15 January 1966 January Leadingb Articles MEDICAL~~~MEDICAL IJ 119 every human bowel. The expression " faulty handling " as noid " and " non-paranoid " groups, and also according to an explanation of staphylococcal food-poisoning is a little whether or not they had exhibited one or more of Karl Br Med J: first published as 10.1136/bmj.1.5480.119 on 15 January 1966. Downloaded from ambiguous, for the fault lies not so much in the method of Schneider's so-called first-rank symptoms.10 Relating the manipulation as in the fact that the operator is a carrier, chemical data to these subgroups, the authors conclude: or even-as in one famous outbreak-has a whitlow on his " When the individuals are classified as being Schneider posi- finger. The association of inferior cheese and of canned peas tive and non-paranoid this sub-class has a significantly higher with this kind of food-poisoning also deserves mention. incidence of the pink spot than does any other group (83.3 ± The memorandum gives useful practical instructions on 5.75%). Thus to predict the presence of the pink spot the how to ascertain the cause of an outbreak of food-poisoning double classification is the most efficient." The trend in the and to limit its spread, and concludes with a homily on food larger sample was similar, but the use of a more specific bio- hygiene, both commercial and domestic. Particular emphasis chemical technique resulted in a substantially smaller estimate is laid on the necessity for regular and early notification in of patients excreting urine with the pink spot. The pink order that investigations may be started before essential spot was absent from the urine of 20 close relatives of three materials have been lost. schizophrenic patients. Here, then, is evidence in favour of another remarkable addition to the biochemical theories of schizophrenia. Investi- gators in this field, however, have learnt to tread warily round the many pitfalls that beset it, reviewed recently by S. S. Pink Spot in Schizophrenia Kety. Discussing the possible role of transmethylation, Kety cautiously refers to " some interesting findings com- Among the several biochemical processes which have been patible with provocative hypotheses but the findings and the examined as possible links with schizophrenia' an abnormality hypotheses are still in the earliest stages of evaluation." The of adrenaline metabolism has attracted attention since it was broad epidemiological approach of the Liverpool workers has proposed in 1952.2 3 The hypothesis was based originally carried the process of evaluation a stage further, but, as they on the similarity between the chemical formulae of mescaline concede, there are unresolved problems pertaining to both and adrenaline. This suggested that schizophrenics might their methods and the interpretation of their data. The results produce abnormal metabolites of adrenaline similar to mesca- of cognate work now in progress at several centres'2 will be line in their chemical structure and psychotomimetic proper- awaited with interest. ties. An interesting metabolite of mescaline is the compound 3,4-dimethoxyphenylethylamine (D.M.P.E.), a dimethylated derivative of dopamine which Friedhoff and van Winkle first reported as forming a " pink spot " chromatographically in the urine of schizophrenic patients but not in the urine of Methyldopa in Hypertension normal people. This claim, which points to a disorder of The introduction of more and more drugs for the treatment biological trans- poses for the clinician. In any methylation, has since been examined in other centres with of hypertension problems http://www.bmj.com/ conflicting results.Y'8 Recently R. E. Bourdillon and his individual case a rational choice of drug should depend on colleagues at the University of Liverpool have tried to whether that particular patient needs to have his blood- evaluate the putative association more closely.9 Using two pressure lowered, the effectiveness of a drug in lowering it, different methods of assessment, they have tested for the and the risks of its possible unwanted effects. In cases of presence of the pink spot among psychiatric in-patients, malignant hypertension with papilloedema the problem is among close relatives of schizophrenics, and among mentally simple enough, since the outlook for untreated patients is so normal people. The published results are bad' 2 that a powerful drug must be given and a high risk

striking. The on 26 September 2021 by guest. Protected copyright. pink spot was identified in the urine of only one of the 391 of unwanted effects accepted. Guanethidine has almost mentally normal people. Clinical and biochemical assess- entirely superseded the ganglion-blocking drugs for this ments were made independently by two pairs of observers purpose, but there is not yet encugh experience to say which, on two separate groups of psychiatric in-patients. In one if any, of guanethidine's relatives-bethanidine,' guanoxan,' sample of 101 cases the pink spot was deemed to be present and guanoclor5-offers real advantages. in 46 out of 84 schizophrenics, and absent in all 17 non- When hypertension is less severe, age and sex are as schizophrenics; in the other sample of 296 cases only 1 out important in prognosis as the level of blood-pressure or the of 77 non-schizophrenics showed the pink spot, while grade of retinopathy.6 For instance, elderly women tolerate it was high pressures for many years. Nevertheless, lowering the detected in the urine of 27 of the remaining 219 patients who I were regarded as suffering from schizophrenia or schizo- blood-pressure reduces mortality' and possibly also the phreniform syndromes. Further, the schizophrenic patients chance of stroke.' " Reserpine and oral diuretics have been in the smaller sample were subdivided clinically into " para- much used, and in the last three years there have been numerous reports of trials of methyldopa."-` The experi- Brit. med. J7., 1963, 1, 695. ence of Drs. P. Johnson, A. H. Kitchin, C. P. Lowther, and 2 Osmond, H., and Srnythies, J.,.Y. ment. Sci., 1952, 98, 309. 8 Harley-Mason, J., ibid., 1952, 98, 313. R. W. D. Turner, of Edinburgh, reported in the B.M.J. this 'Friedhoff, A. J., and van Winkle, E., Nature (Lond.), 1962, 194, 897. week (page 133), is particularly important because they have & Takesada, M., Kakimoto, Y., Sano, I., and Kaneko, Z., ibid., 1963, 199, 203. studied one of the largest groups of patients over a long Perry, T. L., Hansen, S., and Macintyre, L., ibid., 1964, 202, 519. period of time. ?Faurbye, A., and Pind, K., Actafschioa. scand., 1964, 40, 540. 'Kuehl, F. A., et al., Nature (Lonf), 1964, 203, 154. Exactly how methyldopa acts is uncertain, but one of its Bourdillon, R. E., Clarke, C. A., Ridges, A. P., Sheppard, P. M., Harper, metabolites may displace noradrenaline from its site of P., and Leslie, S. A., ibid., 1965, 208, 453. Schneider, K., Fortschr. Neurol. Psychwat., 1957, 25, 487. action.23 Methyldopa is rapidly absorbed and excreted,12 'Kety, S. S., Int. Yt. Psj-chiot., 1965, 1, 4(C9. and thus must be given three or four times a day. It lowers 12 Symposium on Amine Metabolism in Fchizcphrenia, Atlmntic City, April 1965 (in press). blood-pressure whether the patient is lying down or stnd-