Use of Serum
Amylase
lsoenzymes
in Evaluation
of
Pancreatic
Function
Lynn M. Taussig, M.D., Robert 0. Wolf, D.D.S., Robert E. Woods, M.D., Ph.D., and
Richard J. Deckelbaum, M.D.
From the Department ofRe.rpiratory F,,nctic’n, The .Iontreal Children’s Hospital, .%lontreal, Quebec, Canada; and Oral .‘4edicine Branch, ,Vwional institute of Dent’al Research and Pediatric %feutholLun Branch, .\‘ational Institute of Arthritis, ,fetabolic, and Digestite Diseases. Bethesda, .%Iaryland
ABSTRACT. Amylase isoenzyme patterns were evaluated in serum, urine, and duodenal fluid from 19 patients with cystic
fibrosis (CF) and normal subjects. Two thirds of the CF
pa-tients with absent pancreatic enzymes lacked a senim pan-creatic isoamylase band, while the remainder had a marked-ly diminished pancreatic band when compared to the
sali-vary isoamylase. In normal sera the pancreatic band is equal
to or greater than the salivary band. In all patients with ab-sent enzymes the diagnosis of abnormal pancreatic function could have been made by evaluation of serum isoamyla.se patterns thereby avoiding duodenat intubation or collection of 72-hour stools for proteolytic enzyme activities. The pa-tients with normal pancreatic enzyme activities had normal
serum zymograms. No CF patient had a low total serum am-ylase concentration. Total duodenat fluid amylase levels may be misleading in the evaluation of pancreatic function since the amylase may be of salivary origin.
The advantages of this isoamylase method include (1)
sim-plicity and noninvasiveness, requiring only a small blood sample; (2) specificity for pancreatic function; and (3) inde-pendence of pancreatic enzyme medication. Pediatrics,
54:229, 1974, AMYLASE, ISOAMYLASES, AMYLASE 1SOENzYMES, PANCREAS, CYSTIC FiBROSIS.
function. Duodenal intubation with direct
mea-sumement of pancreatic secretions is the most ac-curate diagnostic test of pancreatic function.9 Un-fortunately, such intubation is often difficult to perform, uncomfortable for the patient, time
con-suming for patient and physician alike, and at
times unsuccessful.
Serum and urine alpha-amylase (hereafter
me-femmed to as amylase) can be separated by various methods into its isoenzymes (isoamylases).’#{176}” Such separation of isoamylases recently has been shown to be of benefit in assessing the functional development of the pancreas and salivary glands in human fetuses” as well as in studying
pancre-atic function in sporadic chronic 2
The present study was undertaken to determine if the diagnosis of partial or complete pancreatic insufficiency could be made in CF patients by
ex-amining the isoamylase patterns of serum and
urine for the presence or absence of pancreatic isoamylase.
MATERIALS AND METHODS
Documentation of partial or complete insuffi-ciency of exocrine pancreatic function in infancy and childhood is often very important in the diag-nosis and evaluation of such diseases as cystic fi-brosis (CF),’ hereditary pancreatitis,2 and the syn-drome of pancreatic insufficiency and bone mar-row dysfunction.3 Stool fat and starch excretion, fecal trypsin and chymotrypsin activity,47 serum carotene and cholesterol levels, and other absomp-tion and excretion tests”8 have been used to evalu-ate exocnine pancreatic function. These tests often lack the sensitivity and specificity needed to es-tablish a definite diagnosis of abnormal pancreatic
Serum, urine and duodenal fluid from 19
pa-tients with previously diagnosed CF’ were stud-ied. The patients were 3 weeks to 28 years of age
(Received October 9, 1973; revision accepted for publication January 31, 1974.)
L.N1.T. is a Clinical Fellow, National Cystic Fibrosis Re-search Foundation.
ADDRESS FOR REPRINTS: (L. NI. T.) Department of Pediatrics, Arizona Medical Center, Tucson, Arizona
(11 males and 8 females). The NIFI prognostic scores” for the 15 patients with pulmonary func-tion tests ranged from 58 to 93. Duodenal fluid was collected after a 12-hour fast by intubation with double lumen tubes placed tinder fluoroscopy. The pmoxinal part of the tube was left in the stom-ach to drain gastric secretions while the distal seg-ment (second lumen) was placed in the second and third portions of the duodenum. No duodenal fluid with a pH of less than 6.0 was accepted for study. Pmoteolytic enzyme (chymotrypsin, carboxypep-tidase B, and trypsin) activities were measured by
previously reported methods. ‘‘ Patients who
were taking supplemental pancreatic enzymes
stopped this therapy 48 to 72 hours before intuba-tion.
Control sema and urines were obtained from six male and six female white children,
7
to 16 years of age. Pamotid saliva and duodenal fluid were col-lected as previously described’1’8 from normal subjects and evaluated for comparative purposes.Sera and urines from normal infants and adults
were evaluated in a previous study.h1
Total serum and duodenal arnylase
concentra-tions were measured by an amyloclastic method
based on timed iodine color reactions and
ex-pressed in Somogyi units.’9
A
B
C
D
+
Ftc. 1. Nornial isoamvlase patterns: A, dnodenal fluid (1).F.); B, saliva; C, seruni: I), urine. The major pancreatic
isoamy-lase is towards the cathode while the major salivary isoaIiy-lase is more anodic. Minor isoanylases froii each organ are
also evident. (For Figures 1 to 5, the interface between the
runlling and stacking gels at the right edge of each figure is
comparable to the origin. The stippled graphic represeilta-tion below each gel indicates isoamylase l)and width and
density.)
Isoarnylases of the various specimens were sep-arated according to the method of Wolf and Tay-1or,’ with modifications as described by Wolf and
Taussig.” Briefly, the isoamylases were separated
by
polyacrylamide gel electrophoresis employingthe standard 7% acrylamide separating gel and a
tmis-glycine reservoir buffer at pH 8.3. Sample volumes of 10 to 120il were used. Electmophoresis was carried out for 1.25 hours at a constant amper-age of 5 mA per gel at 0 C. After electrophomesis, the isoamylase bands were identified by squeezing
and incubating the gel columns between two
slides, one of which was coated with a starch agar film. Duodenal fluid and saliva samples were
incu-bated for 15 minutes at room temperature while
semuni and urine (which contain far less amylase) were incubated at 37 C in a moist box for six hours.
After incubation, the gels were removed and the starch slides were developed in an iodine solution. The areas of digested starch, indicating the loca-tions of the isoaniylases, appeared as clear areas against a blue background.
In addition to the evaluation described above,
serum and urine zymogmams were compared be-fore and after the ingestion of supplemental pan-creatic enzymes (Cotazym#{174}#{176})in two CF patients with pancreatic insufficiency. The patients had either discontinued or had taken the enzymes for at least 48 hours before samples were collected.
RESULTS
Normal Isoamylase Patterns (Fig. 1)
Normal pancreatic fluid found in the duodenum (Fig. 1, A) has one major and three to four minor
bands which are more cathodic. Normal saliva (Fig. 1, B) has one major and at least four minor
bands which are more anodic. Normal serum
(Fig. 1, C) has two major bands which are electro-phoretically identical to the major pancreatic and salivary bands, but in reduced concentration. Normal urine (Fig. 1, bottom right) reflects the serum pattern and, therefore, contains the major pancreatic and salivary bands. Occasionally the serum and urine zymogmams reveal additional minor isoamylases from both organs.
The isoamylase patterns of sera and urines from
all 12 control children were similar. These
subjects had major pancreatic and salivary isoen-zymes in both serum and urine. In all cases, the
pancreatic band was approximately equal to or
greater than the salivary band in width and
inten-sity both in serum and urine (Fig. 1, C and D).
Simi-lam results have previously been reported for
PANCREATIC ISOAMYLASES IN VARIOUS BODY FLUIDS
IN CYSTIC FIBROSIS PATIENTS
Requires Proteolytic
Pancreatic isoamylase
Total Serum
Oral Enzyme Pancreatic Duodenal Amylase
Patient Age Therapy Enzymes0 Fluid Serum Urine (Somogyi units)t
1 3weeks Yes N.D.S ND. 0 Low 23
2 3mo Yes ND. ND. 0 0 16
3 10 mo No ND. ND. 0 Low 88
4 3yr Yes 0 0 0 Low 100
5 7 yr Yes 0 0 0 Low 98
6 8yr Yes 0 0 0 Low 132
7 10 yr Yes 0 0 Low Low 140
8 l2yr Yes 0 0 0 Low 100
9 12 yr No Normal Normal Normal Normal 128
10 l4yr Yes 0 0 0 0 210
11 l5yr Yes 0 0 0 Low 83
12 l6yr Yes 0 0 0 Low 108
13 18 yr Yes 0 Low Low Low 94
14 l9yr Yes 0 0 0 0 65
15 20 yr Yes 0 0 Low Low 97
16 25 yr Yes 0 0 Low Low 96
17 25 yr No Normal Normal Normal Normal 147
18 26yr Yes 0 0 0 Low 133
19 28 yr Yes 0 0 0 Low 62
15-19: 10 to 140 Somogyi units; for patients 3-8, 14: 30 to 150 Somogyi units.
+
A
D.F.
B
Serum
C
Urine
D
Urine
FI;. 2. Isoamylase patterns in cystic fibrosis patients with ab-sent pancreatic proteolytic enzymes: A, duodenal fluid; B,
senim; C, urine (absent pancreatic isoamylase); D, urine (di-minished pancreatic band). Duodenal fluid and serum both
lack pancreatic isoamylase. TABLE I
#{176}Collected by duodenal intubation. Normal values for patients 1, 2, 9-13,
N.D. = not done.
fants and The intensity of the various iso- Total duodenal amylase concentrations were
amylase bands from each person correlated di- measured in eight of the patients listed in Table I.
mectly with the individual’s total serum amylase In six (all with absent proteolytic enzymes) no
am-concentration.
CF Patients: Duodenal Fluid
Sixteen of the 19 CF patients had duodenal
intubations; 14 of these had completely absent proteolytic enzyme activity in their duodenal fluid (Table I). Two patients had essentially nor-mal pmoteolytic activity (patient 9: trypsin, 126 units/ml; chymotrypsin, 1,800 units/ml; and car-boxypeptidase B, 217 units/ml; patient 1 7:
tryp-sin,
663
units/ml; chymotmypsin, 4,000 units/ml;and camboxypeptidase B, 165 units/ml. Normal
values in this laboratory are 100 to 1,000 units/ml
for trypsin, 3,000 to 15,000 units/ml for chymo-trypsin, and 100 to 500 units/ml for carboxypep-tidase B).
A
B
C
+
D.
P.
Serum
Urine
Fic. 3. IsoaIvlase patterns fron patient L3. This patient
lacked pancreatic proteolytic enzymes lnt had a faint pan-creatic isoanivlase I)and in his duodenal fluid and serum:
A, duodenal fluid: B. serulli: (, urine.
A
B
C
FIG. 4. lsoa,nvlase patterns in a cystic fibrosis patient svith noriiial pancreatic enzyme activities (patient 9): A. duodenal
fluid; B, serum: C, urine. There is a norlnal paflcreatic isoani-ylase band in all three fluids. Salivary isoansylase is also
evi-dent in the duodenal fluid zvn4ogran.
+
Fi;. 5. Salivary isoainvlase in the dilodenal fluid of a cystic
fi-brosis patient with absent pancreatic enzymes. Total duode-nal fluid amylase activity s’as normal but only salivary iso-amylase could be identified. ‘s. normal duodenal fluid; B,
Pa-tient’s duodenal fluid: C, normal saliva.
ylase could be detected; zymograms also were
negative for amylase. The other two patients,
both
with normal proteolytic enzyme activity, hadnor-mal duodenal aniylase concentrations and
zymo-grams demonstrated the presence of pancreatic amnylase. In three additional young adult CF pa-tients (not shown in Table I), all with absent pro-teolytic enzymes, the duodenal fluid amylase
con-centmations were normal (84,000, 105,000, and
163,000 Somogyi units, normal being greater than 80,000 Somogyi units). However, zymograms me-vealed that only salivary isoamylase was present in these specimens (Fig. 5).
Serum Isoamylase
Pancreatic isoamylase was absent from the sema of ten of the 13 patients with absent pancreatic isoamylase in their duodenal fluid (Fig. 2, B). In the other three patients (7, 15 and 16) a faint
pan-creatic isoamylase band was found in the serum
(Table I). Patient 13, who had absent pmoteolytic
enzymes but a faint pancreatic isoamylase band in his duodenal fluid, also had a weak pancreatic band in his serum (Fig. 3, B). In these four patients,
the serum pancreatic band was markedly
dimin-ished in width and intensity when compared to
their seruni salivary isoamylase bands. Serum pan-creatic isoamylase bands were normal in the two
CF patients with normal pancreatic enzyme
1ev-els (Table I and Fig. 4, B). Total serum amylase concentrations for the CF patients were normal in all cases and even slightly elevated in one patient. Even the patients with no obvious pancreatic iso-aniylase in their sera had normal total serum am-ylase concentrations (Table I).
Urinary Isoamylase
The pancreatic isoamylase band was normal in
the urine from the two patients with normal
pan-creatic enzymes and normal serum pancreatic
.aniylase (Fig. 4, C). No pancreatic isoamylase could be found in the urine of three patients (2, 10 and 14) all of whom lacked pancreatic isoamylase in their serum (Fig. 2, C). In the remaining 14 pa-tients, zymograms of urine revealed pancreatic isoaniylase, but in all of these, the salivary band was always more prominent than the pancreatic band (Figs. 2, D and 3, C). Ten CF patients who did
not have serum pancreatic isoamylase had urine
pancreatic isoamylase. No patient with serum
pancreatic amylase lacked urine pancreatic amy-lase.
DISCUSSION
The separation of amylase isoenzymes by gel
electrophoresis has been shown’#{176}” to be reliable
and reproducible. Our data”’8 as well as that
from other studies’#{176}indicate that both pancreatic
and salivary amylase consist of one major and a
variable number of minor isoamylases. Normal
serum usually consists of the major pancreatic and salivary isoenzymes but occasionally minor bands derived from either organ may be found in addi-tion. Norby2#{176}has shown that duodenal fluid and salivary amylases are electrophometically
identi-cal to amylase found in pancreatic and pamotid
gland extracts, respectively. Approximately 4% of normal children do not have a serum salivary iso-amylase2l; however, isolated absence of the senun
pancreatic band in normal individuals has not
been reported. Urine zymogmams reflect serum
patterns and show the major and some minor
iso-enzymes. The data from our normal infants, chil-dren, and adults” are consistent with these find-ings as all had both major isoamylases in their sema and umines.
The present study indicates that patients with documented absence of pancreatic enzyme activi-ties have abnormal serum isoamylase patterns. In normal sera, the pancreatic isoenzyme is equal to or greater than the salivary isoamylase. Two thirds of the CF patients with absent pancreatic
proteo-lytic enzymes lacked serum pancreatic
isoamy-lase. The remaining third had extremely low
amounts of this isoamylase in their sera as
mdi-cated by the very weak serum pancreatic bands.
Therefore in all of these patients the diagnosis of grossly abnormal pancreatic function could have been made by evaluation of serum isoamylase pat-temns alone.
It should be noted that total absence of the pan-creatic isoamylase in serum is not necessary for the diagnosis of abnormal pancreatic function. Comparison of the pancreatic band to the salivary
isoamylase is also of value in documenting
de-creased pancreatic ftmction. The presence of se-rum pancreatic amylase in four patients with ab-sent duodenal pmoteolytic enzymes suggests that absence of pancreatic enzymes on routine
duode-nal intubation does not always imply total
de-struction of pancreatic acinam tissue. Shwachman
et 22 previously obtained similar results when
they reported that some CF patients with absent enzymes on routine duodenal intubation could ex-crete low levels of pancreatic enzymes after pan-creatic stimulation. The one patient in the present study who had absent proteolytic enzymes but
who also had a faint pancreatic amylase band in
his duodenal fluid supports previous studies2223
which indicated that mechanisms and inhibition of excretion of the various pancreatic enzymes in diseases of the pancreas are variable. Because of this variability, evaluation of serum isoamylases
should not replace duodenal intubation for
de-tailed evaluation of pancreatic function. Evalua-tion of serum isoamylase patterns may prove use-fii1, though, in the study of the progression of pan-creatic involvement in CF and other diseases.
The absence of pancreatic isoamylase in sera of some CF patients is due to pancreatic insufficien-cy per se and is not another unrelated abnormality in this disease, since CF patients with normal 1ev-els of pancreatic enzymes on routine duodenal
collection had normal isoamylase patterns in
serum, urine, and duodenal fluid. Although the ab-solute amount of pancreatic amylase in duodenal fluid increases with age,9 age does not affect the isoamylase patterns since infants, children, and adults have identical zymogmams as demonstrated in the present and previous studies.”
Urine zymograms were similar to the serum
patterns, although most patients had some urine
pancreatic isoamylase. In all of these cases,
though, theme was a reversal of the usual pattern in that the salivary band was always more prominent than the pancreatic band. Aw et al.’2 have shown that normal urine usually contains more
pancre-atic amylase than salivary amylase while urine
from patients with pancreatic insufficiency has less pancreatic than salivary amylase. The results of the present study confirm these observations.
Amylase is cleared by the kidneys and
concen-trated in the urine before excretion.24 Duane et a!. 24.23 have shown in baboons that the renal
clear-ance rate for pancreatic amylase is approximately 1.8 times that for salivary amylase. Therefore,
un-detectable amounts of pancreatic amylase in
serum might be concentrated by the kidneys and
thereby become evident on urine zymograms.
This could explain the apparent absence of
pan-creatic isoamylase in serum but its presence in
urine in some CF patients. These results indicate
that evaluation of serum isoamylase patterns is
more discerning and diagnostic than urine zymo-grams.
While duodenal intubation with direct mea-sumement of pancreatic secretions in the duodenal fluid is generally specific for pancreatic function,
determination of total duodenal fluid amylase
concentrations may be misleading. Three CF
pa-tients with absent proteolytic enzymes had nor-mal total duodenal amylase activity. However,
electmophoresis indicated that the amylase was
solely of salivary origin (Fig. 5). In some CF
stomach unaltered by gastric acid. Alternatively, although double lumen tubes were used, the pres-ence of salivary amylase in the duodenal fluid may represent a “contaminant,” a result of the intuba-tion.
This study suggests that the diagnosis of most
cases of abnormal pancreatic function can be
made by evaluation of serum isoamylases, thus
often avoiding the necessity for duodenal intuba-tion. Measurement of fecal fat may indicate the presence of steatorrhea but does not diagnose the etiology of the fat malabsomption. Therefore, the
examination of serum isoamylases should not
necessarily replace fecal fat measurements, but
should be used in conjunction with them in the
evaluation of a patient with suspected steatomrhea and malabsorption. Other tests of pancreatic func-tion such as quantitative measurements of fecal enzyme levels (chymotrypsin, trypsin) require dis-continuation of oral pancreatic enzyme supple-ments and timed (preferably three-day) stool col-lections. Ingestion of supplemental pancreatic
en-zymes
did
not change the serum and urinezymo-grams, indicating that such medications do not
have to be discontinued before collecting speci-mens for isoamylase determinations.
This method of separation of serum isoamylases should be beneficial in other clinical situations than the diagnosis of total exocrine pancreatic
in-sufficiency. Lilibridge and Townes reported26 a
transient deficiency of pancreatic amylase in an infant with diarrhea. Lowe and May27 also me-ported a case of absent pancreatic amylase and di-minished trypsin activity. The true incidence of these “syndromes” is unknown, but a noninvasive technique, such as serum isoamylase determina-tion, may be beneficial in diagnosing more of these cases as well as in the evaluation of infantile diam-rhea. The evaluation of serum isoamylases would not be of benefit, though, in cases of isolated defi-ciencies of pancreatic proteolytic and lipolytic activity28 or in trypsinogen deficiency29; in these diseases, pancreatic amylase is normal.
REFERENCES
1. di Sant’Agnese, P. A.: The pancreas. in Nelson, %V. E., Vaughn, V. C., III, and McKay, R. J. (eds.):
Text-book of Pediatrics, ed. 9. Philadelphia: W. B. Saun-ders Co., 1969, p. 854.
2. Kattwinkel, J., Lapey, A., di Sant’Agnese, P. A., Ed-wards, W. A., and Hufty, M. P.: hereditary pan-creatitis: Three new kindreds and a critical review of the literature. Pediatrics, 51:55, 1973.
3. Shwachman, H., Diamond, L. K., Oski, F. A., and Khaw, K.-T. : The syndrome of pancreatic insufficiency and bone marrow dysfunction. J. Pediat., 65:645,
1964.
4. Barbero, C. J., Sibinga, M. S., Marino, J.M., and Seibel,
R.: Stool trypsin and chymotrypsin. Amer. J. Dis. Child., 112:536, 1966.
5. Banwell, J.C., Leonard, P. J., and Lobo, R. M. F.: Mea-surenient of trypsin and chymotrypsin activity in
stools to detect chronic pancreatic disease. Gut,
6:143, 1965.
6. Dyck, W. P.: Titrimetric measurements of fecal trypsin
and chyniotrypsin in cystic fibrosis with pancreatic exocrine insufficiency. AIller. J. Dig. Dis., 12:310,
1967.
7. Bonin, A., Roy, C. C., Lasalle, R., Weber, A., and Morin,
C. L.: Fecal chymotrypsin: A reliable index of exo-crine pancreatic function in children. J. Pediat.,
83:594, 1973.
8. Silverlnan, A., Roy, C. C., and Cozzetto, F. J.: Pediatric
Clinical Gastroenterology. St. Louis: C. V. Mosby
Co., 1971.
9. Hadorn, B., Zoppi, G., Shmerling, D. H., Prader, A.,
McIntyre, I., and Anderson, C. M.: uantitative as-sessment of exocrine pancreatic function in infants
and children. J. Pediat., 73:39, 1968.
10. Meites, S., and Rogots, S.: Amyta.se isoenzymes. CRC
Critical Reviews in Clin. Lab. Sd., January 1971,
p. 103.
11. Wolf, R. 0., and Taussig, L. Ni.: Human amniotic fluid
isoamytases :Funct jonal development of fetal pan-creas and salivary glands. Obstet. Gynec., 41:337,
1973.
12. Aw, S. E., Hobbs, J. R., and \Vootton, I. D. P.: Urinary
isoamylases in the diagnosis of chronic
pancreati-tis. Gut, 8:402, 1967.
13. Taussig, L. M., Kattwinkel, J., Friedewald, \V. T., and
di Sant’Agnese, P. A. : A new prognostic score
and clinical evaluation system for cystic fibrosis. J.
Pediat., 82:380, 1973.
14. Northrop, J. H., and Hussey, R. G.: A method for the
quantitative determination of trypsin and pepsin.
J. Gen. Physiol., 5:353, 1923.
15. Schwert, G. ‘V., and Takenaka, Y.: A
spectrophoto-metric deterniination of trypsin and chymotrypsin.
Biochim. Biophys. Acta, 16:570, 1955.
16. Folk, J.E., Piez, K. A., Carroll, \V. R., and Gladner, J.A.: Carboxypeptida.se B: IV. Purification and
charac-terization of the porcine enzyme. J. Biol. Chem., 235:2272, 1960.
17. Shapira, E., Arnon, R., and Russell, A.: Specific imniu-noassay for quantitative deterniination of human trypsin in intestinal content. J. Lab. Clin. Med.,
77:877, 1971.
18. Wolf, R. 0.. and Taylor, L. L. : Isozyme demonstration technique. Amer. J. Clin. Path., 49:871, 1968. 19. Somogyi, M.: Micromethods for the estimation of
dia-stase. J. Biol. Chem., 125:319, 1938.
20. Norby, S.: Electrophoretic non-identity of human sali-vary and pancreatic amylases. Exp. Cell Res.,
36:663, 1964.
21. Kamafyt, J., and Laxov#{225}, R.: Amyla.se heterogeneity.
Huniangenetik, 1:579, 1965.
22. Shwachman, H., Dooley, R. R., Guilmette, F., Patterson, P. R., \Veil, C., and Leubner, 11.: Cystic fibrosis of the pancreas with varying degrees of pancreatic
in-sufficiency. Amer. J. Dis. Child., 92:347, 1956.
23. Goldberg, D. M., and Wormsley, K. G.: The interrela-tionships of pancreatic enzymes in human
duode-nal aspirate. Gut, 11:859, 1970.
24. Duane, W. C., Frerichs, R., and Levitt, M. D.:
Distribu-tion, turnover and mechanism of renal excretion of
25. Duane, W. C., Frerichs, R., and Levitt, M. D.:
Simulta-neous study of the metabolic turnover and renal
ex-cretion ofsalivary amylase _125I and pancreatic
am-ylase _“I in the baboon. J.Clin. Invest., 51:1504, 1972.
26. Lilibridge, C. B., and Townes, P. L.: Physiologic
defi-ciency of pancreatic amylase in infancy: A factor in iatrogenic diarrhea. J. Pediat., 82:279, 1973.
27. Lowe, C. U., and May, C. D.: Selective pancreatic
defi-ciency: Absent amylase, diminished trypsin, and
normal lipase. Amer. J. Dis. Child., 82:459, 1951.
28. Townes, P. L.: Proteolytic and lipolytic deficiency of the exocrine pancreas. J. Pediat., 75:221, 1969. 29. Townes, P. L.: Trypsinogen deficiency disease. J.
Pedi-at., 66:275, 1965.
ACKNOWLEDGMENT
The authors extend their sincerest appreciation to Drs. Paul A. di Sant’Agnese, Pierre Beaudry and Mary Ellen Avery for their support and advice, and to Dr. Mimi Bel-monte for her assistance in referring her patients to us for study.
AN
ACCOUNT
OF
A MONSTROUS
CHILD
BY DR.
JOHN
BURTON,
PHYSICIAN
AT YORK
The case history below, published in 1747, dem-onstrates two things. First, that children could sum-vive in spite of serious congenital anomalies; and second, that physicians’ claims were not always accepted at face value.
-Wright, Spouse to a Ship Carpenter living at Kirk-thorp near Wakefield in Yorkshire, bore a Child that had no Parts of Generation proper either to Male or Female, there not being the least Appearance of such Organs at the Place where we should expect to find those Parts; the child in every other Part was made as is common, except about half Way betwixt the Navel and Os pubic there was a circular Orifice of about an Inch Diameter, in which was a spongious Substance resembling the end of the Glans Penis excoriated;
it did not project in the least from the Body, neither was it covered, but was quite bare, and very sore and tender. Through the several and almost innumerable Pores or On-fices of this spongious Body the Urine ouzed (sic) continually, and sometimes Blood, and at other times a reddish-coloured Serum. The Child lived to the Age of five Years or there-abouts, and died of the small Pox in November last. To the Truth of this I can bring many certificates, as well as living witnesses, if it was thought necessary.’
Noted BY T. E. C., Jr., M.D.
REFERENCE
1. Burton, J.: An account of a monstrous child. Medical Es-says and Observations (Edinburgh), 5: 1747, pp.