Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated serum levels of the prohormone of calcitonin (CT), procalcitonin (ProCT), have been documented in illnesses such as inhalational burn injury, in several sepsis syndromes, and in endotoxemia. In this study, we measured and characterized the circulating precursor forms of CT during the course of infectious pneumonitis. The initial (mean +/- SEM) serum total multiform CT level in 12 patients with acute infectious pneumonia was 1,019 +/- 430 pg/mL. In comparison, the mean level of total CT for 19 age-matched control patients without lung disease was 32 +/- 6 pg/mL (P < 0.001). The mean serum total CT level on initial examination was greater in the 6 patients with bacterial isolates, at 1,793 +/- 752 pg/mL, than in those with nonbacterial infectious pneumonia, at 242 +/- 109 pg/mL (P = 0.018). After admission to the hospital, patients' serum total CT progressively declined concomitantly with the clinical resolution of the pneumonia; at discharge, mean serum level was 121 +/- 34 pg/mL. On discharge, the patients who had persistent radiographic abnormalities had significantly higher levels than did those who had complete resolution. Both the mean serum calcium and phosphate were significantly lower at the initial time of study than at discharge (P < 0.002 and P < 0.0004, respectively). Gel filtration chromatography of sera obtained during the acute pneumonitis phase revealed increased levels of precursor forms of CT, including ProCT; these levels diminished with clinical resolution. In an additional three patients, the serum total CT increased very rapidly after aspiration (within 6 to 12 hours); the peak levels were several times greater than the upper limits of normal. In these patients, the principal serum CT components were ProCT and other precursor forms. These results show that both infectious and aspiration pneumonitis are associated with a rapid increase in circulating ProCT and other precursor forms of CT.
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PMID:Pneumonitis-associated hyperprocalcitoninemia. 868 24

Abnormal systemic and pulmonary vascular reactivity has been demonstrated in numerous models of sepsis and pneumonia. Furthermore, the attenuated hypoxic pulmonary pressor response observed in these animals probably is responsible for the ventilation/perfusion (V/Q) mismatching and consequent arterial hypoxemia. We hypothesized that excess release of endogenous vasodilators such as calcitonin gene-related peptide (CGRP) in pneumonia was responsible for the diminished hypoxic pressor response. Using the CGRP receptor antagonist CGRP (8-37), we examined the role of CGRP in the attenuated hypoxic pulmonary response in a rat model of acute Pseudomonas pneumonia. Sixteen Sprague-Dawley rats were instrumented for chronic hemodynamic monitoring and subsequently randomized to either Pneumonia (n = 8), induced by the instillation of 0.2 ml broth containing 2 x 10(8) colony-forming units (CFU)/ml Pseudomonas aeruginosa into the right lower lobe, or Sham (n = 8) procedure. Hemodynamic measurements and the hypoxic (FiO2 = 0.08) pulmonary pressor response were recorded at baseline, 48 h after the pneumonia or sham procedure and after the administration of 250 micrograms CGRP (8-37) (post-CGRP(8-37)). The regional distribution of pulmonary blood flow was determined by the injection of radioactive microspheres. Forty-eight hours after the instillation of Pseudomonas, Pneumonia animals had significantly increased cardiac output (CO) as compared with Sham (193 +/- 7 vs. 154 +/- 7 ml/min, p < 0.05), slightly decreased mean arterial pressure (MAP 109 +/- 4 vs. 118 +/- 3 mm Hg, p = NS), and reduced total systemic vascular resistance (TSVR 0.57 +/- 0.03 vs. 0.78 +/- 0.05 mm Hg.min.ml-1, p < 0.05). Pneumonia animals were further characterized by increased mean pulmonary artery pressure (MPAP) as compared with Sham (24 +/- 2 vs. 20 +/- 1 mm Hg, p < 0.05) animals, and an increased alveolar-arterial (A-a) oxygen gradient (31 +/- 3 vs. 20 +/- 4 mm Hg, p < 0.05). The administration of CGRP (8-37) did not alter baseline hemodynamic variables and did not change the pressor response to hypoxia in either group. Furthermore, CGRP receptor blockade did not alter the distribution of blood flow in the lung during normoxia or hypoxia. These data suggest that although this model of acute pneumonia is characterized by an attenuated hypoxic pressor response, the mechanism does not appear to be mediated by excess release of the vasodilator CGRP.
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PMID:Calcitonin gene-related peptide does not mediate the abnormal vascular reactivity observed in a rat model of acute Pseudomonas pneumonia. 876 59

This study is aimed to investigate the relationship between plasma concentrations of nitrite and nitrate as a measure of ongoing nitric oxide (NO) production, the vasodilatory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP), endotoxemia and hemodynamic changes in human septic shock. Thirteen patients with septic shock were studied within 6 h after the development of hypotension. Hemodynamic measurements and blood samples were recorded simultaneously at 2-h intervals from study admission. Eighteen normotensive patients with sepsis were included as control group of patients. On study entry, circulating levels of endotoxin did not relate to either CGRP or nitrite and nitrate plasma values. Septic shock patients had significantly higher plasma CGRP, and nitrite and nitrate concentrations, at each of the four time points, than patients with sepsis, as well as both groups of patients compared to normal subjects. No differences were found in plasma SP levels between the two groups of patients. For pooled data from all septic shock patients and measurements (n = 52), both plasma concentrations of CGRP and nitrite and nitrate were inversely correlated, independently from each other, to systemic vascular resistance. On study admission and at 2-h intervals, plasma CGRP concentrations correlated directly with nitrite and nitrate values. Our observations, thus, point to CGRP acting in concert with NO as important mediators responsible for hypotension in human septic shock.
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PMID:Relationship between circulating levels of calcitonin gene-related peptide, nitric oxide metabolites and hemodynamic changes in human septic shock. 888 78

Procalcitonin, the precursor of calcitonin, is elevated in patients with sepsis and infection (base-line values <0.1 ng/ml). We determined PCT in 38 hospitalised patients with suspected malaria. All of them had signs of infection and had recently returned from Africa. Plasmodium vivax was proven in 15, Plasmodium falciparum in one and an infection with both species was found in another case (n = 17). PCT was determined on admission and the days thereafter. In one patient PCT was determined every 4 hours on the first day. The maxima of the PCT concentration on day 0 and 1 were 5.3 ng/ml with proven Malaria and 0.43 ng/ml without. At the following days we found a decrease to normal values (<0.5 ng/ml) which correlated with the general condition of the patient. At a cut-off point of 2 ng/ml we found a sensitivity of 52%, positive predictive value of 74%, specificity of 86%, negative predictive value of 71%. procalcitonin, malaria
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PMID:Procalcitonin in acute malaria. 915 45

The role of the sensory neuropeptide calcitonin gene-related peptide (CGRP) was studied in preterm and term neonates with sepsis and shock. CGRP levels in blood were measured by RIA. The identity of immunoreactive CGRP (irCGRP) in adult and infant human blood was confirmed by reverse phase-HPLC. CGRP levels were analyzed in a total of 189 samples (95 from cord blood and 94 from neonates). The gestational ages ranged from 24 to 43 wk, and the birth weights ranged from 520 to 4445 g. Cord samples were collected immediately after delivery and infant blood samples were collected within 12 h of birth. Samples were coded, and the data were assigned to groups after determination of CGRP levels. There was a weight- and gestation-dependent increase in irCGRP in the newborn population. The direct correlation of circulating CGRP with ascending birth weight and gestation may have significance in the development of the fetus. Infants with and without certain complications were grouped in 500-g intervals. CGRP levels in cord blood were significantly elevated when certain stressful situations existed in the mother. These included culture-positive chorioamnionitis, placental abruption, and severe preeclampsia. There was a similar elevation in CGRP in patient blood in infants with culture-positive sepsis and/or shock with blood pressure <2 SD from the mean for corresponding gestation. CGRP levels did not differ between male and female infants and did not appear to be influenced by type of delivery (vaginal versus cesarean section). There was no significant difference in CGRP level between cord and patient blood in preterm neonates, but at term gestation cord blood levels were slightly higher than those in the patient blood. These results suggest that inflammation and hemodynamic imbalance (e.g. shock) are associated with increased in CGRP levels in the circulation in neonates. Future studies will focus on the biologic effects of elevated CGRP during neonatal complications and will examine the utility of CGRP measurement for diagnosis and treatment of disease in preterm infants.
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PMID:Elevated circulating calcitonin gene-related peptide in umbilical cord and infant blood associated with maternal and neonatal sepsis and shock. 947 97

High serum levels of the calcitonin (CT) prohormone, procalcitonin (pro-CT), and its component peptides occur in systemic inflammation and sepsis. Using two different assays, we undertook a prospective study to determine the utility of serum precalcitonin peptides (pre-CT) as markers in this condition. Twenty-nine patients meeting criteria for the systemic inflammatory response syndrome were studied daily in two intensive care units. Sera were collected, and APACHE II scores were determined until recovery or death. All patients had markedly elevated serum pre-CT. Prognostically, peak values were the most important. The highest values portended mortality, and a lower level could be ascertained below which all patients survived. Peak pre-CT levels were significantly higher in patients with infection documented by blood cultures than in those patients with no documented infection from any source (P < 0.05). Mature CT remained normal or only moderately elevated. Compared with the serum pre-CT levels, receiver operating characteristic curve analysis revealed that the APACHE II scores, although more cumbersome, were better overall predictors of mortality. Thus, pre-CT is an important serum marker for systemic inflammatory response syndrome and is predictive of outcome. It also provides data concerning the presence of severe infection and may prove to be clinically useful for proactive patient care.
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PMID:Serum calcitonin precursors in sepsis and systemic inflammation. 974 44

A rare case of massive osteolysis affecting the pelvis of a young girl is presented. The clinical, radiographic, and histopathological features are described in detail. Septicemia complicated the clinical course and the patient eventually died. Histopathological examination of the pelvic lesion revealed massive osteolysis characterized by prominent osteoclastic activity with extensive bone resorption. A thorough post-mortem histological examination of the thyroid gland showed no C cells. This is an interesting observation, since it is known that thyroid C cells are the primary source of calcitonin. Since the main biological effect of calcitonin is to inhibit osteoclastic bone resorption, there is a possibility that massive osteolysis in our case could have been related to the lack of this hormone. There is a clear need for further investigation regarding the role of thyroid C cells and calcitonin in this puzzling disease.
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PMID:Massive osteolysis in a girl with agenesis of thyroid C cells. 980 85

To understand the presence or absence of bacterial infection in patients with systemic inflammatory response syndrome (SIRS), the level of procalcitonin (PCT), a precursor of calcitonin, was determined. Subjects consisted of 14 SIRS patients without complication by bacterial infection, 14 SIRS patients complicated by sepsis, and 14 SIRS patients complicated by severe sepsis and septic shock. PCT levels in SIRS patients with sepsis (2.9 +/- 2.3 ng/ml) were significantly higher than those in SIRS patients without complication by infection (0.7 +/- 1.1 ng/ml). However, there were no significant differences in the levels of C-reactive protein (CRP), interleukin 6 (I-6) or tumor necrosis factor-alpha (TNF-alpha) between the two groups. PCT levels in SIRS patients with severe sepsis and septic shock (172.2 +/- 276.3 ng/ml) were significantly higher than those in SIRS patients with sepsis. Levels of CRP, IL-6 and TNF-alpha were also significantly higher in the patients with sepsis compared to those in patients with local infection. Significant correlations were observed between the levels of PCT and those of CRP, IL-6 and TNF-alpha in SIRS patients. It was suggested that to measure the levels of procalcitonin in patients with SIRS is useful to diagnose the infection and severity of illness.
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PMID:[Evaluation of procalcitonin levels in patients with systemic inflammatory response syndrome as the diagnosis of infection and the severity of illness]. 1022 64

Adrenomedullin (ADM) is a recently discovered peptide with potent vasorelaxing and natriuretic properties originally isolated from human pheochromocytoma. Adrenomedullin has been reported to be present in normal adrenal medulla, heart, lung and kidney as well as in plasma and urine. ADM shares some structural homology with calcitonin gene related peptide (CGRP). ADM acts on target cells through its unique receptors and CGRP1 receptors. In both cases cyclic AMP seems to be the main second messenger. ADM may function as a circulating hormone and as an autocrine/paracrine mediator involved in the regulation of cardiovascular system and renal function. Plasma concentration of ADM is elevated in patients with congestive heart failure, arterial hypertension, pulmonary hypertension, renal failure and sepsis suggesting its role in pathophysiology of these disorders. Recently another product od adrenomedullin gene, proadrenomedullin N-terminal 20-peptide (PAMP) has been described. This peptide has also vasodilating activity resulting from its inhibitory action on norepinephrine release from sympathetic endings and adrenal medulla.
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PMID:[Adrenomedullin]. 1035 50

Procalcitonin (PCT), the precursor of calcitonin, was recently put forward as a diagnostic marker of systemic bacterial infection and sepsis. The major PCT production site in sepsis still remains unclear. Because of a certain association between increased levels of PCT and leukocyte-derived cytokines during sepsis, we assessed the possible expression of PCT in human peripheral blood mononuclear cells (PBMCs) and the modulation of PCT by lipopolysaccharides (LPS) and various sepsis-related cytokines by reverse transcriptase-polymerase chain reaction (RT-PCR) by using a novel primer set and flow cytometric analysis with intracellular staining with antibodies to the PCT components calcitonin and katacalcin. RT-PCR and flow cytometric analysis demonstrated that PBMCs express PCT both on mRNA and on protein levels. LPS and various proinflammatory cytokines (interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-2) had pronounced stimulatory effects on the expression of PCT mRNA. Under identical experimental conditions the anti-inflammatory cytokine IL-10 had no effect on the expression of mRNA for PCT. Flow cytometric analysis demonstrated increased intracellular amounts of PCT components after LPS stimulation. Thus we demonstrate for the first time that PCT is expressed in PBMCs. This expression is modulated by bacterial LPS and sepsis-related cytokines. Therefore PBMCs may be among the sources of elevated PCT levels in patients with sepsis.
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PMID:Procalcitonin expression in human peripheral blood mononuclear cells and its modulation by lipopolysaccharides and sepsis-related cytokines in vitro. 1040 59


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