood. little), and there is usually an associated field defect, while at Finally, no unequivocal, obviously important abnormality has necropsy infarction of the lingual and fusiform gyri is the been demonstrated in any one ofthese diseases. This contrasts most common finding. with other diseases in which measuring lymphocyte sub- Many disorders of the eye itself can provoke a colour populations is of diagnostic value. Thus the lymphocytes in disturbance. Probably the commonest which presents in this the blood of patients with chronic lymphatic leukaemia way is a central serous retinopathy, a curious little blister predominantly possess B-lymphocyte markers, and in con- which develops at the macula, usually in young men. The genital thymus deficiency lymphocytes with T-cell markers are condition is of unknown aetiology and there is no accepted markedly reduced in number. Indeed, the T-lymphocytes of treatment, but it gradually recedes over the succeeding weeks. some patients with hypogammaglobulinaemia have been shown These patients nearly all notice that the colours are distorted to have abnormally low levels of immunoglobulin synthesis in in the affected eye, blues usually becoming brownish. It seems vitro.14 that most of the young men affected are intelligent and Methods are still lacking which might show immunological artistic-perhaps the dullards simply ignore the symptoms. aberrations in lymphocyte subpopulations in other diseases. Much the most prevalent persistent cause of such colour The sort of technique needed to test the functional capacity changes is a "brown cataract," which gradually degrades the of different subpopulations in normal and diseased subjects is colours from the blue end of the spectrum, and to which the the ability to initiate antibody responses in lymphoid cells of changing style of some artists such as Turner and Mulready human origin.15 Present research methods of evaluating these has been (rather wildly) attributed. Though such a colour cells in man are an imperfect first step in a developing distortion is too gradual to be observed by the patient, their process.16 Their introduction into clinical investigation at sudden translation from a rosy world into a relatively cold, this stage would, for the most part, be premature and of clear but bluish environment by removal of the cataracts quite unproved value. frequently occasions a mild complaint-especially from the 1 Greaves, M. F., Owen, J. T., and Raff, M. C., T and B Lymphocytes. myope, who contrasts his operated and unoperated eyes, Amsterdam. North-Holland 1973. seeing when unbespectacled equally fuzzily with both but in 2 Allison, A. C., Denman, A. M., and Barnes, R. D., Lancet, 1971, 2, 135. 3 Jondal, M., Holm, G., and Wigzell. H., Journal of Experimental Medicine frankly different hues. 1972, 136, 207. 4 Aiuti, F., and Wigzell, H., Clinical and Experimental Immunology, 1973, There are many other organic eye disorders in which colour 13, 171. values change, though this is rarely noticed by the patient, a Chiao, J. W., Pantic, V. S., and Good, R. A., Clinical and Experimental Immunology, 1974, 18, 483. who is much more concerned by the associated overall http://www.bmj.com/ 6 Winchester, R. J., et al., Jrournal of Clinical Investigation, 1974, 54, 1082. blurring of his vision. Thus there is often a red-green 7 Eddleston, A. L. W. F., and Williams, R., Lancet, 1974, 2, 1543. defect 8 Peters, D. K., and Lachmann, P. J., Lancet, 1974, 1, 58. in patients with hereditary degeneration of the macula, in 9 Korsmeyer, S., et al., Gastroenterology, 1974, 67, 569. 10 Bernstein, I. M., et al., Lancet, 1974, 2, 488. which receptor-function is depressed; in contrast there is a 'L Messner, R. P., Arthritis and Rheumatism, 1974, 17, 339. blue-yellow defect accompanying damage to the choroid and 12 Hedfors, E., Holm, G., and Pettersson, D., Clinical and Experimental Immunology, 1974, 17, 219. pigment-epithelium, as in disciform macular degeneration; and 13 Farid, N. R., et al., New England3Journal of Medicine, 1973, 288, 1313. colour impairment has been described in other miscellaneous 14 Waldmann, T. A., et al., Lancet, 1974, 2, 609. 15 disorders of the retina and optic nerve, including glaucoma,

Geha, R. S., et al.,3Journal of Experimental Medicine, 1973, 138, 1230. on 1 October 2021 by guest. Protected copyright. 16 Rowe, D. S., et al., Journal of Experimental Medicine, 1973, 138, 965. toxic amblyopia, and vascular retinopathies. Diabetes and Friedreich's ataxia both tend to provoke yellow-blue blindness. But in fact these changes are hardly ever noticed by the patient, except when contrasted with a fellow, unaffected eye. Colour Disturbance Then there is the erythropsia (red-vision) described after preretinal and vitreous haemorrhages, snow-blindness, and as a Symptom blindness from electric shock. Cyanopsia (blue-vision) or erythropsia may be noted in tabes; and xanthopsia (yellow- Among land-lubbing animals (that is excluding arboreal as vision) is a characteristic feature of poisoning by a wide well as aquatic ones) man is almost unique in his appreciation concourse of drugs such as santonin, sulphonamides, digitalis, of colours. Among invertebrates, too, colour vision barely phenacetin, chromic and picric acids, and even snake-venom. exists except over a restricted and rather different range among It is sometimes said that circulating bile pigments can also the insects, who perhaps count as being air-borne. This give jaundiced patients a genuinely yellowish view of the bizarre faculty of differentiating our limited spectral band of world. Indeed yellow-vision was in classical times a stigma of visible light into those vivid and contrasting rainbow-colours the mentally unsound as well as of those who were simply has long engaged the curiosity of physicists, physiologists, "bilious." Psychosis can, in fact, distort our colour values in philosophers, and aestheticians as well as a host of others in almost any direction, ranging from the kaleidoscopic displays disparate commercial fields. But disturbances of colour vision, induced by hallucinogenic drugs to the shrinking of all colour though quite frequently observed, play little real part in values in schizophrenia. Old age itself tends to give us a clinical diagnosis. slightly more jaundiced outlook, as the pigment at the macula A change in colour-awareness is indeed an incidental lutea accumulates, and we must not forget that 1 in 12 men feature of many ailments; but, since it is usually gradual, it is (but only 1 in 200 women) is born with an inherited failure unnoticed by the patient; and even when observed, unless it to separate clearly their reds and greens. BRITISH MEDICAL JOURNAL 5 APRIL 1975 3 The trouble is that our awareness of and preference among The evidence is, however, at the best only circumstantial, colours is a very personal issue, and that temperamental and and confirmation must await evidence of a clear relation cultural factors generally far outweigh any distortions that are between the circadian rhythm in plasma steroids levels and organically induced, unless such changes are fairly abrupt and that affecting induction-abortion intervals. Meantime it is gross. Most of us have aesthetic or symbolic associations known that synchronization of circadian rhythms can be Br Med J: first published as 10.1136/bmj.2.5961.2 on 5 April 1975. Downloaded from which affect our responses to colour. For some they may have influenced by a variety of environmental factors, and some of a lingering influence as a biological cue (recalling the blue- those which upset the rhythm in Smith and Shearman's series behinded ape). For many the natural environmental associa- might have been expected; but it was surprising to find a tions of colour are powerful (green with plenty, red with disturbing effect on diurnal hormone fluctuations from admis- anger, blood, and sex), and even spill over widely into every sion to hospital for two to four hours before treatment. other sensory field; we may even hear our music in differing Information is scarce in this area, and one can only speculate colours, or think and taste to a coloured background. Colours whether similar circadian influences might be concerned in can caparison our dreams in a capricious way, and most of the induction of abortion when PGE2 rather than PGF2c is us probably hallucinate gently in colours half the time, just used or when the alternative extra-amniotic route is chosen. as we did when, as children, we watched kaleidoscopic Smith and Shearman used a method which in most published displays behind our closed eyelids. But we don't usually talk series'5 has given 95% success in 48 hours; with a mean about it because we have ceased to pay attention to these induction-abortion interval of 28-30 hours. More recent intra- colour-associations-which in any case are rather private and amniotic and extra-amniotic techniques16-18 have reduced the difficult to explain to others. mean induction-abortion time by about half and might not So, all in all, outside the world of physiological optics, necessarily be subject to the same circadian influences. colours occupy a tantalizing limbo, their relevance as a diagnostic symptom may be scant and imprecise, their 1 Karim, S. M. M., and Sharma, S. D., Lancet, 1971, 2, 47. 2 Ballard, C. A., and Quilligan, E. J., in Advances in Biosciences, ed. S. psychological significance shifting and elusive, but they remain Bergstrom. Oxford, Pergammon, 1973, 9, 55. a constant source of speculation and delight. 3 Bygdeman, M., et al., in Advances in Biosciences, ed. S. Bergstrom, Oxford, Pergammon, 1973, 9, 525. 4 Gillett, P. G., et al., Advances in Biosciences, 1973, 9, 545. 1 Meadows, J. C., Brain, 1974, 97, 615. 5 Wiqvist, N., and Bygdeman, M., Lancet, 1970, 2, 761. 6 Embrey, M. P., and Hillier, K., British Medical journal. 1971, 1, 588. 7 Embrey, M. P., Hillier, K., and Mahendran, P., in Advances in Bio- sciences, 1973, 9, 507. 8 Miller, A. W. F., Calder, A. A., and Macnaughton, M. C., Lancet, 1972, 2, 5. 9 Smith, I. D., and Shearman, R. P.,Journal of Obstetrics and Gynaecology of the British Commonwealth, 1974, 81, 841. Circadian Rhythms 10 Kaiser, I. H., and Halberg, F., Annals of New York Academy of Science, 1962, 98, 1056. and Abortion '. Kreiger, D. T., et al., Journal of Clinical Endocrinology, 1971, 32, 266. 12 Lacerda, L. de, Kowarski, A., and Migeon, C. J., Journal of Clinical Endocrinology and Metabolism, 1973, 36, 289. 13 Mathur, R. S., et al., Journal of Steroid Biochemistry, 1974, 5, 363. The prostaglandins PGE2 and PGF2a are now well established 14 Townsley, J. D., et al., Journal of Clinical Endocrinology and Metabolism, 1973, 36, 289. as effective abortifacients, and they have an important clinical http://www.bmj.com/ 15 Wiqvist, N., Bygdeman, M., and Toppozada, M., in Prostaglandins in role in the termination of second trimester pregnancy. Experi- Fertility Control, ed. S. Bergstrom, 1973, 3, 80. Karolinska Institutet, Stockholm. ence has shown that local routes ofadministration are superior 16 MacKenzie, I. A., Embrey, M. P., and Hillier, K., J7ournal of Obstetrics to methods which depend on systemic absorption, and intra- and Gynaecology of the British Commonwealth, 1974, 81, 554. 17 Karim, S. M, M and Sharma, S. D.,Journal of Obstetrics and Gynaecology uterine administration (either intra-amnioticl-4 or extra- of the British 6;ommonwealth, 1972, 79, 737. amniotic3 5-8) iS therefore now preferred. 18 Wiqvist, N., et al., in Advances in Biosciences, 1973, 9, 831. Recently Smith and Shearman9 have reported that the effectiveness of intra-amniotic administration of PGF2", in induction of abortion is influenced by the time of injection- on 1 October 2021 by guest. Protected copyright. the optimum response (in terms of induction-to-abortion interval, dose of PGF2a, and stay in hospital) resulted from Why So Few Pacemakers? injection at 6 p.m. Since the intra-amniotic method has already been used in many hundreds ofpatients it may seem surprising Implantable cardiac pacemakers have now been in use for that similar findings have not been reported by others; but almost 16 years. During this time there have been considerable these observations, if corroborated, are not only intrinsically improvements in the technique of implantation, technical interesting as another example of circadian rhythm but could problems associated with the pulse generator and electrode have obvious practical implications for the gynaecologist. design have been largely overcome, and battery longevity has Circadian periodicity has been observed in the timing of increased.' In addition there have been advances in methods delivery after spontaneous and induced labour,'0 and it might for detecting pacemaker failure; one such method whereby well be supposed that such rhythms, as well as that reported the endocardial threshold may be measured noninvasively in by Smith and Shearman, are to be explained on endocrine patients with suspected exit block or unstable electrode grounds. A fall in plasma progesterone either precedes or position was recently described by Roy and Sowton.2 These accompanies prostaglandin-induced abortion, and there is improvements have reduced the mortality associated with fragmentary evidence that rising levels of corticosteroids and pacemaker implantation to negligible proportions: of 372 oestrogen with diminishing levels of progesterone may be the patients with implanted pacemakers over a 10-year period3 endocrine milieu favouring the onset of parturition. Some, if there were no deaths associated with the procedure, and the not all, investigators'l-14 have reported diurnal variations in subsequent annual mortality was less than 5%. plasma steroid levels (better established for corticosteroids Why is it, then, that the number ofpacemaker implantations than ovarian steroids) which appear to mimic these changes in Britain is considerably less than that in many other Euro- and at the same time are consistent with the peak incidence of pean countries ? The estimated rate ofpacemaker implantation abortion observed by Smith and Shearman. for the British Isles is about 22 per million population,4 as com-