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sensitive. In contrast, association of these words for “living things and measuring systems” with “two factors” (4), namely, measurement error divided by the response per unit of stimulus, associates these terms exclusively with measured amounts of stimuli (e.g., s[D]0 (3)), a result with profound consequences. For example, using this interpretation, the terms could no longer be used in a subjective sense such as purely qualitative chemical analyses, alarms, light activated door openers, remote controls, responses of our skin to sun, etc., for which the sole function is to detect, sense, or respond to events or stimuli without in any way measuring their magnitudes (8). The comment related to “minimal information” (1), far from de-emphasizing the importance of “precision” (4), emphasizes the association of sensitivity with complete precision and error profiles rather than just one value (s[D]0) of just one factor (imprecision) that influences the error profile. Any confusion associated with the use of sensitivity results from and resides with those who convolute the term with measurement error. By treating sensitivity and measurement error separately, the IUPAC interpretation leads to a perfectly logical conclusion that a low sensitivity coupled with small measurement error can result in a small detection limit. However, by convoluting these two factors (4), the imprecision interpretation leads to a semantic contradiction. For example, substituting the equality, sensitivity 5 “the imprecision of the zero dose measurement (s[D]0)” (3), into the statement “. . . maximal sensitivity is achieved when the imprecision of the zero dose measurement (i.e., s[D]0) is least. . . ” (3), yields, “maximal sensitivity is achieved when sensitivity is least”. It is difficult to understand how this conclusion or replacement of “standard deviation” with another term as a quantitative descriptor of imprecision will reduce semantic confusion.
Letters
Finally, the second sentence under “Linear dynamic range” (1), should read, “If one knows the sensitivity of a method and the values of the signal or other measurement objective corresponding to the lower and upper ranges of linearity, then the concentrations corresponding to the lower and upper limits of the linear range can be computed as the quotient of each signal divided by the sensitivity”. Having informed the authors of this correction, it surprising that the meaning remains unclear.
summary The response/stimulus and IUPAC interpretations result from literal applications of explicit statements in dictionary definitions (5, 6) and the scientific literature dating to the latter part of the 19th century (1, 7–10). They do not convolute factors that are best considered separately for both subjective and quantitative uses of the terms, and they yield straightforward, unambiguous information for any situation for which response/stimulus data can be obtained. Readers, editors, and official committees are not expected to be “intimidated” (4) by the teachings of anyone, regardless of the area of expertise. However, given that this discussion focuses on analytical systems (3), it seems reasonable that all should value the opinions of analytical chemists whose teachings do not focus on a single application but are formulated to be applicable to the widest possible range of situations. References 1. Pardue HL. The inseparable triad: analytical sensitivity, measurement uncertainty, and quantitative resolution. Clin Chem 1997;43: 1831–7. 2. IUPAC. Analytical Chemistry Division. Nomenclature, symbols, units and usage in spectrochemical analysis-II. Data interpretation. Anal Chem 1976;48:2294 – 6. 3. Ekins R, Edwards P. On the meaning of “sensitivity”. Clin Chem 1997;43:1824 –31. 4. Ekins R, Edwards P. On the meaning of “sensitivity”: a rejoinder. Clin Chem 1998;44:xxxx-xx. 5. The Oxford English dictionary, 2nd ed. Vol. XIV. Oxford: Clarendon Press, 1989:986. 6. Webster’s new international dictionary, unabridged. Springfield MA: G & C Merriam Co., 1961:2068. 7. Maxwell JC. A treatise on electricity and mag-
8.
9. 10.
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netism, 3rd ed. Oxford: Clarendon Press, 1882:351,360. Maxwell JC. An elementary treatise on electricity, 3rd ed. Oxford: Clarendon Press, 1881: 186,194. Treadwell FP, Hall WT. Analytical chemistry, Vol. 2. New York: Wiley, 1919:7– 8. Kolthoff IM, Sandell EB. Textbook of quantitative inorganic analysis. New York: Macmillan, 1949:202–3. Websters seventh new collegiate dictionary, Springfield, MA: G & C Merriam Co., 1963: 223. Lim KB, Pardue HL. Error-compensating method for enzymatic determination of DNAs. Clin Chem 1993;39:1850 – 6. Foley JP. Systematic errors in the measurement of peak area and peak height for overlapping peaks. J Chrom 1987;384:301–13.
Harry L. Pardue Department of Chemistry 1393 BRWN BLDG. Purdue University West Lafayette, IN 47907 Fax 1-765-496-1200 E-mail
[email protected]
Serum Procalcitonin, but not C-reactive Protein, Identifies Sepsis in Trauma Patients
To the Editor: Trauma is a major cause of a biphasic Systemic Inflammatory Response Syndrome (SIRS), making the clinical diagnosis of infection difficult, especially during the late inflammatory phase (around day 7) (1). A biological indicator is needed to reinforce the presumption and to indicate specific bacterial examinations. Serum procalcitonin (PCT) is related to the evolution of infection in a medical setting (2). We presently report serum PCT during the late posttraumatic phase when infections usually occur (3), and we compare the informative value of PCT to that of C-reactive protein (CRP). Consecutive severe [Injury Severity Score (ISS) .16] and young (age ,55 years) trauma patients without previous chronic disease, admitted to our Surgical ICU between January 1, 1996, and April 30, 1996, were included in the study. Each day, patients were classified as exhibiting SIRS or sepsis according to the previously proposed definitions (4). Each patient was examined daily for
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Fig. 1. Comparison of serum procalcitonin (A) and C-reactive protein (B) relative concentrations between the three groups of trauma patients, according to their clinical status on day 7 of stay. No SIRS, absence of inflammatory syndrome; SIRS, Systemic Inflammatory Response Syndrome; Sepsis, SIRS related to infection.
the presence of infection. Blood cultures (three times a day) and urine cultures (twice a week) were systematically done in patients exhibiting SIRS, and specific bacteriological examinations were performed when indicated. Bacterial infections were defined according to the criteria of the Centers for Disease Control (5). Blood sampling was done at day 7 for determination in duplicate of CRP and PCT serum concentrations. CRP was measured by rate nephelometry immunoassay with a Beckman Array System (Beckman Instruments; upper reference limit in our population ,6 mg/L). PCT was measured by an immunoluminometric assay (LUMItest PCT, Brahms Diagnostica; normal value ,0.5 mg/L). Comparison between the clinical status of patients and the biological indicators was performed by the Kruskal–Wallis rank test, followed if indicated by a Mann–Whitney Utest. A P value ,0.05 was considered to be significant. Twenty-one patients were included [ages, 29 (20 –52); ISS, 27 (17– 48), median and range]; one patient died at day 4. At day 7, 12 patients exhibited a SIRS; 4 patients exhibited a SIRS related to an infection (i.e., a sepsis) documented between day 5 and day 8: two bacteremic pneumo-
nias (Escherichia coli and Pseudomonas aeruginosa) and two bacteremias (Enterobacter cloacae). As shown in Fig. 1, the median values of PCT and CRP were higher during sepsis than either during SIRS or absence of inflammation. However, a clear overlapping of CRP values was observed between septic and nonseptic patients, in contrast to PCT results, because CRP was increased in 17 out of the 20 survivors whatever the clinical status. Sepsis may lead to a lethal multiple organ failure in trauma patients, especially in cases of delayed diagnosis of infection. A secondary increase in serum PCT seems to be an adequate indicator of severe and/or bacteremic infection during the late posttraumatic SIRS, in contrast to the classical acute phase protein, CRP. Indeed CRP, is increased for at least 2 weeks after severe injury in the absence of sepsis (6). A significant increase in PCT may justify a complete bacteriological screening (7) in trauma patients. References 1. Moore FA, Moore EE. Evolving concepts in the pathogenesis of postinjury multiple organ failure. Surg Clin N Am 1995;75:257–77. 2. Assicot M, Gendrel D, Carsin H, Raymond J, Guilbaud J, Bohuon C. High serum procalcitonin concentrations in patients with sepsis and infection. Lancet 1993;341:515– 8. 3. Waydhas C, Nast-Kolb D, Jochum M, Trupka A,
4.
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Lenk S, Fritz H, et al. Inflammatory mediators, infection, sepsis, multiple organ failure after severe trauma. Arch Surg 1992;127:460 –7. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992;20:864 – 74. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC definitions for nosocomial infections. Am J Infect Control 1988;16:128 – 40. Fassbender K, Pargger H, Mu¨ller W, Zimmerli W. Interleukin-6 and acute-phase protein concentrations in surgical intensive care unit patients: diagnostic signs in nosocomial infection. Crit Care Med 1993;21:1175– 80. Meduri GH, Mauldin GL, Wunderink RG, Leeper KV, Jones CB, Tolley E, Mayhall G. Causes of fever and pulmonary densities in patients with clinical manifestations of ventilator-associated pneumonia. Chest 1994;106:221–35.
Jean-Franc¸ois Benoist1 Olivier Mimoz2 Marcel Assicot1 Alain Edouard2* 1 Service de Biochimie B Institut Gustave Roussy 94805 Villejuif, France 2
Service d’Anesthe´sie-Re´animation Centre Hospitalier de Biceˆtre 94275 Le Kremlin Biceˆtre, France
*Author for correspondence. Fax 33-145-21-28-75; e-mail
[email protected].
