- Email: [email protected]
GASTRITIS AND CIMETIDINE: A POSSIBLE EXPLANATION
1095 amination of the oropharynx and larynx. Only mild congestion in an occasional patient, while larynx and vocal cords were normal; gag reflex was present in all patients. Mucosal biopsies taken from different parts of the oropharynx and laryngeal surface from a different group of leprosy patients
SIR,-Dr Branda and colleagues claim (April 1, p. 688) that plasmapheresis accelerated clearance of circulating anti-platelet factors in fulminant autoimmune thrombocytopenic purpura. We do not agree with this interpretation. Their patient had had thrombocytopenia for only 2 months, and it is not
only. We infer that the
clear how long the disease lasted after discharge from hospital. This point is crucial because acute thrombocytopenic purpura is often due to circulating immune complexes,’ as are some cases of chronic thrombocytopenia. The specificity and the sensitivity of methods for detecting platelet antibodies in different forms of thrombocytopenia are open to question. We and others2-6 obtained various percentages of positivity in autoimmune thrombocytopenic purpura investigated by tests for platelet-factor-3 availability, "C-serotonin release, complement fixation, and lymphocyte stimulation. Branda et al. used a new immunohistochemical method which is as yet only semiquantitativeand the evaluation of the degree of positivity seemed to be partly subjective. We do not know how sensitive this method is to the presence of immune complexes; only one
was seen
revealed occasional patchy granulomas
cough response is impaired in leprosy patients because of involvement of the afferent vagal fibres supplying the irritant receptors. The involvement must be diffuse throughout the respiratory tract because ultrasonically nebulised aerosols do reach the peripheral parts of the lung. We are now investigating other vagal nerve functions in this disease. S. K. MALIK KHER VIJAY Diseases and Divisions of Chest Dermatology, Postgraduate Institute of Medical Education and Research., BHUSHAN KUMAR SURINDER KAUR Chandigarh, India PLASMAPHERESIS FOR THROMBOCYTOPENIA
case
SIR,-Success with plasma exchange in
patient with idiowas described pathic thrombocytopenic purpura by Dr Branda and colleagues (April 1, p. 688). I have had a similar experience in a patient with thrombotic thrombocytopenic purpura. a
Although Branda et al. did not specify the type and amount of fluid replacement they used for the plasma exchange, it appears that massive infusion of fresh frozen plasma along with plasma removal by plasmapheresis is an important factor in such patients.’,2 A 70-year-old woman was seen because of generalised weakness and episodes of confusion and disorientation lasting about half an hour. Blood-pressure 140/68 mm Hg, pulse 104/min, respiration 18/min, temperature normal. She seemed frail but was alert and in no distress. There were hxmorrhagic lesions on the lower left lip and petechiae on the lower extremities and on the palate. She had a grade II-VI systolic ejection murmur. There was no hepatosplenomegaly. The cranial-nerve system was intact. Hxmatological data were: Hb 9.7 g/dl, h2ematocrit 9.1%, red blood-cells 3.42 x 1O%J.l, white blood-cells 4.2x103/1, with schistocytes 1+, poikilocytosis 2+. Plateletcount was 29 000/1. The differential count was segmented neutrophils 70, lymphocytes 22, monocytes 3, eosinophils 3, basophils 2. Factor v 126%; factor viu 176%. Coombs test negative. The patient
had been on co-trimoxazole for 10 days for a She had a history of hypertension for 5 years and of anterolateral myocardial infarction 6 months before admission, and her treatment included hydrochlorothiazide and warfarin sodium. The anticoagulant had been discontinued 3 days before admission. On the second day in hospital she became very disoriented and unresponsive. Prednisone was given. On the third day, because of her progressive deterioration and enlarging petechiar, plasmapheresis was done, with a Hxmonetics model 30 blood processor with a 225 ml disposable bowl. 1875 ml plasma was removed after four cycles. During this process eight units of fresh frozen plasma were infused. The estimated plasma removal was 1400 ml, or 60% of her total plasma volume. Three additional units of fresh frozen plasma were given on the fourth day. She also received two units of packed cells. On the day after plasmapheresis, the patient began responding well with rapid recovery of plateletcount. On day 11 she was discharged, with Hb 11.0 g/dl, platelets 275 000/1;and white blood-cells 6.9x 103/ul (bands 1, segmented neutrophils 57, lymphocytes 29, monocytes 10, metamyelocytes 3. 40 days after the patient’s discharge her platelet-count was 243 000/1, Hb 11.7 g/dl, white blood-cells 5-6xlOVI. A review of the smears, however, showed occasional schistocytes.
urinary-tract infection.
Lutheran General Hospital, Park Ridge, Illinois 60068, U.S.A.
TAKASHI OKUNO
1. Byrnes, J. J., Khurana, M. New Engl. J. Med., 1977, 297, Reiss, R., and others Blood, 1978, 51, 560.
2.
1386.
of lupus erythematosus was analysed.’
We think that the increase in platelet-count after plasma exchange can be attributed to the clearance of immune com-
plexes or to the administration of a plasma substance(s) with thrombocytopoietic activity.* Moreover, the patient was treated with high doses of prednisone and with vincristine; both drugs often induce an increase in platelet-count after some days of administration. Laboratory of Blood Coagulation, Institute of Medical Pathology I, University of Rome, Rome, Italy
G. M. GANDOLFO A. AFELTRA G. M. FERRI
GASTRITIS AND CIMETIDINE: A POSSIBLE EXPLANATION
SiR,-Webster et all reported erosive gastritis and duodenitis in a patient taking cimetidine. We suggest that one possible explanation for this unexpected association is related to colonisation of the gastrointestinal tract with Candida albicans. The not infrequent observation of candida within the ulcer slough of gastric and duodenal ulcers obtained at endoscopy prompted us to investigate the frequency of C. albicans in peptic ulcers. In the years 1972 to 1977 candida was found in 37% of 54 specimens, in contrast to 19% of 67 for the period 1950-53. Confirmation of the presence of candida in a significant proportion of ulcers suggests not only that colonisation and invasion by this pathogen (see figure) may delay or even prevent healing but also that the marked rise in the frequency of candida infection in the past few years may reflect the effects of newer therapeutic agents such as cimetidine. The rise in gastric pH which cimetidine brings about might encourage growth of C. albicans; in support of this view is the finding that gastric aspirates taken after vagotomy frequently grow candida on culture. 10 While the invasion of previously normal gastric mucosa by candida is rare, it has been recorded and shown to cause multiple ulcers 11 It is possible, therefore, that the gastritis seen 1. Mueller-Eckhardt, C. Semin. Thromb. Hemostas., 1977, 3, 125. 2. Mueller-Eckhardt, C., Mersch-Bausnert, K. Vox Sang 1977, 33, 221. 3. Mueller-Eckhardt, C., Mayser, B., Heinrich, D. ibid. p. 234. 4. Gandolfo, G. M., Afeltra, A., Amendolea, M. A., Mannella, E., Masala, C. Acta hœmat. 1977, 58, 10. 5. Gandolfo, G. M., Afeltra, A., Mannella, E., Costantini, G. Scand. J. Hœmat.
1977, 19, 355. Handin, R. I., Piessens, W. F., Moloney, W. C. New Engl. J. Med. 1973, 289, 714. 7. Tate, D. Y., Sorenson, R. L., Genard, J. M., White, J. G., Krivit, W. Br. J. Hœmat 1977, 37, 265. 8. Abildgaard, C. F., Simone, J. V. Semin. Hemat. 1967, 4, 424. 9. Webster, J., Petrie, J. C , Mowat, N. A. G. Br. med. J. 1978, i, 20. 10. Brooks, J. R., Smith, H. F., Pease, F. B. Ann. Surg. 1974, 179, 859. 11. Nelson, R. S., Bruni, H. C., Goldstein, H. M. Gastrointest. Endosc. 1975, 22, 92. 6.
1096 the nervous system. There was no abnormality of higher intellectual function. He had a mild pyramidal weakness of the left upper limb and both lower limbs. Tone was normal in the upper limbs, increased in the lower limbs with clonus at knees and ankles. The deep tendon reflexes in the lower limbs were exaggerated. The plantar responses were extensor. Posterior to
column sensory modalities were impaired to the costal margins and his gait was ataxic. The cimetidine treatment was stopped, and over the ensuing 5 days his neurological status returned to normal. He was dis.
,
charged symptom-free. The association of this patient’s symptom complex with cimetidine may have been fortuitous, but we feel that the onset of confusion and unsteadiness in a patient taking cimetidine should be an indication to stop the drug. Regional Neurological Centre, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
W. J. K. CUMMING J. B. FOSTER
PHENYTOIN/DEXAMETHASONE INTERACTION: A Tissue from bed of and yeasts.
gastric
ulcer
showing
candida
pseudohyphx
(Periodic-acid/Schiff; 220.) x
during cimetidine therapy may be the result of primary candidiasis of the gastric mucosa, in the presence of a raised intraluminal pH. The presence of candida infection in the gastrointestinal tract cannot be attributed entirely to a raised pH. Other factors which should also be taken into account are changing flora of the gastrointestinal tract due to the introduction of antibiotic therapy. Nevertheless, we suggest that when delay or failure of healing occurs, or if there is evidence of erosive gastritis or duodenitis, biopsy material and stool cultures should be examined for C. albicans; if cultures are positive a trial of oral nystatin should be considered while cimetidine therapy is continued. Department of Histopathology, Westminster Medical School, London SW1P 2PP
P. E. NICHOLLS KRISTIN HENRY
CIMETIDINE-INDUCED BRAINSTEM DYSFUNCTION
SIR,-An association between cimetidine and mental confusion has been reported several times.1-S We have seen a patient with clinical features suggesting brainstem ischemia which seemed to have been precipitated by cimetidine. The patient, aged 54, had a 7-year history of dyspepsia. On Oct. 13, 1977, gastroscopy showed a duodenal ulcer. He was treated with cimetidine 200 mg three times a day plus 400 mg at night. On Oct. 15 he noted some lightheadedness without true vertigo and complained to his wife of frontal headache. He continued the medication over the next 10 days, and complained of progressive unsteadiness as a result of which he had frequent falls. He had episodes of transient bilateral visual impairment and became deaf in his left ear. His speech became progressively dysarthric to the point where it was unintelligible, and he had been doubly incontinent. He complained of
parxsthesix. There
pital
on
was no relevant past history. He was admitted to hosOct. 26, where the abnormal findings were confined
1. Menzies-Gow, N. Lancet, 1977, ii, 928. 2. Nelson, P. G. ibid. p. 928. 3. Robinson, T. J. Mulligan, T. O. ibid. p. 719. 4. Delaney, J. C., Ravey, M. ibid. p. 512. 5. McMillen, M. A., Ambis, D., Siegel, J. H. New Engl. J. Med. 1978,
298, 284.
CLINICAL PROBLEM
SIR,-Phenytoin affects steroid metabolism-notably that of dexamethasone- by stimulating hepatic microsomal hydroxylating enzymes.’ This effect has been reported mainly in the context of the dexamethasone suppression test,2.3 but it has also been recorded in systemic lupus erythematosus.4 Otherwise little has been published on this problem in a clinical setting. We have seen a case where this interaction was of clini-’ cal significance. A 53-year-old woman presented in August, 1977, with a history of progressive left-sided weakness. After decompression craniotomy and biopsy of a right temporal lobe astrocytoma, she received radical radiotherapy, completing treatment in early October. She was discharged on a daily dose of 6 mg dexamethasone and 300 mg phenytoin with only slight weakness and dysphasia. When seen on Nov. 1 the patient had deteriorated, with episodes of urinary incontinence and increasing drowsiness. She was admitted and her dexamethasone dose was doubled. Computerised axial tomography suggested progression of the tumour, and it was agreed that nothing further should be done. By the next morning she had improved remarkably. After 48 h she was changed back to oral dexamethasone (administered intramuscularly while she was semicomatose) but she deteriorated again. We therefore felt that the method of administration must be important. Back on intramuscular dexamethasone she once again improved and on 12 mg/day became alert with no demonstrable weakness. After 10 days we made plans to discharge her, and so put her back on oral dexamethasone 12 mg/day. 5 days later she was once again confused, drowsy, and hemiplegic. At this point a drug interaction was considered. On Nov. 26 the patient was put on sodium valproate 200 mg three times a day and on Dec. 1 oral dexamethasone was restarted. The valproate dose was doubled on Dec. 13 because the patient reported an episode of tingling and twitching in the left hand. The dexamethasone has been reduced gradually, and, apart from bronchopneumonia in February, 1978, she remains well 4 months later. In this patient phenytoin probably accelerated the metabolism of the steroid (dexamethasone) given to control cerebral oedema. Three times a change to intramuscular dexamethasone 1. Haque, N., Thrasher, K., Werk, E. E., Knowles, H. C., Sholiton, L. J. J. clin. Endocr Metab. 1972, 34, 44. 2. Jubiz, W., Meikle, A. W., Levinson, R. A., Mizutani, S., West, C. D., Tyler, F. H. New Engl. J. Med. 1970, 283, 11. 3. Werk, E. E., Choi, Y., Sholiton, L. J., Olinjer, C., Haque, N., ibid. 1969, 281, 32. 4. Boylan, J. J., Owen, D. S., Chin, J. B. J. Am. med. Ass. 1976, 235, 803.
SIR,-Dr Branda and colleagues claim (April 1, p. 688) that plasmapheresis accelerated clearance of circulating anti-platelet factors in fulminant autoimmune thrombocytopenic purpura. We do not agree with this interpretation. Their patient had had thrombocytopenia for only 2 months, and it is not
only. We infer that the
clear how long the disease lasted after discharge from hospital. This point is crucial because acute thrombocytopenic purpura is often due to circulating immune complexes,’ as are some cases of chronic thrombocytopenia. The specificity and the sensitivity of methods for detecting platelet antibodies in different forms of thrombocytopenia are open to question. We and others2-6 obtained various percentages of positivity in autoimmune thrombocytopenic purpura investigated by tests for platelet-factor-3 availability, "C-serotonin release, complement fixation, and lymphocyte stimulation. Branda et al. used a new immunohistochemical method which is as yet only semiquantitativeand the evaluation of the degree of positivity seemed to be partly subjective. We do not know how sensitive this method is to the presence of immune complexes; only one
was seen
revealed occasional patchy granulomas
cough response is impaired in leprosy patients because of involvement of the afferent vagal fibres supplying the irritant receptors. The involvement must be diffuse throughout the respiratory tract because ultrasonically nebulised aerosols do reach the peripheral parts of the lung. We are now investigating other vagal nerve functions in this disease. S. K. MALIK KHER VIJAY Diseases and Divisions of Chest Dermatology, Postgraduate Institute of Medical Education and Research., BHUSHAN KUMAR SURINDER KAUR Chandigarh, India PLASMAPHERESIS FOR THROMBOCYTOPENIA
case
SIR,-Success with plasma exchange in
patient with idiowas described pathic thrombocytopenic purpura by Dr Branda and colleagues (April 1, p. 688). I have had a similar experience in a patient with thrombotic thrombocytopenic purpura. a
Although Branda et al. did not specify the type and amount of fluid replacement they used for the plasma exchange, it appears that massive infusion of fresh frozen plasma along with plasma removal by plasmapheresis is an important factor in such patients.’,2 A 70-year-old woman was seen because of generalised weakness and episodes of confusion and disorientation lasting about half an hour. Blood-pressure 140/68 mm Hg, pulse 104/min, respiration 18/min, temperature normal. She seemed frail but was alert and in no distress. There were hxmorrhagic lesions on the lower left lip and petechiae on the lower extremities and on the palate. She had a grade II-VI systolic ejection murmur. There was no hepatosplenomegaly. The cranial-nerve system was intact. Hxmatological data were: Hb 9.7 g/dl, h2ematocrit 9.1%, red blood-cells 3.42 x 1O%J.l, white blood-cells 4.2x103/1, with schistocytes 1+, poikilocytosis 2+. Plateletcount was 29 000/1. The differential count was segmented neutrophils 70, lymphocytes 22, monocytes 3, eosinophils 3, basophils 2. Factor v 126%; factor viu 176%. Coombs test negative. The patient
had been on co-trimoxazole for 10 days for a She had a history of hypertension for 5 years and of anterolateral myocardial infarction 6 months before admission, and her treatment included hydrochlorothiazide and warfarin sodium. The anticoagulant had been discontinued 3 days before admission. On the second day in hospital she became very disoriented and unresponsive. Prednisone was given. On the third day, because of her progressive deterioration and enlarging petechiar, plasmapheresis was done, with a Hxmonetics model 30 blood processor with a 225 ml disposable bowl. 1875 ml plasma was removed after four cycles. During this process eight units of fresh frozen plasma were infused. The estimated plasma removal was 1400 ml, or 60% of her total plasma volume. Three additional units of fresh frozen plasma were given on the fourth day. She also received two units of packed cells. On the day after plasmapheresis, the patient began responding well with rapid recovery of plateletcount. On day 11 she was discharged, with Hb 11.0 g/dl, platelets 275 000/1;and white blood-cells 6.9x 103/ul (bands 1, segmented neutrophils 57, lymphocytes 29, monocytes 10, metamyelocytes 3. 40 days after the patient’s discharge her platelet-count was 243 000/1, Hb 11.7 g/dl, white blood-cells 5-6xlOVI. A review of the smears, however, showed occasional schistocytes.
urinary-tract infection.
Lutheran General Hospital, Park Ridge, Illinois 60068, U.S.A.
TAKASHI OKUNO
1. Byrnes, J. J., Khurana, M. New Engl. J. Med., 1977, 297, Reiss, R., and others Blood, 1978, 51, 560.
2.
1386.
of lupus erythematosus was analysed.’
We think that the increase in platelet-count after plasma exchange can be attributed to the clearance of immune com-
plexes or to the administration of a plasma substance(s) with thrombocytopoietic activity.* Moreover, the patient was treated with high doses of prednisone and with vincristine; both drugs often induce an increase in platelet-count after some days of administration. Laboratory of Blood Coagulation, Institute of Medical Pathology I, University of Rome, Rome, Italy
G. M. GANDOLFO A. AFELTRA G. M. FERRI
GASTRITIS AND CIMETIDINE: A POSSIBLE EXPLANATION
SiR,-Webster et all reported erosive gastritis and duodenitis in a patient taking cimetidine. We suggest that one possible explanation for this unexpected association is related to colonisation of the gastrointestinal tract with Candida albicans. The not infrequent observation of candida within the ulcer slough of gastric and duodenal ulcers obtained at endoscopy prompted us to investigate the frequency of C. albicans in peptic ulcers. In the years 1972 to 1977 candida was found in 37% of 54 specimens, in contrast to 19% of 67 for the period 1950-53. Confirmation of the presence of candida in a significant proportion of ulcers suggests not only that colonisation and invasion by this pathogen (see figure) may delay or even prevent healing but also that the marked rise in the frequency of candida infection in the past few years may reflect the effects of newer therapeutic agents such as cimetidine. The rise in gastric pH which cimetidine brings about might encourage growth of C. albicans; in support of this view is the finding that gastric aspirates taken after vagotomy frequently grow candida on culture. 10 While the invasion of previously normal gastric mucosa by candida is rare, it has been recorded and shown to cause multiple ulcers 11 It is possible, therefore, that the gastritis seen 1. Mueller-Eckhardt, C. Semin. Thromb. Hemostas., 1977, 3, 125. 2. Mueller-Eckhardt, C., Mersch-Bausnert, K. Vox Sang 1977, 33, 221. 3. Mueller-Eckhardt, C., Mayser, B., Heinrich, D. ibid. p. 234. 4. Gandolfo, G. M., Afeltra, A., Amendolea, M. A., Mannella, E., Masala, C. Acta hœmat. 1977, 58, 10. 5. Gandolfo, G. M., Afeltra, A., Mannella, E., Costantini, G. Scand. J. Hœmat.
1977, 19, 355. Handin, R. I., Piessens, W. F., Moloney, W. C. New Engl. J. Med. 1973, 289, 714. 7. Tate, D. Y., Sorenson, R. L., Genard, J. M., White, J. G., Krivit, W. Br. J. Hœmat 1977, 37, 265. 8. Abildgaard, C. F., Simone, J. V. Semin. Hemat. 1967, 4, 424. 9. Webster, J., Petrie, J. C , Mowat, N. A. G. Br. med. J. 1978, i, 20. 10. Brooks, J. R., Smith, H. F., Pease, F. B. Ann. Surg. 1974, 179, 859. 11. Nelson, R. S., Bruni, H. C., Goldstein, H. M. Gastrointest. Endosc. 1975, 22, 92. 6.
1096 the nervous system. There was no abnormality of higher intellectual function. He had a mild pyramidal weakness of the left upper limb and both lower limbs. Tone was normal in the upper limbs, increased in the lower limbs with clonus at knees and ankles. The deep tendon reflexes in the lower limbs were exaggerated. The plantar responses were extensor. Posterior to
column sensory modalities were impaired to the costal margins and his gait was ataxic. The cimetidine treatment was stopped, and over the ensuing 5 days his neurological status returned to normal. He was dis.
,
charged symptom-free. The association of this patient’s symptom complex with cimetidine may have been fortuitous, but we feel that the onset of confusion and unsteadiness in a patient taking cimetidine should be an indication to stop the drug. Regional Neurological Centre, Newcastle General Hospital, Newcastle upon Tyne NE4 6BE
W. J. K. CUMMING J. B. FOSTER
PHENYTOIN/DEXAMETHASONE INTERACTION: A Tissue from bed of and yeasts.
gastric
ulcer
showing
candida
pseudohyphx
(Periodic-acid/Schiff; 220.) x
during cimetidine therapy may be the result of primary candidiasis of the gastric mucosa, in the presence of a raised intraluminal pH. The presence of candida infection in the gastrointestinal tract cannot be attributed entirely to a raised pH. Other factors which should also be taken into account are changing flora of the gastrointestinal tract due to the introduction of antibiotic therapy. Nevertheless, we suggest that when delay or failure of healing occurs, or if there is evidence of erosive gastritis or duodenitis, biopsy material and stool cultures should be examined for C. albicans; if cultures are positive a trial of oral nystatin should be considered while cimetidine therapy is continued. Department of Histopathology, Westminster Medical School, London SW1P 2PP
P. E. NICHOLLS KRISTIN HENRY
CIMETIDINE-INDUCED BRAINSTEM DYSFUNCTION
SIR,-An association between cimetidine and mental confusion has been reported several times.1-S We have seen a patient with clinical features suggesting brainstem ischemia which seemed to have been precipitated by cimetidine. The patient, aged 54, had a 7-year history of dyspepsia. On Oct. 13, 1977, gastroscopy showed a duodenal ulcer. He was treated with cimetidine 200 mg three times a day plus 400 mg at night. On Oct. 15 he noted some lightheadedness without true vertigo and complained to his wife of frontal headache. He continued the medication over the next 10 days, and complained of progressive unsteadiness as a result of which he had frequent falls. He had episodes of transient bilateral visual impairment and became deaf in his left ear. His speech became progressively dysarthric to the point where it was unintelligible, and he had been doubly incontinent. He complained of
parxsthesix. There
pital
on
was no relevant past history. He was admitted to hosOct. 26, where the abnormal findings were confined
1. Menzies-Gow, N. Lancet, 1977, ii, 928. 2. Nelson, P. G. ibid. p. 928. 3. Robinson, T. J. Mulligan, T. O. ibid. p. 719. 4. Delaney, J. C., Ravey, M. ibid. p. 512. 5. McMillen, M. A., Ambis, D., Siegel, J. H. New Engl. J. Med. 1978,
298, 284.
CLINICAL PROBLEM
SIR,-Phenytoin affects steroid metabolism-notably that of dexamethasone- by stimulating hepatic microsomal hydroxylating enzymes.’ This effect has been reported mainly in the context of the dexamethasone suppression test,2.3 but it has also been recorded in systemic lupus erythematosus.4 Otherwise little has been published on this problem in a clinical setting. We have seen a case where this interaction was of clini-’ cal significance. A 53-year-old woman presented in August, 1977, with a history of progressive left-sided weakness. After decompression craniotomy and biopsy of a right temporal lobe astrocytoma, she received radical radiotherapy, completing treatment in early October. She was discharged on a daily dose of 6 mg dexamethasone and 300 mg phenytoin with only slight weakness and dysphasia. When seen on Nov. 1 the patient had deteriorated, with episodes of urinary incontinence and increasing drowsiness. She was admitted and her dexamethasone dose was doubled. Computerised axial tomography suggested progression of the tumour, and it was agreed that nothing further should be done. By the next morning she had improved remarkably. After 48 h she was changed back to oral dexamethasone (administered intramuscularly while she was semicomatose) but she deteriorated again. We therefore felt that the method of administration must be important. Back on intramuscular dexamethasone she once again improved and on 12 mg/day became alert with no demonstrable weakness. After 10 days we made plans to discharge her, and so put her back on oral dexamethasone 12 mg/day. 5 days later she was once again confused, drowsy, and hemiplegic. At this point a drug interaction was considered. On Nov. 26 the patient was put on sodium valproate 200 mg three times a day and on Dec. 1 oral dexamethasone was restarted. The valproate dose was doubled on Dec. 13 because the patient reported an episode of tingling and twitching in the left hand. The dexamethasone has been reduced gradually, and, apart from bronchopneumonia in February, 1978, she remains well 4 months later. In this patient phenytoin probably accelerated the metabolism of the steroid (dexamethasone) given to control cerebral oedema. Three times a change to intramuscular dexamethasone 1. Haque, N., Thrasher, K., Werk, E. E., Knowles, H. C., Sholiton, L. J. J. clin. Endocr Metab. 1972, 34, 44. 2. Jubiz, W., Meikle, A. W., Levinson, R. A., Mizutani, S., West, C. D., Tyler, F. H. New Engl. J. Med. 1970, 283, 11. 3. Werk, E. E., Choi, Y., Sholiton, L. J., Olinjer, C., Haque, N., ibid. 1969, 281, 32. 4. Boylan, J. J., Owen, D. S., Chin, J. B. J. Am. med. Ass. 1976, 235, 803.