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BLOOD IN THE STOOLS

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503 Annotations CORTISONE AND A.C.T.H. THE dramatic results achieved with ’ Cortisone’ and adrenocorticotropic hormone have fixed our attention on the adrenal gland ; and we have thus tended to lose sight of the interdependence of this and other endocrine organs. Elsewhere in this issue Dr. Long and Dr. Miles, of the National Institute for Medical Research, develop the evidence for a balanced opposition between thyroid and adrenal hormones. Their article is also notable for containing the first report on work carried out in Britain with cortisone. In the U.S.A. the Mayo Clinic workers 1 have brought together and extended the clinical and biochemical data on both cortisone and A.c.T.H. They have confirmed the capacity of cortisone, administered in sufficiently large doses over a long period, to induce most of the clinical and metabolic features of Cushing’s syndrome. The features induced in this way include rounding of the facial contour, hirsutism, acne, keratosis pilaris, muscular weakness, oedema, amenorrhoea, cutaneous striae, mental ’depression, impaired carbohydrate toler- ance, negative nitrogen balance, increased excretion of corticosteroids in the urine, and hypochloraemic hypo- potassaemic alkalosis. Both cortisone and A.C.T.H. have been found to promote urinary excretion of creatine and uric acid, and to give rise sometimes to a negative potassium balance. Their effects on sodium and chloride balances are variable, the usual pattern being retention, followed by increased excretion, of salt ; sometimes urinary excretion of calcium and phosphorus is slightly increased. The report provides further evidence that protracted administration of cortisone depresses adrenal cortical function ; and the Mayo Clinic group suggest that the 17-ketosteroids excreted during its adminis- tration are derived largely, if not entirely, from the cortisone. It seems that A.C.T.H. stimulates the adrenal cortex to secrete, not cortisone (17-hydroxy-11-dehydro- corticosterone), but the closely allied Compound F (17-hydroxycorticosterone). Injection of pituitary thyrotropic or gonadotropic hormone is well known to induce in animals of hetero- logous species a refractory state associated with demon- strable anti-hormones in the serum. That this reaction extends to A.C.T.H. has been demonstrated, in the rat, by Chase 2 ; and her report has been followed by one from Gordon 3 showing that rats gradually became refractory to hog A.c.T.H. in doses comparable, on a body-weight basis, to those used in man to alleviate rheumatoid arthritis. It has already been established that continued injection of pituitary extracts from heterologous species may render animals refractory to their own pituitary hormones, with subsequent atrophy of the " target " glands 4 ’; and Gordon concludes that " one might speculate as to the possible effect of antihormone on the pituitary-adrenal system of a refractory animal or patient who continues to receive heterologous A.C.T.H:" As time goes on, we are likely to see still more clearly how right the initiators of the method have been in insisting that A.C.T.H., and cortisone, must for the present be regarded as research tools rather than sure means of treatment. The national councils advising the United States Public Health Service on medical-research problems have in fact urged that both drugs should be used only for reseach; and that most of the -basic reseach on treatment, side-effects, and mode of action should be made with animals." 1. Sprague, R. G., Power, M. H., Mason, H. L., Albert, A., Mathieson, D. R., Hench, P. S., Kendall, E. C., Slocumb, C. H., Polley, H. F. Arch. intern. Med. 1950, 85, 199. 2. Chase, J. Endocrinology, 1949, 45, 96. 3. Gordon, G. L. Ibid, p. 571. 4. Bachman, C. J., Collip, J. B., Selye, H. Proc. Soc. exp. Biol., N.Y. 1934, 32, 544. Severinghaus, A. E., Thompson, K. W. Amer. J. Path. 1939, 15, 391. 5. New York Times, suppl. March 12. BLOOD IN THE STOOLS THE passing of blood in the faeces is a common feature of disease. It must always be regarded seriously because all its common causes, except internal piles, are serious. The blood may be obvious or it may be occult and detected only by special methods. Melaena means the passage of a shiny black (.7,xm«= black) tarry stool, consisting largely of partly digested blood, but the term is often applied loosely to any passing of blood from the anus. Bleeding in the upper part of the bowel, including the small intestine, usually produces melaena, and as little as 50-60 ml. of blood will render the stool black,! Red blood in the faeces usually indicates bleeding from the colon, rectum, or anal canal. The diagnosis of the cause of blood in the stool is the diagnosis of alimentary disease. It rests on careful routine history-taking, complete physical examination, and the results of investigations. In every case there are two questions to be answered : (1) " What is the site of the bleeding ? ", and’ (2) " What is the pathological lesion ? " In the history other symptoms must be noted. Haematemesis commonly precedes melæna when the oesophagus, stomach, or duodenum is bleeding. There may be a typical ulcer dyspepsia, but this is not invariable in cases of bleeding peptic ulcer. If there is colic and diarrhoea, with mucus as well as blood in the stools, enteritis or colitis is probably the cause. If there are symptoms of large bowel obstruction, with streaks of red blood in the stools, the most likely lesion is a carcinoma of the pelvic colon or rectum. The physical examination must include a search for evidence of general systemic disease such as purpura or uraemia. There may be an obvious source of bleeding in the mouth or nose ; splenomegaly may suggest ’bleeding from ceso- phageal varices ; and so on. Rectal examination, which must be done in every case, may reveal an anal polyp or fissure, or a carcinoma of the rectum. The finger should always be examined for blood after it is with- drawn. Piles can only be diagnosed by proctoscopy unless they are prolapsing or thrombosed. Internal piles are the commonest source of blood in the stool, but we must remember that the piles may be secondary to pregnancy, portal obstruction, or carcinoma of the rectum. Anyone who complains of piles for the first time over the age of 40 should be examined with a sigmoidoscope. Many cases of bleeding per anum will need further investiga- tions. Radiography with the barium swallow, barium meal, and barium enema can be very helpful. Sigmoido- scopy is essential for the examination of the rectum and pelvic colon, but cesophagoscopy and gastroscopy are usually reserved for cases in which the X-ray findings are inconclusive. The faeces must be examined for pathogenic bacteria and for amoebae when an infection is suspected. Blood diseases, haemorrhagic states, enteric infections, and uraemia, all of which may cause intestinal bleeding, can be detected by blood examination. In a few cases, especially when bleeding is the only symptom or sign, the cause will remain obscure. These must be followed carefully and re-investigated if the bleeding is repeated or if new features develop. Occasionally laparotomy is necessary to establish the cause, and more rarely it has to be done urgently to stop bleeding from an unknown source. In the U.S.A., Thompson and mcGuffin 2 have analysed 293 consecutive cases with blood in the stools as a prominent feature, excluding those in which the bleeding was in the anal canal. Peptic ulcer accounted for 30% of the cases, and, though 80% of these had hæmatemesis at some time, the blood appeared first in the stool in 62%. Next came bacillary dysentery with 21% of cases, most of them in children, while non-specific enteritis and colitis accounted for less than 1%. In Britain there are 1. Winters, W. L., Egan, S. J. Amer. med. Ass. 1939, 113, 2199. 2. Thompson, H. L., McGuffin, De V. W. Ibid, 1949, 141, 1208.
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Page 1: BLOOD IN THE STOOLS

503

Annotations

CORTISONE AND A.C.T.H.

THE dramatic results achieved with ’ Cortisone’ and

adrenocorticotropic hormone have fixed our attentionon the adrenal gland ; and we have thus tended to losesight of the interdependence of this and other endocrineorgans. Elsewhere in this issue Dr. Long and Dr. Miles,of the National Institute for Medical Research, developthe evidence for a balanced opposition between thyroidand adrenal hormones. Their article is also notable for

containing the first report on work carried out in Britainwith cortisone.

In the U.S.A. the Mayo Clinic workers 1 have broughttogether and extended the clinical and biochemical dataon both cortisone and A.c.T.H. They have confirmedthe capacity of cortisone, administered in sufficientlylarge doses over a long period, to induce most of theclinical and metabolic features of Cushing’s syndrome.The features induced in this way include rounding ofthe facial contour, hirsutism, acne, keratosis pilaris,muscular weakness, oedema, amenorrhoea, cutaneousstriae, mental ’depression, impaired carbohydrate toler-ance, negative nitrogen balance, increased excretion ofcorticosteroids in the urine, and hypochloraemic hypo-potassaemic alkalosis. Both cortisone and A.C.T.H. havebeen found to promote urinary excretion of creatine anduric acid, and to give rise sometimes to a negativepotassium balance. Their effects on sodium and chloridebalances are variable, the usual pattern being retention,followed by increased excretion, of salt ; sometimes

urinary excretion of calcium and phosphorus is slightlyincreased. The report provides further evidence thatprotracted administration of cortisone depresses adrenalcortical function ; and the Mayo Clinic group suggestthat the 17-ketosteroids excreted during its adminis-tration are derived largely, if not entirely, from thecortisone. It seems that A.C.T.H. stimulates the adrenalcortex to secrete, not cortisone (17-hydroxy-11-dehydro-corticosterone), but the closely allied Compound F(17-hydroxycorticosterone).

Injection of pituitary thyrotropic or gonadotropichormone is well known to induce in animals of hetero-logous species a refractory state associated with demon-strable anti-hormones in the serum. That this reactionextends to A.C.T.H. has been demonstrated, in the rat,by Chase 2 ; and her report has been followed by one fromGordon 3 showing that rats gradually became refractoryto hog A.c.T.H. in doses comparable, on a body-weightbasis, to those used in man to alleviate rheumatoidarthritis. It has already been established that continuedinjection of pituitary extracts from heterologous speciesmay render animals refractory to their own pituitaryhormones, with subsequent atrophy of the " target "glands 4 ’; and Gordon concludes that " one mightspeculate as to the possible effect of antihormone on thepituitary-adrenal system of a refractory animal or

patient who continues to receive heterologous A.C.T.H:"As time goes on, we are likely to see still more clearlyhow right the initiators of the method have been in

insisting that A.C.T.H., and cortisone, must for the presentbe regarded as research tools rather than sure means oftreatment. The national councils advising the UnitedStates Public Health Service on medical-researchproblems have in fact urged that both drugs should beused only for reseach; and that most of the -basicreseach on treatment, side-effects, and mode of actionshould be made with animals."1. Sprague, R. G., Power, M. H., Mason, H. L., Albert, A.,

Mathieson, D. R., Hench, P. S., Kendall, E. C., Slocumb, C. H.,Polley, H. F. Arch. intern. Med. 1950, 85, 199.

2. Chase, J. Endocrinology, 1949, 45, 96.3. Gordon, G. L. Ibid, p. 571.4. Bachman, C. J., Collip, J. B., Selye, H. Proc. Soc. exp. Biol.,

N.Y. 1934, 32, 544. Severinghaus, A. E., Thompson, K. W.Amer. J. Path. 1939, 15, 391.

5. New York Times, suppl. March 12.

BLOOD IN THE STOOLS

THE passing of blood in the faeces is a common featureof disease. It must always be regarded seriously becauseall its common causes, except internal piles, are serious.The blood may be obvious or it may be occult anddetected only by special methods. Melaena means the

passage of a shiny black (.7,xm«= black) tarry stool,consisting largely of partly digested blood, but the termis often applied loosely to any passing of blood from theanus. Bleeding in the upper part of the bowel, includingthe small intestine, usually produces melaena, and as

little as 50-60 ml. of blood will render the stool black,!Red blood in the faeces usually indicates bleeding fromthe colon, rectum, or anal canal.The diagnosis of the cause of blood in the stool is the

diagnosis of alimentary disease. It rests on carefulroutine history-taking, complete physical examination,and the results of investigations. In every case thereare two questions to be answered : (1) " What is the siteof the bleeding ? ", and’ (2)

" What is the pathologicallesion ? " In the history other symptoms must be noted.Haematemesis commonly precedes melæna when the

oesophagus, stomach, or duodenum is bleeding. There

may be a typical ulcer dyspepsia, but this is not invariablein cases of bleeding peptic ulcer. If there is colic anddiarrhoea, with mucus as well as blood in the stools,enteritis or colitis is probably the cause. If there are

symptoms of large bowel obstruction, with streaks ofred blood in the stools, the most likely lesion is a

carcinoma of the pelvic colon or rectum. The physicalexamination must include a search for evidence of generalsystemic disease such as purpura or uraemia. There

may be an obvious source of bleeding in the mouth ornose ; splenomegaly may suggest ’bleeding from ceso-

phageal varices ; and so on. Rectal examination, whichmust be done in every case, may reveal an anal polypor fissure, or a carcinoma of the rectum. The fingershould always be examined for blood after it is with-drawn. Piles can only be diagnosed by proctoscopyunless they are prolapsing or thrombosed. Internal pilesare the commonest source of blood in the stool, butwe must remember that the piles may be secondary topregnancy, portal obstruction, or carcinoma of the rectum.Anyone who complains of piles for the first time over theage of 40 should be examined with a sigmoidoscope. Manycases of bleeding per anum will need further investiga-tions. Radiography with the barium swallow, bariummeal, and barium enema can be very helpful. Sigmoido-scopy is essential for the examination of the rectum andpelvic colon, but cesophagoscopy and gastroscopy areusually reserved for cases in which the X-ray findingsare inconclusive. The faeces must be examined for

pathogenic bacteria and for amoebae when an infectionis suspected. Blood diseases, haemorrhagic states, entericinfections, and uraemia, all of which may cause intestinalbleeding, can be detected by blood examination. In afew cases, especially when bleeding is the only symptomor sign, the cause will remain obscure. These must befollowed carefully and re-investigated if the bleedingis repeated or if new features develop. Occasionallylaparotomy is necessary to establish the cause, and morerarely it has to be done urgently to stop bleeding froman unknown source.

In the U.S.A., Thompson and mcGuffin 2 have analysed293 consecutive cases with blood in the stools as a

prominent feature, excluding those in which the bleedingwas in the anal canal. Peptic ulcer accounted for 30%of the cases, and, though 80% of these had hæmatemesisat some time, the blood appeared first in the stool in 62%.Next came bacillary dysentery with 21% of cases, mostof them in children, while non-specific enteritis andcolitis accounted for less than 1%. In Britain there are

1. Winters, W. L., Egan, S. J. Amer. med. Ass. 1939, 113, 2199.2. Thompson, H. L., McGuffin, De V. W. Ibid, 1949, 141, 1208.

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504

probably fewer dysenteric and more non-specific casesof enterocolitis. Œsophageal varices (9%), carcinoma ofthe stomach (8%), carcinoma of the rectum and pelviccolon (6%), idiopathic ulcerative colitis (5-5%), diverticu-litis of the colon (4%), and uraemic colitis (3%) came nextin frequency. Intussusception was the cause of only1-4%, and there were no examples of blood diseases.Lesions of the small intestine, which formed only 2%of this series, are rare in most people’s experience,though from time to time Meckel’s diverticulum, Crohn’sdisease, mesenteric thrombosis, and tumours of the smallbowel do cause bleeding without much other evidenceof their true nature. The causes of small intestinal

bleeding have lately been reviewed by Hodes andEdeiken.3

.

Tests for occult blood in the stools have fallen intodisrepute in some quarters, but their results may bevaluable if they are interpreted critically. Bleedinggums and piles, and meat in the food, may give positivereactions, and constipation may cause false negativeresults. When using the benzidine test a meat-free dietfor at least two days is essential, and the stools mustalways be examined for meat fibres. The test should bedone on at least three separate occasions. Hoerr and

colleagues 5 favour a modification of the guaiac test, easilyperformed in the consulting-room. This is not sensitive

enough to be affected by meat and can therefore be doneon outpatients, provided they are not taking iron. Whilenegative reactions are unreliable, they claim that positiveguaiac reactions denote significant organic bleeding in ahigh proportion of cases. The test is simple :A smear of faeces (from a fingerstall) is placed on a filter

paper, and one or two drops each of guaiac solution, glacialacetic acid, and hydrogen peroxide, in that order, are placednear the faeces. If a blue or dark green colour appears within30 seconds the result is positive.Dunphy 6 reports 2 cases of resectable carcinoma of thesmall intestine which had produced positive guaiacreactions but could not be demonstrated by routineradiology. In each case a Miller-Abbott tube was passeduntil a level was reached from which the aspirated samplescontained occult blood. That part of the bowel was thenfilled selectively with barium through the tube, and thelesion was demonstrated radiologically. This rather

complex test will be worth the extra trouble if it willlocate even an occasional growth of the small gut at acurable stage.PENETRATION OF OVUM BY SPERM IN VITRO

EARLY in 1948 Menkin and Rock announced that

they had obtained fertilisation and cleavage of humanova removed from ovaries by dissection in vitro underaerobic conditions. They had made the attempt 138times and had obtained cleavage in 4 ova. -This caused astir in the popular press ; but more sober observers werenot so readily convinced, and Rock himself admittedthat parthenogenesis could not entirely be ruled out.After working on the subject for several years, Moricardand Bossu 8 report that their attempts to obtain fertilisa-tion and cleavage of rabbit ova under aerobic conditions,as described- by Menkin and Rock, were invariablynegative in 60 cases ; the spermatozoa never succeededin penetrating the membrana pellucida. But, whenrabbit spermatozoa and ova were brought togetherunder relatively anaerobic conditions in the presence oftubular epithelium and seminal plasma, penetrationoccurred every time in 8 cases. By cutting serial sectionsthey have observed and demonstrated the very earlieststages in the process of fertilisation. They believe thattheir technique will be applicable to human spermatozoa3. Hodes, P. J., Edeiken, J. Ibid, p. 1284.4. Necheles, H. Ibid, p. 1217.5. Hoerr, S. O., Bliss, W. R.. Kauffmann, J. Ibid, p. 1213.6. Dunphy, J. E. Ibid, p. 1217.7. Menkin, M., Rock, J. Amer. J. Obstet. Gynec. 1948, 55, 440.8. Moricard, R., Bossu, J. Bull. Acad. Méd. Paris, 1949, 133, 659.

and ova, and, if so, this will mark a definite step forwardin the struggle to unravel the complex physiology ofmammalian ova, spermatozoa, and tubular epithelium.FLUOROSCOPIC EXAMINATION OF THE CHEST

IN the early days of radiography " screening " wasused freely in diagnosis ; but as films became easier totake it dropped into the background. It is so pleasantand convenient to be able to back one’s opinion with apermanent record that the temptation to ask for a filmis very strong, both for the physician and the radiologist.However, things have reached such a pass that our X-raydepartments are congested by the amount of work

pouring into them, and our task is how to think of waysof lightening the load. Dr. Stephen Hall and Dr. WilliamTattersall, on another page, advocate a return to a muchwider use of fluoroscopy. Not only would this save timeand money, but it would also, they suggest, give informa-tion which could not readily be obtained in other ways.Thus it is possible by changing the tilt of the patient’sbody, and by making him bend, breathe deeply, or pant,to estimate the depth of various shadows, and to avoidsome common pitfalls of diagnosis from the film. Fluoro-

scopy, they say, differs from inspection of the film inthe same way that cinephotography differs from still

photography ; and they have found that the information itgives tallies well with that to be expected of the fixed film.

Fluoroscopy has its drawbacks however, one of thembeing that radiologists, like other people, differ in theirpowers of dark adaptation. Hall and Tattersall suggestthe use of dark glasses to enable the radiologist to go onworking while his visual purple is collecting ; and

evidently they are themselves both capable of goodadaptation. But, as Mr. Cecil Ashwin, M.s.R., has pointedout,l in a review of prevailing opinion on the value offluoroscopy in tuberculosis case-finding, " the ability ofan individual to see in the dark depends on many factorssuch as temperament, physiological condition and vitaminintake : further, this function can vary from day to day."This variability probably accounts for the large body ofopinion he is able’to report against the value of fluoro-scopy. He quotes Garland, who put the percentageerror in the detection of tuberculosis with this method(as compared with radiography) between 13 and 35 ;Fellows and Ordway, from a study of 2500 cases, agreedwith this figure, and Voigtlander, from another 2500cases, concluded that in 32% the diagnosis by fluoroscopywas either incorrect or insufficient. Schaare found anerror of 18% in fluoroscopic findings ; while Edwardand Ehrlich, after reviewing mass surveys of 100,000people, decided that the drawbacks of fluoroscopy out-weighed the advantages. Ashwin quotes other opinionsof the same kind, but sets them against an equallyweighty set of favourable reports.

It seems that if fluoroscopy is to be widely used weneed some method of testing the accuracy of the observer.A test of visual adaptation in darkness has been devisedby Chantraine and Cramer, which consists, Ashwin says,in enumerating, from a fixed distance, lead numbers ofvarious sizes mounted on a standard fluorescent screen.Of 30 doctors tested in this way, only 6 were " good,"10 were " medium " and 14 were " poor." Two-thirdsof them needed more than ten minutes to attain minimumdark adaptation. Ashwin suggests that patients shouldbe sieved first by mass radiography ; and that suspectedcases should then be fluoroscoped by a capable observer,and a spot film taken of any suspicious area. This wouldenable the preliminary sifting to be done in the absenceof the radiologist, and would make a full-size filmnecessary only in exceptional cases. Hall and Tattersallbelieve that screening alone can safely be used to excludetuberculous lesions and will thus save many films whichare at present wasted.

1. Med. Lab. Progress, 1949, 10, 141.


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