SERUM-VITAMIN-B12 AND CHLORPROMAZINE

931 and diuretics, which produced some clinical improvement, although albuminuria did not clear completely.

prednisone

readmitted in day and a serum-albumin of 0-3 g. per 100 ml. Prednisone was re-started and albuminuria decreased for two weeks until absent, but the prednisone then had to be stopped because of severe hypertension, and the patient relapsed. He continued to have generalised oedema, and in April, 1957, was admitted to Bristol Children’s Hospital. Investigations at this time showed : bloodurea 114 mg. per 100 ml. ; urine-albumin 12 g. per day; plasmaalbumin 1-3 g. per 100 ml.; serum-cholesterol 730 mg. per 100 ml. ; and a urine deposit of red-blood cells and granular casts. Prednisone in doses up to 20 mg. per day produced no significant improvement, and he continued on a maintenance dose of 10 mg. per day. In February, 1958, so severe was the oedema that the use of Southey’s tubes was considered. The patient went home and continued to be given prednisone. At this time the general practitioner (the late Dr. John Evans) changed the prednisone 20 mg., to triamcinolone 24 mg. per day. The albuminuria rapidly disappeared; there was simultaneous diuresis and clinical improvement. The patient was on triamcinolone for several weeks, and remained in remission for three years, except for minor episodes of albuminuria, usually following upper respiratory infection which responded to an antibiotic and a short course of triamcinolone. In April, 1961, the patient relapsed, and was readmitted with gross oedema. He was given prednisone, but his condition had not responded after two weeks and so triamcinolone in :omparable doses was given instead, and a complete remission developed in the next ten days. During this admission renal biopsy was performed and showed minimal glomerular damage with slight thickening of the basement membrane, and foam cells in the tubules. Since then the patient has received a maintenance dose of triamcinolone, usually 8 mg. daily, and has remained free of proteinuria, except for minor relapses which respond to an increase in dose. CASE 2.-This boy was aged sixteen years when he developed oedema in June, 1964, a week after an upper respiratory infection. He was admitted to hospital with generalised oedema two weeks later. Blood-pressure was normal. Investigations showed: urine-protein 12 g. per day; blood-urea 15 mg. per 100 ml.; plasma-albumin 1-4 g.; and serumcholesterol 496 mg. per 100 ml. Renal biopsy showed, on light microscopy, minimal glomerular damage, and on electron microscopy, smudging of podocytes and a normal basement membrane. He was treated with a single dose of corticotrophin1 (80 units), followed by prednisone 60 mg. a day for the first ten days, and 40 mg. a day afterwards. The patient was transferred to this infirmary five months after admission. He was cushinoid with prominent striae and generalised slight cedema. Investigations showed : urineprotein 10 g. per day; serum-albumin 0-2 g. per 100 ml.; serum-cholesterol 520 mg. -per 100 ml.; L.E. cells not found; antistreptolysintitre normal; and erythrocyte-sedimentation rate (E.S.R.) (Wintrobe) 38 mm. in the lst hour. The prednisone was reduced slowly with improvement in the cushinoid features, but protein loss continued at 4-10 g. per day. In January, 1965, the patient was started on triamcinolone 16 mg. daily, and within three days he felt better, and lost weight owing to diuresis. All urinary protein disappeared within a week. The plasma-proteins returned to normal, and the E.s.R. to 2 mm. in the 1st hour. He has remained well since this time, but there was an asymptomatic return of slight proteinuria when the dose was reduced to 8 mg. daily, but this disappeared when the dose was increased to 12 mg. per day. A similar response in infancy has been reported by Paul,2 who found three patients in whom triamcinolone was more effective than prednisone. Since reversible myopathy is a well-recognised complication of triamcinolone therapy3 it is

He relapsed

on

stopping

the

drug,

and

was

September, 1956, with albuminuria of 16-20

1. 2. 3.

g. per

Lancet, March 19, 1966, p. 644. Paul, F. M. Singapore med. J. 1961, 2, 58. Williams, R. S. Lancet, 1959, i, 698.

better to start with prednisone or prednisolone, but we suggest that rather than continue these steroids for three months the prednisolone failures should be given triamcinolone for the last six weeks. The number of patients in whom it is necessary to use the potentially toxic alternatives suggested might be reduced, and a more significant estimate of the value of triamcinolone could be obtained. Department of Medicine, M. S. KNAPP Royal Infirmary, Bristol 2. J. E. CATES.

RABIES SiR,—The possibility raised by Dr. Grant (April 16) of rabies being brought into the country by infected bats is real, although evidence is not available that this has happened yet. Rabies has, however, been found in a recently imported monkey,l and it may be emphasised again that other animals, including leopards, foxes, skunks, racoons, and the mongoose family, are also susceptible. To the persons at risk through exposure abroad it may now be necessary to add those who handle various animal species in this country either as pets or while the animals are in transit, and persons whose curiosity impels them to handle bats or animals found in unusual circumstances. The precise role of bats in rabies epizootics is uncertain, however. Most of the United States have reported rabies in bats, but there is apparently no good evidence either that there is a rabies reservoir in normal bats or that bats may initiate new foci of rabies in animals. In the report by Constantine2 the 22 animals which developed rabies consisted of coyotes and foxes; 5 other animal species, including domestic dogs, cats, racoons, skunks, and opossums, similarly exposed did not develop rabies, perhaps indicating a greater resistance on their part to the bat-strain of virus. There

are two

points

which may be made:

1. Persons handling exotic animals in transit should be advised to have rabies vaccine prophylactically. 2. When there is a possibility of rabies, diagnosis is by fluorescentantibody and mouse-inoculation techniques, and this laboratory is willing to accept suspect material for investigation. Virus Reference Laboratory, Central Public Health Laboratory, London N.W.9.

A. D. MACRAE.

SERUM-VITAMIN-B12 AND CHLORPROMAZINE SiR,—The isotope dilution or saturation assay-method for measuring serum-vitamin-B123 has been in use in this laboratory since 1960. In our technique normal serum is used as a binding reagent, and free and bound fractions are separated by charcoal (whether coated or not is irrelevant), although in our initial studies equilibrium dialysis was employed as the method of

separation. In 1963 the Radiochemical Centre, Amersham, informed us production of 5’Co-labelled vitamin B12 of a nominal specific activity of 300 jj.C per .g., and kindly supplied us with it for use in our assay procedure. We have reported our preliminary findingswhich indicated that sensitivities below 1 [1.[1.g. per ml. of incubation medium could be attained. We subsequently noted that we could not confirm the figure for specific activity claimed by the Radiochemical Centre despite chromatographic purification of the radioactive vitamin B12 undertaken in an attempt to exclude possible unlabelled contaminants which might simulate vitamin B12 in our assay.5 We have repeatedly confirmed these findings on several batches of vitamin B12 of high specific activity, and we have therefore slightly modified our method, pending resolution of our disagreement with the Radiochemical Centre, so that a precise

of the

1. 2. 3. 4. 5.

Sunday Times, April 17, 1966. Constantine, D. G. Publ. Hlth Rep., Wash. 1962, 77, 287. Barakat, R. M., Ekins, R. P. Blood, 1963, 21, 70; Lancet, 1961, ii, 25. Ekins, R. P., Sgherzi, A. M. Radioaktive Isotope in Klinik und Forschung: vol. VI; p. 466. Munich, 1965. Ekins, R. P., Sgherzi, A. M. Radiochemical Methods of Analysis: vol. II; p. 239. International Atomic Energy Agency, Vienna, 1965.

932 either of the specific activity or of the purity of the material is unnecessary.55 According to our measurements, the highest specific activity of the material prepared by the Radiochemical Centre has been of the order of 80C per g. Measurements of specific activity on crystallised vitamin B12 of nominally lower specific activity (70 C per .g.) have yielded much closer agreement with the Amersham value, our estimate being 61 C per g. We have also examined vitamin B12, of high specific activity, from another commercial source; our results on one batch suggested slightly closer agreement with the value claimed, as well as yielding a figure higher than we had previously encountered (our own estimate was 147 C per-[1.g., compared with the stated value of 268 V.C per (g.). Nevertheless the discrepancy is considerable, and our suspicion remains that unlabelled contaminants, possibly similar in structure and binding characteristics to cyanocobalamin, are present in vitamin-B12 preparations of high specific activity (particularly those not recrystallised before despatch). Using material of over 100 C per .g., we introduce some 10[1.[1.g. of tracer in each assay-tube; lO[1.C, costing some E20, is therefore sufficient for 6000 assay-tubes. In our routine method, 14 tubes in a run represent standards; hence the cost of an assay depends on the number of unknowns included in the run. The total cost of the radioactive vitamin B12 used in an assay of 20 sera (done in duplicate), which constitutes for us an easily manageable set, is thus about 4s., or less than 3d. per

knowledge tracer

serum-sample. Certain reservations that we harbour about the identity of vitamin B12 extracted from serum with crystalline cyanocobalamin usedas a standard have inhibited us from publishing, since 1965, a fuller, definitive, account of our method. Nevertheless we routinely observe a degree of reproducibility and precision superior to microbiological assay, and the cost, both in technicians’ time and in materials used, is small. We have, therefore, no hesitation in commending our radioactive method of vitamin-B12 assay (we cannot speak authoritatively of the method described by Lau et al. 6) as a very simple technique which gives results correlating well with clinical expectation and which is unaffected by the presence of antibiotics in the

assayed serum. Nevertheless a question-mark hangs over the composition of vitamin-B12 preparations of high specific activity. Until the anomaly arising from contradictory estimates of their specific activity is resolved, we advise circumspection in their use in assay methods which implicitly depend on their chemical purity. We are receiving the fullest cooperation from the Radiochemical Centre in attacking this problem. Institute of Nuclear Medicine, ROGER EKINS The Middlesex Hospital, A. M. SGHERZI. London W.1.

" Seymour Jones was a most stimulating person, and at his outpatient and operating sessions was always an exciting experience. His enthusiasm for trying out new surgical procedures, and for improving and adapting them, was inexhaustible, and his training in general surgery made him more able than most of his colleagues to extend the scope of his operative technique. He began his work at a time when men with real surgical experience were taking up the specialty and replacing those whose training had been that of physician or of general practitioner. It was he and his contemporaries who converted rhinolaryngology into a true surgical specialty. He was never satisfied with the existing surgical instruments and was constantly devising new ones. Many were made for him by a firm whose premises were just across Edmund Street, and it was usual for a morning or an afternoon at the hospital to be rounded off by a visit to this firm, with a pocketful of instruments in various stages of development and a head full of new attendance

ideas. He was a true Edwardian in his easy assumption of command in his clinics and in the operating-theatre. At the same time, his entire lack of pomposity and his warm friendliness for those who worked with him differentiated him from his Victorian predecessors. His love of outdoor pursuits and sport was again typical of his period, and he was always able to find time for them. It was characteristic that, almost immediately after my appointment as his house-surgeon, he made me a temporary member of his golf club and his tennis club, gave me an introduction to his tailor, and took me home to meet the family. He was able to continue to enjoy his outdoor life, especially the fishing and shooting in Merionethshire, until his 90th year, when his heart began to fail. He died in peace in his son’s hospital."

In 1906 Mr. Seymour Jones married Hilda Katherine Poole. She survives him with a daughter and a son, who is senior ear, nose, and throat surgeon to the Portsmouth hospital group. A memorial service for Mr. Norman Lake will be held in St, Martin-in-the-Fields Church, Trafalgar Square, on Friday, May 6, at 11.30 A.M.

Appointments M.B.

JONES

He

qualified from St. Thomas’s Hospital in 1901, and served as a house-surgeon in the aural department there under Charles Ballance and Herbert Marriage. He took the F.R.C.S. in 1903 and then went to Vienna where he studied under Adam Politzer. On his return from Austria, Seymour Jones moved to Birmingham and he was appointed to the staff of the Birmingham and Midland Ear, Nose, and Throat Hospital, and joined Colonel Frank Marsh in private practice. During the 1914-18 war Seymour Jones served in the R.A.M.C. as aurist Lau, K.-S., Gottlieb, C., Wasserman, L. R., Herbert, V. Blood, 1965, 26, 202.

Aberd., F.R.C.S.,

F.R.C.S.E.:

consultant surgeon, East

consultant ophthalmic surgeon, London. CRAVEN, J. D., B.M. Oxon., M.R.C.P., F.F.R., D.M.R.D., D.OBST.: consultant radiologist, diagnostic X-ray department, Royal National Orthopedic Hospital, and senior lecturer, Institute of Orthopaedics, London. IRELAND, J. A., M.B. Birm., M.R.C.P., D.P.M.: consultant psychiatrist, Aylesbury/High Wycombe area, based on St. John’s Hospital, Stone. PETTY, B. W., M.B. Birm., M.R.C.P., D.OBST., D.C.H., D.M.R.D.: consultant radiologist, St. Luke’s Hospital and Huddersfield Royal Infirmary. ScoTT, OLIVE, M.D. Sheff., M.R.C.P., D.C.H. : consultant pasdiatric cardiologist, General Infirmary and Killingbeck Hospital, Leeds. SLAWSON, K. B., M.B., B.sc. Edin., F.F.A. R.C.S.: consultant anoesthetist, Edinburgh hospitals, mainly Western General Hospital. M.B.

St. Bartholomew’s

Mr. B. Seymour Jones, who died on March 24, at the age of 90, was for many years in practice in Birmingham. He was also surgeon to the Birmingham and Midland Ear and Throat Hospital.

6.

F. C. 0. writes:

ABERNETHY, B. C., Fife hospitals. BEDFORD, M. A.,

Obituary BERTRAND SEYMOUR F.R.C.S.

hospitals in the Southern Command, and in the 1939-45 war he returned from his retirement in Merionethshire to work at hospitals in Towyn and Machynlleth under the Emergency Medical Service. He continued as consultant to these hospitals until 1953. to

Lond., Hospital,

F.R.C.S.:

South West Metropolitan Regional Hospital Board: ASHWORTH, A. N., M.D. Manc., D.O.M.S. : consultant ophthalmologist, Chichester and Graylingwell hospital group. CooMES, E. N., M.D. Lond., M.R.C.P., D.PHYS.MED. : consultant rheumatologist, Chelsea and Kensington hospital group. DE MOWBRAY, M. S., B.M. Oxon., D.P.M.: consultant psychiatrist, Banstead Hospital, Sutton, and St. Mary Abbots Hospital, London. DuNN, T. L., M.B. Belf., M.R.C.P., M.R.C.P.G., D.P.M.: consultant psychiatrist, Belmont Hospital, Sutton. FRIEDMANN, A. 1., M.B. W’srand., F.R.C.S., D.O.M.S. : consultant ophthalmologist, South West London hospital group, and clinical reader, research department of ophthalmology, Royal College of Surgeons of England. LYTTON, ALFRED, M.B. Lond., F.R.C.S., D.o.: consultant ophthalmologist, Worthing hospital group and West Sussex school eye clinics. WHITELEY, J. S., M.B. Leeds, M.R.C.P.E., D.P.M. : medical director, Henderson Hospital, Sutton.