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CHRONIC CONSTIPATION IN CHILDHOOD
153 There were very discrete signs of cholestasis, moderate steatosis in the hepatocytes. Alcoholic hyaline was not detected. The paracetamol elimination capacity was determined 1 month after admission. The patient was given 1 g paracetamol (body-weight 78 kg), and the serum-paracetamol concentration was monitored.2 The paracetamol half-life was 263 min which is much higher than the 172:t91 (s.D.) min in fifteen controls, but similar to the 234 ±81 min in seven cirrhotics without ascites.2 The inactive fibrous septa in the patient’s liver biopsy cannot have been caused by the 2-week ingestion of paracetamol. The patient firmly denied alcohol abuse apart from that 1 year, 7 years earlier. However, he had a long history of backache and may have taken paracetamol before: it was not possible to get a reliable drug history from the patient. We cannot rule out the possibility that his inactive liver fibrosis was produced by previous subclinical drug-induced liver damage. The most reasonable explanation for the pronounced acute liver reaction in this patient seems to be paracetamol, although the histological picture did not correspond to that described3 in paracetamol overdose reactions. However, the liver steatosis and the lack of inflammatory changes indicated a toxic rather than hypersensitivity reaction. Alcohol was considered as explanation because of the history of former alcohol abuse, but such a pronounced increase in aminotransferases is not consistent with a reaction to alcohol, nor is the marked predominance of serum A.L.A.T. over A.S.A.T.4 (see table).
and and
histiocytes.
a
Medical Clinic II,
Sahlgren’s Hospital, S-413 45 Göteborg, Sweden
ROLF OLSSON
DIPYRIDAMOLE IN MIGRAINE
SIR,-If platelet aggregability is abnormal in patients with migraine, either chronicallyor in relation to an attack,6a
logical approach would be to attempt to reduce platelet aggregability. A double-blind cross-over trial of dipyridamole (’Persantin’) versus placebo was started, the aim being a series of fifty patients. All patients admitted to the trial had classical or common migraine and had at least two attacks per month. Dipyridamole was administered in a dose of 100 mg four times a day for 12 weeks and identical lactose tablets were given for the same period. Patients kept a daily record of tablet consumption and frequency and severity of headaches. I saw them before the trial and 12 and 24 weeks afterwards. All other treatment was withdrawn except for essential treatment during the attack. The trial was abandoned after the ninth patient had been entered. One patient defaulted. In four patients dipyridamole administration was associated with very severe headaches coming on within the first 4 days. The headaches were far worse than usual. Two patients abandoned dipyridamole within the first 5 weeks and one at 10 weeks because of increased headache. The remaining patients took the active drug for the required 12 weeks but the frequency of headache had doubled. Only four patients took the placebo and none reported any adverse effects. There seemed little doubt that dipyridamole was exacerbating the migraine. There was no reason to suspect this might have been a psychogenic response because no reactions developed to placebo tablets. Dipyridamole is a vasodilator and presumably this outweighs any possible advantage conferred
its action on platelets. Headache was a frequent but temporary side-effect in an earlier trial of dipyridamole in transient cerebral ischsemic attacks.’ It has been postulated5 that excessive platelet aggregation in
by
migraine
causes
the release of vasoactive substances such
as
serotonin, adrenaline, and prostaglandins E2 and F2cx and that this process could be inhibited by aspirin or flufenamic acid. Hence trials of these substances would seem well justified.5 Dipyridamole is being tested in cardiac and cerebral ischxmia, so investigators should be alert to the aggravation of pre-
existing migraine. I thank
Boeringher-Ingelheim
Ltd. for their assistance in this trial.
Department of Neurology, Ipswich Hospital, Ipswich, Suffolk IP4 5PD.
C. H. HAWKES
CHRONIC CONSTIPATION IN CHILDHOOD
SIR,-In your editorial6 you state "A suitable stool softener is dioctyl sodium sulphosuccinate (D.S.S.): this is best used on its own", and you cite one of us as a supporting reference. In fact the referenceexpresses doubts about the wisdom of oral administration of synthetic detergents such as D.s.s., which can cause mucosal damage in stomach,8 small intestine,9 and colon,’O and has other adverse effects. Given an intact gut neuromusculature, most functional motility disorders can be controlled by dietary means, with the added stimulus when required of small amounts of a chemical laxative (e.g., standardised senna). Restoration of "normal" peristalsis renders stool softeners unnecessary. D.S.S. should be restricted to the rectal route. Gastroenterology Unit, Royal Infirmary, Glasgow G4 0SF Fairlands, Totland, Isle of Wight PO39 0EB
R. I. RUSSELL
E. W. GODDING
IMMUNOLOGY OF PRE-ECLAMPSIA
SIR,-Dr Lewkonia’ rightly suggests that our finding of depressed immunological activity and increased histocompatibility in pre-eclampsia2 points to the possibility that injection of a paternal blood fraction, such as a B-lymphocyte preparation, may offer a method of therapy. The study of pre-eclampsia has suffered from an excess of speculation so we endeavoured to restrict ourselves as far as possible to the facts. In our original manuscript we referred to the possibility of a "protective blood-product inoculation", with a paternal lymphocyte preparation in mind. The reference to protection by "a gammaglobulin", which appeared in the final version, implies something different. There are obvious problems about following this approach, particularly the lack of a suitable animal model. However, our line of thought has been much influenced by observations on improved renal-allograft survival in association with prior blood-transfusion. It would be of the greatest interest to know if injection of lymphocytes of the kidney donor has an effect superior to that of an unrelated individual. If this proved to
4. Acheson, J., Danta, G., Hutchinson, E. C. Br. med. J. 1969, i, 614. 5. Dishmukh, S. V., Meyer, J. S., Mouch, R. J. Thrombos. Hæmostas. 1976,
36, 319. 2. Amman, R., Olsson, R. Acta hepato-gastroent. (in the press). 3. James, O., Lesna, M., Roberts, S. H., Pulman, L., Douglas, A. P., Smith, P. A., Watson, A. J. Lancet, 1975, ii, 579. 4. Cohen, J. A., Kaplan, M. M. Gastroenterology, 1975, 69, 3 A-13/813. 5. Couch, J. R. Hassanein, R. S. Neurology, 1976, 26, 348. 6 Deshmukh, S. V. Meyer, J. S. ibid, p. 347. 7. Vineberg, A. M., Chari, R. S., Pifarre, R. Mercierc Can. med. Ass. J. 1962,
87, 336.
6. Lancet, 1977, ii, 1064. 7. Godding, E. W. Br. med. J. 1976, i, 838. 8. Cochran, K. M., Nelson, L. M., Russell, R. I. Gut, 1977, 18, A422. 9. Saunders, D. R., Sillery, J., Rachmilewitz, D Gastroenterology, 1975, 980. 10. Donowitz, M., Binder, H. J. ibid. 1975, 69, 941. 1. Lewkonia, R. M. Lancet, 1978, i, 1212. 2. Scott, J. S , Jenkins, D. M., Need, J. ibid. p. 704.
69,
and and
histiocytes.
a
Medical Clinic II,
Sahlgren’s Hospital, S-413 45 Göteborg, Sweden
ROLF OLSSON
DIPYRIDAMOLE IN MIGRAINE
SIR,-If platelet aggregability is abnormal in patients with migraine, either chronicallyor in relation to an attack,6a
logical approach would be to attempt to reduce platelet aggregability. A double-blind cross-over trial of dipyridamole (’Persantin’) versus placebo was started, the aim being a series of fifty patients. All patients admitted to the trial had classical or common migraine and had at least two attacks per month. Dipyridamole was administered in a dose of 100 mg four times a day for 12 weeks and identical lactose tablets were given for the same period. Patients kept a daily record of tablet consumption and frequency and severity of headaches. I saw them before the trial and 12 and 24 weeks afterwards. All other treatment was withdrawn except for essential treatment during the attack. The trial was abandoned after the ninth patient had been entered. One patient defaulted. In four patients dipyridamole administration was associated with very severe headaches coming on within the first 4 days. The headaches were far worse than usual. Two patients abandoned dipyridamole within the first 5 weeks and one at 10 weeks because of increased headache. The remaining patients took the active drug for the required 12 weeks but the frequency of headache had doubled. Only four patients took the placebo and none reported any adverse effects. There seemed little doubt that dipyridamole was exacerbating the migraine. There was no reason to suspect this might have been a psychogenic response because no reactions developed to placebo tablets. Dipyridamole is a vasodilator and presumably this outweighs any possible advantage conferred
its action on platelets. Headache was a frequent but temporary side-effect in an earlier trial of dipyridamole in transient cerebral ischsemic attacks.’ It has been postulated5 that excessive platelet aggregation in
by
migraine
causes
the release of vasoactive substances such
as
serotonin, adrenaline, and prostaglandins E2 and F2cx and that this process could be inhibited by aspirin or flufenamic acid. Hence trials of these substances would seem well justified.5 Dipyridamole is being tested in cardiac and cerebral ischxmia, so investigators should be alert to the aggravation of pre-
existing migraine. I thank
Boeringher-Ingelheim
Ltd. for their assistance in this trial.
Department of Neurology, Ipswich Hospital, Ipswich, Suffolk IP4 5PD.
C. H. HAWKES
CHRONIC CONSTIPATION IN CHILDHOOD
SIR,-In your editorial6 you state "A suitable stool softener is dioctyl sodium sulphosuccinate (D.S.S.): this is best used on its own", and you cite one of us as a supporting reference. In fact the referenceexpresses doubts about the wisdom of oral administration of synthetic detergents such as D.s.s., which can cause mucosal damage in stomach,8 small intestine,9 and colon,’O and has other adverse effects. Given an intact gut neuromusculature, most functional motility disorders can be controlled by dietary means, with the added stimulus when required of small amounts of a chemical laxative (e.g., standardised senna). Restoration of "normal" peristalsis renders stool softeners unnecessary. D.S.S. should be restricted to the rectal route. Gastroenterology Unit, Royal Infirmary, Glasgow G4 0SF Fairlands, Totland, Isle of Wight PO39 0EB
R. I. RUSSELL
E. W. GODDING
IMMUNOLOGY OF PRE-ECLAMPSIA
SIR,-Dr Lewkonia’ rightly suggests that our finding of depressed immunological activity and increased histocompatibility in pre-eclampsia2 points to the possibility that injection of a paternal blood fraction, such as a B-lymphocyte preparation, may offer a method of therapy. The study of pre-eclampsia has suffered from an excess of speculation so we endeavoured to restrict ourselves as far as possible to the facts. In our original manuscript we referred to the possibility of a "protective blood-product inoculation", with a paternal lymphocyte preparation in mind. The reference to protection by "a gammaglobulin", which appeared in the final version, implies something different. There are obvious problems about following this approach, particularly the lack of a suitable animal model. However, our line of thought has been much influenced by observations on improved renal-allograft survival in association with prior blood-transfusion. It would be of the greatest interest to know if injection of lymphocytes of the kidney donor has an effect superior to that of an unrelated individual. If this proved to
4. Acheson, J., Danta, G., Hutchinson, E. C. Br. med. J. 1969, i, 614. 5. Dishmukh, S. V., Meyer, J. S., Mouch, R. J. Thrombos. Hæmostas. 1976,
36, 319. 2. Amman, R., Olsson, R. Acta hepato-gastroent. (in the press). 3. James, O., Lesna, M., Roberts, S. H., Pulman, L., Douglas, A. P., Smith, P. A., Watson, A. J. Lancet, 1975, ii, 579. 4. Cohen, J. A., Kaplan, M. M. Gastroenterology, 1975, 69, 3 A-13/813. 5. Couch, J. R. Hassanein, R. S. Neurology, 1976, 26, 348. 6 Deshmukh, S. V. Meyer, J. S. ibid, p. 347. 7. Vineberg, A. M., Chari, R. S., Pifarre, R. Mercierc Can. med. Ass. J. 1962,
87, 336.
6. Lancet, 1977, ii, 1064. 7. Godding, E. W. Br. med. J. 1976, i, 838. 8. Cochran, K. M., Nelson, L. M., Russell, R. I. Gut, 1977, 18, A422. 9. Saunders, D. R., Sillery, J., Rachmilewitz, D Gastroenterology, 1975, 980. 10. Donowitz, M., Binder, H. J. ibid. 1975, 69, 941. 1. Lewkonia, R. M. Lancet, 1978, i, 1212. 2. Scott, J. S , Jenkins, D. M., Need, J. ibid. p. 704.
69,