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PATIENT’S SCORES BEFORE AND AFTER TREATMENT WITH L-DOPA ANDRo 4-4602

Methods, see ref. 1.

100 ml.); urine copper, 312 g. per 24 hours (normalmaximum=50 {j.g. per 24 hours) before treatment and1812 g. per 24 hours after penicillamine. There was alsoabnormal aminoaciduria, with an excessive amount of

tyrosine (determination by courtesy of Dr. C. R. Scriver).A genetic study revealed the following values for plasma-copper : brother, 70 {jLg. per 100 ml.; father, 125 µg. per100 ml.; mother, 156 (.Lg. per 100 ml. The patient wastreated with D-penicillamine (maintenance dose 2 g. daily),pyridoxine 50 mg. daily, and potassium sulphide 20 mg.daily. Despite continuous treatment over a 15-month

period, her neurological condition deteriorated rapidly and,when readmitted to hospital at age 17, in October, 1969, shewas a total invalid. She had marked rigidity, a constantflapping tremor of all four limbs, and severe akinesia. Shewas unable to enunciate a single word, but her comprehen-sion was less affected. She communicated using a board onwhich frequently used words and letters of the alphabetwere printed. Her face was rigid and expressionless; hermouth was always open, and large quantities of saliva

dripped from it. She was able to turn very slowly in bed,but could not feed herself, walk, or even sit without assist-ance. There were flexion contracture in both knees, andbed-sores. No Kayser-Fleisher rings were now observed.She was transferred to the Hotel-Dieu Hospital for experi-mental treatment with L-dopa. All medication was stoppedand the biochemical tests were repeated. Caeruloplasminwas 3-2 mg. per 100 ml. (normal range 20-35 mg. per 100ml.). Urinary catecholamines were: dopamine, 194 g. perg. creatinine (normal=250-400 (.Lg.); noradrenaline, 47 (.Lg.per g. creatinine (normal=0-30 lig.); adrenaline 11-2 (.Lg.per g. of creatinine (normal=0-15 (.Lg.). Blood-phenyl-alanine was 16.0 mg. per 100 ml. (normal=12-20 g.);blood-tyrosine=5-3 Af per 100 ml. (normal=5-12 Af).Liver-function tests were grossly abnormal, and hepato-splenomegaly was confirmed by colloidal-gold (198Au)studies. Phagocytosis was grossly diminished and plasmaclearance of 198Au was lengthened (74-3% retention after4-5 minutes; normal <60%). A skin-biopsy specimenshowed typical changes of cutis hyperelastica, with fragmen-tation of deep elastic fibres and new vessel formation. Thisresembled the collagen defect reported with penicillamineby Nimni and Bavetta.9 The various symptoms, signs, andactivities before and after treatment are summarised in theaccompanying table. They were also recorded on moviefilm.Treatment was initiated with L-dopa and a peripheral

decarboxylase inhibitor, Ro 4-4602. After 2 months’ treat-ment (1000 mg. L-dopa and 200 mg. Ro 4-4602 daily) therewas a notable improvement in both rigidity and akinesia.The patient could now eat alone, get up from a chair, andwalk with the help of callipers. When L-dopa was increasedto 1250 mg. daily, she began to have great difficulty inswallowing, became catatonic, and had frequent oculogyriccrises. The drugs were stopped until all these symptomsdisappeared. Unfortunately the previous rigidity andakinesia reappeared within 6 days. L-dopa and Ro 4,4602were restarted. 1 month later (at a dose of 300 mg. L-dopa

9. Nimni, M. E., Bavetta, L. A. Science, N. Y. 1965, 150, 905.

and 150 mg. Ro 4-4602 daily) the patient had regained allthe benefits illustrated in the table and was discharged.Taking into account a 20% improvement that could beascribed to special care, physiotherapy, and placebo effect,we estimate that the patient had a further 25 &deg;o functionaland physical improvement due to L-dopa therapy. Despitetreatment, caeruloplasmin remained at 3-6 mg. per 100 ml.Serum phenylalanine (15 mg. per 100 ml.) and tyrosine(7-2 fLM per 100 ml.) were not significantly modified.The treatment of choice for Wilson’s disease is still

D-penicillamine. However, a few patients rapidly deteriorateneurologically despite adequate chelation. In those patientswe suggest that L-dopa should be tried. It is conceivablethat the specific tyrosinuria observed in this patient maycontribute to a deficit in dopamine within the alreadydamaged striatum. The new constellation of symptomsobserved in this patient with supramaximal dosage ofL-dopa may also be relevant to the aetiology of catalepsy.We thank Dr. W. MacPherson for referring the patient. The

laboratory studies were carried out with the help of grantsMA-2530 and SP-1 from the Medical Research Council of Canada.

ANDR&Eacute; BARBEAUHENRY FRIESEN.

Clinical Research Instituteof Montreal and

Royal Victoria Hospital,Montreal, Canada.

LITHIUM DEPLETION AND ATHEROSCLEROTIC

HEART-DISEASE

SIR,-Following reports on the lithium content of hardwater,’ Dr. A. W. Voors has proposed a relationshipbetween lithium insufficiency and atherosclerotic heart-disease.3 He suggests that the higher cardiovascular

mortality in softer water areas may be at least partiallyexplainable by the higher concentrations of lithium inhard water.

For the hypothesis to be even worthy of consideration, itis vital, as Dr. Voors implies, that the major component ofthe dietary lithium should originate from the ingested localwater and not from food. He concludes that this is so, andcites a review article by Schou. Unfortunately this referencedoes not directly provide the relevant data. One is forced toconclude that data from food are extrapolated from thedata on vertebrate-tissue levels of lithium (referred to inSchou’s review)-average 0-017 meq. per kg. dry weight(range 0’003-0’11).6 Dr. Voors appears to have incorrectlyconverted this figure to mg. per kg. dry weight of lithium,finding a value of 0-003 instead of 0-12 mg. per kg. dryweight.

Dr. Voors’ paper 3 suggests that, in a hard-water area, alithium level of 20 g. per litre is representative. Assumingthat 1 litre is a reasonable figure for water intake from localsources, 0-02 mg. of lithium per day are ingested from thissource. From the limited data on food values of lithium, 6,7it is clear that food sources of lithium can easily be in excessof the water source. Furthermore, from metabolic balancework by Kent and McCance it may be calculated that thedaily absorbed lithium from dietary sources is 0-7 mg.

Since the dietary contribution of lithium from watersources would then appear insignificant compared with foodsources-even in a hard-water area with relatively highlithium concentrations-the whole basis for the hypothesislinking water-lithium and cardiovascular mortality lacks

1. Blachly, P.H. New Engl. J. Med. 1969, 281, 682.2. Voors, A. W. ibid. p. 1132.3. Voors, A. W. Lancet, 1969, ii, 1337.4. Crawford, M. D., Gardner, M. J., Morris, J. N. ibid. 1968, i, 827.5. Schou, M. Pharmac. Rev. 1957, 9, 17.6. Bertrand, D. C. r. hebd. S&eacute;anc. Acad Sci., Paris. 1944, 218, 84.7. Bertrand, D. ibid. 1943, 217, 707.8. Kent, N. L., McCance, R. A. Biochem. J. 1941, 35, 837.

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experimental support. It is not surprising that an inverserelationship exists between atherosclerotic heart-diseaseincidence and lithium concentration in drinking-water sincethe data in Dr. Voors’ article show a direct relationshipbetween lithium levels and degree of hardness in drinking-water. Clearly the inverse relationship between water-lithium and atherosclerotic heart-disease is an artifact of theinverse relationship between water hardness and athero-sclerotic heart-disease. The latter relationship continuesto present a puzzle, but one not made any simpler by theintroduction of lithium.

HUGH D. LIVINGSTON.

Department of Medicine,Bowman-Gray School

of Medicine,Winston-Salem,

North Carolina 27103.

SOCIAL CLASS AND SERUM-URIC-ACID

SIR,-It is generally believed that gout is a disease ofthe rich and overindulgent, usually associated with a raisedserum-uric-acid. One may, therefore, expect some asso-ciation between the serum-uric-acid level and social class,but the reported results are contradictory. While mostprevious workers suggested a tendency for those in the highersocial classes to have higher serum-uric-acids,l,2 recentlyAcheson 3 failed to observe any such association. Wemeasured the serum-uric-acid levels in 35 female students

doing a health visitors’ course and 44 female medicalstudents of comparable age and race. We noticed a signi-ficant difference between the serum-uric-acid levels inthese two groups (P<0-02). The values (mean _hs.E.) forserum-uric-acid in the health visitors and medical studentswere respectively 3-05:0-08 and 3-32:0-07 mg. per 100 ml.The health-visitor students came from economically poorfamilies with average monthly incomes of Rs. 200 or lessand an average of six members, whereas the female medicalstudents came from economically privileged families withmonthly incomes of Rs. 500 or more, and an average offive members. This supports the view that people ofhigh social class have higher levels of serum-uric-acid.

N. SAHAB. BANERJEE.

Department of Physiology,Faculty of Medicine,

University of Singapore,Singapore 3.

STARTING FROM SCRATCH

SIR,-Sitting in my armchair, I have been able to museover my experience of fifty years or so as a pathologist andthe lessons this has brought me. Two things I havelearnt-and they may not be common knowledge, or

even true.

The first is that status asthmaticus is due to the blockageof the smaller air-passages by mucus. The second came tome as I was musing over the relief of itching by scratching(as a sufferer from pruritus senilis I have a personal interestin this), and I conceived it might be due to the release ofhistamine. Having sold my medical books and not knowingwhether histamine is a vasodilator or a vasoconstrictor, Itelephoned my friend Dr. John Mills, who also confessedhimself stumped. However, about four hours later he rangback to say,

" The information you require is in a book byDible and Davie, lst ed., 1939, p. 11." Oh Humble Pie-how revolting is thy taste.

J. HENRY DIBLE.Gerrards Cross, Bucks.

1. Cobb, S., Dunn, J. P., Brooks, G., Rodman, G. P. Arthr. Rheum.1961, 4, 412.

2. Dunn, J. P., Brooks, G. W., Mausner, J., Rodnan, G. P., Cobb, S.J. Am. med. Ass. 1963, 185, 431.

3. Acheson, R. M. Br. med. J. 1969, iv, 65.

Obituary

DULCIE ALLDIS

M.B., B.Sc. W’srand, M.R.C.Path., D.C.P.

Dr. Dulcie Alldis, who held a temporary appoint-ment of pathology at the Royal Postgraduate MedicalSchool, where she had also held previous posts, diedon April 7.

She was trained originally as a chemist and graduatedB.SC. in 1937 from Witwatersrand University. She workedin industry for a number of years, and then returned to theuniversity to study medicine. She graduated M.B. in 1950,and was appointed lecturer in the clinical pathology depart-ment of the medical school. After three years, she emi-grated to England and studied at the Royal PostgraduateMedical School. She became registrar, and later seniorregistrar and tutor at the school. In 1964, she was appointedconsultant pathologist at Watford and Mount VernonHospitals, a post which she held until 1969. A temporaryappointment at the Royal Postgraduate Medical Schoolfollowed.

I. D. P. W., to whom we are grateful for these bio-graphical details, writes:

" In her work, Dulcie Alldis’s early training as an analy-tical chemist showed clearly. The standard of work that shedemanded was difficult to achieve, no less for herself thanfor her colleagues and staff. Combined with this was a

deep interest in medical problems and a genuine concernfor the well-being of the patients. She was an exceptionalteacher, experienced and sympathetic. Her dual traininggave her a special insight into the problems of trainingmedical staff in laboratory science. Her last nine monthswas spent doing a characteristically thorough job at theRoyal Postgraduate Medical School, overhauling and

bringing up to date an important part of the hospitallaboratory service.

" Dulcie was a delightful person to know, and will besorely missed by the many friends that she made in thiscountry. She was a cultured woman with a considerableknowledge and interest in music and the visual arts. Shemade full use of the opportunities available in London."

Births, Marriages, and Deaths

BIRTHSFox-To Susan and Robin Fox, of Rotherfield, Sussex, a daughtel(Katharine) and a son (Duncan), on May 19.

AppointmentsARONSTAM, ANTHONY, M.B. Cape Town, M.R.C.PATH. : consultant

pathologist, Wessex R.H.B.BENNETT, R. J., M.B. Birm., F.R.c.s.: consultant E.N.T. surgeon, United

Birmingham Hospitals.BOLD, A. M., B.M. Oxon., M.R.C.PATH., M.C.B.: consultant chemical

pathologist, United Birmingham Hospitals.CRAWFORD, J. W., M.B. Glasg., M.R.C.O.G., D.OBST.: consultant obstetrician

and gynaecologist, Dundee and Angus area.CURRIE, SIMON, M.B. Cantab., M.R.C.P. : consultant neurologist, St.

James’s Hospital, Leeds.LLOYD-DAVIES, R. W., M.B., M.S. Lond., F.R.C.S.: consultant surgeon, St.

Thomas’s Hospital, London.METHVEN, C. T., M.B. St. And., D.P.M. : consultant psychiatrist, Greenock

and District Hospitals.POWELL, DONALD, M.B. Lond., F.F.A. R.C.S., D.OBST.: consultant ansesthe-

tist, United Leeds Hospitals.PRINSLEY, D. M., M.D. Durh., M.R.C.P.E.: consultant geriatrician, St.

James’s Hospital, Leeds.ROBINSON, D. C., B.M. Oxon., M.R.C.P. : consultant pmdiatridan, York

County Hospital and Fulford Maternity Hospital, York.