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

Sclerosing encapsulating peritonitis (SEP) is characterized by the diffuse appearance of marked sclerotic thickening of the peritoneal membrane. We experienced a case with SEP accompanied by regional changes of peritoneum. A 37-year-old woman with end-stage renal failure was started on continuous ambulatory peritoneal dialysis in 1985 and was transferred to hemodialysis in 1997. She was admitted because of ileus in 1998 with SEP and died of septicemia. The diagnosis of SEP was confirmed via the autopsy. The root of the mesentery was retracted and shortened. Since the peritoneal change was marked in the regions with free margin of mesentery and was less apparent in the regions not adhered to mesentery, it is indicated that mechanical stress also contributes to the occurrence of SEP. Since calcification and ossification were only seen in a free margin of small bowel from mesentery, it is suggested that there is a close relationship between calcification and ossification. Since fibrosis invaded into the muscle layer, dysfunction of bowel movement as well as bowel obstruction contributed to the appearance of ileus. It is suggested that mechanical stress by the root of mesentery which is retracted and shortened also contributes to the appearance of SEP.
Nephron 2002 Oct
PMID:Sclerosing encapsulating peritonitis: regional changes of peritoneum. 1221 37

Acute renal failure (ARF) is a common and important complication of critical illness and many interventions have been proposed to prevent it. The pathogenesis of acute renal failure during critical illness is poorly understood. Animal models are based on the induction of renal ischemia and do not reflect the dominance of sepsis as a cause of ARF in the clinical arena. Although biological rationale exists for several interventions, none have been shown to be effective in large randomized double-blind multicentre trials. The only interventions with close to level I evidence are confined to the attenuation of radiocontrast nephropathy. The effect on such interventions is, however, of limited clinical relevance to critically ill patients. The maintenance of adequate intravascular filling, cardiac output and renal perfusion pressure and the avoidance of hypoxemia, marked anemia and nephrotoxins remain the only justifiable interventions at this time.
Nephron Clin Pract 2003 Jan
PMID:Prevention of acute renal failure in the critically ill. 1241 54

Sepsis and septic shock are the leading causes of death in non-cardiological intensive care units in developed countries despite recent advances in critical care medicine. Sepsis is the systemic inflammatory response to infection, often associated with hypoperfusion followed by tissue injury and organ failure. Activation of monocytes/macrophages and neutrophils with consecutive release of proinflammatory mediators and activation of the coagulation cascade, seem to play a key role in the pathogenesis of sepsis. Elimination of the septic focus,antimicrobial therapy and supportive treatment are the cornerstones of sepsis therapy. Adequate and rapid volume replacement and if necessary application of catecholamines are of highest priority to optimize tissue perfusion. Norepinephrine is the vasopressor of choice and dobutamine the preferred inotropic agent. Most experts recommend hemoglobin levels of 8-10 g/dl in severe sepsis. In addition,lung protective ventilatory strategies as well as enteral and parenteral nutrition are part of the clinical management of septic patients. In mechanically ventilated patients intensive insulin therapy to maintain blood glucose at a level between 80 and 110 mg/dl has significantly reduced mortality.Furthermore,prophylaxis of deep vein thrombosis and of stress ulcer bleeding are individually applied to septic patients. Treatment of septic patients with anti-mediator strategies or high dose AT III were not successful so far. In contrast,now two new promising treatment options may be emerging: application of small doses hydrocortisone and activated protein C [drotrecogin alfa (activated)]. Large and in part multicentric studies especially in the last 2 years now allow the practicing clinician to perform a partially evidence-based management of patients with sepsis. In addition, for the first time two options for specific therapy of sepsis,application of small doses hydrocortisone and activated protein C [drotrecogin alfa (activated)],are available which may further improve prognosis for septic patients.
 ...
PMID:[Clinical management of patients with sepsis]. 1257 61

Norepinephrine (NE) is mostly used to treat severe hypotension. However, NE has potentially adverse vasoconstrictive effects on regional vascular beds of kidney, liver, and gut, with a potential for ensuing organ dysfunction. NE therefore is considered as a last reserve in otherwise refractory hypotension. During sepsis, a loss of catecholamine responsiveness occurs that is often interpreted as down-regulation of catecholamine receptors. Therefore, the doses of NE needed to maintain or restore blood pressure may be extremely high. Surprisingly, no adverse vasoconstriction with subsequent hypoperfusion occurs during sepsis, despite the high doses of NE administered. Instead, NE rather causes an increase in blood flow and oxygen delivery.
 ...
PMID:Norepinephrine in septic patients--friend or foe? 1271 59

During sepsis, limited data on the survival effects of vasopressors are available to guide therapy. Therefore, we compared the effects of three vasopressors on survival in a canine septic shock model. Seventy-eight awake dogs infected with differing doses of intraperitoneal Escherichia coli to produce increasing mortality were randomized to receive epinephrine (0.2, 0.8, or 2.0 microg.kg(-1).min(-1)), norepinephrine (0.2, 1.0, or 2.0 microg.kg(-1).min(-1)), vasopressin (0.01 or 0.04 U/min), or placebo in addition to antibiotics and fluids. Serial hemodynamic and biochemical variables were measured. Increasing doses of bacteria caused progressively greater decreases in survival (P <0.06), mean arterial pressure (MAP) (P <0.05), cardiac index (CI) (P <0.02), and ejection fraction (EF) (P=0.02). The effects of epinephrine on survival were significantly different from those of norepinephrine and vasopressin (P=0.03). Epinephrine had a harmful effect on survival that was significantly related to drug dose (P=0.02) but not bacterial dose. Norepinephrine and vasopressin had beneficial effects on survival that were similar at all drug and bacteria doses. Compared with concurrent infected controls, epinephrine caused greater decreases in CI, EF, and pH, and greater increases in systemic vascular resistance and serum creatinine than norepinephrine and vasopressin. These epinephrine-induced changes were significantly related to the dose of epinephrine administered. In this study, the effects of vasopressors were independent of severity of infection but dependent on the type and dose of vasopressor used. Epinephrine adversely affected organ function, systemic perfusion, and survival compared with norepinephrine and vasopressin. In the ranges studied, norepinephrine and vasopressin have more favorable risk-benefit profiles than epinephrine during sepsis.
 ...
PMID:Differing effects of epinephrine, norepinephrine, and vasopressin on survival in a canine model of septic shock. 1531 5

Previously, we have reported that the susceptibility of burned patients to infectious complications is increased when the production of CC-chemokine ligand 3 (CCL3) is impaired. In this study, the role of the sympathetic nervous system on impaired CCL3 production and antibacterial resistance following burn injuries was investigated. Normal mice were resistant (65% survival) to cecal ligation and puncture (CLP)-induced sepsis, while the same CLP killed 90% of thermally injured mice (TI-mice). However, TI-mice resisted CLP-induced sepsis (60% survival) when they were previously treated with CCL3 or sympathectomized with 6-hydroxydopamine (6-OHDA). Augmentation of host resistance against CLP-induced sepsis by 6-OHDA was abrogated by anti-CCL3 mAb treatment. Norepinephrine (NE) production was increased in circulation of TI-mice, and treatment of TI-mice with 6-OHDA resulted in the inhibition of NE secretion. CCL3 production was impaired in cultures of T cells from TI-mice or normal T cells treated with NE, even when stimulated with anti-CD3 mAb. However, CCL3 was produced by mAb-stimulated T cells from TI-mice previously treated with 6-OHDA. These results indicated that by inhibiting CCL3 production the sympathetic nervous system contributes to the increased susceptibility of TI-mice to sepsis.
 ...
PMID:Contribution of the sympathetic nervous system on the burn-associated impairment of CCL3 production. 1576 Jun 77

Limited information is available about selection of the threshold for arterial blood pressure in critically ill patients, particularly in sepsis when normal organ blood flow autoregulation may be altered. The present experimental study investigated whether increasing perfusion pressure using norepinephrine in normotensive hyperdynamic porcine bacteremia affects intestinal macro- and microcirculation. Nine pigs received continuous i.v. administration of Pseudomonas aeruginosa (PSAE) to develop hyperdynamic, normotensive (mean arterial pressure [MAP] 65 mm Hg) sepsis. Norepinephrine was used to achieve 10-15 % increase in MAP. Mesenteric arterial blood flow (Q(gut)), ileal mucosal microvascular perfusion (LDF(gut)) and ileal-end-tidal PCO(2) gap (PCO(2) gap) were measured before norepinephrine, after 60 min of norepinephrine infusion and 60 min after norepinephrine infusion had been discontinued. During a 12 h period of PSAE infusion all pigs developed hyperdynamic circulation with significantly decreased MAP. Although the mesenteric blood flow remained unchanged, infusion of PSAE resulted in a gradual fall of ileal microvascular perfusion, which was associated with progressively rising PCO(2) gap. Norepinephrine which induced a 10-15 % increase in perfusion pressure (i.e. titrated to attain near baseline values of MAP) affected neither Q(gut) nor the intestinal blood flow distribution (Q(gut)/CO). Similarly, norepinephrine did not change either LDF(gut) or PCO(2) gap. In this hyperdynamic, normotensive porcine bacteremia, norepinephrine-induced increase in perfusion pressure exhibited neither beneficial nor deleterious effects on intestinal macrocirculatory blood flow and ileal mucosal microcirculation. The lack of changes suggests that the gut perfusion was within its autoregulatory range.
 ...
PMID:Perfusion pressure manipulation in porcine sepsis: effects on intestinal hemodynamics. 1634 46

Acute renal failure (ARF) induced by sepsis has a high mortality but lacks effective treatments. To develop novel therapies we must diagnose renal injury early and accurately in septic patients and identify any additional insults such as nephrotoxic drugs and ischemia. In this short review we describe our experience using MRI with dendrimer-based contrast agents in mouse models of ARF. This technique can diagnose early renal injury before serum creatinine is elevated, distinguish different ARF etiologies, track drug therapy and predict outcome. As an ARF biomarker, MRI with dendrimer-based contrast is a promising technique deserving further development.
Nephron Clin Pract 2006
PMID:Imaging acute renal failure with polyamine dendrimer-based MRI contrast agents. 1654 55

"Severe sepsis" is defined by organ dysfunction due to infection-induced hypoperfusion. "Septic shock" is defined by hypotension refractory to fluid resuscitation, associated with organ dysfunctions or hypoperfusion. Mortality from severe sepsis and from septic shock is high. Guidelines to help physicians improve the survival of patients with severe sepsis comprise one part of an international project called the Surviving Sepsis Campaign. They bring together treatment innovations based on monitoring aimed at ensuring comprehensive management of tissue oxygen levels (central venous oxygen saturation: SvcO2). They are based on the optimization of early treatment, during the first six hours of severe sepsis, and ensuring no delay in fluid resuscitation. In case of septic shock, fluid resuscitation must be rapidly accompanied by administration of vasoconstrictive catecholamines. Noradrenaline is preferred to dopamine. Dobutamine is recommended when the cardiac index is less than 2.5 L x min(-1) x m(-2). Because of the relative adrenal insufficiency that occurs during septic shock, corticoids are recommended, after a synacthen test. Activated protein C is currently the only therapy produced by biotechnology that reduces mortality from severe sepsis. Global management of septic shock must form an integral part of resuscitation guidelines and include protocols for, among other things, sedation, ventilation, strict glycemic control, and prophylaxis for deep vein thrombosis and stress ulcers.
 ...
PMID:[Non-infective treatments for septic shock]. 1678 62

Treatment of hemodynamic instability in septic shock often demands the administration of vasopressor agents, although these may have deleterious effects on microcirculatory homeostasis. Inhibition of nitric oxide synthase (NOS) has been suggested as an alternative therapeutic approach, as NO formation may be excessively increased in sepsis. To compare the effects of epinephrine titration, non-selective NOS inhibition by L-NMMA and selective inhibition of inducible NOS (iNOS) by 1400W on hemodynamics and on the regulation of microcirculation in a rat model of endotoxic shock, we intravenously injected endotoxin (LPS) or saline to male Wistar rats and after 2 hours randomized LPS treated rats into four different groups that received either saline, norepinephrine, L-NMMA or 1400W (n = 6 per group). Three hours after LPS administration, rats presented with severe systemic arterial hypotension (64 +/- 3 vs. 115 +/- 4 mmHg, p < 0.001), unresponsiveness to volume treatment, lactate acidosis and a marked increase in plasmatic nitrite and nitrate levels (15 +/- 8 vs. 263 +/- 47 microM, p < 0.001). Measurement of the tissue oxygenation in the ileum mucosal layer by the Erlangen micro-lightguide spectrophotometer (EMPHO) technique demonstrated marked heterogeneity of hemoglobin saturation, with appearance of low oxygenated areas. Norepinephrine, usually stabilizing blood pressure (99 +/- 7 vs. 67 +/- 4 mmHg 60 min after infusion, p < 0.01), increased lactate formation (7.9 +/- 0.2 vs. 3.7 +/- 0.5 mM, p < 0.001) and drastically increased low oxygenated regions in the ileum mucosal layer. L-NMMA similarly increased blood pressure (92 +/- 6 vs. 67 +/- 4 mmHg 60 min after infusion, p < 0.05), but did not enhance lactate acidosis. However, some further deterioration of mucosa oxygenation was again noted. 1400W forwarded stabilization of blood pressure (88 +/- 5 vs. 67 +/- 4 mmHg 60 min after injection, p < 0.05), reduced plasmatic nitrite and nitrate levels similar to L-NMMA, without an aggravation of lactate acidosis. In addition, mucosal oxygenation did not deteriorate in response to this agent. Thereby, we conclude that in a rat model of endotoxic shock selective iNOS inhibitors are superior to non-specific NOS inhibitors and in particular to norepinephrine for the treatment of macro- and microcirculatory abnormalities in experimental septic shock.
 ...
PMID:Effect of nitric oxide synthase (NOS) inhibition on macro- and microcirculation in a model of rat endotoxic shock. 1660 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>