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production of keratohyalin, and the " hard keratin"which results has physical and chemical peculiarities.The distal nail-bed as well as the matrix has no granularlayer, and unless it were " onychogenic " one would

expect to find it giving rise to parakeratotic horn, whichis friable. The enlargement and disappearance of thesespots are less easily explained if they are due to structuralchanges in the nail, since one must then assume that fullyformed nail is still alive. If the white spots were due tofoci of parakeratosis it seems most improbable that thiscould be altered to give rise to normal nail.White spots are common in normal people but are

apparently confined to the finger-nails. They may becongenital and affect a single nail or part of a nail.Disorders to which leukonychia has been ascribed includepsoriasis, leprosy, fevers, arsenic and thallium poisoning,fluorosis, and trichinosis. The common disorders of thenails-psoriasis, eczema, and fungus infections-usuallydiscolour the nails yellow, brown, or black. Withsubungual haemorrhage the nail is blue or black. Anunfamiliar cause of such haemorrhage is epidermal hyper-sensitivity provoked by " undercoats " applied to rendernail-varnish more permanent. Argyria causes bluish-violet coloration of the nails ; and a fixed drug eruptiondue, for example, to phenolphthalein may appear in thenail-bed as a dusky erythematous patch. Violaceousbands have been seen in congenital syphilis ; and thosewho served in the Far East in the late war became accus-tomed to a purplish discoloration of the nail-bed inmen who were taking mepacrine prophylactically. Greennails have been attributed to infection with commonskin fungi or to superinfection with Pseudornonas

aeruginosa. Heller 4 lists as occupational stigmata greennails in pea-shellers, red nails in vineyard workers, andblack nails in feltmakers ; and he has seen blackish-brown nails in April to June, due to exposure to formicacid, in " seekers after ants’ eggs."

4. Heller, J. Die Krankheiten der Nägel. Berlin, 1900.5. Rylander, G. Int. Congr. Phys. 1947.6. Halstead, W. C., Carmichael, H. T., Bucy, P. C. Amer. J.

Psychiat. 1946, 103, 217.7. Halstead, W. C. Brain and Intelligence. Chicago, 1947.8. Le Beau, J., Petrie, A. J. ment. Sci. 1953, 99, 53.9. Petrie, A. Personality and the Frontal Lobes. London, 1952;

see Lancet, 1952, ii, 770.

ASSESSMENT OF LEUCOTOMY

PREFRONTAL leucotomy should be a convenient

meeting-ground for clinician and experimental psycho-logist. By providing what is practically an experimentalincision into the frontal lobe it has challenged the

ingenuity of the research-worker to uncover the functionsof a part of the brain of which little is known with

precision. At first this ingenuity was limited to specula-tion, and " a skyscraper of theory was erected on anunstable foundation of insufficient fact " 5; but when theexperimental psychologist entered the field, the ingenuitywas extended to method. One American worker, who hadcomplained that " not a single patient has been ade-quately studied," produced a book in which mathe-matical treatment ran riot ; and the same line of

approach is taken in an article by Le Beau and Petrie.8 8Giving brief statistical conclusions from the applicationof ten or more tests to 35 patients, who among themhad some twelve different operative lesions, this workadds to the number of combinations of cuts, tests, andpatients which Mrs. Petrie described previously.9 Therisk in such work, however, is that zeal for objectivitymay lead to a preoccupation with technique. Theclinician, at least, is likely to find himself less interestedin the test data than in the authors’ observation (men-tioned almost as an afterthought) on the patients’attitude to time. We know that after leucotomy somepatients have an altered appreciation of time, and thisM something not yet analysed. In relation to pain,Le Beau and Petrie say there is increased orientation

to the present, as opposed to the past and future ; theleucotomised patient contends with present pain only,thus making a long-continued pain more bearable.This touches one of the clinician’s topical interests, andis the kind of observation that could be followed by anempirical investigation along traditional lines.

"

Science," says Professor Zangwill, " aims at a

quantitative treatment of its data, but the scientistshould never allow himself to become bemused by theprestige of numbers." 10 " In studying problems of

temperament," he continues, " it may well turn outthat the descriptive method, despite its notable lack ofprecision, has the greater value. Empirical science isnot in the first place a technique : it is an attitude ofmind." To the clinician it must seem that what isneeded for the assessment of leucotomy is the use ofestablished case-history methods, but in a more controlledfashion than is commonly needed in clinical practice,combined (where appropriate) with a more generousand flexible use of psychometric tests.

10. Zangwill, O. L. Introduction to Modern Psychology. NewYork, 1950.

11. See Lancet, 1952, ii, 122, 377.12. Lasky, M. A., Pincus, M. H., Katlan, N. R. J. Amer. med. Ass.

1953, 151, 1403.13. Valentine, R. C., Bradfield, J. R. G. Nature, Lond. 1953, 171, 878.

TOXICITY OF CHLORAMPHENICOLADMINISTRATION of chloramphenicol may result in

aplastic anaemia 11 or other side-effects, including anaphy-lactic reactions, cutaneous eruptions, moniliasis, andirritation of the mucous membranes. Lasky et al. 12

describe a case of bacterial endocarditis in which adminis-tration of 6 g. of the drug daily for six weeks led tosevere anaemia followed by retinal haemorrhages andbilateral optic neuritis. After the chloramphenicol wasdiscontinued the anaemia disappeared, but the visionremained seriously and permanently affected. This

report should not deter doctors from using chlor-

amphenicol ; for the dosage was very large, and thedrug was given for a long period. It is well known that

compounds containing a benzene ring with a nitro-groupattached-as in chloramphenicol-are potentially toxic.In moderate dosage, and for short-term administration,chloramphenicol is safe enough ; but the use of otherantibiotics should always be considered if medicationhas to be long continued.

COUNTING BACTERIAIN microbiology it is often necessary to determine the

number of living or dead bacteria contained in a fluid-for example, milk or a bacterial vaccine. The number ofliving organisms is usually estimated by counting thenumber of colonies which develop after a known volumeof the fluid has been spread over a solid medium ; whiletotal bacteria, living or dead, are usually enumerated bycomparing the fluid with tubes of standard opacity.Both these techniques are subject to various errors, andtheir use in assessing the proportion of living bacteriain a fluid is liable to be fraught with inaccuracy. Valentineand Bradfield 13 have now described an elegant andaccurate method for determining the number of livingand dead bacteria simultaneously. The method dependson the fact that 3% urea inhibits cell-division of certainorganisms but does not affect cell-growth, so that livingbacilli develop into long filaments, which can easily bedistinguished microscopically from the normal-sized deadbacilli.By this method a collodion film, supported on a

stainless-steel specimen grid, is laid on to nutrient agarcontaining 3% urea. A drop of the fluid in which thebacteria are to be enumerated is placed on the collodionand the whole is incubated at 37°C for 3 hours. The gridis then fixed in osmium tetroxide or formalin vapour,washed in distilled water, dried, and examined with anelectron microscope. The proportion of living organisms

1240

is readily determined by a differential count of thenumbers of filamentous and normal cells.The method appears to give accurate results within the

limits of normal sampling errors. It has its disadvantages,however. The use of an electron microscope is perhapsnot essential, though it seems to provide the only reliablemeans of distinguishing between very short bacilli andparticles of medium or detritus. Electron microscopy isalso necessary if lysed cells are to be included in thecount. The main disadvantage of the technique is that itcannot be used to count cocci, which do not develop intogiant forms in the presence of urea, or organisms whichnormally contain filamentous cells. The organisms whichhave been counted successfully are various strains ofbacterium, chromobacterium, pseudomonas, and a

paracolon bacillus. -

The usefulness of this method in routine work is clearlylimited, but it may find a place in the armamentarium ofthe research-worker. Valentine and Bradfield have

applied it successfully to the study of the resistance ofbacteria to drying and also of the effects of radiations onbacterial cells.

1. Lejars, F., Rubens-Duval, H. Rev. Chir., Paris, 1910, 41, 751.2. de Santo, D. A., Tennant, R., Rosahn, P.D. Surg. Gynœc.

Obstet. 1941, 72, 951.3. Harkness, G. G. Aust. N.Z. J. Surg. 1952, 22, 60.4. Hale, DeF. E. Amer. J. Roentgenol. 1951, 65, 769.5. Wright, C. J. E. J. Path. Bact. 1952, 64, 585.6. King, E. S. J. J. Bone Jt Surg. 1952, 34B, 97.7. Haagensen, C. D., Stout, A. P. Ann. Surg. 1944, 120, 826.

MALIGNANT SYNOVIOMA

TuMOURS arising from synovial membrane were firstdescribed in 1910 by Lejars and Rubens-Duval.1 Notall tumours in synovial tissue, however, are synoviomas ;and de Santo et al.2 have for this reason criticised theuse of the term. Today " synoviomas " are known tofall into two groups-the malignant and the benign.Harkness,3 Hale,4 and others have emphasised that atoperation the former may appear innocent.

In 47 examples of malignant synovioma collected byWright,5 close on three-quarters of the patients died ofgeneralised metastases, with an average survival-timeof twenty-three months. 10 are still alive today : 2have survived twenty-four and thirteen years, while4, though still alive after nine years, have had recurrencesof the tumour. The findings of King 6 in a smallerseries are substantially similar. The majority of the

malignant tumours studied by Wright were devoid of

giant-cells, but even in the most malignant of them

synovial characters were recognisable : they were, there-fore, essentially mixed tumours, and either the endo-thelial or the sarcomatous element preponderated-usually the former. In the well-differentiated and some-times encapsulated forms of malignant synovioma, cavityformation was conspicuous ; and then, but for the factthat the lining cells had no true border but mergedimperceptibly with the diffusely arranged surroundingcells, their differentiation from true epithelial cellsbecame somewhat difficult. The first of the 2 cases

described by Harkness,3 for instance, distinctly resemblesa spheroidal-cell carcinoma of the breast, as also doesthe original case figured by Lejars and Rubens-Duval.Haagensen and Stout 7 illustrate in their series well-differentiated columnar cells. Carcinomatoid featuresin the malignant synovioma are paralleled in certain

inflammatory states of synovial membrane by an

exuberance of the endothelium with groups of spheroidalcells resembling epithelium. In the well-differentiatedforms of malignant synovioma, sarcomatous and endo-thelial elements are usually equally prominent, the formerbeing mainly spindle-cells with varying amounts of

collagen. Mucin production is usual. Giant cells are

occasionally seen in malignant synoviomas, and con-fusion may then arise with the benign variety ; in

Wright’s experience, however, the malignant tumours

are the more cellular and show fairly numerous foci ofnecrosis, mitoses, and a tendency to form synovialcavities. The only giant-cell synovial tumours whichmetastasised were distinctly anaplastic, and for thatreason were readily recognised. Infiltration of muscle,however, was noted in one of the well-differentiated

giant-cell tumours, so that their malignant charactercannot be doubted.

Fisher,8 de Santo et al.,2 and King have all builtup their histological classifications on slightly differentlines ; but they recognise the essential unity of themalignant synovioma. King remarks that in assessingthe malignancy of any particular tumour it is necessaryto consider the characters of any group of rapidly grow-ing cells rather than the general degree of differentiationfound throughout the tumour. Metastases may beconfined to the regional lymph-nodes but are apt to bewidespread : the lungs and the bones are evidentlycommon sites. Cases have been recorded where meta-stases developed seven, ten, and twelve years after

amputation. Of Wright’s series a definite history of localinjury was obtained in 28% ; but in only 1 of the 17cases reported from the Massachusetts General Hospitalby Hale 4 was there a reliable history of trauma. de Santoand his co-workers concluded that trauma occasionallyinitiated symptoms but by no means produced thetumour. Rarely, they thought, a chronic bursitis mightpredispose to the onset of a synovial sarcoma.The commonest site of this tumour seems to be the

lower limb, especially in the region of the knee. Fisher 8

drew attention to tumours histologically of the samepattern but occurring in the limbs outside joints and notin relation to bursae or tendon-sheaths ; while Haagensenand Stout emphasised that often the tumour does notarise in actual synovial membrane. King 6 believes that,given the appropriate stimulus, connective-tissue cells

anywhere are capable of the particular kind of differentia-tion found in synoviomas. The tissue-culture studies ofVaubel9 show the potentialities of embryonic synovialtissue, especially histiocytic.The radiographic findings are fairly characteristic

but not diagnostic. A soft tissue mass in or near a

joint, lobulated, often with a fine speckled type ofcalcium, and sometimes associated with periostealproliferation, is suggestive of this disease.4 4 For the

encapsulated uniformly well-differentiated growths,Wright 5 regards local excision as adequate but in the

, poorly differentiated tumour amputation offers the onlyhope-and it is not a good one. The prognosis apparentlydepends more on histological structure than on the modeof surgical treatment. It is a disease more of the youngthan the old, the average age of the patients beinglower than that of those with fascial and relatedsarcomata. 6 It has been recognised in a nine-month-old child in whom the history dated back to the age oftwo months.1O In the Boston series females were more

commonly affected than males ; but in most otherseries males have predominated.

8. Fisher, H. R. Amer. J. Path. 1942, 18, 529.9. Vaubel, E. J. exp. Med. 1933, 58, 63.

10. Coley, B. L., Pierson, J. C. Surgery, 1937, 1, 113.

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