Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The simultaneous occurrence of different types of thyroid carcinoma in a single patient is an unusual event. We report the case of a 52-year-old man with the history of two previous thyroid operations for benign goiters, who developed a recurrent goiter. The patient was referred to our department for thyroidectomy. In the pathohistological examination the specimen showed a 5 cm follicular carcinoma and a 0.3 cm papillary microcarcinoma in the right lobe as well as a 1.5 cm medullary carcinoma in the left lobe. All tumors were clearly separated from each other, representing the pure entity of each type. Postoperatively, RET germline mutation was ruled out by sequence analysis of peripheral blood leucocytes. Postoperative I-131-radioiodine scan showed multiple lung and liver metastases, while calcitonin was negative. There is no known common cause of these three different tumor types and they developed most independently from each other. The personal history of our patient was interesting in two aspects: (1) he suffered a period of severe staphylococcal sepsis with temporal immunosuppression and (2) he worked for long years as a coremaker in a foundry. This work represented possible long term exposure to inhalative carcinogenous toxins like hydrazine, which caused thyroid parafollicular cell adenomas in an animal model.
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PMID:Synchronous occurrence of a follicular, papillary and medullary thyroid carcinoma in a recurrent goiter. 1586 62

Sepsis is still a major cause of postoperative morbidity and mortality. Numerous biochemical indicators have been evaluated regarding their potential in predicting prognosis in sepsis. Generally, one must differentiate between indicators: those for preoperative detection of patients at risk for lethal sepsis and those for early prediction of lethal outcome of septic complications. The first include the analysis of mononuclear phagocyte interleukin (IL)-12-synthesizing capability. Reduced IL-12 levels were associated with higher lethality. Cytokine-associated gene polymorphisms such as the loss of monocyte HLA-DR expression and homozygotism for the tumor necrosis factor B2 allele have a place in preoperative risk evaluation, as they were associated with worse prognosis in sepsis. Among the most important biochemical indicators for early prediction of lethal outcome in sepsis are decreased L-selectin and elevated IL-18, IL-6, and PCT plasma concentrations. Increased nuclear factor kappaB activity in mononuclear phagocytes and elevated calcitonin gene-related protein plasma concentrations were associated with unfavourable prognosis.
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PMID:[Indicators for early prediction of outcome in sepsis]. 1609 22

Adrenomedullin (ADM) is a 52-amino acid peptide with structural homology to calcitonin gene-related peptide (CGRP) initially isolated from human pheochromocytoma. ADM is synthesized and is secreted from many mammalian tissues, including the adrenal medulla, endothelial and vascular smooth muscle cells, as well as the myocardium and central nervous system. ADM has been implicated as a mediator of several diseases such as cardiovascular and renal disorders, sepsis, inflammation, diabetes and cancer. ADM is also expressed in a variety of tumors, including breast, endometrial and prostate cancer. ADM has been shown to be a mitogenic factor capable of stimulating growth of several cancer cell types. In addition, ADM is a survival factor for certain cancer cells and an indirect suppressor of the immune response. ADM plays an important role in environments subjected to low oxygen tension, which is a typical feature of solid tumors. Under these conditions, ADM is up regulated and acts as a potent angiogenic factor promoting neovascularization. The major focus of this review will be on the role of ADM in cancer, with emphasis on its utility in diagnostic and prognostic terms, along with its relevance as a therapeutic target.
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PMID:Adrenomedullin: a tumor progression factor via angiogenic control. 1710 May 69

Tumor necrosis factor (TNF) is critically involved in biological responses against various insults. TNF excessively produced by monocytes or macrophages activates endothelial cells and neutrophils, thereby inducing endothelial cell injury. Endothelial cells are capable of inhibiting TNF production by producing prostaglandins that inhibit TNF production. Sensory neurons play an important role in promotion of the endothelial production of prostaglandins by releasing calcitonin gene-related peptide. Neutrophils activated by TNF release a huge amount of neutrophil elastase that is capable of decreasing endothelial prostaglandin production. Consequently, TNF production is enhanced, leading to the development of multi-organ failure in sepsis. E-selectin, an endothelial leukocyte adhesion molecule, is released from the endothelial cell membrane by the action of TNF and exists as soluble E-selectin in plasma. The detection of increases in plasma levels of soluble E-selectin in patients with systemic inflammatory response syndrome predicts the imminent onset of acute respiratory syndrome. Early detection of increases in plasma levels of soluble E selectin by a rapid assay system, developed by the authors, enables early effective treatment of patients with sepsis.
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PMID:[Role of endothelial dysfunction in the development of severe sepsis--the pathomechanism, evaluation by laboratory tests and new therapeutic strategies]. 1744 73

Metabolic disorders and endocrine changes are common and relevant in critically ill patients. Thereby, endocrinopathies, electrolyte or metabolic derangements may either pre-exist or develop, and left unattended, may lead to significant morbidity and mortality. The homeostatic corrections which have emerged in the course of human evolution to cope with the catastrophic events during critical illness involve a complex multisystem endeavour, of which the endocrine contribution is an integral component. Although the repertoire of endocrine changes has been probed in some detail, discerning the vulnerabilities and failures of this system is far more challenging. The ensuing endocrine topics illustrate some of the current issues reflecting attempts to gain an improved insight and clinical outcome for critical illness. Disturbances in glucose and cortisol homeostasis during critical illness are two controversially debated topics in the current literature. The term "hormokine" encompasses the cytokine like behaviour of hormones during inflammation and infections. The concept is based on an ubiquitous expression of calcitonin peptides during sepsis. Adrenomedullin, another member of the calcitonin peptide superfamily, was shown to complement and improve the current prognostic assessment in lower respiratory tract infections. Procalcitonin is the protopye of "hormokine" mediators circulating procalcitonin levels increase several 10,000-fold during sepsis improve the clinical assessment especially of respiratory tract infections and sepsis safely and markedly reduces antibiotic usage in non-bacterial respiratory tract infections and meningitis. Adrenomedullin, another member of the calcitonin peptide superfamily, was shown to complement and improve the current prognostic assessment in lower respiratory tract infections. Hormokines are not only biomarkers of infection. Hormokines are also pivotal inflammatory mediators. Like all mediators, their role during systemic infections is basically beneficial, possibly to combat invading microbes. Yet, with increasing levels they can become harmful for their host. Multiple mechanisms of action were proposed. In several animal models the modulation and neutralization of hormokines during infection was shown to improve survival and thus might open new treatment options for severe infections, especially of the respiratory tract.
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PMID:Endocrine aspects of critical illness. 1766 55

Used appropriately, biomarkers improve the assessment of respiratory tract infections and sepsis. Most prominently, circulating procalcitonin levels increase by a factor of several tens of thousands during sepsis. Using a sensitive assay, procalcitonin safely and markedly reduces antibiotic usage in respiratory tract infections and nonbacterial meningitis. Procalcitonin is the protopye of hormokine mediators. The term "hormokine" encompasses the cytokine-like behaviour of hormones during inflammation and infections. The concept is based on a ubiquitous expression of calcitonin peptides during sepsis. Adrenomedullin, another member of the calcitonin peptide superfamily, was shown to complement and improve the current prognostic assessment in lower respiratory tract infections. Other peptides share some features of hormokines, e.g. natriuretic peptide and copeptin. Hormokines are not only biomarkers of infection but are also pivotal inflammatory mediators. Like all mediators, their role during systemic infections is basically beneficial, possibly to combat invading microbes. However, at increased levels they can become harmful for their host. Multiple mechanisms of action were proposed. In several animal models the modulation and neutralisation of hormokines during infection was shown to improve survival, and thus might open new treatment options for severe infections, especially of the respiratory tract.
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PMID:Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators. 1776 33

We aim to test the hypothesis that hypercalcemia produces pulmonary edema (PE) and to elucidate the mechanism. Experimentations were carried out in conscious rats and isolated perfused rat lungs. We evaluated PE by lung weight changes, protein concentration in bronchoalveolar lavage, dye leakage, and microvascular permeability. Plasma nitrate/nitrite, methyl guanidine (MG), proinflammatory cytokines, procalcitonin levels, and histopathological examinations were evaluated. Immunochemical staining and reverse-transcriptase polymerase chain reaction (RT-PCR) were used to detect inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) in the lungs. Hypercalcemia was produced in the conscious rat and isolated perfused lungs. Calcitonin and L-N(6) (1-iminoethyl)-lysine (L-Nil) were administered before hypercalcemia to observe their effects. Hypercalcemia caused severe PE in rats. Pathological and immunochemical examinations revealed hemorrhagic edema with iNOS activity in the alveolar macrophages and epithelial cells. RT-PCR showed an increase in iNOS mRNA expression. Hypercalcemia increased nitrate/nitrite, MG, proinflammatory cytokines and procalcitonin levels. Pretreatment with calcitonin or L-Nil prevented these changes. In conclusion, hypercalcemia caused PE in conscious rats and isolated perfused rat lungs. The increases in nitrate/nitrite, free radicals, proinflammatory cytokines, procalcitonin and iNOS activity suggest that hypercalcemia induces a sepsis-like syndrome. The effect of hypercalcemia on the lung may involve iNOS and NO.
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PMID:The detrimental role of inducible nitric oxide synthase in the pulmonary edema caused by hypercalcemia in conscious rats and isolated lungs. 1790 44

Procalcitonin (PCT) is the precursor of calcitonin, normally synthesized in the C-cells of the thyroid gland. Systemic inflammation and sepsis induce PCT production by various cell types, including hepatocytes, nephrons, monocytes. PCT begins to rise four hours after exposure to bacterial endotoxins, peaking at six to eight hours, and remaining raised for at least 24 hours with a half-life of 25-30 hours. Serum PCT levels significantly increase in systemic bacterial infection, necrotizing enterocolitis, and during both early and late onset neonatal sepsis. By using a cut-off limit of 0,5 microg/L, the PCT positive likelihoud ratio was found of 12.5. PCT has a theoretical advantage as a marker of systemic induction in sepsis and its half-life suitable for daily monitoring of disease progress. PCT may be useful in assessing the severity of infection, following the progress of treatment, and predicting outcomes.
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PMID:Biochemical markers for the early assessment of neonatal sepsis: the role of procalcitonin. 1807 78

The diagnosis of diabetic foot infection (DFI) is usually a challenge to the clinician. Procalcitonin (PCT), a 116-amino acid propeptide of calcitonin, is a new marker of bacterial infections and sepsis. We evaluated the serum value of PCT as a marker of bacterial infection in diabetic patients with foot ulcers. Forty-nine diabetic patients with foot ulcers were consecutively enrolled into the study. DFI was diagnosed clinically by the presence of purulent secretions or at least two of the symptoms of inflammation including redness, warmth, swelling, and pain. According to these criteria, DFI was determined in 27 patients (DFI group) and not detected in 22 patients (NDFI group). The blood samples were taken for biochemical analysis on admission. PCT, white blood cell count (WBC) and erythrocyte sedimentation rate (ESR), but not C-reactive protein (CRP), was found significantly higher in DFI group compared with NDFI group. The best cut-off value, sensitivity and specificity were 0.08 ng/ml, 77% and 100% for PCT, 32.1 mg/dl, 29% and 100% for CRP, 8.6 10(9)/L, 70% and 72% for WBC and 40.5 mm/h, 77% and 77% for ESR, respectively. The area under the receiver operating characteristic curve for infection identification was greatest for PCT (0.859; p < 0.001), followed by WBC (0.785; p = 0.001), ESR (0.752; p = 0.003), and finally CRP (0.625; p = 0.137). These results suggest that PCT may be a useful diagnostic marker for DFI. Additional research is needed to better define the role of PCT in DFI.
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PMID:Procalcitonin as a diagnostic aid in diabetic foot infections. 1807 34

Accumulating evidence has suggested that hydrogen sulfide (H(2)S) is endogenously generated in many types of mammalian cells. Since H(2)S plays an important role in cardiovascular, central nervous and gastrointestinal systems, it is currently considered to be the third gaseous mediator. Recently, more and more attention has been paid to the biological functions of H(2)S in inflammation. In various animal models of inflammatory diseases (such as acute pancreatitis, sepsis and endotoxemia), endogenous H(2)S has been shown to be overproduced and participate in regulating the severity of inflammatory response and associated organ injury. Inhibition of H(2)S formation is likely to protect animals against these inflammatory diseases. H(2)S may exert its effect on inflammation via regulating the function of leukocytes, leukocyte trafficking and immune cell survival. Furthermore, H(2)S has been suggested to induce the release or production of neuropeptides (substance P and calcitonin gene-related peptide), which are considered to be pro-inflammatory mediators, and therefore contribute to inflammatory response. In addition, some studies reported that low doses of sodium hydrosulfide (NaHS, an H(2)S donor) exhibited some anti-inflammatory effect on local inflammation (such as non-steroidal anti-inflammatory drug-induced gastric injury). Taken together, all these findings demonstrate that in addition to the vasodilation and neuromodulation activity of H(2)S, it may contribute to the pathogenesis of inflammatory diseases via regulating the activation of leukocytes.
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PMID:Hydrogen sulfide: a novel mediator of leukocyte activation. 1867 Nov 60


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