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      High serum procalcitonin concentrations in patients with sepsis and infection

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      , PhD a , , PhD * , a , , MD b , , MD c , , MD d , , MD d
      Lancet (London, England)
      Published by Elsevier Ltd.

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          Abstract

          High concentrations of calcitonin-like immunoreactivity have been found in the blood of patients with various extrathyroid diseases. By means of a monoclonal immunoradiometric assay for calcitonin precursors, we have measured serum concentrations of procalcitonin in patients with various bacterial and viral infections. 79 children (newborn to age 12 years) in hospital with suspected infections were investigated prospectively. 19 patients with severe bacterial infections had very high serum concentrations of procalcitonin at diagnosis (range 6-53 ng/mL) in comparison with 21 children found to have no signs of infection (baseline concentrations <0·1 ng/mL). Serum procalcitonin values decreased rapidly during antibiotic therapy. 11 patients with peripheral bacterial colonisation or local infections without invasive sepsis and 18 (86%) of 21 patients with viral infections had concentrations within or slightly above the normal range (0·1-1·5 ng/mL). Among 9 severely burned patients studied in an intensive care unit, the post-traumatic course of procalcitonin concentrations (range 0·1-120 ng/mL) was closely related to infectious complications and acute septic episodes. Concentrations of mature calcitonin were normal in all subjects, whatever procalcitonin concentrations were found. Concentrations of a substance immunologically identical to procalcitonin are raised during septic conditions. Serum concentrations seem to be correlated with the severity of microbial invasion.

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          Calcitonin gene-related peptide levels are elevated in patients with sepsis.

          Calcitonin gene-related peptide (CGRP), an endogenous vasoactive peptide encoded by the calcitonin gene in nerve cells, is distributed throughout the cardiovascular system and is a potent vasodilator. Plasma levels of CGRP have been elevated in animal models with sepsis. This study was designed to determine whether plasma CGRP levels are elevated in patients with sepsis and perhaps contribute to the hyperdynamic cardiovascular state in sepsis. Plasma CGRP levels were obtained from normal healthy volunteers and from patients with sepsis. Volunteers were afebrile and had normal pulse and blood pressure. Patients with sepsis were selected according to the following criteria: (1) temperature higher than 38.5 degrees C, (2) white blood count greater than 14,000/ml, (3) positive blood culture of bacterial organisms, (4) hemodynamic parameters consistent with hyperdynamic sepsis, and (5) negative history of thyroid or other endocrine abnormalities. CGRP was extracted and assayed by radioimmunoassay for iodine 125-labeled human CGRP. In patients with sepsis, the cardiac index was 5.4 +/- 0.5 L/min/m2 (normal, 3.0); systemic vascular resistance was 7.1 +/- 0.5 mm Hg/L/min (normal, 16); oxygen delivery was 1496 +/- 137 ml/min (normal, 1000). Plasma CGRP levels were significantly elevated in the patients with sepsis, 14.9 +/- 3.2 pg/ml, compared to plasma CGRP levels in control volunteers, 2.0 +/- 0.3 pg/ml (p less than 0.0005). These elevated levels of CGRP may contribute to the decreased vascular resistance and increased cardiac output in the hyperdynamic septic state.
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            Plasma-immunoreactive-calcitonin in patients with non-thyroid tumours.

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              Identification and measurement of calcitonin precursors in serum of patients with malignant diseases.

              Previous studies have suggested that molecular species larger than the mature calcitonin (CT) are produced by tumors of different origin. In order to study these species, we developed a monoclonal immunoradiometric assay for calcitonin precursors (CT-pr). This assay was based on both monoclonal antibody KC01 directed to the 1-11 region of katacalcin and monoclonal antibody CT08 directed to the 11-17 portion of CT. The sensitivity of this monoclonal immunoradiometric assay for CT-pr was less than 100 pg/ml. Only one of 131 healthy subjects had CT-pr serum levels greater than 100 pg/ml; this value was therefore selected as the standard serum value in healthy individuals. CT-pr was present in the serum of seven of ten patients with advanced renal failure and in that of 21 of 52 patients (40%) with benign liver disease but was undetectable in sera of patients with other benign diseases. The serum CT-pr level was correlated with that of mature CT in patients with medullary carcinoma of the thyroid. In contrast, the serum CT-pr level was frequently elevated in the absence of a detectable CT level in patients with various malignant tumors and, particularly, in those with either tumors of the neuroendocrine system (60%) or hepatocellular carcinomas (62%). CT-pr was detected in tumor extract from a patient with a hepatocellular carcinoma. Moreover, hybridization experiments with total RNA extracted from this tumor demonstrated the presence of RNAs hybridizing with complementary DNA encoding for common region, calcitonin, and katacalcin sequences. These results show that CT precursors are excreted by numerous cancers and might well be useful biological markers for the follow-up of productive tumors.
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                Author and article information

                Contributors
                Role: Prof
                Role: Prof
                Role: Prof
                Journal
                Lancet
                Lancet
                Lancet (London, England)
                Published by Elsevier Ltd.
                0140-6736
                1474-547X
                21 September 2003
                27 February 1993
                21 September 2003
                : 341
                : 8844
                : 515-518
                Affiliations
                [a ]Département de Biologie Clinique, Institut Gustave-Roussy, 94805 Villejuif, France
                [b ]Département de Pédiatrie, Hôpital Saint-Vincent-de-Paul, Paris, France
                [c ]Laboratoire de Microbiologie, Hôpital Saint-Vincent-de-Paul, Paris, France
                [d ]Centre de Traitement des Brulés, Hôpital d'Instruction des Armèes Percy, Clamart, France.
                Author notes
                [* ]Correspondence to Prof Claude Bohuon
                Article
                0140-6736(93)90277-N
                10.1016/0140-6736(93)90277-N
                7141580
                8094770
                036c3179-8725-403b-9784-413c7f05917e
                Copyright © 1993 Published by Elsevier Ltd.

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