Procalcitonin versus C-reactive protein: review of kinetics and performance for diagnosis of neonatal sepsis.

Procalcitonin (PCT) and C-reactive protein (CRP) are commonly used biomarkers, but their diagnostic advantage for neonatal early-onset (EOS) or late-onset (LOS) sepsis is controversial. In a comprehensive literature review we found significant heterogeneity between studies in sample timing, cut-off values, consideration of blood culture results for sepsis classification, and definition of EOS versus LOS. We identified 39 studies directly comparing PCT with CRP, but only four in very low birth weight (VLBW) neonates. The mean sensitivity for EOS, LOS, and EOS + LOS was 73.6%, 88.9%, and 76.5% for PCT, compared to 65.6%, 77.4%, and 66.4% for CRP, respectively. Mean specificity of PCT and CRP was 82.8% versus 82.7% for EOS, 75.6% versus 81.7% for LOS, and 80.4% versus 91.3% for EOS + LOS. More studies directly comparing both biomarkers for EOS and LOS, especially in extremely and very-low-birth-weight infants, are needed to determine their clinical value for guidance of antibiotic therapy in neonatal sepsis.

Human C-reactive protein impedes entry of leptin into the CNS and attenuates its physiological actions in the CNS.

Defective central leptin signalling and impaired leptin entry into the CNS (central nervous system) represent two important aspects of leptin resistance in obesity. In the present study, we tested whether circulating human CRP (C-reactive protein) not only diminishes signalling of leptin within the CNS, but also impedes this adipokine's access to the CNS. Peripheral infusion of human CRP together with co-infused human leptin was associated with significantly decreased leptin content in the CSF of ob/ob mice. Furthermore, following peripheral infusion of human leptin, the CSF (cerebrospinal fluid) concentration of leptin in transgenic mice overexpressing human CRP was sharply lower than that achieved in similarly infused wild-type mice. Administration of LPS (lipopolysaccharide) to human CRP-transgenic mice dramatically elevated the concentrations of human CRP in the CSF. The i.c.v. (intracerebroventricular) delivery of human CRP into the lateral ventricles of ob/ob mice blocked the satiety and weight-reducing actions of human leptin, but not those of mouse leptin. I.c.v. injection of human CRP abolished hypothalamic signalling by human leptin, and ameliorated the effects of leptin on the expression of NPY (neuropeptide Y), AgRP (Agouti-related protein), POMC (pro-opiomelanocortin) and SOCS-3 (suppressor of cytokine signalling 3). Human CRP can impede the access of leptin to the CNS, and elevation of human CRP within the CNS can have a negative impact on the physiological actions of leptin.

Elevated risperidone serum concentrations during acute inflammation, two cases.

Inflammation-mediated changes in drug metabolism may lead to alterations in the absorption, distribution, and clearance of psychotropic drugs and thus elevate drug levels in blood and lead to intoxications. We report about two patients who developed an up to threefold increase of dose-related serum concentrations of risperidone's active moiety (risperidone plus 9-hydroxyrisperidone) during acute inflammation indicated by elevated C-reactive protein. The two female patients (aged 56 and 38 years, respectively) had the diagnoses of paranoid schizophrenia and schizoaffective disorder. For both patients, there was a close time-dependent parallel fluctuation of drug levels and C-reactive protein. Since elevated drug levels could not be attributed to prescribed comedications, it seemed likely that high-serum concentrations of risperidone were due to inflammation. It is concluded that elevated C-reactive protein should be considered as an indication to control blood levels of risperidone and possibly dose adaption.

Prototypic long pentraxin PTX3 is present in breast milk, spreads in tissues, and protects neonate mice from Pseudomonas aeruginosa lung infection.

Newborns and infants present a higher susceptibility to infection than adults, a vulnerability associated with deficiencies in both the innate and adaptive immune systems. Innate immune receptors are sensors involved in the recognition and elimination of microbes that play a pivotal role at the interface between innate and adaptive immunity. Pentraxin 3 (PTX3), the prototypic long pentraxin, is a soluble pattern recognition receptor involved in the initiation of protective responses against selected pathogens. Because neonates are generally resistant to these pathogens, we suspected that PTX3 may be provided by a maternal source during the early life times. We observed that human colostrum contains high levels of PTX3, and that mammary epithelial cell and CD11b(+) milk cells constitutively produce PTX3. Interestingly, PTX3 given orally to neonate mice was rapidly distributed in different organs, and PTX3 ingested during lactation was detected in neonates. Finally, we observed that orally administered PTX3 provided protection against Pseudomonas aeruginosa lung infection in neonate mice. Therefore, breastfeeding constitutes, during the early life times, an important source of PTX3, which actively participates in the protection of neonates against infections. In addition, these results suggest that PTX3 might represent a therapeutic tool for treating neonatal infections and support the view that breastfeeding has beneficial effects on the neonates' health.

Procalcitonin and C-reactive protein kinetics in postoperative pediatric cardiac surgical patients.

OBJECTIVE: To determine the kinetics of procalcitonin (PCT) and C-reactive protein (CRP) concentration after pediatric cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, clinical cohort study. SETTING: A fifteen-bed tertiary-care pediatric intensive care unit. PATIENTS: Fourteen pediatric patients admitted for cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Serum PCT and CRP were measured before cardiopulmonary bypass (CPB); after CPB; and on the first, second, and third days after surgery by means of immunoluminometry and nephelometry, respectively. Reference values for systemic inflammatory response syndrome are 0.5 to 2.0 ng/mL for PCT and <5 mg/L for CRP. Baseline serum PCT and CRP concentrations were 0.24 +/- 0.13 ng/mL and 4.06 +/- 3.60 mg/L (median 25th percentile-75th percentile), respectively. PCT concentrations increased progressively from the end of CPB (0.62 +/- 0.30 ng/mL), peaked at 24 hours postoperatively (POD1) (0.77 +/- 0.49 ng/mL), and began to decrease at 48 hours or POD2 (0.35 +/- 0.21 ng/mL). CRP increased just after CPB (58.82 +/- 42.23 mg/L) and decreased after 72 hours (7.09 +/- 9.81 mg/L). CONCLUSION: An increment of both PCT and CRP was observed just after CPB. However, PCT values remained within reference values, whereas CRP concentrations increased significantly after CPB until the third day. These preliminary results suggest that PCT was more effective than CRP to monitor patients with SIRS and a favorable outcome.

Utilidad de la proteína C reactiva en apendicitis aguda / Utility of the C reactive protein in acute appendicitis

El objetivo de este trabajo es evaluar el rol de Proteína C reactiva (PCR) como marcador de inflamación en el diagnóstico de la apendicitis aguda y relacionarlo con la histopatología de una serie de pacientes intervenidos por sospecha de apendicitis aguda. Pacientes y métodos: 36 pacientes consecutivos fueron operados por sospecha de apendicitis aguda. A todos ellos como parte del estudio se les solicitó en forma preoperatoria PCR. Una vez apendicectomizados, las biopsias fueron estudiadas en el Isntituto de Anatomía del Hospital y correlacionadas con el valor de la PCR. Resultados: Del total de pacientes, en 33 de 36 la sospecha clínica fue confirmada como apendicitis aguda y 3 biopsias fueron informadas normales. PCR se encontró elevada en 31 casos y en 5 con valores bajo los 5 mg/dl. Al analizar los resultados histopatológicos con PCR se encuentra que en el 87,8 por ciento de los casos que tuvieron apendicitis, la PCR se encontraba elevada y de los casos que tenían elevación de la PCR un 93,5 por ciento tenían apendicitis. Conclusiones: La elevación de la PCR tiene un alto valor predictivo positivo (93,5 por ciento) apendicitis aguda en ausencia de otra causa de inflamación sistémica. Puede ser utilizada como ayuda diagnóstica en los casos donde la clínica no puede aclarar el diagnóstico.

Biodistribution and clearance of 125I-labeled C-reactive protein and 125I-labeled modified C-reactive protein in CD-1 mice.

Iodinated forms of C-reactive protein (CRP), soluble modified CRP (mCRP-sol), and suspended mCRP (mCRP-susp) were injected iv into CD-1 mice, for analysis of their pharmacokinetics (PK) and biodistribution (BD). The plasma half-life of 125I-CRP, measured as 4.7 hr, agrees closely with previous reports. The PK and BD characteristics for 125I-mCRP-sol and 125I-mCRP-susp were comparable to each other and were distinctly different from those measured for CRP. Whereas approximately 50% of 125I-CRP was recoverable from plasma 5 min after injection, only approximately 5% of 125I-mCRP was similarly recoverable. The estimated volume of distribution at steady state calculated for either form of 125I-mCRP was approximately 10-fold greater than that calculated for 125I-CRP (23. 4-27.6 and 2.4 ml, respectively). The estimated mean residence times for 125I-mCRP were approximately 2 times longer than that measured for 125I-CRP (9.5-11.5 hr, compared with 4.9 hr). At both 4- and 24-hr time points, substantial amounts of 125I-mCRP were selectively distributed in the bone marrow. At 24 hr, approximately 25% of the injected 125I-mCRP-sol and 125I-mCRP-susp was localized to the bone marrow (corresponding to 92% of injected dose/g of tissue). At this time point, only 8% (or 27%/g) of 125I-CRP was localized to the bone marrow. Overall, the data presented indicate that 1) mCRP has PK and BD characteristics distinct from those of CRP; 2) injected mCRP, although it is rapidly cleared from the general circulation, accesses large body areas and is selectively localized to the bone marrow; and 3) all forms of CRP appear to be excreted in the urine.

[Plasma concentration of C-reactive protein in patients with high estrogen levels]. / Concentration plasmatique de la protéine réactive C chez des patientes en situation de forte imprégnation estrogénique.

The monitoring of inflammatory activity in patients with a high level of estrogen is controversial because the significance of a raised estradiol level on C-reactive protein (CRP) concentrations is a debated question. This prompted us to assay CRP by a sensitive Elisa in a sample of 30 patients with ovarian stimulation for in vitro fertilization, thus with high levels of estradiol. For 15 of these women, six to nine plasma samples were analyzed allowing a kinetic study of plasma levels of CRP, estradiol and sex steroid-binding plasma protein (SBP). No significant correlation was found between the concentrations of estradiol and CRP for the 30 patients. In the kinetic study, as mean estradiol levels rose exponentially from 50 to 1400 ng/l between day 5 and 14, the CRP level tended to vary markedly from one patient to another and sometimes from day to day, but there was never any relation with estradiol level. Furthermore, CRP did not significantly modify the slope of the regression line between estradiol concentration and the day of the menstrual cycle. In contrast, the effect of estradiol on SBP was clear, which supports the absence of estradiol effect on CRP level.

Value of C-reactive protein in reflecting the magnitude of complement activation in children undergoing open heart surgery.

The kinetics of C-reactive protein (CRP) were studied prospectively in 30 children (aged 21 days - 16 years) undergoing open heart surgery. CRP was related to the kinetics of total haemolytic complement, complement C3a and postoperative complications. Two (7%) patients died and ten (33%) had postoperative complications. The patients with complications were younger (p less than 0.035), underwent longer perfusions (p less than 0.001) and had longer aortic cross-clamping times (p less than 0.003). The mean peak CRP level after surgery (108 mg/l) was reached, on the average, in 43 h. No statistical difference in CRP concentrations was found between the complication and non-complication groups. Extensive complement activation was seen in every patient. CRP did not reflect the magnitude of complement activation induced by cardiopulmonary bypass. The patient sample was too small to draw reliable conclusions about the value of CRP in detecting postoperative complications after open heart surgery in children.

Kinetics of C-reactive protein in acute viral hepatitis.

The significance of C-reactive protein (CRP) in acute viral hepatitis was studied by measuring the serum CRP level in patients with acute hepatitis type A (AHA), B (AHB), and non-A, non-B (AHNANB) and examining its localization in liver biopsy specimens by the immunohistochemical method. The mean value of the serum CRP level determined by enzyme immunoassay (EIA), was markedly increased in the acute phase of AHA and AHB, particularly the former. It decreased rapidly in both AHA and AHB during the convalescent phase, but was generally low in AHNANB with no marked difference between the acute phase and the convalescent phase. Under light microscopy, CRP was stained in the cytoplasm of hepatocytes, and immuno-reactive products were observed in the rough endoplasmic reticulum (RER) by electron microscopy. In the acute phase, the intensity of staining was slightly greater in AHA, decreasing during the convalescent phase in AHA and AHB, but only weak staining was observed in all patients with AHNANB. Evaluation of CRP may be useful for clarification of differences in clinical manifestations and the mechanisms of inflammation among different types of hepatitis.