- Email: [email protected]
Urinary catecholamines and metabolites in children
266
Brief clinical and laboratory observations
prothrombin levels from 2 to 10% o f normal have been reported to have epistaxis, bruising, mcnorrhagia, hematuria, and bleeding after surge D' and dental extractions. Despite the severe deficiency of prothrombin and marked prolongation of the prothrombin time in our patient, she has had only mild bleeding to date. lter activity has not been restricted. One episode of oral bleeding was managed with topical thrombin and epsilon-aminocaproic acid (Amicar), a treatment which has been used successfully by us for similar bleeding episodes in children with Factor VIII or Factor IX deficiency. Prothrombin has a biologic half-life of approximately 50 to 80 hours '~ and is present in both stored and freshfrozen plasma. The exact level necessary for hemoslasis is not known but is probably 10 to 15% for minor hemorrhages and 20 to 4070 for major trauma or surgery." Thus effective treatment is possible using plasma. The prothrombin complex concentrates, which also contain Factors Vll, IX, and X, have an increased risk of transmitting hepatitis compared to plasma and have been associated with thrombotic episodes, particularly in patients with liver disease. We feel that bleeding in congenital hypoprothrombinemia should be treated with plasma, unless this therapy is ineffective. Although prothrombin is present in stored plasma, the use of freshfrozen plasma will ensure the delivery of adequate amounts of active prothrombin. ADDENDUM A recent report describes a 31-year-old Chicano man with bleeding of moderate severity and biologic and immunologic levels of prothrombin similar to those in our patient (Montgomery RR, Otsaku A, and llathaway WE: Hypoprothrombinemia: Case report, Blood 51:299, 1978).
The Journal of Pediatrics August 1978
The authors thank Ms. Susannah McCord, Marge DeSipin, and Grace Terry for their expert technical assistance. REFERENCES !. Shapiro SS, Martinez J, and Ilolburn RR: Congenital dysprothrombinemia: An inherited structural disorder of human prothrombin, J Clin Invest 48:2251, 1969. 2. Kattlove HE, Shapiro SS, and Spivack M: Hereditary prothrombin deficiency, N Engl J Med 282:57, 1970. 3. Girolami A: The hereditary transmission of congenital "true" hypoprothrombinaemia, Br J Haematol 21:695, 1971. 4. Baudo F, de Cataldo F, Josso F, and Silvello L: Hereditary hypoprothrombinaemia, Acta Haematol 47:243, 1972. 5. Pina-Cabral JM, and Benvindo J: Congenital hypoprothrombinemia in a Portuguese family, Thromb Diath Haemorrh 30:451, 1973. 6. Josso F, Monasterio de Sanchez J, Lavergne JM, Menache D, and Soulier JP: Congenital abnormality of the prothrombin molecule (factor Ii) in four siblings: Prothrombin Barcelona, Blood 38:9, 1971. 7. Shapiro SS, Maldonado M, Fradera J and McCord S: Prothrombin San Juan: A complex new dysprothrombihernia, J Clin Invest 53:73a, 1974. 8. Girolami A, Bareggi G, Brunetti A, and Sticchi A: Prothrombin Padua: A "new" congenital dysprothrombinemia, J Lab Clin Med 84:654, 1974. 9. Kahn MJP, and Govaerts A: Prothrombin Brussels: A new congenital defective protein, Thromb Res 5:i41, 1974. 10. Shapiro SS and Martinez J: Ituman prothrombin metabolism in normal man and in hypocoagulable subjects, J Clin Invest 48:!292, 1969. I1. Johnson AJ, Aronson DL, and Williams WJ: P~'eparation and clinical use of plasma and plasma fractions, in Williams WJ, Beutler E, Erslev AJ, and Rundles RW, editors: ltematology, ed 2, New York, 1977, McGraw-llill Book Co., Inc., pp 1561-1582.
Urinar), catecholamines and metabolites in children Andr~ F. De Schaepdr~'ver, M.D.,* Carlos Hooft, M.D., Marie-Jeanne Delbeke, M.D., and Mare Van"den Noortgaete, M.D., Ghent, Belgium
DATA on the urinary excretion of catecholamines and metabolites by healthy children according to age are From the He)'mans lnstitttte of Phartnacology and the Pediatric Clinic, Ghent University Medical School. Aided b)' a grant from the National Fund for Medical Research Belgium (No. 3.0092. 74/20.499). *Reprint address: lle)'mans Institute of Pharmacolog)'. University of Ghent Medical School, De Pintelaan 135, B.9000 Ghent, Belgium
scarce and incomplete.'-' The present paper sets out the values of urinary catecholamines and metabolites found in essentially normal children from one month to 16 years of age. METHODS One-hundred and four children of both sexes, hospitalized for mild diseases, were studied while at bed rest. Twenty-four-hour urine specimens were collected and 0022-3476/78/0293-0266S00.30/0 9 1978 The C. V. Mosby Co.
Voh,ne 93 Number 2
Brief cfinical and laboratory observatimu
267
Table I. T w e n t y - f o u r - h o u r urinary excretion o f c a t e c h o l a m i n e s a n d m e t a b o l i t e s (~ -4- SD) in n o r m a l children according to age a n d surface a r e a
Age*
<6m~176 .4, Noradrenaline ~ug/24 hr 9.1 • 5.5 #g/m2/24 hr 31.9 • 17.2 Adrenaline /ag/24 hr !.2 • 0.6 pg/m*/24 hr 4.3 • 2.0 Normetanephrine ~g/24 hr 12.1 • 7.3 ~g/mV24 hr 42.7 • Metanephfine ~tg/24 hr 3.9 • 2.6 /tg/mV24 hr 13.5 • 7.9 3-Methoxy-4-hydroxymandelic acid mg/24 hr 1.0 • 0.5 m g / m ' / 2 4 hr 3.5 • 1.5 Dopamine gg(24 hr 59.1 • 27.7 gg/m~/24 h r 206.7 • 94.8 Homovanillic acid mg/24 hr 0.9 • 0.5 mg/mV24 hr 3.4 • 1.7
C'"
6-10)'r (Js)
8.8 • 25.9 •
3.8 11.6
1.8 • 5.3 •
1.4 3.9
2.1 • 4.8 •
1.0 2.5
8.1 • 23.3 •
5.7 15.3
10.9 • 24.9 •
3.4 8.8
4.8 • 9.4 •
5.9 3.7
4.5 • 10.3 •
2.6 5.9
1.3 • 4.1 •
0.6 2.7
1.3 • 0.5 3.0 ___ 1.4
1.4 __. 0.9 2.6 • 2.2
71.0 • 35.5 213.1 • 118.8
84.6 • 39.1 196.6 • 101.0
82.6 • 34.1 141.9 • 87.7
1.4 • 4.2 •
0.7 2.2
8.1 __. 4.1 19.4 • 11.2
1.2 • 2.8 •
13.5 • 5.1 22.4 • 10.3 4.0 • 6.6 •
10-16)r (2z)
22.3 • 16.0 25.9 ___ 18.4
3.1 5.3
5.7 ___ 3.0 6.9 • 4.2
18.1 +- 12.7 28.3 • 14.3
26.5 • 13.1 30.8 • 15.9
5.3 • 9.0 •
0.7 1.8
i.7 • 3.1 •
3.2 5.9
1.1 2.2
9.7 • 5.6 10.9___ 6.3 2.3 • 2.6 •
1.2 1.4
114.6 • 45.6 124.7 • 49.8 2.1 • 2.3 •
1.0 1.3
22.6 • 10.7 18.0 • 7.4 6.9 • 5.5 •
3.7 2.8
23.7 • 11.0 19.3 • 9.1 8.4 • 7.1 •
4.2 3.5
2.6 • 1.3 •
1.2 1.0
112.4 • 53.9 92.6 • 43.5 3.3 • 2.8 •
1.5 1.5
"Number in parenthesis is number of children in each age group. assayed for c a t e c h o l a m i n e s a n d m e t a b o l i t e s a c c o r d i n g to the m e t h o d o f De S c h a e p d r y v e r a n d M o e r m a n . ~ U r i n a r y creatinine was m e a s u r e d according to the m e t h o d o f Jaffr. 6 Specimens c o n t a i n i n g less t h a n 1 g m c r e a t i n i n e / 2 4 h o u r s were assumed to reflect incomplete collections ~ a n d were not included in the study. RESULTS T h e values for 24-hour urinary excretion o f catechola m i n e s a n d metab01ites in the six groups o f c h i l d r e n studied are given in T a b l e I. A progressive increase with increasing age for t h e absolute excretion values o f all substances assayed can be observed, r e a c h i n g a m a x i m u m in the g r o u p o f children six to ten years o f age. A highly significant ( P <: 0.001) !ncrease in n o r a d r e n a l i n e excretion was observed in the 2- to 6-year age g r o u p c o m p a r e d to the I- to 2-year ag e group. Presenting the data using surface area as a reference instead o f total 24-hour excretion resulted in c o m p a r a b l e excretion rates in the various age groups. N o consistent c h a n g e with increasing size was noted. DISCUSSION Because collection o f 2 4 - h o u r urine s p e c i m e n s is often difficult in infants, we a t t e m p t e d to use the v a l u e for urinary creatinine as a basis for d e t e r m i n a t i o n s d o n e o n a n i n c o m p l e t e 24-hour collection a n d to .express the
results as g g / g m o f urinary creatinine. It was observed, however, that considerable v a r i a t i o n o f u r i n a r y creatinine o u t p u t does occur in the s a m e child, both f r o m voiding to voiding within the same d a y a n d from day to day, confirming previous reports, s-''- Accordingly, urinary excretion o f creatinine was n o t used as a reference value in expressing the data. As m e n t i o n e d previously urinary c r e a t i n i n e values below 1 g m / 2 4 h o u r s were t a k e n as a n indication t h a t the 2 4 - h o u r collection o f urine was incomplete a n d these urine specimens were excluded. This study confirms a n d extends previous r e p o r t s ; " ' the daily u r i n a r y excretion o f c a t e c h o l a m i n e s a n d metabolites increases with age in n o r m a l children i n d e p e n d e n t l y o f the size o f the child. We acknowledge the technical assistance of V. Geers and R. Vandenbroeck. REFERENCES 1. K/irki NT: The urinary excretion of noradrenaline and adrenaline in different age groups, its diurnal variation and the effect of muscular work on it, Acta Physiol Scand. 39:(Suppl): 132, 1956. 2. Cession-Fossion A, Libotte G, and Chantraine JM: Elimination urinaire des cat~cholamines et de leur m~tabolite, l'acide vanillylmandrlique, chez I'enfant normal, Acta Paediatr Belg 18:i04, 1964.
268
Brief clinical and laboratory observations
3. Voorhess ML: Urinary catecholamine excretion by healthy children, J PEDtATR39:252, 1967. 4. Beauvallet hi, Blancher G, and Solier hi: Adrenaline et noradr~naline urinaires au cours du d,~veloppemen t de I'enfant, Th~rapie 27:535, 1972.5. De Schaepdryver AF, and Moerman EM: Simultaneous estimation of catecholamines and metabolites in urine, Clin Chim Acta 85: No. I, April 3, 1978. 6. Jaff6 hi: Uber den Niederschlag, welchen PikrinsSure in normalen ttarn erzeugt, und fiber eine neue Reaktion des Kreatinins, Z Physiol Chem 10:391, 1886. 7. Epstein SE, and Schriever IIG: Creatinine excretion, Lancet 1:192, 1970.
The Journal of Pediatrics August 1978 8. Vestergaard P, and Leverett R: Constancy of urinary creatinine excretion, J Lab Clin Med 51:211, 1958. 9. Bleiler RE, and Schedl HP: Creatinine excretion: variability and relationships to diet and body size, J Lab Clin Med 59:945, 1962. I0. Korte R, Wiersinga A, and Simmons WK: Urinary creatinine excretion, Am J Clin Nutr 23:869, 1970. I 1. Lis AW, McLaughin D I, McLaughin RK, and de llackbeil KF: The function of creatinine: II nocturnal-diurnal variation, Physiol Chem Phys 4:70, 1972. 12. Peters WH, Grosset V, and Knapp A: The creatinine excretion in women during fasting, Clin Chim Acta 39:273, 1972.
Acute leukemia and granulocyte transfusion" Fatal graft-versus-host reaction following transfusion of cells obtained from normal donors Ronald C. Rosen, M.D., Douglas W. Huestis, M.D., and James J. Corrigan, Jr., M.D.,* Tucson, Ariz.
DESPITE newer 9 regimens and the use of various isolation techniques, infection continues to be the leading cause of death in children with acute leukemia.' Prolonged periods on immunosuppressiv e chemotherapy and resultant neutropenia appear to be the major variables associated with this risk. Since the degree of granulocytopenia is directly related to ihe high risk of bacterial and fungal infections, granulocyte replacement has become a logical part of treatment of proven infections in neutropenic children not responding to conventional antibiotic therapy. ~" :~ Heretofore, graft-versus-host reaction has been reported in only one recipient of granulocytes from a normal donor.' It is the purpose of this article to report a second instance, the first in a child, which occurred in a patient with acute lymphoblastic leukemia. CASE REPORT" The patient was a 7V2-year-old white girl who had had acute lymphoblastic leukemia for two and a half years before her final admission. Her course was complicated by three hematologic relapses and two episodes ofcentral nervous system leukemia, all of which were successfully treated with intensive chemotherapy, including prednisone, vincristine, L-asparaginase, adriamycin, cyclophosphamide, methotrexate, and 6-mercaptopurine. Cen-
From the Departments of Pediatrics and Pathology University of Arizona Health Sciences Center. *Reprint address: Universityof Arizona Health9 Center9 Tucson, AZ 85724.
tral ne~'ous system management included radiotherapy and intrathecal administration of methotrexate, cytosine arabinoside, and hydrocort!sone. Because of her frequent relapses and chemotherapeuti c immunosuppression, she had many infections, including otitis media, upper respiratory infections, bronchitis and bronchiectasis, herpes zoster, ltemophih~s influenzae bronchopneumonia, oral candidiasis, perianal abscess (Proteus mirabiffs and Escherichia coli), periorbital cellulitis (Staphylococcus attreus and Streptococcus pneumoniae), many urinary tract infections (E. coli, Klebsiella, and Pseudomonas aerttgh!osa), and septicemic episodes (Staph)'lococcus attreus, Streptococcus pneumoniae and E. colO. Abbreviations used hiE ratio: myeloid: erythroid ratio GVII: graft-versus-host lg: immunoglobulin On her last admission, the patient had severe granulocytopenia (120 cells/mm 3 absolute count), lymphocytopen!a (336 cells/ mnP), and clinical manifestations of sepsis. She weighed 18 kg. Staph)'lococctts attreus was isolated from her blood and Klebsiella pneutnoniae from the urinary tract. She was treated with antibiotics plus four separate granulocyte transfusions obtained from normal nonrelated donors, on consecutive days. Normal9blood donors were screened by the standard Red Cross procedure, and were matched to the recipient according to the ABO system; they were not HLA matched. Simultaneous granulocyte and platelet concentrates were collected with the Haemoneties model 30 blood processor (Haemonetics Corporation, Natick, MA 01760) without pi'ior stimulation by corticosteroids. The infections cleared after these therapeutic maneuvers, ttowever, ten days 0022-3476/78/0293-0268500.30/0 9 1978 The C. V. Mosby Co.
Brief clinical and laboratory observations
prothrombin levels from 2 to 10% o f normal have been reported to have epistaxis, bruising, mcnorrhagia, hematuria, and bleeding after surge D' and dental extractions. Despite the severe deficiency of prothrombin and marked prolongation of the prothrombin time in our patient, she has had only mild bleeding to date. lter activity has not been restricted. One episode of oral bleeding was managed with topical thrombin and epsilon-aminocaproic acid (Amicar), a treatment which has been used successfully by us for similar bleeding episodes in children with Factor VIII or Factor IX deficiency. Prothrombin has a biologic half-life of approximately 50 to 80 hours '~ and is present in both stored and freshfrozen plasma. The exact level necessary for hemoslasis is not known but is probably 10 to 15% for minor hemorrhages and 20 to 4070 for major trauma or surgery." Thus effective treatment is possible using plasma. The prothrombin complex concentrates, which also contain Factors Vll, IX, and X, have an increased risk of transmitting hepatitis compared to plasma and have been associated with thrombotic episodes, particularly in patients with liver disease. We feel that bleeding in congenital hypoprothrombinemia should be treated with plasma, unless this therapy is ineffective. Although prothrombin is present in stored plasma, the use of freshfrozen plasma will ensure the delivery of adequate amounts of active prothrombin. ADDENDUM A recent report describes a 31-year-old Chicano man with bleeding of moderate severity and biologic and immunologic levels of prothrombin similar to those in our patient (Montgomery RR, Otsaku A, and llathaway WE: Hypoprothrombinemia: Case report, Blood 51:299, 1978).
The Journal of Pediatrics August 1978
The authors thank Ms. Susannah McCord, Marge DeSipin, and Grace Terry for their expert technical assistance. REFERENCES !. Shapiro SS, Martinez J, and Ilolburn RR: Congenital dysprothrombinemia: An inherited structural disorder of human prothrombin, J Clin Invest 48:2251, 1969. 2. Kattlove HE, Shapiro SS, and Spivack M: Hereditary prothrombin deficiency, N Engl J Med 282:57, 1970. 3. Girolami A: The hereditary transmission of congenital "true" hypoprothrombinaemia, Br J Haematol 21:695, 1971. 4. Baudo F, de Cataldo F, Josso F, and Silvello L: Hereditary hypoprothrombinaemia, Acta Haematol 47:243, 1972. 5. Pina-Cabral JM, and Benvindo J: Congenital hypoprothrombinemia in a Portuguese family, Thromb Diath Haemorrh 30:451, 1973. 6. Josso F, Monasterio de Sanchez J, Lavergne JM, Menache D, and Soulier JP: Congenital abnormality of the prothrombin molecule (factor Ii) in four siblings: Prothrombin Barcelona, Blood 38:9, 1971. 7. Shapiro SS, Maldonado M, Fradera J and McCord S: Prothrombin San Juan: A complex new dysprothrombihernia, J Clin Invest 53:73a, 1974. 8. Girolami A, Bareggi G, Brunetti A, and Sticchi A: Prothrombin Padua: A "new" congenital dysprothrombinemia, J Lab Clin Med 84:654, 1974. 9. Kahn MJP, and Govaerts A: Prothrombin Brussels: A new congenital defective protein, Thromb Res 5:i41, 1974. 10. Shapiro SS and Martinez J: Ituman prothrombin metabolism in normal man and in hypocoagulable subjects, J Clin Invest 48:!292, 1969. I1. Johnson AJ, Aronson DL, and Williams WJ: P~'eparation and clinical use of plasma and plasma fractions, in Williams WJ, Beutler E, Erslev AJ, and Rundles RW, editors: ltematology, ed 2, New York, 1977, McGraw-llill Book Co., Inc., pp 1561-1582.
Urinar), catecholamines and metabolites in children Andr~ F. De Schaepdr~'ver, M.D.,* Carlos Hooft, M.D., Marie-Jeanne Delbeke, M.D., and Mare Van"den Noortgaete, M.D., Ghent, Belgium
DATA on the urinary excretion of catecholamines and metabolites by healthy children according to age are From the He)'mans lnstitttte of Phartnacology and the Pediatric Clinic, Ghent University Medical School. Aided b)' a grant from the National Fund for Medical Research Belgium (No. 3.0092. 74/20.499). *Reprint address: lle)'mans Institute of Pharmacolog)'. University of Ghent Medical School, De Pintelaan 135, B.9000 Ghent, Belgium
scarce and incomplete.'-' The present paper sets out the values of urinary catecholamines and metabolites found in essentially normal children from one month to 16 years of age. METHODS One-hundred and four children of both sexes, hospitalized for mild diseases, were studied while at bed rest. Twenty-four-hour urine specimens were collected and 0022-3476/78/0293-0266S00.30/0 9 1978 The C. V. Mosby Co.
Voh,ne 93 Number 2
Brief cfinical and laboratory observatimu
267
Table I. T w e n t y - f o u r - h o u r urinary excretion o f c a t e c h o l a m i n e s a n d m e t a b o l i t e s (~ -4- SD) in n o r m a l children according to age a n d surface a r e a
Age*
<6m~176 .4, Noradrenaline ~ug/24 hr 9.1 • 5.5 #g/m2/24 hr 31.9 • 17.2 Adrenaline /ag/24 hr !.2 • 0.6 pg/m*/24 hr 4.3 • 2.0 Normetanephrine ~g/24 hr 12.1 • 7.3 ~g/mV24 hr 42.7 • Metanephfine ~tg/24 hr 3.9 • 2.6 /tg/mV24 hr 13.5 • 7.9 3-Methoxy-4-hydroxymandelic acid mg/24 hr 1.0 • 0.5 m g / m ' / 2 4 hr 3.5 • 1.5 Dopamine gg(24 hr 59.1 • 27.7 gg/m~/24 h r 206.7 • 94.8 Homovanillic acid mg/24 hr 0.9 • 0.5 mg/mV24 hr 3.4 • 1.7
C'"
6-10)'r (Js)
8.8 • 25.9 •
3.8 11.6
1.8 • 5.3 •
1.4 3.9
2.1 • 4.8 •
1.0 2.5
8.1 • 23.3 •
5.7 15.3
10.9 • 24.9 •
3.4 8.8
4.8 • 9.4 •
5.9 3.7
4.5 • 10.3 •
2.6 5.9
1.3 • 4.1 •
0.6 2.7
1.3 • 0.5 3.0 ___ 1.4
1.4 __. 0.9 2.6 • 2.2
71.0 • 35.5 213.1 • 118.8
84.6 • 39.1 196.6 • 101.0
82.6 • 34.1 141.9 • 87.7
1.4 • 4.2 •
0.7 2.2
8.1 __. 4.1 19.4 • 11.2
1.2 • 2.8 •
13.5 • 5.1 22.4 • 10.3 4.0 • 6.6 •
10-16)r (2z)
22.3 • 16.0 25.9 ___ 18.4
3.1 5.3
5.7 ___ 3.0 6.9 • 4.2
18.1 +- 12.7 28.3 • 14.3
26.5 • 13.1 30.8 • 15.9
5.3 • 9.0 •
0.7 1.8
i.7 • 3.1 •
3.2 5.9
1.1 2.2
9.7 • 5.6 10.9___ 6.3 2.3 • 2.6 •
1.2 1.4
114.6 • 45.6 124.7 • 49.8 2.1 • 2.3 •
1.0 1.3
22.6 • 10.7 18.0 • 7.4 6.9 • 5.5 •
3.7 2.8
23.7 • 11.0 19.3 • 9.1 8.4 • 7.1 •
4.2 3.5
2.6 • 1.3 •
1.2 1.0
112.4 • 53.9 92.6 • 43.5 3.3 • 2.8 •
1.5 1.5
"Number in parenthesis is number of children in each age group. assayed for c a t e c h o l a m i n e s a n d m e t a b o l i t e s a c c o r d i n g to the m e t h o d o f De S c h a e p d r y v e r a n d M o e r m a n . ~ U r i n a r y creatinine was m e a s u r e d according to the m e t h o d o f Jaffr. 6 Specimens c o n t a i n i n g less t h a n 1 g m c r e a t i n i n e / 2 4 h o u r s were assumed to reflect incomplete collections ~ a n d were not included in the study. RESULTS T h e values for 24-hour urinary excretion o f catechola m i n e s a n d metab01ites in the six groups o f c h i l d r e n studied are given in T a b l e I. A progressive increase with increasing age for t h e absolute excretion values o f all substances assayed can be observed, r e a c h i n g a m a x i m u m in the g r o u p o f children six to ten years o f age. A highly significant ( P <: 0.001) !ncrease in n o r a d r e n a l i n e excretion was observed in the 2- to 6-year age g r o u p c o m p a r e d to the I- to 2-year ag e group. Presenting the data using surface area as a reference instead o f total 24-hour excretion resulted in c o m p a r a b l e excretion rates in the various age groups. N o consistent c h a n g e with increasing size was noted. DISCUSSION Because collection o f 2 4 - h o u r urine s p e c i m e n s is often difficult in infants, we a t t e m p t e d to use the v a l u e for urinary creatinine as a basis for d e t e r m i n a t i o n s d o n e o n a n i n c o m p l e t e 24-hour collection a n d to .express the
results as g g / g m o f urinary creatinine. It was observed, however, that considerable v a r i a t i o n o f u r i n a r y creatinine o u t p u t does occur in the s a m e child, both f r o m voiding to voiding within the same d a y a n d from day to day, confirming previous reports, s-''- Accordingly, urinary excretion o f creatinine was n o t used as a reference value in expressing the data. As m e n t i o n e d previously urinary c r e a t i n i n e values below 1 g m / 2 4 h o u r s were t a k e n as a n indication t h a t the 2 4 - h o u r collection o f urine was incomplete a n d these urine specimens were excluded. This study confirms a n d extends previous r e p o r t s ; " ' the daily u r i n a r y excretion o f c a t e c h o l a m i n e s a n d metabolites increases with age in n o r m a l children i n d e p e n d e n t l y o f the size o f the child. We acknowledge the technical assistance of V. Geers and R. Vandenbroeck. REFERENCES 1. K/irki NT: The urinary excretion of noradrenaline and adrenaline in different age groups, its diurnal variation and the effect of muscular work on it, Acta Physiol Scand. 39:(Suppl): 132, 1956. 2. Cession-Fossion A, Libotte G, and Chantraine JM: Elimination urinaire des cat~cholamines et de leur m~tabolite, l'acide vanillylmandrlique, chez I'enfant normal, Acta Paediatr Belg 18:i04, 1964.
268
Brief clinical and laboratory observations
3. Voorhess ML: Urinary catecholamine excretion by healthy children, J PEDtATR39:252, 1967. 4. Beauvallet hi, Blancher G, and Solier hi: Adrenaline et noradr~naline urinaires au cours du d,~veloppemen t de I'enfant, Th~rapie 27:535, 1972.5. De Schaepdryver AF, and Moerman EM: Simultaneous estimation of catecholamines and metabolites in urine, Clin Chim Acta 85: No. I, April 3, 1978. 6. Jaff6 hi: Uber den Niederschlag, welchen PikrinsSure in normalen ttarn erzeugt, und fiber eine neue Reaktion des Kreatinins, Z Physiol Chem 10:391, 1886. 7. Epstein SE, and Schriever IIG: Creatinine excretion, Lancet 1:192, 1970.
The Journal of Pediatrics August 1978 8. Vestergaard P, and Leverett R: Constancy of urinary creatinine excretion, J Lab Clin Med 51:211, 1958. 9. Bleiler RE, and Schedl HP: Creatinine excretion: variability and relationships to diet and body size, J Lab Clin Med 59:945, 1962. I0. Korte R, Wiersinga A, and Simmons WK: Urinary creatinine excretion, Am J Clin Nutr 23:869, 1970. I 1. Lis AW, McLaughin D I, McLaughin RK, and de llackbeil KF: The function of creatinine: II nocturnal-diurnal variation, Physiol Chem Phys 4:70, 1972. 12. Peters WH, Grosset V, and Knapp A: The creatinine excretion in women during fasting, Clin Chim Acta 39:273, 1972.
Acute leukemia and granulocyte transfusion" Fatal graft-versus-host reaction following transfusion of cells obtained from normal donors Ronald C. Rosen, M.D., Douglas W. Huestis, M.D., and James J. Corrigan, Jr., M.D.,* Tucson, Ariz.
DESPITE newer 9 regimens and the use of various isolation techniques, infection continues to be the leading cause of death in children with acute leukemia.' Prolonged periods on immunosuppressiv e chemotherapy and resultant neutropenia appear to be the major variables associated with this risk. Since the degree of granulocytopenia is directly related to ihe high risk of bacterial and fungal infections, granulocyte replacement has become a logical part of treatment of proven infections in neutropenic children not responding to conventional antibiotic therapy. ~" :~ Heretofore, graft-versus-host reaction has been reported in only one recipient of granulocytes from a normal donor.' It is the purpose of this article to report a second instance, the first in a child, which occurred in a patient with acute lymphoblastic leukemia. CASE REPORT" The patient was a 7V2-year-old white girl who had had acute lymphoblastic leukemia for two and a half years before her final admission. Her course was complicated by three hematologic relapses and two episodes ofcentral nervous system leukemia, all of which were successfully treated with intensive chemotherapy, including prednisone, vincristine, L-asparaginase, adriamycin, cyclophosphamide, methotrexate, and 6-mercaptopurine. Cen-
From the Departments of Pediatrics and Pathology University of Arizona Health Sciences Center. *Reprint address: Universityof Arizona Health9 Center9 Tucson, AZ 85724.
tral ne~'ous system management included radiotherapy and intrathecal administration of methotrexate, cytosine arabinoside, and hydrocort!sone. Because of her frequent relapses and chemotherapeuti c immunosuppression, she had many infections, including otitis media, upper respiratory infections, bronchitis and bronchiectasis, herpes zoster, ltemophih~s influenzae bronchopneumonia, oral candidiasis, perianal abscess (Proteus mirabiffs and Escherichia coli), periorbital cellulitis (Staphylococcus attreus and Streptococcus pneumoniae), many urinary tract infections (E. coli, Klebsiella, and Pseudomonas aerttgh!osa), and septicemic episodes (Staph)'lococcus attreus, Streptococcus pneumoniae and E. colO. Abbreviations used hiE ratio: myeloid: erythroid ratio GVII: graft-versus-host lg: immunoglobulin On her last admission, the patient had severe granulocytopenia (120 cells/mm 3 absolute count), lymphocytopen!a (336 cells/ mnP), and clinical manifestations of sepsis. She weighed 18 kg. Staph)'lococctts attreus was isolated from her blood and Klebsiella pneutnoniae from the urinary tract. She was treated with antibiotics plus four separate granulocyte transfusions obtained from normal nonrelated donors, on consecutive days. Normal9blood donors were screened by the standard Red Cross procedure, and were matched to the recipient according to the ABO system; they were not HLA matched. Simultaneous granulocyte and platelet concentrates were collected with the Haemoneties model 30 blood processor (Haemonetics Corporation, Natick, MA 01760) without pi'ior stimulation by corticosteroids. The infections cleared after these therapeutic maneuvers, ttowever, ten days 0022-3476/78/0293-0268500.30/0 9 1978 The C. V. Mosby Co.