D. B., and Go, V. L. W., Hemoccult detection of fecal occult blood quantitated by radioas- say. Am. J. Dig. Dis. 21, 841 (1976). 3. Goodman, M. J., Mass screening ...
activity were gifts from the Finnish dealer at the time (1972-73) when we wished to test Hemoccult. They were not outdated and they were stored according to the instructions. 3. Dr. Wells states that the change in color of the Hemoccult paper slightly increased
the sensitivity
of the test. The
reason why the in vivo sensitivity decreased in our experiments in the period 1972-77 may therefore be due to the change in the composition of the developer or more likely to the combination of the alterations of both developer and paper. In vivo sensitivity changes may not be observable by in vitro tests because fresh blood added to feces differs considerably from the blood products occurring in feces. One Hemoccult instruction from 1972 claims that the slides “begin to detect fecal blood near the upper limit of normal.” This seems in practice (see, e.g., Table 3 of our
publication) and according to recent literature (1-4) not to be true anymore, which indicates that something has happened since 1972 with respect to the sensitivity. According to the manufacturer, Hemoccult is positive if 2-4 ml of blood is added to 100 g of feces. It may be mentioned that Fecatest is positive if about 1 ml of blood is mixed with 100 g of feces. It must be emphasized that these in vitro results do not mean that the tests can detect such small amounts of actual bleeding in vivo, because the pseudoperoxidase activity is destroyed
to a considerable
extent
in the intes-
tines.
4. There are obviously several versions of the instructions for Hemoccult. The abstract (5) cited by Dr. Wells, which we cited in our publication, makes it clear that the water is added to the specimen and not to the paper. The instructions read: “Rehydration is accomplished by the addition of a drop of water, either deionized or tap, to the specimen.” Thus our citation was correct. Obviously the instructions have changed since the abstract was written, but we did not know it. In Germany and Austria, the instructions (at least for 1977 and 1978) say that the sample must dry before the test is carried out and that if it is fresh one has to drop 1-2 drops of the developer directly on the feces sample (not onto the paper, our
remark) [translated from the instructions of R#{246}hm Pharma GmbH, Darmstadt, Germany]. Unfortunately, this seems to have caused some confusion. Finally,
Dr.
Wells
claims
that
He-
moccult is an effective, sensitive, reliable, etc., test. It is easy to get very good reproducibility for a comparatively insensitive test which gives a high proportion of negative results. That is the reason why the reproducibility is so high (97%) for Hemoccult. We think Hemoccult is not sensitive enough for clinical 2210
purposes. CLINICAL CHEMISTRY.
Vol. 24, No. 12,
4430 mg/liter.
References 1. Dybdahl, Pavisning av menlignende Hemoccult
J. H., and Andersgaard, H., okkult blod i faeces. En samunders#{216}kelse mellom benzidin, og en difenylaminmetode. Nor. Legeforen. 95, 1224 (1975).
Tidsskr.
2. Stroehlein, J. R., Fairbanks, V. F., McGill, D. B., and Go, V. L. W., Hemoccult
detection
of fecal occult blood quantitated by radioassay. Am. J. Dig. Dis. 21, 841 (1976). 3. Goodman, M. J., Mass screening for cobrectal cancer-a negative report, J. Am. Med. Assoc. 237, 2380 (1977). 4. Heinrich, H. C., Gesamtkorper-59Fe-Eliminations-Messungen
zuverlassiger
und
empfindlicher als Haemoccult-Test f#{252}r Nachweis und Quantifizierung okkulter Blutverluste im Stuhl. Dtsch. Med. Wochenschr. 103, 753 (1978). 5. Wells, H. J. and Pagano, J. F., ‘Hemoccult’TM test-reversal of false-negative results due to storage. Gastroenterology 72, 1148 (1977). Abstract.
Herman Kristian Department of Clinical University of Helsinki Meilahti Hospital SF-00290 Helsinki 29 Finland
Adlercreutz Liewendahl Pertti Virkola Chemistry
The user has the option
of
running this assay blanked (as described in the “Assay” unblanked.
section
of the insert)
or
The application followed by the authors for the Triglycerides Stat-Pack reagent on the CentrifiChem is not the recommended protocol for the Triglycerides S.V.R. The application recommended by Calbiochem-Behring Corp. is based on a two-point kinetic assay,
with use of a calibrator to determine the correlation between rate and triglycerides concentration. Application instructions are available from Calbiochem-Behring
Corp.
for various
cen-
trifugal analyzers (Rotochem, GEMSAEC, and CentrifiChem). The kinetic procedure as established eliminates need for sample blanking.
The problems bidity
were
the
related to sample tur-
not
ignored
by
Calbio-
chem-Behring Corp. The reagent direction insert describes the effect of sample turbidity and an optical method to correct for it. We are not in agreement with the findings of the authors concerning the performance of the Triglycerides S.V.R. at above-normal concentrations, because the protocol used was not the procedure
recommended
Calbiochem-Behring the CentrifiChem.
Corp. for use on
by
References
Evaluationof Caibiochem-Behring Corp.TriglyceridesS.V.R.TM (Single Vial Reagent) To the Editor:
Peake, Sontrop, and Fraser have described their assessment of the Calbiochem-Behring Corp. Single Vial Reagent systems for cholesterol and triglycerides investigators
determinations found the
(1). These cholesterol
procedure acceptable, but do not recommend the triglycerides analysis by a manual procedure. They found the triglycerides assay on a centrifugal analyzer (CentrifiChem) to have acceptable short-term
precision,
1. Peake, M. J., Sontrop, M. D., and Fraser, C. G., Manual and centrifugal analyzer determination of cholesterol and triglycerides with single-vial enzymatic reagents. Clin. Chem. 24, 2026-2031 (1978).
Ralph Calbiochem-Behring P.O. Box 12087 San Diego, Calif.
but unacceptable
at high concentrations of triglycerides. I would like to comment on
To the Editor:
their evaluation of the triglycerides reagent. As pointed out in the “Limitations” and “Assay” section of the Triglycerides S.V.R. direction insert, there is a nega-
quential
tive contribution
of the sample turbidity concentration as measured in the manual assay. The expected performance of the unblanked assay
triglycerides
is described
Characteristics” insert. tained
in the “Performance
section of the direction
Comparison of assay using the Triglycerides
results obS.V.R. to
those obtained using the Triglycerides StatPackTM reagent (a blanked procedure) results in a linear regression formula of y = O.92x + 1 (r = 0.995) for triglycerides concentration from 430 to 1978
92112
Consequencesof TestingLiver Function
accuracy
to the
P. McCroskey Corp.
Cembrowski assessment, outcome
et al. (1), discussing
chemical
testing
found that
applied
“therapy
seto liver
and
would not have been affected”
by the results they provide. Yet they go on to assert that by anticipating laboratory requests “the time required for a diagnosis is shortened, the hospital stay is abbreviated, sooner, and
treatment is initiated medical costs are re-
duced.” The first statement is inconsistent with the second. Furthermore, the asserted benefits of such testing on admission to hospital have not been demonstrated in controlled trials (2, 3). Indeed, it is at times difficult for clinicians to assess liver problems. the authors’ intention to improve
Thus, labo-
ratory service is most laudable. However, instead of reiterating the expedient justification for better liver assessment, it would surely be desirable to look closer and tease out actual
of enhancing
consequences
clinical competence.
Reference I. Cembrowski, G. S., Larson, F. C., Huntington III, R. W., et a!., Computer-controlled instrument system for sequential chemical testing. III. Application to liver assessment. Clin. Chem. 24, 555 (1978). 2. Whitehead, T. P., and Wootton, I. D. P., Biochemical profiles for hospital patients. Lancet ii, 1439 (1974). 3. Leonard, J. V., Clayton, E. B., and Colley, J. R. T., Use of biochemical profile in children’s hospital. Result of two controlled trials. Br. Med. J. ii, 662 (1975).
Timothy
C. Durbridge
Institute of Medical and Veterinary Science, Adelaide, South Australia.
Two authors of the paper offer the following response other comments.
in question to this and
To the Editor:
Davis and Pottgen (1) doubt the assumption of Cembrowski et al. (2) that a clinical laboratory cian by providing
can assist laboratory
a physidata in
advance of or at the same time he examines the patient. They cite a study by Durbridge et al. (3) [and therefore also Hecker (4)1 in support of their contention that anticipatory testing is unlikely to improve care. Furthermore, they suggest
that this practice
would increase
costs and might interfere with the clinician’s assessment of the patient. The Durbridge study was of interest to us, partly
because
their
findings
were not
what one would logically expect and partly because our experience was quite the opposite. Immediately after multitest screening was introduced at our hospital in 1965, the average length of inpatient stay was shortened by a full day.
We accepted the shortened hospital stay as being predictable a priori. Regardless of a clinician’s diagnostic strategy, be it logical or gestalt, there are certain bits of laboratory informationabnormal or normal-which he requires before concluding that a patient has this or that ailment and what to do about it. Obviously, treatment
the
sooner
appropriate
is undertaken, the sooner a patient should be ready for discharge. Were we asked to explain the discrepancy between what we observed and what Durbridge eta!. reported, we could only reply that there are differences in hospitals, in physicians, in patient populations, and in clinical laboratories.
We can report that in the 600-bed University Hospital in Madison, Wisconsin, the introduction of a 16-test admission program, which provided laboratory data on each patient shortly after his arrival on the hospital ward, was followed by a 10% decline in the average duration of hospital stay. Although this was not a controlled experiment, no other factor that might have had this effect was identified. Davis and Pottgen (1) and others in these discussions have used the word, “unsolicited.” It would not be accurate, in our case, to describe out multi-test
tiated sooner, and medical costs are reduced.” First, the two statements are not mutually inconsistent because they are unrelated except, e.g., in the case of an emergency admission. Secondly, as seen in Table 3 of our paper (2), the clinicians
also ordered
follow-up
tests
in the
“ping-pong” fashion described by Altshuler et al. (5). Thirdly, the two
statements
above were out of with regard to sequential testing; the second was from a discussion on admission screening. context.
quoted
The first was stated
screening as “unsolicited.” We presented the case for and against multitest screening to the University Hospital staff before initiating the program. It was unanimously approved, so in at least
Of course Cembrowski
one sense the testing is not unsolicited. As time passed we responded to requests by the staff to add tests to the screening
done is acknowledged in the final paragraph of the paper. It is also true that
panel,
depending upon the service to which the patient is admitted and for what purpose. For example, patients admitted to the surgical services now have alanine aminotransferase, creatine kinase, and pseudocholinesterase measured in addition to the usual screening panels. As to the issue of conl’using physicians by providing them with excessive amounts of laboratory data, we respond by noting that our physicians seem to be aware of the fact that normality is arbitrarily defined, so a certain proportion of normal persons will have values outside these limits. If physicians’ confusion is a problem
elsewhere,
increased
use
and familiarity with laboratory data should gradually resolve it. For those who accept the above argument defending initial multitest screening (and there should be at least a.few), it should follow that, given a certain set of normal and abnormal laboratory results, it would be of additional help to the clinician (and hence to the patient) to perform the tests that he, the clinician, is likely to order after he is given
the first
set of test
results.
The
case for this mode of laboratory operation is well-made by Altshuler et al. (5) in their description of the PAL! system, which, as Cembrowski et a!. (2) reveal, prompted that study. Altshuler et al. refer to the current mode of test or-
dering, recommended by Davis and Pottgen (1), as a “ping-pong” relationship between the clinicians and the laboratory. This would make sense only if it could be played at the pace of a game of table tennis. Durbridge, in the preceding letter, draws attention to an apparent inconsistency in the paper of Cembrowski et a!. that “therapy and outcome would not have been affected” by providing sequential testing and “the time required for a diagnosis is shortened, the hospital stay is abbreviated, treatment is mi-
mented
the
system
described
by
et al. (2) would be auggreatly if data were available
from the history and physical examination. That this should and could be
drugs interfere with the interpretation of laboratory tests, whether solicited or “unsolicited.” We have experimented
with a system in which the laboratory computer
communicates
the pharmacy if a patient
computer,
directly
with
to determine
in fact
is receiving a drug laboratory resuch a link-up will be of value at some future time. The
that might give spurious sults (6, 7). Undoubtedly, communication
could, of course, be di-
rectly with the instrumentation developed by Cembrowski et al. Within the context of a diagnostic work-up, we view the multitest screening and follow-up testing as analogous to the physical examination. Thus, upon initial contact, a complete history,
physical
examination,
and
a general
laboratory examination should be done. When patient has a history of pain in the left lower quadrant, the examiner should not limit the physical examination to the abdomen or the laboratory examination to a leukocyte count. At the point during a physical examination when a physician
discovers something awry, he proceeds to apply non-routine examination techniques observations.
scanning
to confirm Equally,
or to extend his when an initial
panel of laboratory
tests dis-
closes an abnormality, this too should be quickly pursued. This extension of the usual screening panel was the object of the work of Cembrowski et al. (2). It seems to us that the advantages to the physician of this approach to laboratory support are self-evident. The next logical step is not to further question the principle, but to accept it and look at which test sets and sequences will be
most useful
in various
clinical
situa-
tions.
References 1. Davis, E. R., and P. Pottgen, P., How best to use computerization of laboratory tests. Clin. Chem. 24, 1422 (1978). Letter. 2. Cembrowski, G. S., Larson, F. C., Huntington, III, R. W., et a!., Computer-con-
CLINICALCHEMISTRY, Vol. 24,No. 12, 1978 2211
