238 26 July 1969 Correspondence BRITIS

hilarity and movement (presumably includ-ing eye movement) during the compressionphase due to the combined effects of warmthand nitrogen narcosis, thus assisting the flowof nitrogen-laden tears between the lens andcornea, while during decompression thechamber was, as is usual, rather cold andfoggy, with the subjects relatively immobile,thus minimizing any flow of tears whichmight have helped to wash out the nitrogen.As the other eye was only slightly affected, itmust be presumed that there was a differencein the fit, and hence in the flow of tearsunder the two lenses, causing either lessabsorption or better elimination of gas fromthe other eye.-I am, etc.,

JOHN BETTS.Chairman, National Medical Committee.

British Sub-Aqua Club.London N.10.

Bowel Motility and Colonic Cancer

SIR,-Recent studies' and comments2 oncancer of the colon indicate that valuableinformation may be forthcoming from inten-sive studies of bowel motility and faecescomposition in populations with contrastingprevalences of this type of cancer.

In South African Bantu age specificmortality is only a tenth of that in whites.3 '

In preliminary studies on this subject wehave noted two points of interest. In theBantu (children and students studied thus far)a third have three motions daily comparedwith only 1-2 % in whites. Moreover, interms of exposure of bowel mucosa to digesta,carmine studies have revealed that in theBantu the mean transit time of the longestthird is less than the mean time of thequickest third among whites. The findingto be stressed is that even in Bantu and whiteswith the same frequency of defaecation (say,one to two motions per diem) traces of car-mine continue to be seen far longer in stoolsof whites than in Bantu; in whites the periodis sometimes five to seven days. In addition,therefore, to the presumably vulnerable con-stipated moiety of population,1' there is thisfurther moiety with regular motions, not con-stipated, who, unknown to themselves andundetectable clinically, have unduly pro-longed times of traversal of digesta. This isthe condition which conceivably provides thefavourable milieu interieur required forcarcinogenesis, whether of exogenous or

endogenous origin.The second finding to be emphasized con-

cerns the differing ability to produce a stoolquickly on request. Eighty to ninety per cents ofrural Bantu children have this capacity, 70-80%of partially sophisticated urban Bantu, but fewerthan 10% of white children. Previously' I wenoted that when young white adults consumeda very high-residue Bantu-type of diet for severaldays they still could not produce a stool onrequest in the same facile manner as Bantu.Evidently, with "civilization," voluntary controlof the defaecation reflex is largely lost. Maynot differences in physiological tone of the colonbe associated with different susceptibilities tocarcinogenic agents ?The critical question, of course, is whether

the moiety with protracted exposure to possiblecarcinogens is in fact that moiety in whichsufferers from bowel cancer are to be found.Elucidation of this problem will be difficult.For example, verbal questioning regarding bowelhabits, etc., is often worthless; we find a poorcorrelation between frequency from recall andfrequency by keeping a weekly chart. Further,

not recollectable to patients, their bowel habits,etc., at 50-60 years may differ markedly fromthose at 30-50 years.

Obviously, far more explicit data areneeded on populations with contrasting pre-valences of colonic cancer. In the presentcircumstances it would seem that only byimpeding carcinogenic action may prophylaxisbe envisaged. Screening centres have beenadvocated to detect the segment of popula-tion most prone to coronary heart disease, todetect the aglycosuric population who haveabnormal glucose tolerance, etc. Would it betoo far fetched to suggest that the youngeradult population be screened, initially withcarmine, to detect the moiety with very pro-longed transit times, and that such be givendietary or therapeutic advice to accelerateexcretion ?-We are, etc.,

ALEXANDER R. P. WALKER.B. FAITH WALKER.

South African Institute forMedical Research,

Johannesburg,South Africa.

REFERENCESWynder, E. L., and Shigemetsu, Cancer (Phila-

delphia), 1967, 20, 1520.2 Lancet, 1968, 1, 627.3Oetfli, A. G., 7ournal of the National Cancer

Institute, 1964, 33, 383.4Higginson, J., journal of the National Cancer

Institute, 1966, 37, 527.5 Walker, A. R. P., Nature, 1949, 164, 825.6 Walker, A. R. P., unpublished work.

Pigmentation in Megaloblastic Anaemia

SIR,-We have read with interest thedescription by Dr. N. Baumslag and Dr. J.Metz of spotty pigmentation of palms, soles,and tongue in lactating Africans with folatedeficiency (21 June, p. 737). Clinicians inIbadan are aware of the possibility of hyper-pigmentation in patients with megaloblasticanaemia, as it has been seen in one Nigerianwith vitamin B12 deficiency, but it has notbeen noticed in folate deficiency, thoughabout 200 women with severe megaloblasticanaemia associated with pregnancy are seeneach year. No areas of hyperpigmentationwere revealed by a detailed dermatologicalexamination of six women with profoundanaemia in pregnancy.

Failure to observe pigmentation in Ibadanmay be because it has not been looked forclosely enough, or it may be related to thedifferent presentation of folate deficiency-anaemia is seen most commonly near the endof the second trimester, while the SouthAfrican patients were seen during lactation.The South Africans may have been deficientfor longer than the Nigerians, and shown anearly stage of a skin lesion which is muchmore remarkable in vitamin B12 deficiency, 2a condition which develops insidiously and isalmost always long-standing at the time ofpresentation.

Biopterin is the coenzyme required forhydroxylation of phenylalanine to tyrosine,and it has been found in abnormally highconcentration in the serum of folate-deficientpregnant I4igerians.' Widespread disturbanceof amino-acid metabolism has been found inpregnant Nigerians with megaloblasticanaemia, but no evidence of a failure to con-vert phenylalanine to tyrosine (Jacobs, S.,and Fleming, A. F., unpublished observa-tions). There is a lower than normal histidinea-deaminase activity in the skin from vitamin

B12 or folate-deficient Indians with hyper-pigmentation.4 None of these abnormalitiesof amino-acid metabolism help us to under-stand the accumulation of melanin in megalo-blastic anaemia. A possible explanation isthat it is the result of abnormal cell division.-We are, etc.,

A. F. FLEMING.Department of Obstetrics and Gynaecology,

University of Western Australia,Nedlands, Western Australia.

Skin Department, F. A. IVyE.Dryburn Hospital,Durham, England.

REFERENCESWatson-Williams, E. J., and Fleming, A. F.,

Blood, 1966, 28, 770.2 Baker, S. J., Ignatius, M., Johnson, S., and

Vaish, S. K., British Medical 7ournal, 1963, 1.1713.

3 Fleming, A. F., and Broquist, H. P.. American7ournal of Clinical Nutrition, 1967, 20 613.

Satwekar, K., Radhakrishnan, A. N., an Baker,S. J., Clinica Chimica Acta, 1968, 20, 53.

Hypokalaemia after Treatment withDuogastrone (Carbenoxolone)

SIR,-Dr. J. Forshaw's Memorandum onhypokalaemic muscle weakness complicatingthe use of Duogastrone (position-releasecarbenoxolone sodium) (14 June, p. 674)prompts me to record a similar case.A woman of 55 developed pins and needles In

the fingers of both hands while cooking oneevening. This lasted only 30 minutes, but anhour later she noticed weakness of both handsand the next day her right arm was weak. Overthe next 24 hours the weakness spread to botharms, the shoulders, and then to the thighs andback muscles and she had difficulty in holdingup her head. She had no muscle pain, no diffi-culty in swallowing, and no visual symptoms.Her general health was good and there had beenno diarrhoea or vomiting. She had neversuffered from muscle weakness before, nor wasthere any family history of a similar condition.A duodenal ulcer had been demonstrated 23years previously, but had always responded toconservative treatment. She had been takingDuogastrone, 200 mg. four times a day, forsix weeks; the course of tablets had finishedone day before the onset of her presentsymptoms.On examination she was a fit-looking woman.

General examination was negative except for ablood pressure which varied between 200/120and 140/80, and a small nodule in the thyroidgland. There was slight weakness of jaw open-ing and weakness of the sternomastoids so thatshe had difficulty in lifting the head from thepillow. She had severe flaccid weakness in thelimbs affecting proximal muscles more thandistal and the arms more than the legs. Therewas no fasciculation or muscle tenderness, andthe tendon reflexes were absent in the armsand at the ankles. The plantar responses wereflexor. There was no impairment of sensationand the peripheral nerves were not thickened.The relevant investigations were as follows:

Serum electrolytes (mEq/l.): Na 149, K 1-7, Cl101, CO,-combining power 32. Serum enzymes(units): Aldolase 160, S.G.O.T. 244, S.G.P.T.200. Glucose tolerance test (30 minute intervalsfollowing the ingestion of 50 g. glucose): 117,162, 175, 206, 209 mg./100 ml.Electromyogram (right deltoid): mean muscle

action potential duration 10 msec. (normal 14-3± 20%) and incidence of polyphasic potentials16% (normal 3-12%). Maximum effort showeda normal interference pattern of reduced voltage.Conduction velocities in the ulnar and lateralpopliteal nerves were within normal limits.These results strongly suggested a myopathiclesion (Dr. J. S. Chopra). Electrocardiograki:depression of ST segment in leads 1, 2, AVL,V5, and V6: QT interval 0 4 sec: prominentU waves in chest leads.

26 July 1969 Correspondence BRITIB s 239

Other investigations were normal, includingchest x-ray, cerebrosp.nal fluid, tests of thyroidfunction, intravenous pyelogram, urinary keto-,and hydroxysteroids, urinary aldosterone andplasma cortisol levels. Urine electrolyte ex-cretion was at all times within normal limits.There was no myoglobinuria, but this test wasnot done until two weeks after admission tohospital. Muscle biopsy (left deltoid) showed noabnormality apart from one small collection oflymphocytes (Dr. Ingrid Allen). Efforts to pro-voke muscle weakness by administering glucoseand insulin were unsuccessful.

For the first few days after admission tohospital there was some spontaneous improve-ment in muscle power; treatment was thenstarted with potassium chloride by mouth,2 g. three times a day, and she was dischargedafter six weeks with only minimal residualweakness. The serum enzymes returned tonormal within four weeks, the hypertensiondisappeared, and a repeat glucose tolerancetest after three weeks was normal. Electro-myography four months later still showedslight myopathic changes, but by this time

clinical recovery was complete and thetendon reflexes had returned.

In this case special efforts were made toeliminate other causes of hypokalaemia (forexample, familial periodic paralysis, hyper-thyroidism, potassium-losing nephropathy, andhyperaldosteronism) and carbenoxolone seemsto be the most likely cause for the syn-drome. The occurrence of reversible hyper-tension and diminished glucose tolerance inthe acute phase is compatible with the" steroid-like" action of this drug. LikeDr. Forshaw's case, the implication of thedrug therapy which the patient had beenreceiving was not realized until some daysafter admission to hospital. It is also ofinterest that significant spontaneous improve-ment in muscle power had already com-menced before treatment with oral potassiumwas started.-I am, etc.,

MICHAEL SWALLOWDepartment of Neurology,

Royal Victoria Hospital andClaremont Street Hospital.

Belfast.

Scanning Electronmicroscopy in Dermatology

SIR,-The scanning electron microscope isa promising tool for the study of the surfacemorphology of biological specimens,`4 and

can be of value in comparative studies of theskin and of its appendages. In this studya number of observations are reported on the

following specimens: normal and diseasedhuman hairs, psoriatic nail, and molluscumcontagiosum lesions of the skin. These speci-mens were chosen because their low watercontent minimizes shrinkage artifacts, whichcould occur during processing, since it isnecessary to examine the tissues undervacuum without prior embedding.The specimens were air-dried, mounted on

a Dural specimen holder, coated with approxi-mately 500 A of evaporated gold/palladiumalloy, and examined in the scanning electronmicroscope (Stereoscan Mk II, CambridgeInstrument Co. Ltd.).The normal human hair showed a charac-

teristic surface topography with well-definedindividual scales (Fig. la). The surface aspectsof the scales were more easily seen with thescanning electron microscope than with theusual replica techniques, and was of particularadvantage in the study of diseased hairs(Fig. lb). Similarly, modifications in the surfaceappearance of diseased nails were easily recog-nized, such as the characteristic surface pittingof the psoriatic nail (Fig. 2).The great depth of focus of the scanning

electron microscope allowed the whole specimenfrom the central cornified region of molluscumcontagiosum lesions to be examined, providinga three-dimensional view of the inclusion bodies.These inclusion bodies consisted of hundreds ofviral elements clumped together in an almostcontinuous array (Fig. 3). The viral elements

..

...~~~~~~~~~~~~~~~~~~~~~~~~t..,..~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~4 .~~~~~~~~.....

FIG.2...~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~..

FIG. 2.-Surfacepitting of a~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~.psoriaticnail.(X120.)~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~..diisrto

(x3,340.)~~~~~~~~~~~~~~~~~X115. X ,0.

contagiosum .showing surface~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~details of particles. (x 10,920.) FIG 3 FIG 4~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~..