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1. Scott, A. Brit. J. Derm. 1957, 69, 40.

ness of educational activities, in collaboration withpractising physicians, official and voluntary health

associations, and interested community agencies." With

prevention as with research, they point clearly to thebroad highway but give little guidance through the lanesand byways which lead up to it. Appreciation of theirexcellent report is tempered only by regret that they werenot kept together long enough to go into more detail.

SULPHUR AND SEBORRHŒIC DERMATITIS

THE rate and route by which substances pass throughthe skin from the exterior have been studied by meansof radioactive isotopes. The best-known of these investi-gations concerned the vesicant war gases. Scott 1 has

lately investigated the beneficial effect of sulphur appliedlocally in various dermatoses.There is no doubt that sulphur is absorbed through the

skin, since local application can lead to sulph,.3emoglobin-semia. It has been thought that it penetrates as a

sulphide, but that its therapeutic effects follow its modifi-cation into H2S506’ For this reason, treatment withpolythionic acids was introduced, but it does not seem tohave been widely successful. Sulphur is normally presentin the skin as sulphydryl and disulphide groups probablyrepresenting sulphur-containing amino-acids, particularlyin the proteins of enzyme systems. It is also representedin the intercellular ground-substance as an ingredientof mucopolysaccharides. Disturbances in local sulphurmetabolism may therefore have pathological conse-

quences. A striking example is blistering from the

poisoning of enzyme systems by heavy metals and itsrelief by offering alternative thiol groups in the form ofdimercaprol (BAL).

Scott has tackled the problem using radioactive sulphurby autoradiography. She applied 35S to the skin of

healthy subjects and took biopsy specimens at fixedintervals. Having established the normal rate and routeof absorption, she repeated these studies in cases ofseborrhceic dermatitis, acne vulgaris, psoriasis, and a fewother disorders.

In normal skin, absorption began two hours after appli-cation, and the element had completely crossed the

epidermis within eight hours. With many substancesthere is preferential absorption through the pilosebaceousfollicles, but this was not observed with sulphur. Aftersixteen hours most of the sulphur was in the dermis,little remaining in the epidermal layers. Within twenty-four hours it had disappeared, and since it did not recrossthe epidermis it must have been taken up systemically.There was no microscopical evidence that the sulphurwas handled by the epidermal cells, its path beingapparently intercellular.

In seborrhoeic dermatitis, penetration began withinhalf an hour of the application of radioactive sulphur,which accumulated in the mid-epidermis during the firsttwenty-two hours, none going into the basal layers orbeyond. Thereafter the sulphur migrated outwards, andduring its residence in the epidermis it was apparentlyattached to cells. In acne there was normal penetrationof the epidermis, but concentration and persistenceoccurred in the pilosebaceous follicles from which it didnot appear to be absorbed into the dermis ; but the reverseis inferred from the " corresponding dermal accumula-tions of sulphur adjacent to the glands." In psoriasissulphur penetrated to the basal layer within four hours,and much greater quantities were absorbed than in normalskin. Little entered the dermis and most was shed out-wards through the epidermis. Again, there appeared tobe intracellular localisation of 35S. In the miscellaneous

group, including contact dermatitis, there was little

departure from normal apart from accelerated passagethrough the epidermis. Lichenification, however, wasassociated with a generally slower rate of absorption.

With improvement of seborrhoeic and psoriatic lesionsthe behaviour of sulphur reverted to normal. Scott

suggests that sulphur applied to the skin in these derma-toses may have some significant biological action, suchas involvement in the intracellular systems involving SSand SH groups.We do not yet know whether the behaviour of sulphur

in these cases is peculiar to that element. Would it notbe reasonable to repeat the study with some elementforeign to the skin ? This might dispose of the suspicionthat all that the tracer is doing is to reveal the dynamicsof the epidermis. Two factors should be considered:first, the influence of oedema, and secondly the rate ofcell division and outward migration. (Edema, mightfavour absorption, and Scott herself observed that ery-thema produced with ultraviolet light caused sulphur topenetrate much more rapidly. Cell division wouldinfluence outward transference of the element; thus inlichenification, with increased cell multiplication, thereis diminished absorption. Combinations of differentdegrees of the two factois would cause varied patterns of"

absorption." .

Scott’s findings, if substantiated, will necessitate therecognition of seborrhoeic dermatitis as a genuine entityby those who regard it as merely one manifestation ofeczema, and will call for further biochemical studies ofthis disease.

1. Millbourn, E. Acta chir. scand. 1949, 98, 1.2. Warren, K. W. Surgery, 1951, 29, 643.3. Sinclair, I. S. R. Brit. J. Surg. 1956, 44, 250.

EXTERNAL PANCREATIC FISTULA AFTERGASTRECTOMY

THE pancreas has been likened to a powder-keg whichresponds capriciously to handling. The dangers of oper-ating on the pancreas, even for biopsy, are well known;and experienced surgeons are aware of the hazard of

injuring this gland during subtotal gastrectomy. Mill-bourn has shown that pancreatic damage, judged by asignificant increase of urinary diastase, was present in 13of 147 patients after gastric resection ; but evidence ofsevere pancreatic involvement was clinically manifest inonly 5, of whom 2 died. Both he and Warren 2 havediscussed modifications in the technique of gastric resec-tion to avoid such catastrophes.When external pancreatic fistula follows operation on

the stomach one of the major pancreatic ducts has

usually been injured, either as it lay in the floor of apenetrating ulcer when the ulcer was being dissected offthe pancreas or when the duodenal stump was mobilised.Usually these nstulae are incomplete and close spontane-ously, since in gastric resection for duodenal ulcer theduct of Santorini, being the more vulnerable, is the mostcommonly injured, and only rarely, as in one ofMillbourn’s fatal cases, does this duct exclusively drainthe larger part of the pancreas.

Sinclair 3 describes an external fistula which persisted,after Polya gastrectomy for duodenal ulcer, for ten weeks,during which he studied pancreatic function. The

pancreas responded poorly to intravenous secretin andpancreozymin ; and, though the dosage of these hormonalextracts was small, this suggests that the function of thegland may have been impaired by duct injury at opera-tion-a suggestion supported by the radiographicevidence of a dilated duct system and by the increase inserum or urinary enzymes found in the same circum-stances in other cases. Moreover after the Polya gastrec-tomy the low acidity of the chyme deviated from theduodenum and passed directly into the upper jejunummay have modified the response of the pancreas to

physiological stimulants such as food. Such variablefactors as these may explain conflicting reports on

external pancreatic fistulae in man.When damage of a pancreatic duct or the common

bile-duct is recognised at operation the duct should be

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4. Hellsten, H., Olsson, O. Acta chir. scand. 1954, 108, 443.5. Lahey, F. H., Lium, R. Surg. Gynec. Obstet. 1937, 64, 79.6. Cattell, R. B. Surg. Clin. N. Amer. 1949, 29, 779.7. Warren, K. W. Ibid, 1951, 31, 789.8. DuVal, M. K. Ann. Surg. 1954, 140, 775.9. McDonald, J. H., Heckel, N.J. J. Amer. med. Ass. 1957, 163, 911.

sutured at once to the duodenum or jejunum, opposingmucosa to mucosa. (A severed duct of Santorini whichcan be shown to connect with the main pancreatic ductmay be ligatured with safety.) When injury to a ductat operation is not detected at the time, it usuallydeclares itself on the second postoperative day by upper-abdominal pain and pyrexia associated with raised serumor urinary amylase levels. If division of the duct of

Wirsung is suspected the region of the head of the

pancreas should be drained and repair of the ductdeferred to a more propitious time. Otherwise the

patient is treated as if he had acute pancreatitis, withcontinuous aspiration of the gastric remnant and intra-venous administration of fluids and electrolytes ; if

necessary glucose and protein hydrolysates can be givenintravenously; and the use of broad-spectrum anti-biotics, though these do not pass into pancreatic juice,is justified at this stage. In desperate circumstancesa jejunostomy to feed the patient may be life-saving,though in Sinclair’s patient glucose given directly intothe jejunum by tube stimulated the flow of pancreaticjuice.Should an external fistula follow, this will usually close

spontaneously ; and meanwhile conservative treatmentis directed towards protecting the skin from digestion,maintaining fluid and electrolyte balance, and if necessaryreplacing lost pancreatic enzymes. It is doubtful whethermeasures usually recommended to depress the externalpancreatic secretion, in order to encourage the fistula toclose, are of much value.4 When food is taken by moutha bland mixed diet is probably best, since fat and proteinproduce less pancreatic juice than carbohydrate. Ephe-drine, atropine, and propantheline (’ Probanthine ’) haveall been recommended to reduce the volume of secretion.Conservative measures should be persisted in for severalmonths ; but if the fistula has not closed after sixmonths, or if closure leads to pain, v-omiting, or cystformation, then operation should be considered. The

Lahey operation,5 which consists in implanting thefistulous track into the jejunum, occasionally failsbecause the fistulous duct, having no epithelium, closesand pancreatic cysts form. In these rare circumstancessome other manoeuvre, such as excision of the distal partof the pancreas together with the origin of the fistula,6 7may be necessary. A possible alternative is a retrogradeor caudal pancreatico-jejunostomy, as performed byDuVal 8 in cases of chronic relapsing pancreatitis.

CUTANEOUS URETEROSTOMY

URINARY diversion by implanting the divided endsof the ureters into the abdominal wall has never beenwidely favoured, for it requires a urinary collectingapparatus. On the other hand, with this method thereis less risk of biochemical imbalance and ascendingpyelonephritis than with ureterosigmoidostomy; andin certain cases, particularly where only one functioningkidney remains, its adoption may be advisable. Standardtechniques, however, commonly involve an indwellingureteral catheter, which may predispose to the veryhazard that the method is supposed to avert-namely,stenosis of the ureteral stump and retrograde sepsis.McDonald and Heckel 9 now describe a plastic procedureby means of which long-continued catheterisation isavoided and the incidence of stricture reduced. Brieflythe operation consists in splitting the end of the dividedureter and embedding each half subcutaneously intotwo infolded skin flaps cut from the margins of the mainincision. Subsequent retraction of the skin flaps during

healing maintains the patency of the ureteral orifice,and indwelling catheters can then be dispensed with.Satisfactory results are claimed in 13 cases out of 22

operated on during the past eighteen years. Although thistechnique does not entirely eliminate the risks andinconveniences of cutaneous ureterostomy, because ofits simplicity it has much to recommend it.

1. Lancet, Jan. 5, 1957, p. 31.2. Pickering, G. W. Ibid, p. 1.3. Brit. med. J. 1955, i, 555.4. Sanjivi, K. S. Lancet, Feb. 2, 1957, p. 267 ; Ibid, March 16,

1957, p. 589.5. Rambling, J. Ibid. Feb. 16, 1957, p. 372.

CONTROLLED TRIALS NEEDED

SOME of us are concerned because the rate of theincrease in true knowledge in medicine seems slow inrelation to the immense amount of work done. It may bethat, as science progresses, more effort must be expendedto achieve a commensurate advance. But too often resultsare obtained whose worth is small-though much time,thought, and money has been used up-because they arebased on too small a series of observations. Thus on

many topics a great mass of information has beencollected which cannot be integrated because the con-ditions under which it was collected varied so much.When a subject is being tackled for the first time, manysmall-scale- experiments are needed to get a general ideaof what is involved ; but once this stage is over, largecontrolled experiments are often needed to test the hypo-theses that have arisen. We have called for a certainreturn to planning in our professional affairs,’- and moreplanning in experimental clinical medicine would bewelcome. -

An example is the treatment of high blood-pressure.Professor Pickering 2 lately contrasted our ignorance(after twenty years’ experience) of how useful is

sympathectomy for hypertension, with our sure knowledgeof the place of drugs in tuberculosis-for there have beenfew controlled trials of sympathectomy. We do notcertainly know whether surgery benefits hypertensives(except in very severe cases), much less whichoperation is most beneficial. With the hypotensive drugs,which have been the subject of so much investigation,the position is likely to be little better until a big trial ismade with all the major variables controlled. No one

group of physicians could expect to see enough cases toconduct such a trial : but if a large number of workerscould be persuaded to treat patients in a controlledfashion as part of a prearranged plan, we might gainreliable evidence as to which drugs are indicated for whichpatients, and when other treatments (e.g., dietary orsurgical) are needed. That such cooperative schemescan be successful is obvious from many reports of theMedical Research Council, and from such joint efforts asAnglo-American investigation of the treatment ofrheumatic fever.3 -

Professor Sanjivi 4 has proposed that patients withhypertension but no symptoms should be treated withdrugs in an attempt to keep the blood-pressure normal,and has given an account of some of his patients treated(without controls) with reserpine. Dr. Rambling 5

expressed the misgivings that many doctors will feel,especially in view of the side-effects of such drugs :and in our correspondence columns this week Dr.Muhammad takes the view that Professor Sanjivi’spatients would have done equally well with reassuranceand sedation. But the simple fact is that we do notknow whether or not they would have done as well ;and the only way to decide the very important questionof whether or not active hypotensive treatment is worthwhile is to begin a controlled trial, treating some patientswith drugs designed to lower the blood-pressure andothers with reassurance and mild sedation. This would