FOLIC ACID IN AGRANULOCYTOSIS

827 with homologous phage. Micro-plaques are also found in certain cross-reactions. Plaques of subnormal size are sometimes encountered in atypical strains belonging to those that usually yield plaques of normal size. Since the routine test concentrations of the phage preparations are adjusted for the development of plaques of normal size, such atypical strains will show only imperfect clearing in the area covered by homologous phage. In an extreme case, where interpretation is doubtful, it will be necessary to resort to indirect typing by growing Vi-phage 11 on the strain and testing the phage preparations on cultures of the reference type-strains. Preservation and Maintenance of Type Cultures.-There is ample evidence that environmental conditions prevailing during long-term preservation of strains of 8,. typhi may influence their degree of susceptibility to Vi-phage 11. Reference has been made to the appearance of Type A in cultures of strains belonging to different Vi-phage types, and to a change in the direction of decreased specificity on the part of others. The relationship of such variations to medium used for the maintenance of stock cultures requires long-term study. Some strains may have a greater inherent capacity to vary than other strains. It is also possible that undesirable variants may selectively grow and survive in the presence of certain metabolites or at certain final hydrogen-ion concentrations which do not necessarily bear any relationship to that of the uninoculated medium. Meanwhile it is recommended that cultures of the Vi-type strains be maintained on Dorset egg medium, being stored in a dark and cool place, preferably at 4°C, after a minimum of incubation at 37-38°C. Fresh stock cultures should always be prepared from the oldest viable stock culture available. The following procedure has proved to be satisfactory : transfer from old Dorset egg slant to fresh Dorset egg slant and incubate over. night ; plate on agar plate and incubate overnight ; select about a dozen of the best-looking opaque smooth colonies and seed together on slants of Dorset egg medium for storage. Preservation by special procedures, such as drying, is to be avoided for the time being.

FOLIC ACID IN AGRANULOCYTOSIS

’

Preservation of Phage Preparations.-Concentrated fluid preparations of Vi-phage 11, if free from living bacteria, retain their potency unaltered for years at 4°C. The high dilutions

used for typing also keep well, at least for several months, but it is desirable to keep the volume of these to a convenient minimum, replacing them at intervals from suitable intermediate concentrations.

Vi-PHAGE

TYPING OF OTHER MEMBERS OF THE

SALMONELLA GROUP

The arrangement of types and subtypes of S. paratyphi B in the typing scheme suggested by Felix and Callow (1943) has also been based on the principles recommended here. The same applies to a typing scheme of S. typhi-murium, devised by Felix and Callow but not yet published, which has been used in the epidemiological investigation of outbreaks of food-poisoning in Britain during the past few years. For the sake of uniformity it is highly desirable that the same procedure should be followed in any future attempt at phage typing of S. paratyphi A or other member of the salmonella family. Our thanks are due to Miss B. R. Callow, of London, and Miss E. M.

testing

of of the

Clark,

some

Toronto, for

their help in preparing and and in maintaining the

bacteriophages

cultures., REFERENCES

(1940) Ibid, 31, 4 (Abstract). (1941) Piersol and Bortz, Cyclopedia of Medicine, Philadelphia, section of bacteriology, p. 5. (1942) Canad. publ. Hlth J. 33, 41. Yen, C. H. (1937) Trans. roy. Soc. Can. 31, section V, p. 79. (1938) Canad. publ. Hlth J. 29, 448, 484. Desranleau, J. M. (personal communication). A. Felix, (1943) Brit. med. J. i, 435. (1944) Brit. med. Bull. 2, 269. Callow, B. R. (1943) Brit. med. J. ii, 127. Pitt, R. M. (1934) J. Path. Bact. 38, 409. Helmer, D. E., Kerr, D. E., Dolman, C. E., Ranta, L. E. (1940) Canad publ. Hlth. J. 31, 433. Kauffmann, F. (1935) Z. Hyg. InfektKr. 116, 617. Leishman, W. (1905) J.R. Army med. Cps, 5, 1. Wilson, W. J. (1938) J. Hyg., Camb. 38, 507. Yen, C. H. (1939) Proc. Soc. exp. Biol., N.Y. 41, 162. —

—

—

-

—

—

—

-

M.B. Mane.

M.D. St.

LECTURER

IN

MEDICINE

CHIEF ASSISTANT

DEPARTMENT OF MEDICINE, ROYAL

INFIRMARY, MANCHESTER

IT has been known for some time that folic acid is effective in correcting nutritional cytopenia in monkeys (Wilson et al. 1942) ; and the granulopenia produced in rats by sulphonamides can also be prevented by folic acid. In human beings, Menten and Graff (1946) found that sulphonamide granulopenia gave no very definite response to pyridoxine and folic acid, but their daily dosage of folic acid was less than 0.2 mg. Watson et al. (1945) reported improvement in irradiation leucopenia with folic acid. In the two cases of agranulocytosis reported below the granulocytes returned to the blood-stream within forty-eight hours of giving adequate doses of folic acid. Case 1.—A woman, aged 51, was admitted to a surgical ward on Jan. 18, 1947, for operative treatment of toxic goitre. A month earlier she had had a sore throat and skin rash following barbiturate medication ; no blood-count had been done and she had recovered after the barbiturate had been

stopped.

On Jan. 18 she was given gr. 11/2 ofDial.’ Next day she became severely ill, with fever and sore throat. A bloodcount on the-20th confirmed the diagnosis of agranulocytosis-white cells c.mm. 1600 per

(0-5% polymorphs). Treatment

with

30,000 penicillin units three-hourly and ’Pentnucleotide ’ 40 ml. dailv

begun

on

the

20th ; and

on

the,

was

21st she began to have pyridoxine 200 daily. She

mg.

remained febrile, and her blood-count ’did not improve. On the 24th treatment with folic acid 20 mg. daily was started. Within forty-eight hours her temperature had fallen to normal, granulocytes had returned to the blood-stream, and she was clinically much better. A marrow smear done by Dr. H. Lempert on the 21st had shown a strik-

Fig. I—Treatment, temperature, cell counts in

case

and white-

I.

granulocytes. On the 27th granulocytes, from promyelocyte stage to fully mature polymorphs, had reappeared in the marrow. The time-relations of treatment and improvement in the temperature and blood-count are shown in fig. 1. Case 2.-A woman, aged 53, was admitted to hospital on April 5, 1947. with a history that, three weeks earlier, she had developed a vague febrile illness diagnosed as influenza. ing

lack of

the

Buckle, G. (1946) Med. J. Aust. ii, 365. Craigie, J. (1939) Canad. publ. Hlth J. 30, 37 (Abstract). —

S. W. STANBURY

D. A. K. BLACK And., M.R.C.P.

Vi-phage types

Convalescence had been slow, and on March 23 she had become with sore throat, headache, and fever. On this and several subsequent days she had been given an amidopyrine hypnotic for control of headache (she had also had amidopyrine in 1945 for migrainous headache). A throat swab had been negative, and she had been given penicillin 200,000 units b.d. for four days. She had remained ill and febrile, and on April 1 she had been given penicillin again, 400,000 units b.d.

acutely ill,

828 A blood smear taken on March 31 had been reported as suggesting leucopenia, with lymphocytes predominating, and retrospective inquiry showed that no polymorphs were seen. A firm diagnosis of agranulocytosis was not, however, made until April 5, when her total white cells numbered 900 per c.mm. After admission to hospital on April 5 treatment was with penicillin 62,500 units three-hourly ; intravenous pyridoxine 300 mg. within, the first twenty-four hours and folic acid 100 mg. followed by 20 mg. daily. Within forty-eight hours her temperature had settled and granulocytes had returned to the blood-stream. A bone-marrow smear, taken ten to twelve hours after the start of therapy, showed maturation arrest at the promyelocyte level; no mature granulocytes were seen. A further marrow smear, taken just over twenty-four hours later, showed

granulocyte development along normal lines.

Fig. 2 shows the time-relation between treatment and

improvement. COMMENTS

These two illustrate the of value penicillin in cases

maintaining

TRAUMATIC NEURITIS OF THE DEEP PALMAR BRANCH OF THE ULNAR NERVE

W. RITCHIE RUSSELL

C. W. M. WHITTY M.D. Edin., F.R.C.P. B.M. Oxfd, M.R.C.P. From the Department of Neurology, Radcliffe Infirmary, Oxford THE correct diagnosis of the cause of wasting of themuscles of the hand is clearly a matter of practical importance, and in this connexion Russell Brain et al. (1947) have recently clarified the causes of median neuritis. We draw attention here to another cause of wasting of the hand which is in our experience specially liable to faulty diagnosis. Traumatic, occupational, or pressure neuritis of theulnar nerve is a relatively common cause of such wasting. In most cases the neural injury occurs either at theelbow or at the wrist, and injury at these sites can bedistinguished by studying the muscles paralysed and theextent of the sensory loss. Injury to the deep palmar branch of the ulnar nerve’ may, however, provide a clinical picture quite unlike that generally associated with ulnar paralysis. When, it occurs without any obvious injury to the hand, the nature of the lesion is apt to be overlooked by the clinician, and indeed there is a danger that motor-neurone diseasemay be diagnosed. Anatomy.—The anatomy of the nerve in the palm is given in Cunningham’s (1937) textbook as follows : " The ulnar nerve in the hand divides under cover of the palmaris brevis muscle into its two terminal branchessuperficial and deep. The deep palmar branch is almost purely motor. It passes deeply between the flexor and abductor minimi digiti ; it supplies these muscles and the opponens digiti minimi, then turning laterally along the line of the deep palmar arch, and under cover of the deep, flexor tendons, it supplies branches to the following muscles : interossei, third and fourth lumbricals, the adductor pollicis, and the deep part of flexor pollicis brevis."

life during the period of

agranulocytosis. Pyrexia, however, continues

despite penicillin and does not settle until

po,lymorphs reappear in the circula-

ting

blood.

There is

no

a-priori to that penicillin has any stimulant action on leucopoiesis, and in both patients granulocytes had not returned after five days’ penicillin therapy. Apart from penicillin, the only drug other than folic acid given to both patients was pyridoxine ; in the first patient pyridoxine had been given, without response, for three days before folic acid was added. We realise that spontaneous remission may occur at any time in this disease, and that the appearance of granulocytes within forty-eight hours of giving folic acid to these two patients may have been merely a coincidence. We propose to treat subsequent patients with folic acid and penicillin alone ; but, since agranulocytosis is comparatively rare, others may have an opportunity of testing the value of folic acid before another case is available to us. Fig. 2-Treatment, temperature,

and

white-cell

counts in case 2.

We

are

reason

suspect

indebted to Messrs. Lederle, Inc., New York, for

supply ofFolvite.’ REFERENCES

Menten, M. L., Graff, E. (1946) Amer. J. med. Sci. 211, 672. Watson, C. J., Sebrell, W. H., McKelvey, J. L., Daft, F. S. (1945) Ibid, 210, 463. Wilson, H. E., Doan, C. A., Saslaw, S., Schwab, J. L. (1942) Proc. Soc. exp. Biol., N.Y. 50, 341.

This is its usual anatomy, but it should be borne in mind that there may be variations. The nerve occasionally supplies opponens and abductor pollicis brevis ;flexor pollicis rarely has an entirely median supply (Highet. 1943) ; and the first two palmar interossei are sometimes innervated by the median (Pollock 1919). This may cause some difficulty in interpreting theclinical signs of injury. When the deep palmar branch is injured at its origill without involvement of the superficial branch, the muscles supplied by the ulnar nerve are paralysed without sensory loss. Hunt (1914) quotes six cases observed by him in which this occurred. When, however, the deep palmar nerve is injured after its branches to the hypothenar muscles have been given off, and while running laterally with the deep palmar arch, the interossei and adductor pollicis are paralysed but the hypothenar muscles are unaffected. This isolated muscular paralysis without sensory loss constitutes the essential clinical feature of the cases here recorded. ’

Case 1.—An R.A.S.C. sergeant, aged 24, reported weakness of the right hand, with difficulty in writing, which had been present for about 15 days. Some 3 weeks previously he had ridden a motor-cycle with a defective twist-grip throttle from Algiers to Sousse, at times over rough and. difficult roads. For 24 hours after completion of this journey he had noticed paraesthesia in the little and ring fingers of the right hand. This had cleared spontaneously. During the ensuing 3 weeks he had been employed on routine short motor-cycle journeys. He had noted the weakness when trying to write a letter about a week after his long journey. It appeared to’ be

increasing.

On examination he appeared a healthy rather thick-set manThe only abnormality in the central nervous system was: weakness and slight wasting in the interossei and adductor