Intestinal Hormones and Insulin

35

acid and liver disease in over 60,000 barium-enema examinations at the Massachusetts General Hospital between 1947 and 1963. KEMP HARPER 34 reached a similar conclusion in a survey at St. Bartholomew’s Hospital, London, of every patient who was admitted with liver disease, or in whom it developed later, in the years 1948-63-during which tannic acid had been used in barium enemas in about 15,000 patients. A prospective study by STAAB and VIX 35 did not demonstrate any significant rise in serum-glutamicoxalacetic-transaminase (S.G.O.T.) in 92 out of 94 patients who had had a barium enema with 0-25% added tannic acid. Changes in the other 2 patients could be accounted for by other disease processes. BURHENNE et al,36 did liver-function tests in 45 patients after a cleansing enema containing 0-25% tannic acid and a barium-enema mixture with 0-5% added tannic acid, and found no significant changes. MARGULis and his colleagues 31 37 38 have investigated the effects of the concentration of tannic acid in the enema and the duration of its retention on absorption and toxic action in rats. Repeated colonic lavage seems to produce oedema and inflammation of the colonic mucosa which may increase the absorption of tannic acid. Even preparatory enemas of isotonic saline may do this, and this may explain the deaths described by McALISTER et al.30 Both greater concentration of tannic acid in the enema, and increased retention-time, resulted in greater absorption. After instillation of 1% tannic-acid enemas, no tannic acid could be detected in the portal vein even if retained for one hour, but minute quantities could be detected if 2% was used and retained for one minute. KEMP HARPER 39 has now summed up the situation, pointing out that most of the patients who died had repeated and sometimes frequent cleansing enemas, the last of which often contained tannic acid, in addition to that in the barium enema. Several patients had had repeated stool softeners; and extensive reflux into the small bowel took place in others. More effective radiographic examination of the colon is certainly possible if tannic acid is added to barium enemas, and provided that it is not used in a cleansing enema it may be reasonable to use 1-1-5% in the barium enema. Its use is followed by prompt evacuation of most of the colonic contents, so that little is left to be absorbed. MARGULIs et al.3137 38 and BURHENNE et al.,36 however, suggest that 0-5-0-75% is safer. The relation between ulcerative colitis and liver dysfunction must be born in mind. KIMMELSTIEL et al.40 found evidence of pericholangitis in 10% of patients with ulcerative colitis, and this was only six years after the first use of tannic acid in barium enemas, whereas VINNIK et a1.41 in 1963 found pericholangitis in as many 34. Kemp Harper, R. A. Lancet, 1965, i, 1396. 35. Staab, E. V., Vix, V. A. Radiology, 1965, 84, 1087. 36. Burhenne, H. J., Vogelaar, P., Arkoff, R. S. Am. J. Roentgenol. 1966,

96, 510. 37. 38.

39. 40. 41.

O. N., Zboralske, F. F., Harris, P. A., Riegelman, S., Margulis, A. R. ibid. p. 488. Harris, P. A., Zboralske, F. F., Rambo, O. N., Margulis, A. R., Riegelman, S. ibid. p. 498. Kemp Harper, R. A. Br. J. Radiol. 1966, 39, 401. Kimmelstiel, P., Large, H. L., Verner, H. D. Am. J. Path. 1952, 28, 259. Vinnik, I. E., Kern, F., Corley, W. D. Gastroenterology, 1963, 45, 492.

Rambo,

27% of such patients. Evidence of liver damage is usually found in the later stages of the disease, when the patient may have had many barium enemas, and it would be of interest to know the state of the liver in patients who have not been investigated, and whether such examinations predispose patients to further liver damage as

from the disease itself.

Intestinal Hormones and Insulin A FEW weeks ago1 we discussed the role of the duodenal mucosa in controlling the secretion of acid by the stomach. This regulating activity does not seem to be a lone phenomenon, since recent work has suggested that carbohydrate metabolism might be influenced by a release of hormone from the intestine. When glucose is given by mouth to rats it is apparently removed from the circulation more quickly than when it is infused intravenously.22 This difference can be explained by the observations of McINTYRE and ELRICK and their co-workers 3that plasma-insulin levels rise higher after oral glucose loading, compared with intravenous loading. Possibly, a hormonal substance was being released from the gut wall during the absorption of sugar, causing insulin to be liberated by the pancreas. This substance might be secretin, for ZUNZ and LA BARREhad shown in 1928 that impure secretin had a hypoglycasmic effect. Further evidence 6favouring this hypothesis came when purified secretin was shown to stimulate the release of insulin by in-vitro preparations of dog and rabbit pancreas, while DupRE and BECK8 report that a crude secretin extract will enhance plasma insulin-like activity and increase the rate of disposal of a glucose load. Another hormone, however, could be the mediator in an intestinal-pancreatic hormonal pathway, and that is glucagon. Glucagon, like secretin, will increase glucose toleranceand stimulate the release of insulin, both in vitro 10 and in vivo.9Furthermore, the oral administration of glucose leads to a rise in the blood-glucagon level (an effect which does not follow when glucose is given intravenously) 11 12 ; and glucagon-like activity and immunoreactive glucagon have been isolated from gastrointestinal tissues.13 14 In preliminary communications in this issue Dr. DUPRÉ and his colleagues show that secretin will stimulate the release of insulin by the pancreas in vivo in man without, apparently, any detectable rise in portal-blood glucagon values-a result 1. 2. 3. 4.

Lancet, 1966, i, 588. Scow, R. D., Cornfield, J. Am. J. Physiol. 1954, 179, 435. McIntyre, N., Holdsworth, C. D., Turner, D. S. Lancet, 1964, ii, 20. Elrick, H., Stimmler, L., Hlad, C. J., Arai, Y. J. clin. Endocr. 1964, 24, 1076. 5. Zunz, E., La Barre, J. C. r. Soc. Biol. Paris, 1928, 98, 1435. 6. McIntyre, N., Turner, D. S., Holdsworth, C. D. Diabetologia, 1965, 1, 73.

Pfeiffer, E. F., Telib, M., Ammon, J., Melani, F., Ditschuneit, H. ibid. p. 131. 8. Dupré, J., Beck, J. C. Diabetes, 1966 (in the press). 9. Samols, E., Marri, G., Marks, V. Lancet, 1965, ii, 415. 10. Turner, D. S., McIntyre, N. ibid. 1966, i. 351. 11. Samols, E., Tyler, J., Marri, G., Marks, V. ibid. 1965, ii, 1257. 12. Lawrence, A. M. Proc. natn. Acad. Sci. U.S.A. 1966, 55, 316. 13. Makman, M. H., Sutherland, E. W. Endocrinology, 1964, 75, 127. 14. Ketterer, H., Dupré, J., Eisentraut, A. M., Unger, R. H. Diabetes, 1966 (in the press). 7.

36

which suggests that the insulin response to secretin is not mediated by circulating glucagon. In dogs the endoportal injection of crude or purified secretin was followed within 3 minutes by a rise in the insulin content of blood in the pancreaticoduodenal vein-a quicker rise than was achieved by injections of glucagon. Since infusion of acid into the duodenum will normally cause the release of secretin, BoYNS et al.15 measured glucose and insulin levels in the plasma after the instillation of glucose and citric acid into the human duodenum, but they failed to detect any consistent effect on plasma insulin and glucose concentrations when the citric acid was given. They suggested therefore that secretin was unlikely to mediate an intestinal pancreatic response. This result is somewhat at variance with earlier work.16 After reviewing extensive early evidence suggesting a hypoglycaemic effect of intestinal tissue extracts, SHAY et al.16 found that infusions of hydrochloric acid or a variety of other substances were hypoglycxmic in man provided that at the time of infusion the blood-sugar concentration was above the fasting level. Further experiments are clearly necessary to clarify the situation; but a defective intestinal hormone response to glucose as part of diabetes mellitus is an interesting

ventional education is

largely a reading world, and Shirley painted a vivid picture, which many teachers and parents will recognise, of the misery and despair these children experience, and the complete emotional blockage to all forms of learning that they may develop when no help is given. Severe forms of the trouble will often be suspected by the observant teacher or parent, but lesser degrees are usually mistaken for laziness, carelessness, or stupidity, to the sad detriment of the child. Fortunately methods of treatment,which emphasise individual attention and exploit repetitive association of visual patterns with sounds, have proved of value and are still being developed. The disability in all its aspects and repercussions was admirably reviewed by Critchley.21 Views on causation vary. A family history has suggested a constitutional factor .22 A high incidence of ambidexterity and left-handedness seemed to implicate an incomplete hemisphere dominance.23 Minor degrees of cerebral birth injury have also been invoked. 24 Since it is essentially remediable, the condition should be known to teachers and school doctors. It was a school medical officer, Dr. James Kerr,25 later a well-known pioneer in the L.C.C. medical service, who in 1896 first mentioned the condition as a problem in education. 20

speculation. THE E.G.A. HOSPITAL 100 YEARS OLD

Annotations CONGENITAL WORD BLINDNESS

IN 1877 Kussmaul 17 described, as a limited form of aphasia-a loss of ability to read words-while speech and intelligence were preserved. He used the term " word blindness " for this condition. Subsequent observations suggested that a lesion in the left (dominant) occipitoparietal region was responsible. In 1896 Morgan 18 extended the concept to an inborn disability-congenital word blindness-to explain the case of a schoolboy of 14, who seemed generally intelligent, was good at arithmetic and algebra, and learned quickly by oral instruction, but had a quite disproportionate difficulty with spelling and reading. The condition was further defined clinically by Hinshelwood.19 Such children have great difficulty in learning to read, and, indeed, may never achieve it, despite otherwise normal intelligence and general ability. The term congenital word blindness, more homely and descriptive than its rival, dyslexia, has been criticised but is still used. Its importance as an educational hazard was soon recognised in this country and the United States. In Denmark the founding of a Word Blind Institute in Copenhagen emphasised the size of the problem. The disability, it was found, could usually be much relieved by the method of auditory repetition; and oral instruction, instead of written, quickly led to learning. Since these children may be of average or even above-average intelligence, their education is vital to their happiness and to their contribution to the community. The world of con15. 16.

Boyns, D. R., Jarrett, R. J., Keen, H. Lancet, 1966, i, 409. Shay, H., Gershon-Cohen, J., Fels, S. S. Ann. intern. Med. 1938, 11, 1563.

17. 18. 19.

Kussmaul, A. Cyclopædia of the Practice of Medicine: vol. XIV, p. 770. New York, 1877. Morgan, W. P. Br. med. J. 1896, ii, 1378. Hinshelwood, J. Congenital Word Blindness. London, 1917.

Elizabeth Garrett qualified as a doctor in 1865 and immediately started in practice at 20 Upper Berkeley Street. Private practice, however, did not satisfy her. She had no hope of obtaining an appointment in a hospital. Her only chance of widening her experience and of reaching the poorer women and children whom she was eager to help was to start her own dispensary. So it was that on July 2, 1866, she opened St. Mary’s Dispensary for Women and Children at 69 Seymour Place, in a densely crowded and poor part of Marylebone. The scare caused by the cholera epidemic which was then spreading in London contributed to the welcome given to her venture. Patients paid ld. per outpatient attendance, and were visited at home if they were too ill to go to the dispensary. 3000 new patients attended in the first year. By 1871 women were coming from all over London to take the opportunity of being examined and treated for gynaecological complaints by a woman. Beds for inpatient treatment had to be found, and thus was started the New Hospital for Women, with 10 beds above the dispensary. Three years later, it moved to two converted houses at 222 and 224 Marylebone Road. There room was found for 26 beds and an operating-theatre. In these quarters, cramped but spotlessly clean and gay with flowers, the hospital gained fame, and the staff of four married women doctors were hardworked. Mrs. Garrett Anderson (she had married Skelton Anderson in 1871) was the only member of the staff competent to undertake

major surgery. When 14 years later the lease of the houses expired, the committee showed astounding courage and foresight. The site of 144 Euston Road was bought for E3000 in 1888. By 1889, the foundation stone was laid, and (they 20. 21. 22. 23. 24. 25.

Shirley, L. F. Calif. Med. 1955, 83, 79. Critchley, M. Developmental Dyslexia. London, 1964. Stephenson, S. Ophthalmoscope, 1907, 5, 9. Orton, S. T. New Engl. J. Med. 1928, 199, 1046. Currier, F. P., Dewar, M. J. Mich. St. med. Soc. 1927, 26, Kerr, J. Jl. R. statist. Soc. 1897, 60, 613.

300.