SANATORIA

402

Letters to the Editor

SANATORIA a great service to the and it is with regret that one sees the passing of such a world-famous institution as the Trudeau Sanatorium. Yet this must be only the beginning of a long series of inevitable closures unless these institutions are diverted to other work-a trend already obvious in certain sanatoria in the London area where non-tuberculous thoracic surgery is now commonplace. It is not only " declining morbidity " and the advent of chemotherapy which has produced the present lower rate of admission to sanatoria : the increasing use of domiciliary management of patients, so successful at a time when sanatorium beds were at a premium, plays its part. Experiments with ambulant chemotherapy, mentioned by Dr. Pritchard (Feb. 5), are a logical step forward, particularly for early cases of doubtful activity and " chronics." (Paradoxically, however, reliable trials of such methods would probably be best carried out in sanatoria where controlled conditions could be obtained.) One is on more debatable ground with the ill patient. Is such a patient to enter sanatorium ? I feel that an integrated scheme managed entirely from the chest clinic (" clinic management ") would make this unneces. sary. Such a scheme must include local hospital beds with thoracic surgical facilities, a well-organised domiciliary service, and provision for ambulant chemotherapy. This has positive advantages over sanatorium admission.

SIR,—Sanatoria have performed

FAULTY DETOXICATION IN SCHIZOPHRENIA

SIR,-Quastel and Wales12 showed that in catatonic forms of schizophrenia hippuric-acid excretion is lowered after administration of sodium benzoate. Others 34 have confirmed these results and extended them to other schizophrenic conditions. Various explanations were later suggested for this " faulty detoxication in schizophrenia.3 5-7 Our

present knowledge indicates acid requires the conjugation

hippuric

that the formation of of glycine and benzoate

in the presence of adenosine triphosphate, magnesium ions, and coenzyme A.8-10 In some acute schizophrenics we have found high amounts of glycine in the early morning urine (e.g., 90 µg. per mg. creatinine, as measured by quantitative paper chromatography). These patients had a low hippuricacid excretion (approximately 2 g.) during the four hours after the subsequent oral administration of 6 g. of sodium benzoate ; the amount of glycine in this urine was substantially diminished compared with the glycine in the early

morning specimen. Partial starvation, high protein katabolism, decreased thyroid function 11—13 (which is believed to be connected with the regulation of the coenzyme-A level 9), and decreased basal 5

metabolic-rate seem to be among the factors involved in this inverse relationship. Simultaneous administration of sodium benzoate and a surplus of glycine raises significantly the excretion of hippuric acid in certain schizophrenics, but only slightly in normal people.3 A surplus of substrate, however, could raise the concentration of its enzyme ; hence it is likely that decreased conjugation (utilisation) of glycine prevails during those phases of the schizophrenic process which are characterised

by low hippuric-acid test. The urinary glycine of normal people we found to be higher during the night (40-80 µg. per mg. creatinine) than in the morning (30-50 µg. per mg. creatinine). These values were also inversely related to the hippuric-acid values in normal persons after ingestion of sodium benzoate which we had found earlier to be about 10% lower during the night than in the morning.4 a

These and other data5 14—16 have led us to regard the metabolic pattern of healthy people during the night as equivalent to the metabolic pattern of certain schizophrenics during the daytime ; such a change in the diurnal rhythm suggests new lines of research in schizophrenia. A detailed account of our method and data is to be published elsewhere. These studies were made under the direction of the Saskatchewan Committee on schizophrenia research, and supported by the Department of National Health and Welfare, Ottawa, and by the Rockefeller Foundation, New York. We are indebted to Dr. Ian Clancey and Dr. J. Lucy, clinical directors, Dr.’ J. Stephen, director of laboratories, and Miss Helen Keay for their help. Department of Laboratories, General Hospital, and Division of Psychiatric Research, Saskatchewan Department of Public Health, General Hospital, ALLAN TREW Munroe Wing Research Laboratory, ROLAND FISCHER. Regina, Saskatchewan, Canada. 1. Quastel, J. H., Wales, W. T. Lancet, 1938, ii, 301. 2. Quastel, J. H., Wales, W. T. Ibid, 1940, i, 402. 3. Georgi, F., Fischer, R., Weber, R., Weis, P. Schweiz. med. Wschr. 1948, 78, 1144. 4. Fischer, R., Georgi, F., Weber, R., Piaget, R. M. Ibid, 1950,

80, 129.

5. Fischer, R. Mschr. Psychiat. Neurol. 1953, 126, 315. 6. Keup, W. Ibid, 1954, 128, 56. 7. Graetz, B., Reiss, M., Waldon, G. J. ment. Sci. 1954, 100, 145. 8. Ringler, I., Leonard, S. L. Endocrinology, 1954, 55, 363. 9. Tabachnick, I. I. A., Bonnycastle, D. D. J. biol. Chem. 1954, 207, 757. 10. Zieve, L., Hanson, M. J. Lab. clin. Med. 1953, 42, 872. 11. Malis, G. Nevropat. i. Psikhiat. 1947, 16, 66. 12. Danziger, L., Kindwall, J. A. Dis. nerv. Syst. 1953, 14, 3. 13. Reiss, M. J. ment. Sci. 1954, 100, 687. 14. Hoffer, A. Arch. Neurol. Psychiat., Chicago, 1954, 72, 348. 15. Fischer, R. To be published. 16. Ploog, D. Fortschr. Neur. Psychiat. 1953, 21, 16.

community

The patient and his family remain under the care of one physician and his team throughout the period of management - a factor of vital importance in a long-term illness involving many social and psychological factors (not to mention differin clinical opinion !). The whole of the treatment is managed locally, permitting daily visits by relatives to patients in hospital (most important for contentedness, cooperation, and good morale). The segregation of the patient in a distant institution, which houses only T.B." sufferers and is remote from civilisation, increases the sense of stigma which, all too frequently, afflicts the tuberculous patient. This is largely avoided in clinic management, for contact with ences

’’

the outside world is maintained. Sufferers from other illnesses are treated in the same hospital and patients who are back at work are met at the clinic. Under these conditions the patient’s outlook remains more normal and his return to employment needs less psychological readjustment. What will be thelong-term clinical results of such schemes? A recent five-year follow-up of 64 patients managed from Hammersmith Chest Clinic in the pre-chemotherapy era, and with much simpler facilities than those now available,’ reveals a most encouraging picture : 100% survival and 100% quiescence for 12s! cases ; 93% survival and 76% quiescence for 41 B2 cases ; 82% survival and 64% quiescence for 11 B3 cases. Satisfactory as these figures are, further improvement can confidently be expected with modern chemotherapy. Finally, the possible danger of infection in hospital and home should be mentioned because it has been grossly exaggerated, particularly recently in relation to generalhospital admission. There is no greater danger of infection in a well-run hospital containing tuberculosis wards than in one without them. In fact there is an advantage, for patients in the general wards, found to have tuberculosis, can be promptly transferred to the tuberculosis unit where special nursing precautions are taken.2 Good living standards, B.c.G. vaccination, and adequate medical supervision of the nursing staff reduce the danger to minimal levels.3 Infection in the home can also be combated once the source case is diagnosed and appropriate action taken. This depends chiefly on in hygiene,4including effective sputumadequate instruction disposal methods.5

be

I cannot agree with Mr. Temple (Jan. 8) that it would a wise investment to rebuild some of the sanatoria.

1. Stradling, P. Tubercle, 1955 (in the press). 2. Ball, K. P., Joules, H., Toussaint, C. H. C., Heady, J. A. Lancet. 1950, ii, 121. 3. Sinamonds, F. A. H. The Protection of the Nurse Against Tuberculosis. National Association for the Prevention of Tuberculosis, London, 1952. 4. Grenville-Mathers, R., Trenchard, H. J. Proc. R. Soc. Med. 1953, 46, 809. 5. Stradling, P. Lancet, 1953, ii, 1185.

403 the passing of the of the disease to which it owes its existence is bound to favour this trend. Meanwhile, we have an effective substitute in a chesteliuic service and its related hospital beds, forming a network over the country. Great improvement of this flexible service, of preventive methods and early diagnosis, should form the basis of an all-out drive against tuberculosis, needed even more now that eradication is

However much

one

may

regret

sanatorium, the steady reduction

76%, included focal abnormalities, predominantly in the temporal leads. Phenytoin sodium was the most effective anticonvulsant for the prevention of attacks, and phenobarbitone or suppositories of ergotamine tartrate and

of value in their alleviation. in each of these patients,/was of the autonomic type. The three main criteria which favour this diagnosis are : (1) recurrent and paroxysmal nature of attacks ; (2) absence of intrinsic disease of abdominal and other viscera ; and (3) positive practicable. evidence of- cerebral dysfunction as manifested by a Hammersmith Chest Clinic, PETER STRADLING. London, W.12. personal or family history of epilepsy, including migraine, a history of acquired brain damage, abnormal neurologiTHE FAMILY IN THE MODERN WORLD cal signs, E.E.G. abnormalities, and a beneficial response SIR,—It was interesting to read the condensed version to anti-epileptic drugs. With the recognition of a cerebral (Feb. 5) of Dr. Henry Dicks’s valuable paper on the origin for cyclical vomiting and other periodic dispredicament of the family in the modern world, with the orders, the child may be released from prolonged and emphasis on the harmful effect of modern urban repeated investigation, and the seizures prevented by industrialisation and housing. regular anticonvulsant medication. The prevalence of the neuroses and psychosomatic Department of Pharmacology and Pediatrics, University of disease among relatively young people is only too obvious Utah College of Medicine, and must be a reflection in considerable measure of J. GORDON MILLICHAP. Salt Lake City, Utah. the unrest and instability in the lives of many families. But we can really censure urban industrialisation for LUNGS, BONES, AND JOINTS more than a small share of this, and are Dr. Dicks’s SIR,—Your annotation last week on this subject is of long-term recommendations anything more than hopeful special concern to those, like myself, interested in the thinking ? relationship between joint and lung lesions. In 194711 Surely, the well-being, happiness, and stability of the I drew attention to fully developed Bamberger-Marie’s family are largely dependent on the influence of the disease with its soft-tissue, bone, and joint swellings mother. She should be the unobtrusive centre and —" hypertrophic pulmonary osteo-arthropathy "-occurtornerstone around which the whole unit revolves and ring as a presenting feature in some cases of bronchial devolves. May I ask what training she receives for this carcinoma. Indeed, in some of these cases the arthritic highly difficult, anxious, and onerous task ? manifestations of rheumatoid disease, the so-called Can we not lay the blame squarely on the shoulders rheumatoid arthritis, had been diagnosed and treated of our educationalists for failing to train and prepare as such for several months and yet in none were there the young girl for her vital life’s work as a wife and symptoms referable to the chest. mother? Is not the present schoolgirls’ curriculum Your annotation fails to stress the remarkable response hopelessly ill-fitted and ill-adapted for the important of such joint lesions to lung resection, when within a duties which most of them will have to fulfil in their day or two complete reversion from crippledom is future lives ?It would be a pleasant and revealing task achieved. Patients totally dependent in daily life become to design a suitable syllabus, but I am not aware that self-supporting overnight. doctors are usually accepted as educationalists. Opening a discussion on unusual manifestations of bronchial carcinoma at the section of medicine at the JOHN ROBERTS. Bangor. Royal Society of Medicine,2 I described 6 cases, from a CYCLICAL VOMITING series of 200 consecutive cases of bronchial carcinoma, to 2 cases of who presented with joint manifestations in the form of SIR,—I was interested by the reference " cyclical vomiting as " masked epilepsy in the article an acute or chronic polyarthritis as the initial complaint. In none was there any real evidence of extensive tissue by Dr. Wallis in your issue of Jan. 8. At the annual meeting of the Western Society for breakdown or appreciable infection, and the association Pediatric Research, held in Los Angeles on Nov. 20, of the joint and lung conditions on the basis of infection 1954,I presented a paper entitled" cyclic vomiting, a alone or of anoxia is difficult to explain. form of epilepsy in children The possible association of acromegaly and pulmonary (part of an article in the The that this evidence press 1). symptom complex, and osteo-arthropathy noted by Fried 3 occurred in 2 of my other associated periodic disorders of childhood, may be cases with acromegalic features. Large spade-like hands, regarded as examples of autonomic epilepsy was obtained the increased size of the bones due to periosteal reactions, from a study of 33 children. In all patients, a diagnosis of swollen joints, increased soft-tissue swellings with clubbed cyclical vomiting had been made following careful fingers, and a " clubbed nose " occurred in 2 of my cases. clinical studies to exclude intrinsic disease of abdominal The dramatic response of these swellings to lung and other viscera. The vomiting was periodic in type resection would certainly suggest that the causative and of prolonged duration ; it was associated with factor arises from within the lung. Crump4 ineriminates ketosis, and frequently with dehydration. A history of an abnormal substance circulating in the blood and progrand mal or psychomotor epilepsy was obtained in 7 ducing these bone, joint and soft-tissue swellings ; and patients, whose clinical features were similar to those with Aschoff 5 suggests that the lungs, " pulmonary glands," uncomplicated cyclical vomiting. There was a family take on additional functions as secreting organs. The few cases of pleural mesothelioma that I have history of epilepsy in 5 children (15%), 2 of whom were subject to grand-mal seizures. Evidence of acquired seen have not shown arthropathic manifestations, and I brain injury was present in 14 patients (42%), a similar question to what extent the pleura is involved in the number having persistent vomiting or feeding difficulty, osteo-arthropathy. The observations of Ray and Fisher6 including colic and rumination, during infancy. Episodic 1. P. Lancet, 1947, i, 464. symptoms, apart from vomiting, were abdominal pain, 2. Ellman, Ellman, P. Proc. R. Soc. Med. 1953, 46, 851. behaviour skin headache, disorder, fever, rash, and 3. Fried, B. M. Bronchogenic Carcinoma and Adenoma. London, joint pain. The electro-encephalogram was abnormal in 1948 ; p. 60. 4. Crump, C. Virchows Arch. 1929, 271, 467. all patients, and seizure discharges, which occurred in

caffeine

were

Cyclical vomiting, classed as an epilepsy

.

"

5.

1.

Millichap,

J.

G., Lombroso, C., Lennox, W. G. (in the press).

6.

Aschoff, L. Z. ges. exp. Med. 1926, 50, 51. Ray, E. S., Fisher, H. P. Ann. intern. Med. 1953, 38, 239.