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RANITIDINE ALSO REDUCES LIVER BLOOD FLOW
169 RANITIDINE ALSO REDUCES LIVER BLOOD FLOW
EFFECT OF DIFFERENT NUTRITIONAL THERAPY ON ILEAL FLUID
SIR,-Cimetidine reduces liver blood flow in man. We have cimetidine, does repeated these studies on ranitidine which, unlike 2
OSMOLALITY AND VOLUME
not seem to
impair oxidative drug metabolism.2
Six healthy volunteers aged 20 - 36 years (four male, two female) had liver blood flow estimatedl,3 from the clearance of a single dose of indocyanine-green (0’5mg/kg). Subjects were studied, in the supine position after overnight fast, both as controls and one hour following the oral administration of ranitidine (150 mg). Repeated estimations of liver blood flow on the same day are highly reproducible.3,4 Ranitidine prolonged the elimination half-life of indocyanine-green from 2 -9±0 -4(SEM) to 3 -6±0 -3min (p<0 - 05; t test) and reduced its clearance by 18±2%, thus reducing estimated liver blood flow from l105::t 112 to 899±111 ml/min (p<0 05). This study suggests that ranitidine, like cimetidine, reduces liver blood flow, and further supports a physiological role for vascular H2 receptors in man. It has been suggested 1,5 that the effect of H2 blockade on liver blood flow may be of therapeutic value in portal hypertension. A reduction in liver blood flow would be expected to impair the hepatic elimination of drugs, such as propranolol and lignocaine, that are highly extracted by the liver and whose systemic clearance is highly dependent on liver blood flow. Whether this happens with ranitidine remains to be established. Department of Pharmacology and Therapeutics, Ninewells Hospital, Dundee DD1 9SY
Results
range tabulated against the type of nutritional listed in the table. The readings for the day when rice water alone was first introduced were excluded from calculation since these might reflect the effect of the previous day’s milk
therapy are
therapy. Rice water when compared with milk ,produced significantly lower ileal fluid osmolality (p<0 02) and lower ileal fluid volume. When compared with TPN, milk, but not rice water, produced a significantly higher ileal fluid osmolality (p<0’001) and a higher ileal fluid volume (p=0’05). These findings support the recent experimental evidence of osmoregulation of luminal content in rat duodenum and ileum.4With a lower osmolality in the ileum, as produced by rice water in our patients, the ileal fluid volume is lower. On the other hand, milk, which has a much higher osmolality especially after digestion in the intestinal lumen, produces also a higher ileal fluid volume, probably by secretion of water. Our observation therefore provides circumstantial evidence to support the notion that low osmolality is responsible for the efficacy of rice 2 water in the treatment of acute infantile gastroenteritis.
ELIZABETH GUY
RICE WATER AND MILK: EFFECT ON ILEAL FLUID OSMOLALITY AND VOLUME
SIR,-The use of rice water in the treatment of acute infantile gastroenteritis is widely practised as folk remedy in South-East Asia.’ Its efficacy has been found superior to oral electrolyte solution.2Its efficacy may be related to the low osmolality of rice water (8 - 9±3 - 4 mosmol/kg; mean±SD) as compared with that of standard oral electrolyte solution (317-5±77’22 mosmol/kg; p<0 000 1).3 We have lately had the opportunity to study the effect
satisfactory weight gain. The daily ileal fluid volume and ileal fluid osmolality, which was measured by Advanced Osmometer model 3W (Advanced Instruments, Massachusetts), were recorded. The mean, standard J, Wilkinson GR, Wood AJJ. Reduction of liver blood flow and propranolol metabolism by cimetidine. N Engl J Med 1981; 304: 692-95. 2. Henry DA, MacDonald IA, Kitchingham G, Bell GD, Langman MJS. Cimetidine and ranitidine: Comparison of effects on hepatic drug metabolism. Br Med J 1980; 281: 775-77. 3 Caesar J, Shaldon S, Chiandussi L, Guevara L, Sherlock S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci 1961; 21: 43-57. 4. Leevy CM. Mendenhall CI, Lesko W, Howard MM. Estimation of hepatic blood flow with indocyanine green. J Clin Invest 1962; 41: 1169-79. 5. Schneider RE, Bishop H. H2 receptor antagonists for portal hypertension. Lancet 1981; ii: 152. 1 Kleevens JWL Rice water for infantile gastroenteritis. Lancet 1981; ii: 306. 2. Wong HB. Rice water in treatment of infantile gastroenteritis. Lancet 1981; ii: 102-03, 3 Ho TF, Yip WCL, Tay JSH, Wong HB. Rice water and dextrose saline solution: a comparative study of osmolality. J Singapore Paediatr Soc (in press). 1. Feely
mean±SD.
deviation, and
JOHN FEELEY
of rice water and milk on ileal fluid osmolality and volume in two infants who had an ileostomy created for acute intestinal obstruction due to multiple congenital adhesion bands. As far as we are aware, this is the first report of its kind. Both infants, when referred to the university department of paediatrics, Singapore General Hospital, after the ileostomy, had significant failure to thrive but were free from sepsis. They weighed 2’ 05 kg and 2 - 45 kg at 4 and 5 weeks of life, respectively. Total parenteral nutrition (TPN) with ’Aminoplasmal-Ped’, ’Lipofundin I OS’, and dextrose solution was administered to these two patients for a week. Subsequently they were gradually weaned to oral humanised milk. For two days, in between the milk feeding, both parents were put on rice water alone. The volume of fluid given per day throughout the study was 150 ml/kg body weight. After closure of the ileostomy, both patients made an uneventful recovery with
as
Department of Physiology, National University of Singapore, Singapore 0316
T. F. HO WILLIAM C. L. YIP
University Department of Paediatrics, Singapore General Hospital
JOHN S. H. TAY K. VELLAYAPPAN
ZINC AND SMALL BABIES
SIR,-We were interested in Dr Meadows and colleagues’ paper (Nov. 21, p. 1135) since we are in the middle of a similar study. We expected that zinc would be responsible for only a small part of the total variance in fetal growth and that a total population of at least --
200 would be needed to demonstrate an effect, but have been surprised to find, early in the study, a significant relation between the rate of growth in length of the femur measured by ultrasound and maternal leucocyte zinc (n=19; r=0-50; p<0-03). Also, birthweight is correlated with maternal zinc (n=13; r=0’59;
p<0-05). Meadows et al. do not refer to the work of MetcofPs group, who identified zinc as one important factor in the cause of low birthweight for gestational age.1 In view of the absence of a relation between muscle or leucocyte zinc and plasma zinc in Meadows’ study, we need an explanation of the usefulness of plasma zinc in Metcofl’s studies. It is good to see the animal experiments done by Dr Lucille Hurley’s group finding an application in man. However, the other implications of her work should not be forgotten. For example, she found that the malformation rate in zinc deficient but calcium sufficient animals was 45% higher than that in combined zinc and calcium deficiency.2In other words, calcium supplements may 4. Miller
DL, Hamburger SA, Schedl HP. Effects of osmotic gradients on water and vivo studies in rat duodenum and ileum Am J Physiol 1979,
solute transport: In 237: E389-96
Crosby WH, Metcoff J, Costiloe JP, Mancesh M, Sandstead MM, Jacob RA, McClain PE, Jacobson G, Reid W, Burns G. Fetal malnutrition: an appraisal of correlated factors Am JObstet Gynecol 1977; 128: 22-31. 2. Hurley LS, Tao S. Alluration of teratogenic effects of zinc deficiency by simultaneous lack of calcium, Am JPhysiol 1972, 222: 322-25 1.
EFFECT OF DIFFERENT NUTRITIONAL THERAPY ON ILEAL FLUID
SIR,-Cimetidine reduces liver blood flow in man. We have cimetidine, does repeated these studies on ranitidine which, unlike 2
OSMOLALITY AND VOLUME
not seem to
impair oxidative drug metabolism.2
Six healthy volunteers aged 20 - 36 years (four male, two female) had liver blood flow estimatedl,3 from the clearance of a single dose of indocyanine-green (0’5mg/kg). Subjects were studied, in the supine position after overnight fast, both as controls and one hour following the oral administration of ranitidine (150 mg). Repeated estimations of liver blood flow on the same day are highly reproducible.3,4 Ranitidine prolonged the elimination half-life of indocyanine-green from 2 -9±0 -4(SEM) to 3 -6±0 -3min (p<0 - 05; t test) and reduced its clearance by 18±2%, thus reducing estimated liver blood flow from l105::t 112 to 899±111 ml/min (p<0 05). This study suggests that ranitidine, like cimetidine, reduces liver blood flow, and further supports a physiological role for vascular H2 receptors in man. It has been suggested 1,5 that the effect of H2 blockade on liver blood flow may be of therapeutic value in portal hypertension. A reduction in liver blood flow would be expected to impair the hepatic elimination of drugs, such as propranolol and lignocaine, that are highly extracted by the liver and whose systemic clearance is highly dependent on liver blood flow. Whether this happens with ranitidine remains to be established. Department of Pharmacology and Therapeutics, Ninewells Hospital, Dundee DD1 9SY
Results
range tabulated against the type of nutritional listed in the table. The readings for the day when rice water alone was first introduced were excluded from calculation since these might reflect the effect of the previous day’s milk
therapy are
therapy. Rice water when compared with milk ,produced significantly lower ileal fluid osmolality (p<0 02) and lower ileal fluid volume. When compared with TPN, milk, but not rice water, produced a significantly higher ileal fluid osmolality (p<0’001) and a higher ileal fluid volume (p=0’05). These findings support the recent experimental evidence of osmoregulation of luminal content in rat duodenum and ileum.4With a lower osmolality in the ileum, as produced by rice water in our patients, the ileal fluid volume is lower. On the other hand, milk, which has a much higher osmolality especially after digestion in the intestinal lumen, produces also a higher ileal fluid volume, probably by secretion of water. Our observation therefore provides circumstantial evidence to support the notion that low osmolality is responsible for the efficacy of rice 2 water in the treatment of acute infantile gastroenteritis.
ELIZABETH GUY
RICE WATER AND MILK: EFFECT ON ILEAL FLUID OSMOLALITY AND VOLUME
SIR,-The use of rice water in the treatment of acute infantile gastroenteritis is widely practised as folk remedy in South-East Asia.’ Its efficacy has been found superior to oral electrolyte solution.2Its efficacy may be related to the low osmolality of rice water (8 - 9±3 - 4 mosmol/kg; mean±SD) as compared with that of standard oral electrolyte solution (317-5±77’22 mosmol/kg; p<0 000 1).3 We have lately had the opportunity to study the effect
satisfactory weight gain. The daily ileal fluid volume and ileal fluid osmolality, which was measured by Advanced Osmometer model 3W (Advanced Instruments, Massachusetts), were recorded. The mean, standard J, Wilkinson GR, Wood AJJ. Reduction of liver blood flow and propranolol metabolism by cimetidine. N Engl J Med 1981; 304: 692-95. 2. Henry DA, MacDonald IA, Kitchingham G, Bell GD, Langman MJS. Cimetidine and ranitidine: Comparison of effects on hepatic drug metabolism. Br Med J 1980; 281: 775-77. 3 Caesar J, Shaldon S, Chiandussi L, Guevara L, Sherlock S. The use of indocyanine green in the measurement of hepatic blood flow and as a test of hepatic function. Clin Sci 1961; 21: 43-57. 4. Leevy CM. Mendenhall CI, Lesko W, Howard MM. Estimation of hepatic blood flow with indocyanine green. J Clin Invest 1962; 41: 1169-79. 5. Schneider RE, Bishop H. H2 receptor antagonists for portal hypertension. Lancet 1981; ii: 152. 1 Kleevens JWL Rice water for infantile gastroenteritis. Lancet 1981; ii: 306. 2. Wong HB. Rice water in treatment of infantile gastroenteritis. Lancet 1981; ii: 102-03, 3 Ho TF, Yip WCL, Tay JSH, Wong HB. Rice water and dextrose saline solution: a comparative study of osmolality. J Singapore Paediatr Soc (in press). 1. Feely
mean±SD.
deviation, and
JOHN FEELEY
of rice water and milk on ileal fluid osmolality and volume in two infants who had an ileostomy created for acute intestinal obstruction due to multiple congenital adhesion bands. As far as we are aware, this is the first report of its kind. Both infants, when referred to the university department of paediatrics, Singapore General Hospital, after the ileostomy, had significant failure to thrive but were free from sepsis. They weighed 2’ 05 kg and 2 - 45 kg at 4 and 5 weeks of life, respectively. Total parenteral nutrition (TPN) with ’Aminoplasmal-Ped’, ’Lipofundin I OS’, and dextrose solution was administered to these two patients for a week. Subsequently they were gradually weaned to oral humanised milk. For two days, in between the milk feeding, both parents were put on rice water alone. The volume of fluid given per day throughout the study was 150 ml/kg body weight. After closure of the ileostomy, both patients made an uneventful recovery with
as
Department of Physiology, National University of Singapore, Singapore 0316
T. F. HO WILLIAM C. L. YIP
University Department of Paediatrics, Singapore General Hospital
JOHN S. H. TAY K. VELLAYAPPAN
ZINC AND SMALL BABIES
SIR,-We were interested in Dr Meadows and colleagues’ paper (Nov. 21, p. 1135) since we are in the middle of a similar study. We expected that zinc would be responsible for only a small part of the total variance in fetal growth and that a total population of at least --
200 would be needed to demonstrate an effect, but have been surprised to find, early in the study, a significant relation between the rate of growth in length of the femur measured by ultrasound and maternal leucocyte zinc (n=19; r=0-50; p<0-03). Also, birthweight is correlated with maternal zinc (n=13; r=0’59;
p<0-05). Meadows et al. do not refer to the work of MetcofPs group, who identified zinc as one important factor in the cause of low birthweight for gestational age.1 In view of the absence of a relation between muscle or leucocyte zinc and plasma zinc in Meadows’ study, we need an explanation of the usefulness of plasma zinc in Metcofl’s studies. It is good to see the animal experiments done by Dr Lucille Hurley’s group finding an application in man. However, the other implications of her work should not be forgotten. For example, she found that the malformation rate in zinc deficient but calcium sufficient animals was 45% higher than that in combined zinc and calcium deficiency.2In other words, calcium supplements may 4. Miller
DL, Hamburger SA, Schedl HP. Effects of osmotic gradients on water and vivo studies in rat duodenum and ileum Am J Physiol 1979,
solute transport: In 237: E389-96
Crosby WH, Metcoff J, Costiloe JP, Mancesh M, Sandstead MM, Jacob RA, McClain PE, Jacobson G, Reid W, Burns G. Fetal malnutrition: an appraisal of correlated factors Am JObstet Gynecol 1977; 128: 22-31. 2. Hurley LS, Tao S. Alluration of teratogenic effects of zinc deficiency by simultaneous lack of calcium, Am JPhysiol 1972, 222: 322-25 1.