365
requires an extra-amniotic catheter, which may be a disadvantage, and comparable results have been obtained with larger doses given into the posterior vaginal fornix.s The simplicity of this approach is a big advantage. Prostaglandin F 2r.J. also seems to be effective by this route9 and may be valuable in those parts of the world where prostaglandin E2 is available. On p. 376 the Oxford workers present reasons for preferring E2. WILSON10 has lately compared the oral, vaginal, and extra-amniotic routes of prostaglandin E2 as well as the time-honoured technique of intravenous oxytocin infusion. The extra-amniotic route emerged as slightly better than the vaginal and both were superior to the oral route. Intravenous oxytocin seemed to have very little effect. Such comparative studies are, of course, limited by the dosage protocol employed and more work is needed to establish the most suitable means of delivering the prostaglandins. A serious obstacle is the continuing lack of suitable prostaglandin preparations for local use. In all the studies so far reported, the investigators had either to prepare their own gels to which the prostaglandins were then added or to insert into the vagina tablets which were designed for oral use. Let us hope the pharmaceutical industry will soon provide a prostaglandin pessary or gel formulation for vaginal or extra-amniotic use. There is much still to be learned about cervical ripening. The clinical efficacy of prostaglandins suggests that they have a physiological role in the process, and experimental evidence supports this notion." However, in animals several other hormones seem to be involved-œstrogens, progesterone, relaxin. We need to know more, too, about the tissue mechanics of the cervix, about the collagen which seems to be the main structural element, and about the glycosaminoglycans of the ground substance which influence the binding of collagen fibres and thereby the compliance of the tissue. With a fuller understanding of these matters we may be able to offer the fetus a safer passage through the birth canal. not
SAYING WHEN THE old joke that an alcoholic is someone who drinks than his doctor reflects our embarrassed ambivalence about alcohol. Doctors in the West are relatively more
affluent and tend to be sociable; in their social pursuits they are prone to consume moderate amounts of alcohol. The ambivalence arises because of their professional awareness of the widespread physical, mental, and social harm which alcohol in excess may produce. They are aware that there are probably 2000 to 3000 alcoholic doctors, and that alcohol abuse is a frequent reason for colleagues to fall foul of the General Medical Council.
7 Thiery, M., Defoort, P., Benijts, G., Van Eyck, J., Hennay, T., Vankets, H., Martens, G. Prostaglandins, 1977, 14, 381. 8 9 10
MacKenzie, I. Z., Embrey, M. P. Br. med. J. 1977, ii, 1369. MacLennan, A. H., Green, R. C. Lancet, 1979, i, 117. Wilson, PDBr.J. Obstet Gynæc. 1978, 85, 941. 11. Liggins, G. C. in Seminars in Perinatology (edited by T. H. Kirschbaum); vol. II, p. 261. New York, 1978.
T. K. Oliver and
awareness of the alcohol problems in sois ciety increasing because of the growing frequency with which individuals having alcohol-related disease are coming to light, particularly in general practice, in medical wards, and in psychiatric hospitals (which have seen a 25-fold increase in admissions for alcoholism in the past 20 years). The police and the courts are equally conscious of the trend, coping now with 100 000 drunkenness arrests a year, and a rising toll of drunk-driving accidents which now cost C100 million a year. The medical profession has-not hitherto shown the corporate concern about drinking that it has about smoking, but the appearance of a report by a special committee of the Royal College of Psychiatrists’ should mark a change. Dr Griffith Edwards and his colleagues pitch their report for the intelligent layman; it is well written and attractively presented. Its most important attribute, though, is that it is not an evangelistic diatribe. It sets out to inform-where facts are available and indisputable-and honestly to delineate areas where there is doubt and dispute. It deals with every type of alcohol-induced disease, describing them clearly, with illustrative case-histories, and stressing interactions with other drugs. The still tangled arguments about the importance of genetic factors are well presented (final conclusion : "uncertain"). Particular stress is placed on the social aspects of alcoholism; on the effects which overall rises in alcohol consumption have on the "alcohol injury rates". Dr Edwards and his colleagues recognise the attractiveness of the argument that more liberal licensing laws, and the readier availability of alcohol, will simply allow people to drink socially without pressures to "binge", but they judge that extreme relaxation of formal controls would be very risky and less extreme relaxation would have uncertain consequences on health. The epidemiological evidence is given in some detail, and the difficulties of analysis are stressed; the committee had little doubt, though, that on most occasions when a country’s per caput alcohol consumption has risen, so have the numbers of individuals who increase their intake to dangerous levels, and become casualties. When we see that the United Kingdom’s consumption of wine and spirits has just about doubled in the past 10 years the danger seems clear. This conviction leads the psychiatrists who wrote the report to make their first goal the prevention of any further rise in the per caput consumption of alcohol. Because consumption of alcohol bears a close relation to its price, they believe that a major cause of the increase in consumption since 1950 has been its increasing relative cheapness: there is an inverse relation between whisky consumption and price (expressed as percentage of income). To this end, direct fiscal action by Government is urged, first to ensure that consumption does not increase, then to bring it down. "Formal" controls-that is, application of licensing laws and control of outlets-are seen as equally important. Fiscal control of alcohol consumption could not be brought to bear quickly, even if there was public approval, if only because of economic implications ; the manufacture and sale of alcohol create a huge, labour-intensive industry.
Professional
1 Alcohol and Alcoholism: the report of a special committee of the Royal College of Psychiatrists. London: Tavistock Publications. 1979. Pp. 162.
£5.95; paperback £1.95.
366
Education is essential, both to make individuals of the hazards of alcohol, and to create a climate of opinion favourable to the suggested action. This report will be but a small step in that direction, for it will not be easy to remove the popular image of the "friendly drunk", nor to change the accepted British practice of lubricating most social occasions with alcohol. Indeed, prohibition and temperance are not the report’s aim. It seeks to reduce social drinking to a nonharmful level, suggesting as a guideline a maximum intake of four pints of beer, four doubles of spirits, or a bottle of wine in a day (and that is too much if taken regularly). Businesses are urged to examine jobs which seem to necessitate drinking, and we are all urged to examine our own practices as hosts in our own homes. Do we regard our dispensing of drinks with sufficient reaware
sponsibility ?
Does
embarrassment,
belief that it is
polite,
acquaintances indulgence ?
known
or
our
misguided
pour stiffer drinks for be inclined towards over-
cause us to
to
.
This is a well-balanced document which can hardly fail to impress on the reader the size and seriousness of the alcohol problem, and of its disastrous potential over the next few years. Doctors are in a strong position to take a lead in the necessary education campaign, as they have done over smoking. PEPTIC ULCER AFTER RENAL TRANSPLANTATION
’
PATIENTS with renal transplants are susceptible to a depressingly large number of gastrointestinal complications, including fungal oœsophagitis, pancreatitis, smallbowel obstruction or infarction, ischæmic colitis, and colonic perforation.I-4 Probably the commonest of all is peptic ulceration, with a frequency as high as 18%.5 It is a serious disease in transplanted patients, often complicated by perforation or haemorrhage, and carries an overall mortality of 43%.5 The ulcers may have developed before transplantation, for peptic ulceration is not uncommon in renal failure.6 In 377 patients transplanted in Minnesota, evidence of previous peptic ulceration was found in 30.7 Serum-gastrin can be high in renal failure, probably owing to failure of the kidneys to degrade gastrin.8 Basal acid output by the stomach and the peak response to pentagastrin can also be raised,9 especially in patients who have been on haemodialysis for some months.6 After renal transplantation serum-gastrin falls rapidly8 11 but, paradoxically, basal and peak acid secretion can increase further.l2 The role of steroids in causing ulcers has been questioned,13 but there now seems little doubt that large doses increase the E. J., Evans, D. B., Smellie, W. A. B., et al. Lancet, 1971, ii, 781. 2. Julien, P. J., Goldberg, H. I., Margulis, A. R., et al. Radiology, 1975, 117,37. 3. Penn, I., Groth, C. G., Brettschneider, L., et al. Ann. Surg. 1968, 168, 865. 4. Aldrete, J. S., Sterling, W. A., Hathaway, B. M., et al. Am. J. Surg. 1975, 129, 115. 5. Owens, M. L., Passaro, E., Wilson, S. E., et al. Ann. Surg. 1977, 186, 17. 6. Ventkateswaran, P. S., Jeffers, A., Hocken, A. G. Br. med. J. 1972, iv, 22. 7. Spanos, P. K., Simmons, R. L., Rattazzi, L. C., et al. Archs Surg. 1974, 109, 1.
Hadjiyannakis,
193. 8. 9. 10.
Korman, M. G., Laver, M. C., Hansky, J. Br. med. J. 1972, i, 209. Gordon, E. M., Johnson, A. G., Williams, G. Lancet, 1972, i, 226. McConnell, J. B., Stewart, W. K., Thjodleifsson, B., et al. Lancet, 1975, ii,
11. 12. 13.
King, R., Hansky, J. ibid. 1974, i, 169. Chisholm, G. D., Mee, A. D., Williams, G., et al. Br. med. J. 1977, i, Conn, H. O., Blitzer, B. L. N. Engl. J. Med. 1976, 294, 473.
1121.
1630.
risk of peptic ulceration. Conn and Blitzer13 reviewed 42 controlled investigations involving over 5000 patients to whom steroids had been prescribed for various conditions. There was a significant increase in peptic ulceration in patients who received a cumulative total dose of more than 1 g of prednisone.13 Kidney transplant patients frequently receive doses of this order-in fact, it is common practice to administer 1 g of methylprednisolone on the day of transplantation. Nonetheless, the association between the dose of steroids received and ulceration is not completely clear, and in one study steroid dosage was no larger in a group of transplanted patients with ulcers than it was in a group who remained ulcerfree.14 Azathioprine is believed not to cause peptic ulceration.15 In two controlled studies involving 110 patients on steroids for ulcerative colitis, the addition of azathioprine to the treatment of one group was not followed by a greater incidence of peptic ulceration in that group. 16 17 Another possible factor in the xtiology is virus infection, since cytomegalovirus (C.M.V.) is often detectable after transplantation. 18 In patients with other diseases c.M.v. has been discovered in the mucosa of the stomach and duodenum, often in association with ulcers,19 and the virus has been blamed for causing ulceration of the cæcum.20 This evidence is not very strong, and there is so far only one report of c.M.v. being found in association with a peptic ulcer in a patient with a
transplant.4 Immunosuppression does not seem to prevent peptic responding to medical treatment and for uncomplicated ulcers this approach has been recommended. 14 Unfortunately haemorrhage or perforation is often the presenting feature and under these circumstances urgent operation is required. Cimetidine has been used successfully in cases of haemorrhage but half the patients have relapsed within a short period,14 and although further haemorrhage can follow operation,1 ulcers from
seems the safest treatment. Some workers recommend prophylactic ulcer surgery before transplantation in all patients with a history of peptic ulceration, since the frequency of complications may be reduced in this way. 5This will not, however, greatly reduce the overall incidence of complications, since most ulcers arise in transplanted patients who have had no previous symptoms. In fact, Chisholm et al. 12 were quite unable to identify those patients at risk even after examining pre and post transplant measurements of gastric-acid secretion. Enteric-coated steroid tablets and regular antacids do not seem to have much prophylactic value. Some encouraging news has come from King’s College Hospital,21 where 30 transplanted patients were treated with cimetidine in doses up to 1 g a day from the day of transplantation. There were no episodes of hoemorrhage, whereas in a previous series of 33 patients treated with antacids alone there were six such episodes. If these
surgery still
14.
Archibald, S. D., Jirsch,
D.
N., Bear, R. A. Can. med. Ass. J. 1978, 119,
1291.
15. Weinberg, A. L. in Progress in Immunology II: vol. v, Clinical Aspects II (edited by L. Brent and J. Holborow), p. 253 Amsterdam, 1974. 16. Rosenberg, J. L., Wall, A. J., Levin, B., et al. Gastroenterology, 1975, 69, 96.
Jewell, D. P., Truelove, S. C. Br. med. J. 1974, iv, 627. Summons, R. L., Lopez, C., Balfour, H., et al. Ann. Surg. 1974, 180, 623 Wolfe, B. M., Cherry, J. D. Ann. Surg. 1973, 77, 490. Henson, D. Archs. Path. 1972, 93, 477. 21. Jones, R. H., Rudge, C. J., Bewick, M., et al. Br. med. J. 1978, i, 398. 17. 18. 19. 20.
requires an extra-amniotic catheter, which may be a disadvantage, and comparable results have been obtained with larger doses given into the posterior vaginal fornix.s The simplicity of this approach is a big advantage. Prostaglandin F 2r.J. also seems to be effective by this route9 and may be valuable in those parts of the world where prostaglandin E2 is available. On p. 376 the Oxford workers present reasons for preferring E2. WILSON10 has lately compared the oral, vaginal, and extra-amniotic routes of prostaglandin E2 as well as the time-honoured technique of intravenous oxytocin infusion. The extra-amniotic route emerged as slightly better than the vaginal and both were superior to the oral route. Intravenous oxytocin seemed to have very little effect. Such comparative studies are, of course, limited by the dosage protocol employed and more work is needed to establish the most suitable means of delivering the prostaglandins. A serious obstacle is the continuing lack of suitable prostaglandin preparations for local use. In all the studies so far reported, the investigators had either to prepare their own gels to which the prostaglandins were then added or to insert into the vagina tablets which were designed for oral use. Let us hope the pharmaceutical industry will soon provide a prostaglandin pessary or gel formulation for vaginal or extra-amniotic use. There is much still to be learned about cervical ripening. The clinical efficacy of prostaglandins suggests that they have a physiological role in the process, and experimental evidence supports this notion." However, in animals several other hormones seem to be involved-œstrogens, progesterone, relaxin. We need to know more, too, about the tissue mechanics of the cervix, about the collagen which seems to be the main structural element, and about the glycosaminoglycans of the ground substance which influence the binding of collagen fibres and thereby the compliance of the tissue. With a fuller understanding of these matters we may be able to offer the fetus a safer passage through the birth canal. not
SAYING WHEN THE old joke that an alcoholic is someone who drinks than his doctor reflects our embarrassed ambivalence about alcohol. Doctors in the West are relatively more
affluent and tend to be sociable; in their social pursuits they are prone to consume moderate amounts of alcohol. The ambivalence arises because of their professional awareness of the widespread physical, mental, and social harm which alcohol in excess may produce. They are aware that there are probably 2000 to 3000 alcoholic doctors, and that alcohol abuse is a frequent reason for colleagues to fall foul of the General Medical Council.
7 Thiery, M., Defoort, P., Benijts, G., Van Eyck, J., Hennay, T., Vankets, H., Martens, G. Prostaglandins, 1977, 14, 381. 8 9 10
MacKenzie, I. Z., Embrey, M. P. Br. med. J. 1977, ii, 1369. MacLennan, A. H., Green, R. C. Lancet, 1979, i, 117. Wilson, PDBr.J. Obstet Gynæc. 1978, 85, 941. 11. Liggins, G. C. in Seminars in Perinatology (edited by T. H. Kirschbaum); vol. II, p. 261. New York, 1978.
T. K. Oliver and
awareness of the alcohol problems in sois ciety increasing because of the growing frequency with which individuals having alcohol-related disease are coming to light, particularly in general practice, in medical wards, and in psychiatric hospitals (which have seen a 25-fold increase in admissions for alcoholism in the past 20 years). The police and the courts are equally conscious of the trend, coping now with 100 000 drunkenness arrests a year, and a rising toll of drunk-driving accidents which now cost C100 million a year. The medical profession has-not hitherto shown the corporate concern about drinking that it has about smoking, but the appearance of a report by a special committee of the Royal College of Psychiatrists’ should mark a change. Dr Griffith Edwards and his colleagues pitch their report for the intelligent layman; it is well written and attractively presented. Its most important attribute, though, is that it is not an evangelistic diatribe. It sets out to inform-where facts are available and indisputable-and honestly to delineate areas where there is doubt and dispute. It deals with every type of alcohol-induced disease, describing them clearly, with illustrative case-histories, and stressing interactions with other drugs. The still tangled arguments about the importance of genetic factors are well presented (final conclusion : "uncertain"). Particular stress is placed on the social aspects of alcoholism; on the effects which overall rises in alcohol consumption have on the "alcohol injury rates". Dr Edwards and his colleagues recognise the attractiveness of the argument that more liberal licensing laws, and the readier availability of alcohol, will simply allow people to drink socially without pressures to "binge", but they judge that extreme relaxation of formal controls would be very risky and less extreme relaxation would have uncertain consequences on health. The epidemiological evidence is given in some detail, and the difficulties of analysis are stressed; the committee had little doubt, though, that on most occasions when a country’s per caput alcohol consumption has risen, so have the numbers of individuals who increase their intake to dangerous levels, and become casualties. When we see that the United Kingdom’s consumption of wine and spirits has just about doubled in the past 10 years the danger seems clear. This conviction leads the psychiatrists who wrote the report to make their first goal the prevention of any further rise in the per caput consumption of alcohol. Because consumption of alcohol bears a close relation to its price, they believe that a major cause of the increase in consumption since 1950 has been its increasing relative cheapness: there is an inverse relation between whisky consumption and price (expressed as percentage of income). To this end, direct fiscal action by Government is urged, first to ensure that consumption does not increase, then to bring it down. "Formal" controls-that is, application of licensing laws and control of outlets-are seen as equally important. Fiscal control of alcohol consumption could not be brought to bear quickly, even if there was public approval, if only because of economic implications ; the manufacture and sale of alcohol create a huge, labour-intensive industry.
Professional
1 Alcohol and Alcoholism: the report of a special committee of the Royal College of Psychiatrists. London: Tavistock Publications. 1979. Pp. 162.
£5.95; paperback £1.95.
366
Education is essential, both to make individuals of the hazards of alcohol, and to create a climate of opinion favourable to the suggested action. This report will be but a small step in that direction, for it will not be easy to remove the popular image of the "friendly drunk", nor to change the accepted British practice of lubricating most social occasions with alcohol. Indeed, prohibition and temperance are not the report’s aim. It seeks to reduce social drinking to a nonharmful level, suggesting as a guideline a maximum intake of four pints of beer, four doubles of spirits, or a bottle of wine in a day (and that is too much if taken regularly). Businesses are urged to examine jobs which seem to necessitate drinking, and we are all urged to examine our own practices as hosts in our own homes. Do we regard our dispensing of drinks with sufficient reaware
sponsibility ?
Does
embarrassment,
belief that it is
polite,
acquaintances indulgence ?
known
or
our
misguided
pour stiffer drinks for be inclined towards over-
cause us to
to
.
This is a well-balanced document which can hardly fail to impress on the reader the size and seriousness of the alcohol problem, and of its disastrous potential over the next few years. Doctors are in a strong position to take a lead in the necessary education campaign, as they have done over smoking. PEPTIC ULCER AFTER RENAL TRANSPLANTATION
’
PATIENTS with renal transplants are susceptible to a depressingly large number of gastrointestinal complications, including fungal oœsophagitis, pancreatitis, smallbowel obstruction or infarction, ischæmic colitis, and colonic perforation.I-4 Probably the commonest of all is peptic ulceration, with a frequency as high as 18%.5 It is a serious disease in transplanted patients, often complicated by perforation or haemorrhage, and carries an overall mortality of 43%.5 The ulcers may have developed before transplantation, for peptic ulceration is not uncommon in renal failure.6 In 377 patients transplanted in Minnesota, evidence of previous peptic ulceration was found in 30.7 Serum-gastrin can be high in renal failure, probably owing to failure of the kidneys to degrade gastrin.8 Basal acid output by the stomach and the peak response to pentagastrin can also be raised,9 especially in patients who have been on haemodialysis for some months.6 After renal transplantation serum-gastrin falls rapidly8 11 but, paradoxically, basal and peak acid secretion can increase further.l2 The role of steroids in causing ulcers has been questioned,13 but there now seems little doubt that large doses increase the E. J., Evans, D. B., Smellie, W. A. B., et al. Lancet, 1971, ii, 781. 2. Julien, P. J., Goldberg, H. I., Margulis, A. R., et al. Radiology, 1975, 117,37. 3. Penn, I., Groth, C. G., Brettschneider, L., et al. Ann. Surg. 1968, 168, 865. 4. Aldrete, J. S., Sterling, W. A., Hathaway, B. M., et al. Am. J. Surg. 1975, 129, 115. 5. Owens, M. L., Passaro, E., Wilson, S. E., et al. Ann. Surg. 1977, 186, 17. 6. Ventkateswaran, P. S., Jeffers, A., Hocken, A. G. Br. med. J. 1972, iv, 22. 7. Spanos, P. K., Simmons, R. L., Rattazzi, L. C., et al. Archs Surg. 1974, 109, 1.
Hadjiyannakis,
193. 8. 9. 10.
Korman, M. G., Laver, M. C., Hansky, J. Br. med. J. 1972, i, 209. Gordon, E. M., Johnson, A. G., Williams, G. Lancet, 1972, i, 226. McConnell, J. B., Stewart, W. K., Thjodleifsson, B., et al. Lancet, 1975, ii,
11. 12. 13.
King, R., Hansky, J. ibid. 1974, i, 169. Chisholm, G. D., Mee, A. D., Williams, G., et al. Br. med. J. 1977, i, Conn, H. O., Blitzer, B. L. N. Engl. J. Med. 1976, 294, 473.
1121.
1630.
risk of peptic ulceration. Conn and Blitzer13 reviewed 42 controlled investigations involving over 5000 patients to whom steroids had been prescribed for various conditions. There was a significant increase in peptic ulceration in patients who received a cumulative total dose of more than 1 g of prednisone.13 Kidney transplant patients frequently receive doses of this order-in fact, it is common practice to administer 1 g of methylprednisolone on the day of transplantation. Nonetheless, the association between the dose of steroids received and ulceration is not completely clear, and in one study steroid dosage was no larger in a group of transplanted patients with ulcers than it was in a group who remained ulcerfree.14 Azathioprine is believed not to cause peptic ulceration.15 In two controlled studies involving 110 patients on steroids for ulcerative colitis, the addition of azathioprine to the treatment of one group was not followed by a greater incidence of peptic ulceration in that group. 16 17 Another possible factor in the xtiology is virus infection, since cytomegalovirus (C.M.V.) is often detectable after transplantation. 18 In patients with other diseases c.M.v. has been discovered in the mucosa of the stomach and duodenum, often in association with ulcers,19 and the virus has been blamed for causing ulceration of the cæcum.20 This evidence is not very strong, and there is so far only one report of c.M.v. being found in association with a peptic ulcer in a patient with a
transplant.4 Immunosuppression does not seem to prevent peptic responding to medical treatment and for uncomplicated ulcers this approach has been recommended. 14 Unfortunately haemorrhage or perforation is often the presenting feature and under these circumstances urgent operation is required. Cimetidine has been used successfully in cases of haemorrhage but half the patients have relapsed within a short period,14 and although further haemorrhage can follow operation,1 ulcers from
seems the safest treatment. Some workers recommend prophylactic ulcer surgery before transplantation in all patients with a history of peptic ulceration, since the frequency of complications may be reduced in this way. 5This will not, however, greatly reduce the overall incidence of complications, since most ulcers arise in transplanted patients who have had no previous symptoms. In fact, Chisholm et al. 12 were quite unable to identify those patients at risk even after examining pre and post transplant measurements of gastric-acid secretion. Enteric-coated steroid tablets and regular antacids do not seem to have much prophylactic value. Some encouraging news has come from King’s College Hospital,21 where 30 transplanted patients were treated with cimetidine in doses up to 1 g a day from the day of transplantation. There were no episodes of hoemorrhage, whereas in a previous series of 33 patients treated with antacids alone there were six such episodes. If these
surgery still
14.
Archibald, S. D., Jirsch,
D.
N., Bear, R. A. Can. med. Ass. J. 1978, 119,
1291.
15. Weinberg, A. L. in Progress in Immunology II: vol. v, Clinical Aspects II (edited by L. Brent and J. Holborow), p. 253 Amsterdam, 1974. 16. Rosenberg, J. L., Wall, A. J., Levin, B., et al. Gastroenterology, 1975, 69, 96.
Jewell, D. P., Truelove, S. C. Br. med. J. 1974, iv, 627. Summons, R. L., Lopez, C., Balfour, H., et al. Ann. Surg. 1974, 180, 623 Wolfe, B. M., Cherry, J. D. Ann. Surg. 1973, 77, 490. Henson, D. Archs. Path. 1972, 93, 477. 21. Jones, R. H., Rudge, C. J., Bewick, M., et al. Br. med. J. 1978, i, 398. 17. 18. 19. 20.
