U
.NNA.UL I
I
(amoxicillin)
The new generation broad-spectrum penicillin INDICATIONS AND DOSAGE Infections of the ear, nose and throat due to streptococci, pneumococci, and penicillinsensitive staphylococci; infections of the upper respiratory tract due to H. influenzae; infections of the genitourinary tract due to E. coli, P. mirabilis, and S. faecalis; infections of the skin and soft tissues due to streptococci, pen ciii in-sensitive staphylococci and E. coli: USUAL DOSE: ADULTS 250 mg every 8 hours CHILDREN 25 mg/kg/day in divided doses every 8 hours In severe infections or infection associated with organisms where sensitivity determinations indicate higher blood levels may be advisable: 500 mg every 8 hours for adults, and 50 mg/kg/day in divided doses every 8 hours for children may be needed. This dosage should not exceed the recommended adult dosage. Infections of the lower respiratory tract due to streptococci, pneumococci, penicillinsensitive staphylococci and H. influenzae: USUAL DOSE: ADULTS 500 mg every 8 hours CHILDREN 50mg/kg/day in divided doses every 8 hours This dosage should not exceed the recommended adult dosage. Urothritis due to N. gonorrhoeae: 3 g as a single oral dose. CONTRAINDICATION In patients with a history of allergy to the penicillins and cephalosporins. Product Monograph available on request. SUPPLIED AMOXIL-250 Capsules-each contains 250 mg amoxicillin (as the trihydrate) AMOXIL-500 Capsules-each contains 500 mg amoxicillin (as the trihydrate) AMOXIL-125 Suspension-125 mg amoxicillin per 5 ml, in 75 ml & 100 ml bottles AMOXIL-250 Suspension-250 mg amoxicillin per 5 ml, in 75 ml & 100 ml bottles AMOXIL Pediatric Drops-is ml (50 mg/mI) in dropper bottle
AYERST LABORATORIES Division of Ayerst, McKenna & Harrison Limited Montreal, Canada Made in Canada by arrangement with BEECHAM, INC. .Regd
Vitamin C for prophylaxis of tyrosinemia in the newborn STATEMENT BY THE NUTRITION COMMITTEE* OF THE CANADIAN PAEDIATRIC SOCIETY
Ascorbic acid supports reduction activation of hepatic p-hydroxyphenylpyruvic acid (p-HPPA) oxidase, the enzyme that converts p-HPPA to homogentisic acid in the catabolism of tyrosine. Thus, when tissue ascorbate concentrations are diminished, the activity of p-HPPA oxidase is impaired. Hypertyrosinemia and tyrosyluria are likely to occur, particularly in the newborn, when the activity of p-HPPA oxidase is insufficient. There are three interrelated causes for hypertyrosinemia in the newborn: 1. Diminished amounts of p-HPPA oxidase apoenzyme in the liver. 2. High dietary intake of tyrosme. 3. Low ascorbate content of the unsupplemented postnatal diet. An unusual enzyme, p-HPPA oxidase is oxidatively inactivated by its own substrate; ascorbate nonspecifically prevents this inactivation. Inhibition of the enzyme is particularly likely to occur in the newborn term infant whose diet provides relatively large amounts of tyrosine and small amounts of ascorbate, and especially in the preterm infant, whose liver contains less apoenzyme than does a mature liver. About 0.5% of all newborns have transient tyrosinemia, and in preterm infants the prevalence can be as high as 50%, particularly when high-protein feedings (> 4 g/kg .d) are given.14 Neonatal tyrosinemia is generally thought to be benign, but this is not certain. Reports appear occasionally that suggest that not all infants with postnatal tyrosinemia escape harm.4 Hypertyrosinemia also occurs in certain inherited conditions but it is not transient and cannot be corrected with ascorbate treatment. A serious and often fatal type occurs in a FrenchCanadian subisolate:5 although the activity of p-HPPA oxidase is impaired, the cause is unclear; the patient benefits from stringent restriction of dietary tyrosine intake. Another type of hypertyrosinemia is due to deficiency of cytosol tyrosine aminotransferase; mental retardation is associated. *Q.frman: J.C. Haworth; members: A.G.F. Davidson, D.A.I. Grewar, B.F. Habbick, JR. Hamilton, A.B. Jones, R. Lachance, J. Letarte, C.C. Roy; consultants: G.H. Beaton, D. Fraser, T.K. Murray, Z.L Sabry, C.R. Scriver; liaison. Canadian Dietetic Association: P. Lynch Reprint requests to: Canadian Paediatric Society, Centre hospitalier universitaire de Sherbrooke, Sherbrooke, PQ J1H 5N4
The ascorbate requirement of some newborns, when considered in terms of tyrosine metabolism, is higher than that of older children and adults. An intake of 100 mg/d, instead of the 20 mg/d recommended by the Canadian dietary standard,6 will reduce the incidence and severity of tyrosinemia,7 provided dietary protein intake is not exceptionally elevated. When this revised ascorbate intake is expressed in terms of body weight, the newborn infant manifests a pharmacologic dependency on the vitamin; his daily need is about 25 mg/kg. For an adult the daily "requirement" is less than 1 mg/kg. More research is needed to provide clear-cut answers to the questions whether neonatal tyrosinemia is harmful and, if it is, whether such harm can be prevented by vitamin C prophylaxis. However, in view of the present uncertainty that neonatal tyrosinemia is completely harmless, and in view of the differences in Canada in neonatal feeding practices, as regards protein and ascorbic acid, it is advisable to recognize the special need for ascorbate of some newborn infants, particularly the preterm. We recommend that infants at risk be given vitamin C supplements (about 100 mg/d) during the 1st week of life; we know of no harm that could result from this dietary intake of ascorbate. After the 1st week care should be taken to ensure that amounts of ascorbic acid sufficient to meet normal nutritional needs (about 20 mg/d) are provided by the diet or by supplements. When possible, blood tyrosine concentration should be monitored in preterm infants and treatment given if values are elevated. References 1. SCRIVER CR, ROSENBERG LE: Disorders of tyrosine metabolism (chap 16), in Amino Acid Metabolism and its Disorders, Philadelphia, Saunders, 1973 2. AVERY ME, CLOW CL, MENKES JH, Ct al: Transient tyrosinemia of the newborn: dietary and clinical aspects. Pediatrics 39: 378. 1967 3. FERNDACH SA, SUMMONS RE, PERaIRA WE, et al: Metabolic studies of transient tyrosinemia in premature infants. Pediatr Res 9: 172, 1975 4. MENKES JH, WELcISER DW, LEvI HS, et al: Relationship of elevated blood tyrosine to the ultimate intellectual performance of premature infants. PediatrIcs 49: 218 1972 5. LAROCHELLE J, MORTEZAK A, BEIANGER M, et al: Experience with 37 infants with tyrosinemia. Can Med Assoc J 97: 1051, 1967 6. Dietary Standard for Canada, rev ed, Ottawa, Health and Welfare Canada, health protection branch, food directorate, bureau of nutritional sciences, 1975 7. LIGHT U, BERRY HK, SUTHERLAND JM: Aminoacidemia of prematurity; Its response to ascorbic acid. Am J Dis Child 112: 229, 1966
CMA JOURNAL/MARCH 6, 1976/VOL. 114 447
.NNA.UL I
I
(amoxicillin)
The new generation broad-spectrum penicillin INDICATIONS AND DOSAGE Infections of the ear, nose and throat due to streptococci, pneumococci, and penicillinsensitive staphylococci; infections of the upper respiratory tract due to H. influenzae; infections of the genitourinary tract due to E. coli, P. mirabilis, and S. faecalis; infections of the skin and soft tissues due to streptococci, pen ciii in-sensitive staphylococci and E. coli: USUAL DOSE: ADULTS 250 mg every 8 hours CHILDREN 25 mg/kg/day in divided doses every 8 hours In severe infections or infection associated with organisms where sensitivity determinations indicate higher blood levels may be advisable: 500 mg every 8 hours for adults, and 50 mg/kg/day in divided doses every 8 hours for children may be needed. This dosage should not exceed the recommended adult dosage. Infections of the lower respiratory tract due to streptococci, pneumococci, penicillinsensitive staphylococci and H. influenzae: USUAL DOSE: ADULTS 500 mg every 8 hours CHILDREN 50mg/kg/day in divided doses every 8 hours This dosage should not exceed the recommended adult dosage. Urothritis due to N. gonorrhoeae: 3 g as a single oral dose. CONTRAINDICATION In patients with a history of allergy to the penicillins and cephalosporins. Product Monograph available on request. SUPPLIED AMOXIL-250 Capsules-each contains 250 mg amoxicillin (as the trihydrate) AMOXIL-500 Capsules-each contains 500 mg amoxicillin (as the trihydrate) AMOXIL-125 Suspension-125 mg amoxicillin per 5 ml, in 75 ml & 100 ml bottles AMOXIL-250 Suspension-250 mg amoxicillin per 5 ml, in 75 ml & 100 ml bottles AMOXIL Pediatric Drops-is ml (50 mg/mI) in dropper bottle
AYERST LABORATORIES Division of Ayerst, McKenna & Harrison Limited Montreal, Canada Made in Canada by arrangement with BEECHAM, INC. .Regd
Vitamin C for prophylaxis of tyrosinemia in the newborn STATEMENT BY THE NUTRITION COMMITTEE* OF THE CANADIAN PAEDIATRIC SOCIETY
Ascorbic acid supports reduction activation of hepatic p-hydroxyphenylpyruvic acid (p-HPPA) oxidase, the enzyme that converts p-HPPA to homogentisic acid in the catabolism of tyrosine. Thus, when tissue ascorbate concentrations are diminished, the activity of p-HPPA oxidase is impaired. Hypertyrosinemia and tyrosyluria are likely to occur, particularly in the newborn, when the activity of p-HPPA oxidase is insufficient. There are three interrelated causes for hypertyrosinemia in the newborn: 1. Diminished amounts of p-HPPA oxidase apoenzyme in the liver. 2. High dietary intake of tyrosme. 3. Low ascorbate content of the unsupplemented postnatal diet. An unusual enzyme, p-HPPA oxidase is oxidatively inactivated by its own substrate; ascorbate nonspecifically prevents this inactivation. Inhibition of the enzyme is particularly likely to occur in the newborn term infant whose diet provides relatively large amounts of tyrosine and small amounts of ascorbate, and especially in the preterm infant, whose liver contains less apoenzyme than does a mature liver. About 0.5% of all newborns have transient tyrosinemia, and in preterm infants the prevalence can be as high as 50%, particularly when high-protein feedings (> 4 g/kg .d) are given.14 Neonatal tyrosinemia is generally thought to be benign, but this is not certain. Reports appear occasionally that suggest that not all infants with postnatal tyrosinemia escape harm.4 Hypertyrosinemia also occurs in certain inherited conditions but it is not transient and cannot be corrected with ascorbate treatment. A serious and often fatal type occurs in a FrenchCanadian subisolate:5 although the activity of p-HPPA oxidase is impaired, the cause is unclear; the patient benefits from stringent restriction of dietary tyrosine intake. Another type of hypertyrosinemia is due to deficiency of cytosol tyrosine aminotransferase; mental retardation is associated. *Q.frman: J.C. Haworth; members: A.G.F. Davidson, D.A.I. Grewar, B.F. Habbick, JR. Hamilton, A.B. Jones, R. Lachance, J. Letarte, C.C. Roy; consultants: G.H. Beaton, D. Fraser, T.K. Murray, Z.L Sabry, C.R. Scriver; liaison. Canadian Dietetic Association: P. Lynch Reprint requests to: Canadian Paediatric Society, Centre hospitalier universitaire de Sherbrooke, Sherbrooke, PQ J1H 5N4
The ascorbate requirement of some newborns, when considered in terms of tyrosine metabolism, is higher than that of older children and adults. An intake of 100 mg/d, instead of the 20 mg/d recommended by the Canadian dietary standard,6 will reduce the incidence and severity of tyrosinemia,7 provided dietary protein intake is not exceptionally elevated. When this revised ascorbate intake is expressed in terms of body weight, the newborn infant manifests a pharmacologic dependency on the vitamin; his daily need is about 25 mg/kg. For an adult the daily "requirement" is less than 1 mg/kg. More research is needed to provide clear-cut answers to the questions whether neonatal tyrosinemia is harmful and, if it is, whether such harm can be prevented by vitamin C prophylaxis. However, in view of the present uncertainty that neonatal tyrosinemia is completely harmless, and in view of the differences in Canada in neonatal feeding practices, as regards protein and ascorbic acid, it is advisable to recognize the special need for ascorbate of some newborn infants, particularly the preterm. We recommend that infants at risk be given vitamin C supplements (about 100 mg/d) during the 1st week of life; we know of no harm that could result from this dietary intake of ascorbate. After the 1st week care should be taken to ensure that amounts of ascorbic acid sufficient to meet normal nutritional needs (about 20 mg/d) are provided by the diet or by supplements. When possible, blood tyrosine concentration should be monitored in preterm infants and treatment given if values are elevated. References 1. SCRIVER CR, ROSENBERG LE: Disorders of tyrosine metabolism (chap 16), in Amino Acid Metabolism and its Disorders, Philadelphia, Saunders, 1973 2. AVERY ME, CLOW CL, MENKES JH, Ct al: Transient tyrosinemia of the newborn: dietary and clinical aspects. Pediatrics 39: 378. 1967 3. FERNDACH SA, SUMMONS RE, PERaIRA WE, et al: Metabolic studies of transient tyrosinemia in premature infants. Pediatr Res 9: 172, 1975 4. MENKES JH, WELcISER DW, LEvI HS, et al: Relationship of elevated blood tyrosine to the ultimate intellectual performance of premature infants. PediatrIcs 49: 218 1972 5. LAROCHELLE J, MORTEZAK A, BEIANGER M, et al: Experience with 37 infants with tyrosinemia. Can Med Assoc J 97: 1051, 1967 6. Dietary Standard for Canada, rev ed, Ottawa, Health and Welfare Canada, health protection branch, food directorate, bureau of nutritional sciences, 1975 7. LIGHT U, BERRY HK, SUTHERLAND JM: Aminoacidemia of prematurity; Its response to ascorbic acid. Am J Dis Child 112: 229, 1966
CMA JOURNAL/MARCH 6, 1976/VOL. 114 447
