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LOPERAMIDE THERAPY IN A CHILD WITH VIPOMA-ASSOCIATED DIARRHOEA
1413
anti-inflammatory effect may be as important as enhanced mucociliary clearance in explaining the subjective benefit experienced by patients with obstructive airways disease following beta-adrenoceptor agonist therapy.
that this
Department of Clinical Pharmacology (Asthma Research Council), Cardiothoracic Institute, Brompton Hospital,
J. MORLEY
London SW3 6HP
W. PAUL
G. S. BASRAN
LOPERAMIDE THERAPY IN A CHILD WITH VIPOMA-ASSOCIATED DIARRHOEA is
SIR,-It suggested that vasoactive intestinal peptide (VIP) may be the major mediator of the severe diarrhoea in the patient with a VIP producing tumour.1 Trifluoperazine, a potent inhibitor of calmodulin, has been successfully used in the treatment of secretory diarrhoea due to vipoma.2Dr Merritt and colleagues (Jan. 30, p. 283) suggest that loperamide exerts its antidiarrhoeal effect by inactivating calmodulin. If so, loperamide should be also effective against diarrhoea due to vipoma. We have studied the effect of loperamide on watery diarrhoea in a child with VIP-producing -
ganglioneuroma.
effects of both loperamide and trifluoperazine may be due to inhibition of calmodulin action; however, the site of the antisecretory action of these drugs could be different. More data are needed before the mechanism for the diarrhoea associated with vipoma and the antisecretory mechanism of loperamide can be defined precisely. We thank Prof. H. Kato for his advice and encouragement; Prof. N.
Yanaihara, Shizuoka College of Pharmacy, for the VIP assay; Dr Y. Fukuda and Dr S. Furukawa, department of paediatrics, Juntendo University, for the prostaglandin assay; and Dr K. Obmata, Dr H. Takamatsu, and our surgical staff for collaboration in the management of the patient. Department of Paediatrics, of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113, Japan School
WHICH INSULIN FOR DIABETIC KETOACIDOSIS?
SIR,-We note the comments of Dr McDermott and Dr Cullen (May 15, p. 1129) on insulin treatment of diabetic ketoacidosis. Currently "human insulin" is unavailable for general use in the of diabetes mellitus, and therefore it cannot be considered present for inclusion in the British National Formulary. We do not agree that purified bovine insulin should be recommended for new diabetics presenting with ketoacidosis. Patients previously treated with porcine insulin should also avoid the beef product. Nowadays, with the plethora of insulin preparations, simplification of the management of this potentially life threatening condition is of paramount importance. While purified bovine insulin is suitable for use in patients previously treated with beef preparations the less immunogenic porcine insulin’ is at present the only available suitable preparation for all diabetics presenting with ketoacidosis irrespective of previous insulin regimen. treatment
referred with a 9-week history of persistent watery diarrhoea and abdominal distension. She had hypokalaemia (2 -2 mmol/1) and hyposecretion of gastric acid. Her 24 h urinary vanillylmandelic acid was 58-3 3 g/mg creatinine (normal 8-6-12-5) and homovanillic acid was 208-33 g/mg creatinine (normal 14-5—29-7). Serum adrenaline 1-58 ng/ml (0 - 12) and noradrenaline 3-73 ng/ml (0-06—0-45) were raised, as were plasma prostaglandins E2 at 315 pg/ml (70’ 2) and F2a at 279 - 5 5 pg/ml (93 -2). The plasma VIP was 154-00 pmol/1 (normal <30 - 0). Computerised tomography suggested a 5 cm mass, located at the left adrenal gland. This was completely removed, and the surgeon noted a distended gallbladder and a dilated colon. The tumour was a benign ganglioneuroma. Plasma PGE2, PGF2a, and VIP levels were 37 - 8 pg/ml, 99 - 0 pg/ml, and 29 I pmol/l, respectively, 72 h after the operation. During loperamide therapy (preoperative period) she was given nil by mouth. After a loperamide dose ofO-44 mg/kg daily, the daily stool volume fell from 1079 ml to 221 ml on the first day, to 30 ml on the second day, and to 5 ml on the third day. The serum potassium rose from 2 - 7 mmol/1 to 4 - 9 mmol/1 on the third day. After a 5-day washout period aspirin was started, replacing the loperamide therapy. Although after an aspirin dose of 50 mg per day stool volume fell slightly from 975 ml to 661 ml on the third day there was little change on the first or the second day. Was this child’s diarrhoea caused by VIP or PG or by the two together? Prostaglandins are responsilble in some vipomas3and indomethacin, a potent inhibitor of PG biosynthesis, rapidly eliminated diarrhoea in one patient with vipoma.4It is suggested, on the other hand, that loperamide inhibits PGE2 and cholera-toxininduced secretion. 5-7 In contrast with this case no effect of loperamide and indomethacin on diarrhoea in another child with A 23-month-old
girl
was
vipoma was reported.8 There may be at least two major mediators of the diarrhoea in vipoma-namely, VIP and PG-although a multiplicity of hormones may be produced by the tumour. The antisecretory
at
Victoria
Infirmary, Glasgow G42 9TY Western
SR,
Polak
JM. The role of VIP
in
COLIN M. KESSON
Infirmary,
RICHARD E. YOUNG
Glasgow
CREATINE KINASE MB IN MARATHON RUNNERS
SIR,-Over 1000 of the 16 000 runners in the recent London marathon failed to complete the course, and Press reports suggest that some collapsed. As part ofaa wider study of the effects of exercise on serum enzyme levels we have measured creatine kinase (EC 2.7.3.2) and its MB isoenzyme (CK-MB) in the blood of 70 runners who completed the Cardiff marathon (table). Blood samples were taken the day before and immediately on completion of the run. There was a fourfold increase in mean total enzyme activity after the run to a mean value which was twice the upper limit ofour reference range (130 IU/1). Those runners who completed the run in the shortest time, and were presumably the fittest, showed the smallest increases in activity. The most striking feature, however, was the wide range of values obtained: 2 runners had levels of over 1000 IU/1 immediately after the run and 24 h later levels as high as 5000 IU/1 were detected. The mean level of the heart specific MB isoenzyme was less than 5% of the total immediately after the run, but values ranged from 1 % to
pancreatic cholera. In: Thompson JC, ed. Gastrointestinal hormones. Austin: University of Texas Press, 1975: 635-42. 2. Donowitz M, Elta G, Bloom SR, Nathanson L. Trifluoperazine reversal of secretory diarrhea in pancreatic cholera. Ann Intern Med 1980; 93: 284-85. 3. Jaffe BM, Condon S. Prostaglandin E and F in endocrine diarrheagemc syndromes. Ann Surg 1976; 184: 516-24. 4. Jaffe BM, Kopen DF, DeSchryver-Kecskemeti K, Gingerich RL, Greider M. Indomethacin-responsive pancreatic cholera. N Engl J Med 1977; 297: 817-21. 5. Karim SMM Adaikan PG. The effect of Loperamide on prostaglandin induced diarrhea in rat and man. Prostaglandin 1977; 13: 321-31. 6. Sandhu BK, Tripp JH, Candy DCA, Harries JT. Loperamide inhibits cholera toxin induced small intestinal secretion. Lancet 1979; ii: 689-90. 7. Sandhu BK, Tripp JH, Candy DCA, Harries JT. Loperamide: Studies on its mechanism of action. Gut 1981; 22: 658-62 8. Tiedemann K, Pritchard J, Long R, Bloom SR. Intractable diarrhoea in a patient with vasoactive intestinal peptide secreting neuroblastoma: Attempted control by somatostatin. Eur J Pediatr 1981; 137: 217-19. 1. Bloom
YUICHIRO YAMASHIRO KOICHI YAMAMOTO MITSUYOSHI SATO
as
high as
18%
(see table). Eighteen runners had an MB value
of greater than 6% of total CK activity, a level often associated with 1. Chance RE, Root MA, Galloway JA. The immunogenicity of insulin preparations. Acta Endocrinol (Copenh) 1976; 83: (suppl 205) 185-98. CK ACTIVITY IN MARATHON RUNNERS
Plasma enzyme activity was measured using Merck kits, nos 14328 and 14332 adapted for IL Multistat III centrifugal analyser. Results are expressed as means and ranges.
an
anti-inflammatory effect may be as important as enhanced mucociliary clearance in explaining the subjective benefit experienced by patients with obstructive airways disease following beta-adrenoceptor agonist therapy.
that this
Department of Clinical Pharmacology (Asthma Research Council), Cardiothoracic Institute, Brompton Hospital,
J. MORLEY
London SW3 6HP
W. PAUL
G. S. BASRAN
LOPERAMIDE THERAPY IN A CHILD WITH VIPOMA-ASSOCIATED DIARRHOEA is
SIR,-It suggested that vasoactive intestinal peptide (VIP) may be the major mediator of the severe diarrhoea in the patient with a VIP producing tumour.1 Trifluoperazine, a potent inhibitor of calmodulin, has been successfully used in the treatment of secretory diarrhoea due to vipoma.2Dr Merritt and colleagues (Jan. 30, p. 283) suggest that loperamide exerts its antidiarrhoeal effect by inactivating calmodulin. If so, loperamide should be also effective against diarrhoea due to vipoma. We have studied the effect of loperamide on watery diarrhoea in a child with VIP-producing -
ganglioneuroma.
effects of both loperamide and trifluoperazine may be due to inhibition of calmodulin action; however, the site of the antisecretory action of these drugs could be different. More data are needed before the mechanism for the diarrhoea associated with vipoma and the antisecretory mechanism of loperamide can be defined precisely. We thank Prof. H. Kato for his advice and encouragement; Prof. N.
Yanaihara, Shizuoka College of Pharmacy, for the VIP assay; Dr Y. Fukuda and Dr S. Furukawa, department of paediatrics, Juntendo University, for the prostaglandin assay; and Dr K. Obmata, Dr H. Takamatsu, and our surgical staff for collaboration in the management of the patient. Department of Paediatrics, of Medicine, Juntendo University, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113, Japan School
WHICH INSULIN FOR DIABETIC KETOACIDOSIS?
SIR,-We note the comments of Dr McDermott and Dr Cullen (May 15, p. 1129) on insulin treatment of diabetic ketoacidosis. Currently "human insulin" is unavailable for general use in the of diabetes mellitus, and therefore it cannot be considered present for inclusion in the British National Formulary. We do not agree that purified bovine insulin should be recommended for new diabetics presenting with ketoacidosis. Patients previously treated with porcine insulin should also avoid the beef product. Nowadays, with the plethora of insulin preparations, simplification of the management of this potentially life threatening condition is of paramount importance. While purified bovine insulin is suitable for use in patients previously treated with beef preparations the less immunogenic porcine insulin’ is at present the only available suitable preparation for all diabetics presenting with ketoacidosis irrespective of previous insulin regimen. treatment
referred with a 9-week history of persistent watery diarrhoea and abdominal distension. She had hypokalaemia (2 -2 mmol/1) and hyposecretion of gastric acid. Her 24 h urinary vanillylmandelic acid was 58-3 3 g/mg creatinine (normal 8-6-12-5) and homovanillic acid was 208-33 g/mg creatinine (normal 14-5—29-7). Serum adrenaline 1-58 ng/ml (0 - 12) and noradrenaline 3-73 ng/ml (0-06—0-45) were raised, as were plasma prostaglandins E2 at 315 pg/ml (70’ 2) and F2a at 279 - 5 5 pg/ml (93 -2). The plasma VIP was 154-00 pmol/1 (normal <30 - 0). Computerised tomography suggested a 5 cm mass, located at the left adrenal gland. This was completely removed, and the surgeon noted a distended gallbladder and a dilated colon. The tumour was a benign ganglioneuroma. Plasma PGE2, PGF2a, and VIP levels were 37 - 8 pg/ml, 99 - 0 pg/ml, and 29 I pmol/l, respectively, 72 h after the operation. During loperamide therapy (preoperative period) she was given nil by mouth. After a loperamide dose ofO-44 mg/kg daily, the daily stool volume fell from 1079 ml to 221 ml on the first day, to 30 ml on the second day, and to 5 ml on the third day. The serum potassium rose from 2 - 7 mmol/1 to 4 - 9 mmol/1 on the third day. After a 5-day washout period aspirin was started, replacing the loperamide therapy. Although after an aspirin dose of 50 mg per day stool volume fell slightly from 975 ml to 661 ml on the third day there was little change on the first or the second day. Was this child’s diarrhoea caused by VIP or PG or by the two together? Prostaglandins are responsilble in some vipomas3and indomethacin, a potent inhibitor of PG biosynthesis, rapidly eliminated diarrhoea in one patient with vipoma.4It is suggested, on the other hand, that loperamide inhibits PGE2 and cholera-toxininduced secretion. 5-7 In contrast with this case no effect of loperamide and indomethacin on diarrhoea in another child with A 23-month-old
girl
was
vipoma was reported.8 There may be at least two major mediators of the diarrhoea in vipoma-namely, VIP and PG-although a multiplicity of hormones may be produced by the tumour. The antisecretory
at
Victoria
Infirmary, Glasgow G42 9TY Western
SR,
Polak
JM. The role of VIP
in
COLIN M. KESSON
Infirmary,
RICHARD E. YOUNG
Glasgow
CREATINE KINASE MB IN MARATHON RUNNERS
SIR,-Over 1000 of the 16 000 runners in the recent London marathon failed to complete the course, and Press reports suggest that some collapsed. As part ofaa wider study of the effects of exercise on serum enzyme levels we have measured creatine kinase (EC 2.7.3.2) and its MB isoenzyme (CK-MB) in the blood of 70 runners who completed the Cardiff marathon (table). Blood samples were taken the day before and immediately on completion of the run. There was a fourfold increase in mean total enzyme activity after the run to a mean value which was twice the upper limit ofour reference range (130 IU/1). Those runners who completed the run in the shortest time, and were presumably the fittest, showed the smallest increases in activity. The most striking feature, however, was the wide range of values obtained: 2 runners had levels of over 1000 IU/1 immediately after the run and 24 h later levels as high as 5000 IU/1 were detected. The mean level of the heart specific MB isoenzyme was less than 5% of the total immediately after the run, but values ranged from 1 % to
pancreatic cholera. In: Thompson JC, ed. Gastrointestinal hormones. Austin: University of Texas Press, 1975: 635-42. 2. Donowitz M, Elta G, Bloom SR, Nathanson L. Trifluoperazine reversal of secretory diarrhea in pancreatic cholera. Ann Intern Med 1980; 93: 284-85. 3. Jaffe BM, Condon S. Prostaglandin E and F in endocrine diarrheagemc syndromes. Ann Surg 1976; 184: 516-24. 4. Jaffe BM, Kopen DF, DeSchryver-Kecskemeti K, Gingerich RL, Greider M. Indomethacin-responsive pancreatic cholera. N Engl J Med 1977; 297: 817-21. 5. Karim SMM Adaikan PG. The effect of Loperamide on prostaglandin induced diarrhea in rat and man. Prostaglandin 1977; 13: 321-31. 6. Sandhu BK, Tripp JH, Candy DCA, Harries JT. Loperamide inhibits cholera toxin induced small intestinal secretion. Lancet 1979; ii: 689-90. 7. Sandhu BK, Tripp JH, Candy DCA, Harries JT. Loperamide: Studies on its mechanism of action. Gut 1981; 22: 658-62 8. Tiedemann K, Pritchard J, Long R, Bloom SR. Intractable diarrhoea in a patient with vasoactive intestinal peptide secreting neuroblastoma: Attempted control by somatostatin. Eur J Pediatr 1981; 137: 217-19. 1. Bloom
YUICHIRO YAMASHIRO KOICHI YAMAMOTO MITSUYOSHI SATO
as
high as
18%
(see table). Eighteen runners had an MB value
of greater than 6% of total CK activity, a level often associated with 1. Chance RE, Root MA, Galloway JA. The immunogenicity of insulin preparations. Acta Endocrinol (Copenh) 1976; 83: (suppl 205) 185-98. CK ACTIVITY IN MARATHON RUNNERS
Plasma enzyme activity was measured using Merck kits, nos 14328 and 14332 adapted for IL Multistat III centrifugal analyser. Results are expressed as means and ranges.
an