4 10
Clinical and laboratory observations
REFERENCES
t. Bartlett K, Bennett M J, Hill RP, Lashford LS, Pollit RJ, Worth HGJ. Isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency presenting with life-threatening hypoglycemia. J Inher Metab Dis 1984;7:182. 2. Beemer FA, Bartlett K, Duran M, et al. Isolated biotin-resistant 3-methylcrotonyl-CoAcarboxylasedeficiencyin two sibs. Eur J Pediatr 1982;138:351-4. 3. Gitzelmann R, Steinmann B, Neiderweiser A, Fanconi S, Suormala T, Baumgartner R. Isolated (biotin resistant) 3-methylcrotonyl-CoAcarboxylasedeficiencypresenting at the age of 20 months with sopor, hypoglycaemia and ketoacidosis. J Inher Metab Dis 1987;10(suppl 2):290-2. 4. Kobori JA, Johnston K, Sweetman L, et al. Isolated 3-methylcrotonyl-CoAcarboxylasedeficiencypresenting as a Reye'slike syndrome [Abstract]. Pediatr Res 1989;25:142A. 5. Layward EM, Tanner MS, Pollitt R J, Bartlett K. Isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency
The Journal of Pediatrics September 1992
presenting as a Reye syndrome-like illness. J Inher Metab Dis 1989;12:339-40. 6. Tsai MY, Johnson DD, Sweetman L, Berry SA. Two siblings with biotin-resistant 3-methylcrotonyl-eoenzyme A carboxylase deficiency. J P~I~ATg 1989;115:110-3. 7. Kaufman AS, Kaufman NL. Kaufman AssessmentBattery for Children. Circle Pines, Minnesota: American Guidance Service, 1983. 8. Bayley Scales of Infant Development.New York: Psychological Corp., 1969. 9. Christensen E, Brock Jacobsen B, Gregersen N, et al. Urinary excretion of Succinylaeetoneand delta-aminolevulinicacid in patients with hereditary tyrosinemia. Clin Chim Acta 1981; 116:331-41. 109 Greter J, Gustafsson J, Holme E. Pyruvate-carboxylase deficiency with urea cycle impairment. Acta Paediatr Scand 1985;74:982-6.
Variability of breath hydrogen excretion in breast-fed infants during the first three months of life J a n e t t e Brand Miller, PhD, Marian B o k d a m , BSc, Patricia M c V e a g h , MB,ChB, FRACP, a n d John J MiLler, PhD From the Human Nutrition Unit, University of Sydney, and the Tresillian Family Care Centres, Sydney, Australia Breath hydrogen excretion was measured serially in breast-fed infants9 There was marked variability in H2 excretion, both within and between infants. The findings indicate that unabsorbed food isnot the only substrate, and that breath H2 may not be an effective method to assess carbohydrate absorption in young infants. (J PEDIAIR1992;421:410-3)
Hydrogen is found in the breath of most healthy infants soon after birth and is assumed to be derived from the microbial fermentation of unabsorbed lactose in the colon.l' 2 The incomplete absorption of lactose is thought to be transient and related to the immaturity of the gut. Although breath H2 excretion in neonates has been studied, 1' 2 there are few data on older infants), 4 Such data are needed to interpret the significance of high breath H2 levels in infants with colic. 5, 6 We measured the excretion of H2 in the breath of 13 exclusively breast-fed infants during the first few months of life. In one infant, we were also;cable to examine the variability of breath Hz excretion until 4 months of age. Submitted for publication Sept. 30, 1991; accepted April 9, 1992. Reprints not available. 9/22/38568
METHODS Thirteen healthy infants were recruited soon after birth from Tresllhan Family Care Centres and Early Childhood Health Centres. Twelve infants were fed human milk exclusively until 12 to 18 weeks of age. In another infant, breast-feeding was switched to formula feeding at 7 weeks of age, and only data up to this age were used. Three infants were classified as having "colic" because of crying and fussing more than 3 hours a day9 The study was approved by Tresillian Family Care Centres. Breath samples were collected in duplicate in the infants' homes, at weekly intervals, between 2 and 7 PM just before feeding and at 90 and 150 minutes after the start of the feeding. In one infant, breath samples were collected during a 24-hour period (9 to 20 duplicates) on 15 days from 2 to 15 weeks of age to examine within-day variability of breath H2 excretion. On 10 of these 15 occasions, breath 9
.
P
9
Volume 121 Number 3
Clinical and laboratory observations
411
70
60
E Q-
50
O)
40
0l i , . "0 >,, /-.
30
t.r
20
10
0 0
' 10
2=0
30
4'0
5 ,0
610
7 I0
8 0I
9=0
1 0, 0
Age (days) Fig. 4. Mean (+SEM) maximum breath H2 excretion as a function of age in all 13 infants studied.
samples were also taken the following day, either in the morning, afternoon, or evening, to assess between-days variability. The methods of collection, storage, and analysis of breath samples have been described. 5 Hydrogen concentrations were normalized to an oxygen concentration of ! 7.0%. The highest breath H2 value of the day (maximum) was used in the analysis because there was no consistent temporal relationship between breath H2 excretion and the start of the feeding. One-way analysis of variance was used to examine the diurnal variation of breath H2. The statistical significance of differences in breath H2 collected during the night, morning, afternoon, or evening was tested by using a two sample t test with ~ adjusted for the number of comparisons made. Within-day variability is shown as a coefficient of variation. Variation between samples at about the same time on consecutive days was estimated by calculating the average of each pair of samples and expressing the difference as a percentage of the average value. Results are shown as mean _+ SEM. RESULTS The mean pattern of breath H2 excretion as a function of age in the group of 13 infants is shown in Fig. 1. Breath H2 excretion was highest in the first month, the peak level of 50 _+ 18 ppm being reached in week 4. This was followed
by a sharp decline in the fifth week to a plateau level of approximately 20 ppm. Nine infants had thei r peak breath H2 levels (range 23 to 174 ppm) in the first month, one infant in the second month (29 ppm), and two infants (40 and 64 ppm) in the third month. Another infant had no age-related pattern. The pattern and range of breath H2 excretion during the first 18 weeks of life in one infant are shown 'in Fig. 2. Within-day variability of breath H2 excretion was 33% ___ 14%. Between-days variability and variation between duplicate samples was 19% + 15% and 10% + 15%, respectively. There was significant diurnal variation of breath Hz excretion (p = 0.047), breath H2 levels being higher in the evening (52 +__4 ppm) than in the morning (38 + 4 ppm) (p = 0.006). Breath H2 levels did not change significantly after feeding and remained elevated despite periods of fasting of 7 to 12 hours. DISCUSSION This study indicates that elevated breath H2 excretion persists well beyond the neonatal period. The striking finding, however, is the marked variability in breath H2 excretion, both within and between infants. In addition, there is no clear relationship between breath H2 excretion and time of feeding. These findings, taken together, not only challenge the assumption that unabsorbed food is the main sub-
4 12
Clinical and laboratory observations
The Journal of Pediatrics September 1992
200 180
160
E (m
140 120
G) 0
100
"ID
80
L_
60
~n
40 20
0
II.
o
I
I
I
i
I
l
I
I
zo
30
40
so
60
70
8o
l:
I
I
I
90
Age (days) Fig. 2. Range of breath H2 excretion as a function of age in one infant during the first 4 months of life. strate for colonic fermentation but also raise the issue of whether breath H2 can be used to assess carbohydrate absorption in young infants. Most infants had peak breath H2 levels in the first month, followed by significantly lower but still elevated levels in months 2 and 3. In contrast, Barret al. 3 reported that breath H2 levels were highest in the second month. Although the pattern of breath H2 excretion in most infants was similar to the mean curve for the group, some individual profiles went against the trend and in one infant no pattern was apparent. The pattern of breath H2 excretion may reflect changes in the quantity of substrate delivered into the colon or developmental changes in the production of H2 and its pulmonary excretion. 3 Another source of variability of breath H2 levels, identified in one infant, was the time of day of sample collection. Significant diurnal variation was obsq~ved; breath H2 levels were higher in the evening than in the morning. It is unclear whether this finding reflects dietary intake or physiologic variation. The report 7 of a significantly increased concentration of oligosaccharides in human milk during the evening offers one explanation for the diurnal variation in
breath H2 excretion. Oligosaccharides compose a significant proportion of the total carbohydrate in human milk and probably escape digestion.8 Our results cause us to question the assumption that unabsorbed dietary lactose is the sole substrate for the production of H2 in the colon. The levels of H2 in the breath were not clearly related to the time of feeding. In older subjects with lactose m~labsorption, there is a well-defined increase in breath ~-~[2 levels after lactose or milk ingestion. 9 The absence of fasting, the frequency of feeding, or the unstructured feeding schedule in the infant 3 may explain our findings. Alternatively, H2 in the breath may not be derived from substrates in the milk or other food. This possibility is supported by the observation in one infant that breath H2 levels remained elevated even after long periods of fasting (> 7 hours). Fermentation of endogenous substrates, such as glycoproteins, may explain these observations. ~~ The variability of breath H2 levels among infants suggests that physiologic differences exist that may be clinically important and detectable at the group level. However, the diurnal variation and, in some infants, day-to-day variability limit the usefulness of breath H2 as a clinical tool.
Volume 121 Number 3
We thank the staff members of Tresillian Family Care Centres and Early Childhood Health Centres for their cooperation, the mothers and infants who participated in the study, and Dr. R. Kamath for his comments. REFERENCES
1. Douwes AC, Fernandes J, Rietveld W. Hydrogen breath test in infants and children: sampling and storing expired air. Clin Chim Acta 1978;82:293-6. 2. MacLean WC, Fink BB. Lactose malabsorption by premature infants: magnitude and clinical significance. J PEDIATR 1980; 97:383-8. 3. Barr RG, Hanley J, Patterson DK, Wooldridge J. Breath hydrogen excretion in normal newborn infants in response to usual feeding patterns: evidence for "functional lactase insufficiency" beyond the first mouth of life. J PEDIATR 1983; 104:527-33. 4. Lifschitz CH, O'Brian Smith E, Garza C. Delayed complete functional lactase sufficiency in breast-fed infants. J Pediatr Gastroenterol Nutr 1983;2:4778-82.
Clinical and laboratory observations
4 13
5. Moore D J, Robb TA, Davidson GP. Breath hydrogen response to milk containing lactose in colicky and noncolicky infants. J PEDIATR 1988;113:979-84. 6. Miller J J, McVeagh P, Fleet GH, Petocz P, Brand JC. Breath hydrogen excretion in infants with colic. Arch Dis Child 1989;64:725-9. 7. Viverge D, Grimmonprez L, Cassauas G, Bardet L, Bonnet H, Solere M. Variation of lactose and oligosaccharides in milk from women of blood types secretor A or H, secretor Lewis, and secretor H/non-secretor Lewis during the course of lactation. Ann Nutr Metab 1985;29:1-1 l. 8. Newburg DS, Daniel PF, O'Neil NE. High-performance liquid chromatography of oligosaccharides from human milk and colostrum. In: Hamosh M, Goldman AS, eds. Human lactation. New York: Plenum, 1986:581-8. 9. Sotomons NW, Barillas C. The cut-off criterion for a positive breath test in children: a reappraisal. J Pediatr Gastroenterol Nutr 1986;5:920-5. 10. Cummings JH. Fermentation in the large intestine: evidence and implications for health. Lancet 1983;1:1206-8.
Bentiromide test using liquid-chromatographic measurement of p-aminobenzoic acid and its metabolites for diagnosing pancreatic insufficiency in childhood P. R. Durie, MD, FRCP(C), L. Y. Y u n g - J a t o , MSc, S. J. Soldin, PhD, Z. Verjee, PhD, a n d L. Ellis, RN From the Division of Gastroenterology, Departments of Pediatrics and Clinical Biochemistry, and the Research Institute, Hospital for Sick Children, Toronto; the Departments of Pediatrics and Clinical Biochemistry, University of Toronto, Toronto, Ontario, Canada; and the Department of Laboratory Medicine, Childrens Hospital National Medical Center, Washington, D.C.
We assessed the diagnostic c a p a b i l i t y of the bentiromide test using a highpressure liquid-chromatography method to analyze p - a m i n o b e n z o i c acid and its metabolites in plasma as an indirect measure of exocrine pancreatic function. Mean total amine concentration in pancreatic-insufficient subjects was significantly lower than in control subjects. There were 3 of 15 false-negative results and no false-positive results. We conclude that this chromatographic method is an effective means of analyzing p-aminobenzoic acid and its metabolites after ingestion of bentiromide. (J PEDIATR1992;121:413-6)
Supported by a research grant (No. MT6752) from the Medical Research Council of Canada. Submitted for publication July 11, 1991; accepted March 13, 1992. Reprint requests: P. R. Durie, MD, FRCP(C), Division of Gastroenterology, Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada. 9/22/37823
Bentiromide, an orally administered peptide (N-benzoyl-Ltyrosyl-p-aminobenzoic acid), is cleaved by pancreatic chymotrypsin in the duodenal lumen, releasing the marker p - a m i n o b e n z o i c acid, which is absorbed in the small intestine, metabolized in the liver, and excreted in the urine.1 If intestinal absorption and renal excretion are normal, the a m o u n t of P A B A and its metabolites found in urine or
Clinical and laboratory observations
REFERENCES
t. Bartlett K, Bennett M J, Hill RP, Lashford LS, Pollit RJ, Worth HGJ. Isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency presenting with life-threatening hypoglycemia. J Inher Metab Dis 1984;7:182. 2. Beemer FA, Bartlett K, Duran M, et al. Isolated biotin-resistant 3-methylcrotonyl-CoAcarboxylasedeficiencyin two sibs. Eur J Pediatr 1982;138:351-4. 3. Gitzelmann R, Steinmann B, Neiderweiser A, Fanconi S, Suormala T, Baumgartner R. Isolated (biotin resistant) 3-methylcrotonyl-CoAcarboxylasedeficiencypresenting at the age of 20 months with sopor, hypoglycaemia and ketoacidosis. J Inher Metab Dis 1987;10(suppl 2):290-2. 4. Kobori JA, Johnston K, Sweetman L, et al. Isolated 3-methylcrotonyl-CoAcarboxylasedeficiencypresenting as a Reye'slike syndrome [Abstract]. Pediatr Res 1989;25:142A. 5. Layward EM, Tanner MS, Pollitt R J, Bartlett K. Isolated biotin-resistant 3-methylcrotonyl-CoA carboxylase deficiency
The Journal of Pediatrics September 1992
presenting as a Reye syndrome-like illness. J Inher Metab Dis 1989;12:339-40. 6. Tsai MY, Johnson DD, Sweetman L, Berry SA. Two siblings with biotin-resistant 3-methylcrotonyl-eoenzyme A carboxylase deficiency. J P~I~ATg 1989;115:110-3. 7. Kaufman AS, Kaufman NL. Kaufman AssessmentBattery for Children. Circle Pines, Minnesota: American Guidance Service, 1983. 8. Bayley Scales of Infant Development.New York: Psychological Corp., 1969. 9. Christensen E, Brock Jacobsen B, Gregersen N, et al. Urinary excretion of Succinylaeetoneand delta-aminolevulinicacid in patients with hereditary tyrosinemia. Clin Chim Acta 1981; 116:331-41. 109 Greter J, Gustafsson J, Holme E. Pyruvate-carboxylase deficiency with urea cycle impairment. Acta Paediatr Scand 1985;74:982-6.
Variability of breath hydrogen excretion in breast-fed infants during the first three months of life J a n e t t e Brand Miller, PhD, Marian B o k d a m , BSc, Patricia M c V e a g h , MB,ChB, FRACP, a n d John J MiLler, PhD From the Human Nutrition Unit, University of Sydney, and the Tresillian Family Care Centres, Sydney, Australia Breath hydrogen excretion was measured serially in breast-fed infants9 There was marked variability in H2 excretion, both within and between infants. The findings indicate that unabsorbed food isnot the only substrate, and that breath H2 may not be an effective method to assess carbohydrate absorption in young infants. (J PEDIAIR1992;421:410-3)
Hydrogen is found in the breath of most healthy infants soon after birth and is assumed to be derived from the microbial fermentation of unabsorbed lactose in the colon.l' 2 The incomplete absorption of lactose is thought to be transient and related to the immaturity of the gut. Although breath H2 excretion in neonates has been studied, 1' 2 there are few data on older infants), 4 Such data are needed to interpret the significance of high breath H2 levels in infants with colic. 5, 6 We measured the excretion of H2 in the breath of 13 exclusively breast-fed infants during the first few months of life. In one infant, we were also;cable to examine the variability of breath Hz excretion until 4 months of age. Submitted for publication Sept. 30, 1991; accepted April 9, 1992. Reprints not available. 9/22/38568
METHODS Thirteen healthy infants were recruited soon after birth from Tresllhan Family Care Centres and Early Childhood Health Centres. Twelve infants were fed human milk exclusively until 12 to 18 weeks of age. In another infant, breast-feeding was switched to formula feeding at 7 weeks of age, and only data up to this age were used. Three infants were classified as having "colic" because of crying and fussing more than 3 hours a day9 The study was approved by Tresillian Family Care Centres. Breath samples were collected in duplicate in the infants' homes, at weekly intervals, between 2 and 7 PM just before feeding and at 90 and 150 minutes after the start of the feeding. In one infant, breath samples were collected during a 24-hour period (9 to 20 duplicates) on 15 days from 2 to 15 weeks of age to examine within-day variability of breath H2 excretion. On 10 of these 15 occasions, breath 9
.
P
9
Volume 121 Number 3
Clinical and laboratory observations
411
70
60
E Q-
50
O)
40
0l i , . "0 >,, /-.
30
t.r
20
10
0 0
' 10
2=0
30
4'0
5 ,0
610
7 I0
8 0I
9=0
1 0, 0
Age (days) Fig. 4. Mean (+SEM) maximum breath H2 excretion as a function of age in all 13 infants studied.
samples were also taken the following day, either in the morning, afternoon, or evening, to assess between-days variability. The methods of collection, storage, and analysis of breath samples have been described. 5 Hydrogen concentrations were normalized to an oxygen concentration of ! 7.0%. The highest breath H2 value of the day (maximum) was used in the analysis because there was no consistent temporal relationship between breath H2 excretion and the start of the feeding. One-way analysis of variance was used to examine the diurnal variation of breath H2. The statistical significance of differences in breath H2 collected during the night, morning, afternoon, or evening was tested by using a two sample t test with ~ adjusted for the number of comparisons made. Within-day variability is shown as a coefficient of variation. Variation between samples at about the same time on consecutive days was estimated by calculating the average of each pair of samples and expressing the difference as a percentage of the average value. Results are shown as mean _+ SEM. RESULTS The mean pattern of breath H2 excretion as a function of age in the group of 13 infants is shown in Fig. 1. Breath H2 excretion was highest in the first month, the peak level of 50 _+ 18 ppm being reached in week 4. This was followed
by a sharp decline in the fifth week to a plateau level of approximately 20 ppm. Nine infants had thei r peak breath H2 levels (range 23 to 174 ppm) in the first month, one infant in the second month (29 ppm), and two infants (40 and 64 ppm) in the third month. Another infant had no age-related pattern. The pattern and range of breath H2 excretion during the first 18 weeks of life in one infant are shown 'in Fig. 2. Within-day variability of breath H2 excretion was 33% ___ 14%. Between-days variability and variation between duplicate samples was 19% + 15% and 10% + 15%, respectively. There was significant diurnal variation of breath Hz excretion (p = 0.047), breath H2 levels being higher in the evening (52 +__4 ppm) than in the morning (38 + 4 ppm) (p = 0.006). Breath H2 levels did not change significantly after feeding and remained elevated despite periods of fasting of 7 to 12 hours. DISCUSSION This study indicates that elevated breath H2 excretion persists well beyond the neonatal period. The striking finding, however, is the marked variability in breath H2 excretion, both within and between infants. In addition, there is no clear relationship between breath H2 excretion and time of feeding. These findings, taken together, not only challenge the assumption that unabsorbed food is the main sub-
4 12
Clinical and laboratory observations
The Journal of Pediatrics September 1992
200 180
160
E (m
140 120
G) 0
100
"ID
80
L_
60
~n
40 20
0
II.
o
I
I
I
i
I
l
I
I
zo
30
40
so
60
70
8o
l:
I
I
I
90
Age (days) Fig. 2. Range of breath H2 excretion as a function of age in one infant during the first 4 months of life. strate for colonic fermentation but also raise the issue of whether breath H2 can be used to assess carbohydrate absorption in young infants. Most infants had peak breath H2 levels in the first month, followed by significantly lower but still elevated levels in months 2 and 3. In contrast, Barret al. 3 reported that breath H2 levels were highest in the second month. Although the pattern of breath H2 excretion in most infants was similar to the mean curve for the group, some individual profiles went against the trend and in one infant no pattern was apparent. The pattern of breath H2 excretion may reflect changes in the quantity of substrate delivered into the colon or developmental changes in the production of H2 and its pulmonary excretion. 3 Another source of variability of breath H2 levels, identified in one infant, was the time of day of sample collection. Significant diurnal variation was obsq~ved; breath H2 levels were higher in the evening than in the morning. It is unclear whether this finding reflects dietary intake or physiologic variation. The report 7 of a significantly increased concentration of oligosaccharides in human milk during the evening offers one explanation for the diurnal variation in
breath H2 excretion. Oligosaccharides compose a significant proportion of the total carbohydrate in human milk and probably escape digestion.8 Our results cause us to question the assumption that unabsorbed dietary lactose is the sole substrate for the production of H2 in the colon. The levels of H2 in the breath were not clearly related to the time of feeding. In older subjects with lactose m~labsorption, there is a well-defined increase in breath ~-~[2 levels after lactose or milk ingestion. 9 The absence of fasting, the frequency of feeding, or the unstructured feeding schedule in the infant 3 may explain our findings. Alternatively, H2 in the breath may not be derived from substrates in the milk or other food. This possibility is supported by the observation in one infant that breath H2 levels remained elevated even after long periods of fasting (> 7 hours). Fermentation of endogenous substrates, such as glycoproteins, may explain these observations. ~~ The variability of breath H2 levels among infants suggests that physiologic differences exist that may be clinically important and detectable at the group level. However, the diurnal variation and, in some infants, day-to-day variability limit the usefulness of breath H2 as a clinical tool.
Volume 121 Number 3
We thank the staff members of Tresillian Family Care Centres and Early Childhood Health Centres for their cooperation, the mothers and infants who participated in the study, and Dr. R. Kamath for his comments. REFERENCES
1. Douwes AC, Fernandes J, Rietveld W. Hydrogen breath test in infants and children: sampling and storing expired air. Clin Chim Acta 1978;82:293-6. 2. MacLean WC, Fink BB. Lactose malabsorption by premature infants: magnitude and clinical significance. J PEDIATR 1980; 97:383-8. 3. Barr RG, Hanley J, Patterson DK, Wooldridge J. Breath hydrogen excretion in normal newborn infants in response to usual feeding patterns: evidence for "functional lactase insufficiency" beyond the first mouth of life. J PEDIATR 1983; 104:527-33. 4. Lifschitz CH, O'Brian Smith E, Garza C. Delayed complete functional lactase sufficiency in breast-fed infants. J Pediatr Gastroenterol Nutr 1983;2:4778-82.
Clinical and laboratory observations
4 13
5. Moore D J, Robb TA, Davidson GP. Breath hydrogen response to milk containing lactose in colicky and noncolicky infants. J PEDIATR 1988;113:979-84. 6. Miller J J, McVeagh P, Fleet GH, Petocz P, Brand JC. Breath hydrogen excretion in infants with colic. Arch Dis Child 1989;64:725-9. 7. Viverge D, Grimmonprez L, Cassauas G, Bardet L, Bonnet H, Solere M. Variation of lactose and oligosaccharides in milk from women of blood types secretor A or H, secretor Lewis, and secretor H/non-secretor Lewis during the course of lactation. Ann Nutr Metab 1985;29:1-1 l. 8. Newburg DS, Daniel PF, O'Neil NE. High-performance liquid chromatography of oligosaccharides from human milk and colostrum. In: Hamosh M, Goldman AS, eds. Human lactation. New York: Plenum, 1986:581-8. 9. Sotomons NW, Barillas C. The cut-off criterion for a positive breath test in children: a reappraisal. J Pediatr Gastroenterol Nutr 1986;5:920-5. 10. Cummings JH. Fermentation in the large intestine: evidence and implications for health. Lancet 1983;1:1206-8.
Bentiromide test using liquid-chromatographic measurement of p-aminobenzoic acid and its metabolites for diagnosing pancreatic insufficiency in childhood P. R. Durie, MD, FRCP(C), L. Y. Y u n g - J a t o , MSc, S. J. Soldin, PhD, Z. Verjee, PhD, a n d L. Ellis, RN From the Division of Gastroenterology, Departments of Pediatrics and Clinical Biochemistry, and the Research Institute, Hospital for Sick Children, Toronto; the Departments of Pediatrics and Clinical Biochemistry, University of Toronto, Toronto, Ontario, Canada; and the Department of Laboratory Medicine, Childrens Hospital National Medical Center, Washington, D.C.
We assessed the diagnostic c a p a b i l i t y of the bentiromide test using a highpressure liquid-chromatography method to analyze p - a m i n o b e n z o i c acid and its metabolites in plasma as an indirect measure of exocrine pancreatic function. Mean total amine concentration in pancreatic-insufficient subjects was significantly lower than in control subjects. There were 3 of 15 false-negative results and no false-positive results. We conclude that this chromatographic method is an effective means of analyzing p-aminobenzoic acid and its metabolites after ingestion of bentiromide. (J PEDIATR1992;121:413-6)
Supported by a research grant (No. MT6752) from the Medical Research Council of Canada. Submitted for publication July 11, 1991; accepted March 13, 1992. Reprint requests: P. R. Durie, MD, FRCP(C), Division of Gastroenterology, Hospital for Sick Children, 555 University Ave., Toronto, Ontario M5G 1X8, Canada. 9/22/37823
Bentiromide, an orally administered peptide (N-benzoyl-Ltyrosyl-p-aminobenzoic acid), is cleaved by pancreatic chymotrypsin in the duodenal lumen, releasing the marker p - a m i n o b e n z o i c acid, which is absorbed in the small intestine, metabolized in the liver, and excreted in the urine.1 If intestinal absorption and renal excretion are normal, the a m o u n t of P A B A and its metabolites found in urine or
