EXPERIENCE AND REASON-BRIEFLY RECORDED 657
Childrerts Hospital of Los Angeles with the
diag-nosis of status asthmaticus. The onset of
syillp-toms occurred 60 hours prior to admission, at
which time she was seen in the Out-Patient
Dc-partment and recovered after administration of a series of three subcutaneous injections of
epi-nephrine (0.3 ml each injection).0 Symptoms
re-curred 48 hours later and, during the subsequent
10-hour period in the Out-Patient Department,
she received three series of three subcutaneous injections of epinephrine (0.4 ml each injection),0 three intravenous injections of aminophylline (150
mg each), and 1,350 ml intravenous fluids
con-taming 150 ml 7.5% sodium bicarbonate (0.9
mEq/ml). Despite this therapy, she deteriorated
clinicalls and, prior to admission to the ward,
her capillary blood pH and pCO2 were 7.27 and
64 mm Hg, respectively.
Upon admission to the ward, she was cyanotic
and in severe respiratory distress. A 3.6% THAM solution (0.3 mEq/ml) in 5% glucose and water, I.P.P.B., and 100 mg intravenous hydrocortisone
(Solu-Cortef) were administered. Three hours
after initiation of THAM administration, and following infusion of 195 ml of THAM, capillary blood p!-I had increased to 7.31 and there was
marked clinical improvement. Six and one-half
hours later, and after an additional 150 ml of
THAM, pCO decreased to 41 mm Hg and there was further clinical improvement. Fourteen hours
after initiation of THAM administration, blood
[)H was 7.45 and all treatment was discontinued.
COMMENT
The importance of maintaining a normal
hydrogen ion coiicentration or activity in
pa-tients suffering from respiratory insufficiency has been emphasized in the pediatric literature in the last several years.5’6 Acidosis and hyper-capflia have had Il adverse effect upon enzyme
systems, blood flow through various organs
and the oxygen cariying capacity of hemo-globin (Bohr effect); in addition, there may be
a marked elevation of potassium in 5,6
Until recently, sodium bicarbonate was the flloSt effective drug at the clinician’s disposal
for the correction of acidosis. In 1939, THAM
was introduced as a biological alkalinizing
agent after being used for many years in chemical laboratories. Since then , numerous
reports have emphasized its usefulness and
dangers ill tile treatment of a variety of
con-ditions producing acidosis.5
Two patients suffering from status
asthmati-C1I1S, in acidosis, and successfully treated with
0 1:1000 solution.
THAM are presented. After beginning THAM
administration, there was a marked clinical and laboratory improvement within 4 hours and almost complete return to normal within 14 hours.
J
OSE S’nisAuss, M.D.RICHARD N. FINE, M.D.
DAVID A. MEDINA, M.D.
GEORGE N. DONNELL, M.D. Department of Pediatrics
and Division of Metabolic-Renal Disease
Childrens Hospital of Los Angeles
and Department of Pediatrics
University of Southern California School of Medicine
Los Angeles, California
This work was partiall’ supported b NIH
Grants No. HD01213 and HE09351.
The authors express their appreciation to Dr.
J. S. Anderson, Abbott Laboratories, North
Chi-cago, Illinois, for his generous supply of THAM.
REFERENCES
1. Blumenthal, J. S., Blumenthal, NI. N., Brown,
E. B., Campbell, G. S., and Prasad, A.:
Effect of changes in arterial pH on action
of adrenalin in acute adrenalin-fast asth-matics. Dis. Chest, 39:516, 1961.
2. Mithoefer, J. C., Runser, R. H., and Karetzky,
Nf. S.: The use of sodium bicarbonate in the treatment of acute bronchial asthma. New
Eng. J. Med., 272:1200, 1965.
3. Match, C. : Organisk CQr-bufferbehandling (THAM) vid adrenalinresistent status
asth-maticus. Opuscula ?sfedica, 10:42, 1965.
4. Astrup, P., J#{248}rgensen, K., Sigaard Andersen,
0., and Engle, K. : Acid-base metabolism: new approach. Lancet, 1 : 1035, 1960.
5. James, L. S. : Physiology of respiration in new-born infants and the respiratory distress syndrome. PEDIATRICS, 24: 1069, 1959. 6. Usher, R. H. : The respiratory distress
syn-drome of prematurity: I. changes in
potas-sium in the serum and the electrocardio-gram and effects of therapy. PEDIATRICS, 24:
562, 1959.
7. Nahas, C. G. : Use of an organic carbon diox-ide buffer in vivo. Science, 129:782, 1959.
8. Strauss, J.: Acid-base and THAM. Bull.
Chil-drens Hosp. L.A., 12:13, 1965.
Tryptic
and
Chymotryptic
Activity
of
Stools
of Newborn
Infants
Pancreatic exocrifle functional capacity may
evalua-658
..lge (do)
TRYPSIN IN NE\VBORNS
TABLE I NORMAL INFANTS ‘Vu inber of Specimens Trypsin 4verage Range (beg/gm) S.D. C’hyino-trypsin Arerage 3 4 .5 6 41 31 3,5 v25 43 21 73 135 3’2 291 34,5 34v 434 6-140 42-380 53-880 81-640 82-742 111-665 95-966 37 77 I94 146 151 178 237 Range (j.eg/gm) 40- 460 107- 790 146- 970 1ti- 830 16’2- 829 0o- 980
96-1 ,106
184 338 531 408 491 517 558 S.D. 6 77 141 09 189 240 ‘25 14 11.9 0 5.7
tioll of duodenal aspirate. Pancreatic drainage is time consuming, uncomfortable for the pa-tient, and presents difficulties in obtaining all of
the duodenal secretion separated from gastric
juice over specified time periods. It is partidu-larly difficult in neonates because of their size.
The development of specific substrates for
trypsin and chymotrypsin has made possible
the accurate measurement of these enzymes in
the stools.’
As part of a long term study of pancreatic
activity in children with cystic fibrosis, a study of fresh spot stool specimens obtained from healthy newborn infants was undertaken, with
a view to establishing normal values as a tool
in the early diagnosis of cystic fibrosis. Two
hundred and twenty-one specimens were
ob-tamed from 168 infants ranging in age from
birth to 7 days. One child with meconium ileus
was studied in the postoperative period before
enzyme therapy was started.
METHODS USED
Trypsin and chvmotrypsin activities were measured in fecal suspensions utilizing the spe-cific synthetic substrates p-toluene-sulfonyl-L-arginille methyl ester (TAME)#{176} and
n-acetyl-L-tyrosine ethyl ester (ATEE).#{176} Stool suspensions
were prepared by mixing 3 to 5 gm of stool
(weighed to 0. 1 gm accuracy) in sufficient
iso-tonic saline to produce a 1/10 dilution, after
which a hornogenous mixture was obtained b thorough agitation with a Virtis homogenizer.
For the determination of trypsin activity
O.05
to 1.0 ml of the emulsion was diluted with TRIS
buffer (0.005 M tnis hydroxymethyl amino-ethane containing 0.04 M NaCI and 0.02 CaCI5,
0 Obtained from Mann Research Laboratories,
New York, New York.
pH 8.2) to produce a final volume of 9.0 ml.
After 1.0 ml TAME solution was added, the
pH was adjusted to 8.2 with 0.1 N HC1. The
determination of enzymatic activity was per-formed at 27#{176}Cby automatic titration of the
liberated acids with 0.05 to 0.002 N NaOH. The
instrumentf used adds the amount of titrant
required to maintain the pH of the reaction
flliXtUre at the constant pH 8.2 and records the amount of titrant added against a time axis, the slope of the line being a measure of the velocity of the reaction. Trypsin activity s’as calculated by comparison with a standard curve showing the amount of titrant utilized (millequivalents per minute) which depended Oil the amount of
trypsin present. Trypsin activity was expressed
as micrograms of crystalline trvpsin per gram of
stool.
A similar technique was used for chvmotryp-Sill determinations. The stool emulsion was
di-luted to a final volume of 9.0 ml with Tnis
buffer containing 0.05 M NaC1 and 0.005
M CaCl2, whose pH was 7.8. After 1.0 ml of
Radiometer titrator type TTTI and Radiom-eter titragraph type SBRS/SBU and titration
as-sembly, Radionieter Corporation, Copenhagen,
Denmark. TABLE II Age (da)
---Days POSt-opera/ire 3 5 4 6 5 S 7
PATIENT WIT!! MECONIIM ILEUS
Chymoirypsin (jag/gm stool) Trypsin (ng/guz stool) 18 13.3 0
EXPERIENCE AND REASON-BRIEFLY RECORDED 659
TABLE III
FROM BARBERO, C.J., et al.
(ategorij .
‘
A\ umber
Trypsin Range
jag/gui Stool Chymolrypsin
Mean Range
219 75-83!)
87 10-582
9.3 0-189
7.’2 66-155
159 148-441
nig/gris Stool Mean
351
163 17.3
103
23()
Non F(’l)* 54
FCI) on viokase 1
((if viokase 7
Nevliorns meconium 5
fourth (lay 5
80 -74 34 -‘295
1 .3- 30
1 .7- 11 .3 45 -231
* FCD-Fibrocystic disease.
ATEE solution was added, the pH was adjusted
to 7.8 with 0. 1 N HC1. Calculations were
per-formed iii the same manner as in the trypsin
determinations using a standard curve prepared
with crystalline chymotrypsin. The findings are
presented in Tables I and II.
This studs’ Ilas established the range of tryp-sin and chvmotrypsin that may be present in the stool of infants from birth to 7 days of age. A wide range of values for both enzymes was oh-served daily and from day to day in any patient studied. The average levels of both enzymes were observed to rise in the first 3 days of life and then tended to level off.
A somewhat similar study was reported by
G.
J.
Barbero, et al.A group of 54 well children,48 children of various ages (9 days to 15 years) with cystic fibrosis, and 5 newborns were
studied. Of the cystic group, 21 were on a
pan-creatie enzyme supplement (viokase) and 27
were not. Results of their studies may be seen
in Table III.
The wide variation in enzyme content of
stools from day to day and in various age
groups is again noted. It is possible that many factors (such as, gastrointestinal motility, the relation of food intake to enzyme output, and
the presence of potential enzyme inhibitors in
the gastrointestinal secretions) may play a part
in determining the amount of enzyme found in
the stool at any one time.
Studies in one newborn infant in the post-operative period following bowel resection for
meconium ileus showed that there were very low levels of trypsin and chymotrypsin present.
These levels were well below the lowest
ob-served in normal children of similar age.
MARGARET MULLINGER, M.D.
MILAGROS PALASI, B.S. , M.T.
Department of Paediatrics University of British Columbia
Vanco,icer, B.C., Canada
This investigation was aided by the National Health Grant #609-7-122, Department of
Na-tional and Welfare, Ottawa, Canada.
REFERENCES
1. Haverback, B. J., Dyce, B. J., Gutentag, P. J., and Montgomery, D. W. : Measurement of
trvpsin and chymotrypsin in stool.
Gastro-enterologv, 44:588, 1963.
2. Dvck, W. J., and Ammann, R. : Quantitative
determination of fecal chyrnotrypsin as a
screening test for pancreatic exocrine insuf-ficiency. Amer. J. Dig. Dis., 10:531, 1965. 3. Barbero, C. J., Marino, J.
M.,
Seibel, R., andSbinga, sf S. : Tryptic and chyrnotryptic
activity of stools as a diagnostic tool in the
pancreatic insufficiency of cystic fibrosis.
din. Chem., 11:787, 1965.
Group
B
Streptococcal
Infection
in
Infancy: A
Case Report
and
Review
Serious streptococcal infections in the
new-born infant are infrequently reported. The
dangers to the infant of beta-hemolytic
strepto-coccus group B organisms are generally
un-known. The purpose of this report is to describe a case of fulminant meningitis and septicemia due to a group B streptococcus in a 42-day-old, low birthweight infant and to review briefly the
current literature with regard to the im-portance of infections with this organism.
CASE REPORT
B.H., a 1,162 gm female infant, was born at
South Baltimore General Hospital on April 13,
1965, following 30 weeks’ gestation. The labor was 3 hours in duration and complicated by
pre-mature separation of the placenta. The infant cried and breathed promptly. The color and res-pirations were satisfactory, tube feedings were
well tolerated, and oxygen was discontinued on
