MULTIPLE MYELOMATOSIS AND MACROGLOBULINÆMIA

26 himself to walk, invalid chair.

,

during adolescence, by pushing

a

pram

or an

Poliom.yetitzs.-At the age of 33 he had poliomyelitis. On the seventh day of his illness he was admitted to a fever hospital in a confused state, with urinary retention and severe paralysis of both legs. Lumbar puncture produced fluid containing protein 100 mg. per 100 ml. and 80 cells per c.mm., of which 90% were lymphocytes. When I saw him on the ninth day of his illness he was cooperative and intelligent, with normal chewing, swallowing, coughing, and phonation. There were constant incoördinated roving movements of both eyes, of long standing. Apart from an increase of the jaw-jerk his cranial nerves were normal. His arms showed symmetrically increased reflexes, without obvious spasticity or weakness. His trunk showed absent superficial and deep reflexes, and his knee and ankle reflexes also were absent. A pinprick on the foot produced an extensor flicker of the big toe, whereas plantar stroking produced a flexor response. Voluntary movement in the legs was almost completely lost ; but curiously enough there appeared to be some residual spasticity-a finding which Dr. Ritchie Russell, who kindly examined the records, regards as possibly due to shortening and tightening of the muscles. Sensation was normal everywhere, and the urinary bladder was palpable above the pubes. During the seventh week of his illness he was transferred to an orthopsedic ward. Progress.-He was re-examined fifteen months later, when bilateral arthrodesis of the ankle-joints had been performed

Many thanks are due to Dr. J. C. H. Mackenzie and Dr. L. Morris for permission to publish, and to Dr. L. Hahn and Dr. W. Ritchie Russell for helnful criticism. REFERENCES

Apert, E., Duhem, P., Baillet, M. (1931) Bull. Soc. Pédiat. Paris, 29, 74. Russell, W. R. (1947) Brit. med. J. ii, 1023.

Preliminary Communication MULTIPLE MYELOMATOSIS AND MACROGLOBULINÆMIA DIFFERENTIATION BY STARCH-GEL ELECTROPHORESIS

MULTIPLE myelomatosis and macroglobulinaemia are hard to distinguish. The clinical features are not always clear-cut 1; Bence Jones proteins may be present in the urine in both conditions 2 ; the abnormal globulins in the serum cannot be distinguished by paper electrophoresis 1 ; and the Sia water-test is unreliable.3 The only conclusive evidence is an ultracentrifuge finding of significant amounts (more than 5%) of one or more proteins of high molecular weight, with sedimentationconstants, at zero concentration, greater than 15 S.4 I have found, however, in two cases of myelomatosis and two of macroglobulinaemia, that though the abnormal serum-globulins had identical mobilities when subjected to paper-electrophoresis, their mobilities were strikingly

different

starch-gel supporting-medium. Paper-electrophoresis of the sera was carried out essentially by the method of Flynn and De Mayo,5 and showed in each case a sharp, strongly staining band, with the mobility of a slow y-globulin (fig. 1). Starch-gel electrophoresis was carried out as described by Smithies,6 using the filter-paper method of inserting the serum. When the electrophoresis was complete, the starch-gels were stained with naphthalene black. The on a

showed a strong, intense band with the slow mobility y-globulin, which was absent in the macroglobulin sera (fig. 2). On staining with naphthalene black, the papers used for inserting the myeloma sera showed only faint traces of protein remaining after electrophoresis (presumably due to a slight amount of adsorption and to the presence of proteins of such low mobility that they had remained at the starting-

myeloma

sera

of

Patient’s

legs fifteen months after poliomyelitis.

and he

was just beginning to walk on his own with the aid of leg callipers and crutches. He had resumed playing the piano and was regularly accompanying for the Sunday

two

services in the ward. Examination of his cranial nerves showed no change. His arms showed symmetrically increased reflexes, with very slight spasticity limited to the right arm. Apart from a little right deltoid weakness, without apparent wasting, there was no other demonstrable lower-motor-neurone involvement of his upper limbs. The trunk showed slight wasting of the sacrospinalis muscle in its lower portion, with cephalad deviation of the umbilicus on active head flexion. The oblique abdominal muscles were fairly firm, but the psoas-iliacus muscles were greatly weakened. The deep abdominal reflexes were increased, and only the right lower superficial abdominal reflex was absent, as were both cremasteric reflexes. Both legs now showed profuse weakness and wasting with complete flaccidity, the knee, ankle, and plantar reflexes being absent. Sphincter control had returned to normal, and diaphragmatic

a

1. Mackay, I. R. Aust. Ann. Med. 1956, 5, 244. 2. Pernis, B., Wuhrmann, F., Wunderly, C. Acta hœmat. 1954, 11, 309. 3. Waldenström, J. Advanc. intern. Med. 1952, 5, 398. 4. Pederson, K. O. Ultracentrifugal Studies on Serum and Serum Fractions. Uppsala, 1945. 5. Flynn, F. V., De Mayo, P. Lancet, 1951, ii, 235. 6. Smithies, O. Biochem. J. 1955, 61, 629.

were normal on radioscopy. accompanying figure shows the severe wasting of the leg muscles, the formerly more spastic right leg being the more severely affected. Discussion This patient was afflicted with congenital spasticity affecting his lower limbs severely and his right upper limb slightly. When he developed paralytic poliomyelitis, the neurones supplying the spastic limbs were the most affected, and only the spastic limbs developed flaccid

movements

The

paralysis. Spasticity

indicates excessive activity of the lower motor neurone, comparable perhaps to severe exertion in the normal. Possibly this heightened activity was to some extent responsible for the distribution and severity

Fig.

electrophoresis patterns of (I) myeloma serum, (2) normal serum, (3) macroglobulin serum (case 2).

I-Paper

-

of the

paralysis.

27

Reviews of Books The

Uniqueness

of the Individual

MEDAWAR, F.R.S., Jodrell professor of zoology and comparative anatomy, University College, University P. B.

of London. London: Methuen. 1957. Pp. 191. 18s. THE title of this volume is that of its last chapter, in which Professor Medawar describes in summary the position of skin-grafting and transplantation immunity, to which he and his team have contributed many of its modern foundations. The sections of his book are based on previous essays and lectures-they include a commendably incisive presentation of the meaning and importance of the Darwinian and Lamarckian models of evolutionary inheritance, and a critical account of the

handful of " respectable " experiments which have been advanced in support of the Lamarckian;there is also a reprinting of an essay on the nature and study of ageing, and of an inaugural lecture on its evolutionary biology. These contain important matter and have been

frequently quoted ; it is good to see them made accessible here. Essays on the biological imperfections of man, on pattern in organic growth, and on the philosophical implications of the scientific method represent

Fig. 2-Starch gel patterns of (I) myeloma serum, (2) normal serum, (3) macroglobulin serum (case 2). The filter-paper method of sample insertion was used ; the position of sample is indicated by cross-hatching. Nomenclature according to Smithies.

position). In contrast, the papers from the macroglobulin gels stained intensively, indicating that the macroglobulins were still in the paper at the point of insertion. In the ultracentrifuge,* both myeloma globulins gave S2o,w values of 5-8 S at a sernm dilution of 1 :4 in 0-2 Jf NaCl solution. At the same serum dilution, the values for the macroglobulins were S20,W 15.3 S and 13.8 S. When examined over a serum-dilution range, the second macroglobulin serum gave an extrapolation figure at zero concentration of 18.5 S ;an even higher figure would be expected with the first serum.7 These findings suggest that the molecular weights of the macroglobulins are of the order of 1,000,000, and of the myeloma globulins about 150,000. Difference in the size of the macroglobulin and myeloma-globulin molecules could account for their behaviour on starch-gel electrophoresis. But I found that p-liproteins (M.w. 1,300,000 11) migrated through starch gels,9 while Smithies showed that fibrinogen (M.w. =— 300,000 8) would not migrate. It seems likely, therefore, that the behaviour of macroglobulins and indeed other proteins on starch gels is a function of both molecular size and shape, as well as other factors. I am now investigating the possibility of using starchgel electrophoresis as a means of preparing pure macroglobulins and of differentiating macroglobulinaemia from myeloma without the aid of the ultracentrifuge. =

=

I wish to thank Dr. D. H. Curnow for advice and encourage-

ment,and Mr. R. Van Raalte and Mr. M. Hambly, department of medical photography, Royal Perth Hospital, for valuable technical assistance ; also Dr. J. O’Dea, Commonwealth Serum Laboratories, Victoria, for the ultracentrifuge measurements, and Dr. 1. R. Mackay and Dr. T. H. Hurley for kindly supplying the serum of the second case of macroglobulinaemia. Department of

Biochemistry, Royal Perth Hospital, Perth, West Australia *

HELEN JEANETTE

SILBERMAN †

B.Sc. West Australia

Spinco

model-E ultracentrifuge ; rotor An-A ; centrifugal number X gravity 182,000 ; serum-dilution of 1 z 4 in 0-2 M NaCl solution ; pH 7-0; temperature of rotor 20°C. t Present address : Department of Biochemistry, University of Melbourne, Victoria, Australia. 7. Svedberg, T., Pederson, K. O. The Ultracentrifuge. Oxford, 1940 ; pp. 26, 406. 8. Oncley, J. L., Scatchard, G., Brown, A. J. phys. Chem. 1947, 51, 184. 9. Silberman, H. J. Biochim. biophys. Acta (in the press.)

force,

=

=

other facets of the author’s very substantial contribution to the thinking side, as it has been called, of modern biology. His prose style fits well in the English tradition of expository biological writing ; it would repay reading if only for the demonstration it gives of the concrete scientific advantages of literacy, and the medical reader will find few books of comparable length which give so good a picture of the intellectual and practical approach of modern biology to its material. A Student’s Histology H. S. D. GARVEN, B.SC., M.D., F.R.F.P.S., reader in histology, Institute of Physiology, University of Glasgow. Edinburgh : E. & S. Livingstone. 1957. Pp. 650. 55s.

IN the fatter textbooks, it sometimes seems that the ordinary student’s needs are forgotten in the elaboration of the author’s ideas. But Dr. Garven’s new book, big it is, fulfils its title. The text is pleasantly broken up by illustrations, and the frequent paragraph headings also add to the reader’s ease. The liberal use of diagrams is another attractive feature, and by this means Dr. Garven has avoided what can easily become a fault in books designed for studentsover-lavishness with photomicrographs. As well as emphasising points described in the text, good diagrams also serve to direct attention to the study of actual microscopic preparations. Too many photomicrographs may mean that original slides are neglected. Photomicrographs are here confined to the places where they are likely to be most useful; and diagrams in colour emphasise certain features, such as the varying appearances of a single tissue when stained by various techniques. The descriptive writing is clear, and the production of the book excellent. Dr. Garven has brought welcome aid to teachers and students by this lucid exposition of histological essentials. as

Occupational Therapy Principles and Practice.

2nd ed. Edited by WILLIAM RusH DUNTON, JUN., M.D., founder and former editor of the American Journal of Physical Medicine, and SIDNEY LICHT, M.D., editor emeritus of the journal. Springfield, Ill. : Charles C. Thomas. Oxford : Blackwell Scientific Publications. 1957. Pp. 373. 60s.

AN introduction says that this book is written " by If they judge it on that basis, and for physicians." and repetitive. some readers may find it unnecessarily longbut It is not set out as a book of reference, rather as a symposium by seventeen contributors on special aspects of the subject. There are chapters on the special applications of occupa-

tional therapy in paediatrics, psychiatry, cerebral palsy, upper-limb amputations, tuberculosis, and cardiac disease, and an admirable one by Lord Amulree on the specific problems of geriatric practice. Finally, a whole chapter is devoted to the use of music in hospitals and another to what is termed

"

bibliotherapy."