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)

A 47-year-old woman was admitted with fever, hypotension, an elevated serum creatinine kinase level, and electrocardiographic abnormalities, which led to the diagnosis of acute myocarditis. She was placed on percutaneous cardiopulmonary support because of hemodynamic collapse on the third hospital day. Serial echocardiography showed gradual recovery of profound hypokinesis and edematous thickening of the left ventricle, but she died of sepsis on the 17th day without overt renal insufficiency or electrolytic abnormalities. Autopsy revealed myocardial necrosis with lymphocytic infiltrates and extensive myocardial calcification. Calcification was dense in the area of severe myocardial necrosis, and the distribution of calcium deposits suggested that the calcification was a consequence of significant inflammation of the myocardium. Recovery of regional wall motion was prominent in the area of severe inflammatory change. Dissociation between the pathologic and echocardiographic findings suggested the possibility of functional reversibility of severely damaged myocardium and possible mechanisms of abnormal contractile function other than inflammatory change.
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PMID:An autopsied case of acute myocarditis with myocardial calcification. 929 12

Acute, life-threatening complications of lung transplantation are common in all reported series. The clinical courses and images of 70 patients who underwent heart-lung (n = 5), bilateral sequential lung (n = 31), or single-lung (n = 38) transplantation were retrospectively reviewed. Sixty-five acute, life-threatening complications occurred in 26 patients (37%) within 3 months after transplantation. Nine deaths occurred as a result of these complications for a mortality rate due to acute complications of 13%. The deaths were a result of bleeding (n = 4), sepsis (n = 2), severe acute rejection and adult respiratory distress syndrome (n = 1), multiorgan failure (n = 1), and diffuse alveolar damage and respiratory failure (n = 1), a distribution of causes similar to those in other reported series. Specific diagnoses that can be made with imaging include hemothorax, lung torsion, pneumomediastinum, pulmonary embolism, pneumothorax, bronchial anastomotic dehiscence, lung collapse, paralysis of the diaphragm, and sternal dehiscence.
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PMID:Acute, life-threatening complications of lung transplantation. 946 Jan 7

Posttranslational processing of the adrenomedullin gene product results in the formation of at least two biologically active peptides, adrenomedullin (AM) and proadrenomedullin N-20 terminal peptide (PAMP). Produced predominantly in the vasculature, both peptides are potent hypotensive agents, albeit via unique mechanisms of action. The gene is transcribed in a variety of other tissues including brain, pituitary, and kidney. Numerous actions have been reported most related to the physiologic control of fluid and electrolyte homeostasis. In the kidney, AM is diuretic and natriuretic, and both AM and PAMP inhibit aldosterone secretion by direct adrenal actions. In pituitary gland, both peptides at physiologically relevant doses inhibit basal ACTH secretion, again by apparently differing mechanisms. Additionally, AM antagonizes CRH-stimulated ACTH release. The peptides are produced in numerous brain sites, including hypothalamus and brainstem. Inhibition of AVP release has been reported and the physiologic significance of AM's ability to inhibit water drinking and salt appetite has been established. Thus the peptides appear to act in brain and pituitary gland to facilitate the loss of plasma volume, actions which complement their hypotensive effects in the blood vessel. Interestingly, direct cardiac effects (positive inotropism and chronotropism) and CNS actions (sympathostimulation) have been reported, leading to the hypothesis that these peptides also can exert important cardioprotective effects, helping to prevent vascular collapse during states of high AM secretion such as sepsis.
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PMID:Proadrenomedullin-derived peptides. 957 82

Recognition of bacterial endotoxin (LPS) elicits multiple host responses, including activation of cells of the innate immune system. LPS exposure occurs repeatedly during septicemia, making strict regulation of gene expression necessary. Such regulation might prevent, for example, the continuous production of proinflammatory cytokines such as tumor necrosis factor (TNF), which could lead to severe vascular collapse. Tolerance to LPS is characterized by a diminished production of TNF during prolonged exposure to LPS, and is therefore likely to represent an essential control mechanism during sepsis. In the present study, which uses mice with genetic deletions of the proteins of NF-kappaB complex, we provide data demonstrating that increased expression of the p50 subunit of NF-kappaB directly results in the downregulation of LPS-induced TNF production. This contention is supported by the following observations: (1) tolerance to LPS is not induced in macrophages from p50-/- mice; (2) long-term pretreatment with LPS does not block synthesis of TNF mRNA in p50-/- macrophages (in contrast to wild-type macrophages); (3) ectopic overexpression of p50 reduces transcriptional activation of the murine TNF promoter; and (4) analysis of the four kappaB sites from the murine TNF promoter demonstrates that binding of p50 homodimers to the positively acting kappaB3 element is associated with development of the LPS-tolerant phenotype. Thus, p50 expression plays a key role in the development of LPS tolerance.
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PMID:Regulation of an essential innate immune response by the p50 subunit of NF-kappaB. 980 78

In the heart, histamine (H3) receptors may function as inhibitory presynaptic receptors that decrease adrenergic norepinephrine release in conditions of enhanced sympathetic neural activity. We hypothesized that H3-receptor blockade might improve cardiovascular function in sepsis. In a canine model of Escherichia coli sepsis, we found that H3-receptor blockade increased cardiac output (3.6 to 5.3 l/min, P < 0.05), systemic blood pressure (mean 76 to 96 mmHg, P < 0.05), and left ventricular contractility compared with pretreatment values. Plasma histamine concentrations increased modestly in the H3-blocker-sepsis group compared with values obtained in a nonsepsis-time-control group. In an in vitro preparation, histamine H3 activation could be identified under conditions of septic plasma. We conclude that activation of H3 receptors may contribute to cardiovascular collapse in sepsis.
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PMID:Histamine H3 activation depresses cardiac function in experimental sepsis. 980 71

The bacterial endotoxin lipopolysaccharide (LPS) contributes to the cardiovascular collapse and death observed in patients with sepsis. Because LPS has such profound effects on cardiac performance, we speculate that direct effects of LPS could be demonstrated on cardiomyocytes in culture, and that these direct effects are mediated by the LPS receptor, CD14. Accordingly, in this study, we provide evidence for CD14-dependent cardiotoxic effects of LPS including the LPS-stimulated secretion of tumor necrosis factor alpha (TNF-alpha) from cardiomyocytes. TNF-alpha is an inflammatory cytokine which is known for its negative inotropic effects on cardiac performance, but has not until recently been shown to be produced by cardiac cells. In this study, LPS was found to stimulate strongly in a dose-dependent manner the secretion of TNF-alpha from cultured adult rat cardiomyocytes. Further, LPS-induced TNF-alpha secretion was blocked by an inhibitor of TNF-alpha processing, metallomatrix protease inhibitor (TAPI). Molecular and immunological evidence demonstrated the presence of LPS receptors (CD14) on cardiomyocytes. Attenuated TNF-alpha secretion following PI-PLC treatment confirmed the functional importance of CD14 for LPS-mediated myocardial effects. Importantly, LPS also triggered apoptosis in cultured cardiomyocytes as quantified by single-cell gel electrophoresis of nuclei exhibiting DNA fragmentation patterns characteristic of apoptosis (i.e. cardiac comets). Apoptotic cell death was blocked by pre-incubation with the soluble TNF-alpha receptor fragment (TNFRII:Fc), suggesting that LPS-induced apoptosis was TNF-alpha-dependent and probably involved an autocrine function for the TNF-alpha whose secretion was under LPS control. The results of this study suggest that the cardiodepressant effects of LPS are dependent on CD14 signaling and may not only be due to acute negative inotropic effects of TNF-alpha but also may be complicated by TNF-alpha-induced apoptotic cell death which effectively reduces the number of working myocardial cells.
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PMID:LPS-induced TNF-alpha release from and apoptosis in rat cardiomyocytes: obligatory role for CD14 in mediating the LPS response. 999 May 46

The present study examined the effects of mechanical ventilation, with or without positive end-expiratory pressure (PEEP), on the alveolar surfactant system in an animal model of sepsis-induced lung injury. Septic animals ventilated without PEEP had a significant deterioration in oxygenation compared with preventilated values (arterial PO(2)/inspired O(2) fraction 316 +/- 16 vs. 151 +/- 14 Torr; P < 0.05). This was associated with a significantly lower percentage of the functional large aggregates (59 +/- 3 vs. 72 +/- 4%) along with a significantly reduced function (minimum surface tension 17.7 +/- 1.8 vs. 11.8 +/- 3.8 mN/m) compared with nonventilated septic animals (P < 0.05). Sham animals similarly ventilated without PEEP maintained oxygenation, percent large aggregates and surfactant function. With the addition of PEEP, the deterioration in oxygenation was not observed in the septic animals and was associated with no alterations in the surfactant system. We conclude that animals with sepsis-induced lung injury are more susceptible to the harmful effects of mechanical ventilation, specifically lung collapse and reopening, and that alterations in alveolar surfactant may contribute to the development of lung dysfunction.
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PMID:Effects of ventilation on the surfactant system in sepsis-induced lung injury. 1065 4

We studied the hemodynamic responses of 29 anesthetized and mechanically ventilated piglets to acute hypoxia [reduction of Pao2 from 130 to 38 mm Hg induced by inhalation of 7% fraction of inspired oxygen (Fio2) for 7.5 min] before and during group B beta-hemolytic streptococci (GBS) sepsis. During hypoxia, nonseptic piglets maintained stable systemic blood pressure [105+/-9 (SD) to 97+/-14 mm Hg] and cardiac output (CO) (667+/-72 to 685+/-113 mL/min). However, during GBS/hypoxia, systemic blood pressure fell from 94+/-17 to 49+/-25 mm Hg, CO fell from 397+/-146 to 223+/-142 mL/min (both p < 0.001 versus pre-GBS), and cardiac arrest often ensued. We tested three hypotheses that might underlie GBS-induced intolerance to systemic hypoxia: 1) GBS-induced reduction of systemic CO/systemic oxygen delivery (QO2) below a critical QO2 beyond which the superimposition of hypoxia becomes intolerable; this mechanism is unlikely as nonseptic piglets with comparable reductions in CO/QO2 (induced by inflation of a left atrial balloon) tolerated hypoxia well; 2) GBS-induced inhibition of nitric oxide (NO) synthesis that is vital to tolerance of hypoxia; this mechanism is unlikely as infusion of the NO substrate L-arginine did not restore tolerance to hypoxia during GBS infusion (as it did after inhibition of NO synthesis during infusion of N-nitro-L-arginine in nonseptic piglets); and 3) GBS-induced production of pathologic prostaglandins that impaired the piglet's capacity to tolerate hypoxia; this mechanism finds support in the observation that inhibition of prostaglandins with the cyclooxygenase inhibitor indomethacin completely restored the ability of septic piglets to tolerate hypoxia. Further evaluation of GBS-induced intolerance to systemic hypoxia may provide insight into the incompletely understood mechanisms by which sepsis induces circulatory collapse in experimental animals and in humans.
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PMID:Hemodynamic homeostasis during acute hypoxia in septic and nonseptic piglets: differential role of prostaglandins and nitric oxide. 1075 60

The physiological responses to either hemorrhage or sepsis have been well documented, however, their simultaneous delivery, as often seen in penetrating trauma, has not been extensively studied. A terminally-anesthetized porcine model of fixed-volume hemorrhage combined with intraperitoneal sepsis was developed. Large White pigs (45-60 kg) were bled 40% of blood volume and peritonitis was induced using an E. coil (O18:K1:H7) culture. Three groups of animals were sequentially studied. Group A (n = 8) received 10(8) bacteria, and Groups B (n = 4) and C (n = 5) received 10(10) organisms. All animals were maintained on a 2.5 mL/kg/h infusion of 0.9% saline. Group C was autotransfused at 1 h. Animals were monitored for up to 24 h. Cardiovascular features of hypovolemia were recorded in all animals. Animals in Group A improved clinically with little microbiological evidence of systemic sepsis. Group B showed rapid cardiovascular collapse, early E. coil-positive blood cultures, and an early rise in serum TNF-alpha levels. Autotransfusion of Group C significantly improved cardiopulmonary parameters, acid-base status, and survival. A reproducible model of hemorrhage and peritonitis, appropriate for abdominal trauma, which allows investigation of resuscitative and pharmacological interventions has been characterized.
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PMID:A porcine model of sepsis resulting from the combined insults of hemorrhage and peritonitis. 1077 18

The systemic response to endotoxin is characterized by hypotension and severe reductions in blood pressure, leading to cardiovascular collapse that can accompany septicemia. The renin/angiotensin system would normally be expected to respond to hypotensive challenge; however, inflammation appears to modify this response. This study identifies a strong acute phase response of the kidney that is characterized by enhanced expression of serum amyloid A, haptoglobin and tissue inhibitor for metalloproteinase-1 and a reduced expression of renin. Equivalent regulatory effects were observed for the immortalized As4.1 kidney cell line that models certain features of juxtaglomerular cells. Oncostatin M, a known endotoxin-responsive proinflammatory cytokine, proved to be an effective inhibitor of renin gene expression. Suppression by oncostatin M involves activated STAT5 and requires an inhibitory element in the renin promoter that functions separately from cell type-specific enhancer elements. The renal acute phase reaction, unlike the liver acute phase reaction, is more strongly dependent on locally produced inflammatory factors.
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PMID:Endotoxin-induced renal inflammatory response. Oncostatin M as a major mediator of suppressed renin expression. 1080 9


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