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)

A 38-year-old male was admitted to the intensive care unit with a full-thickness burn involving 30 per cent of his total body surface area (TBSA) and severe inhalation injury. Respiratory failure developed within 54 h and CO2 could not be eliminated, even by very invasive mechanical ventilation. Because of the patient's age and the minor extent of the burned TBSA, we started extracorporeal CO2 elimination (ECCO2-R) and continued ECCO2-R for 30 days, when the patient was weaned from ECC. The clinical course during ECCO2-R was complicated by major bleeding from a thoracotomy tube, from the site of tangential excision and by four septic episodes. Lung biopsy was performed twice on day 29 (during ECCO2-R) and day 58 (after ECCO2-R) after admission and revealed bronchiolitis obliterans without tendency to recovery. The patient died of sepsis with multiorgan failure on day 81 after trauma.
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PMID:Inhalation injury treated with extracorporeal CO2 elimination. 924 48

The hemodynamic effects of sepsis have been attributed in part to increased nitric oxide (NO) production and activation of guanylate cyclase, resulting in increased cGMP and relaxation of vascular smooth muscle. Heme oxygenase-1 (HO-1), a heat shock protein, has been shown to increase intracellular cGMP levels by formation of carbon monoxide (CO). We hypothesized that HO may be an important mediator of the hepatic response to infection. Male Swiss Webster mice underwent standard cecal ligation and puncture (CLP, 18 gauge 2X) or sham operation, and received either normal saline (NS) or Zn protoporphyrin IX (ZN PP IX), a competitive HO inhibitor (n = 6-8/group). Hepatic tissue samples were collected at 3, 6, 12, and 24 hr from separate mice. Serum was collected at 3 and 24 hr. A semiquantitative reverse transcriptase polymerase chain reaction method was used to measure HO-1 mRNA levels. Hepatic cGMP levels were measured by ELISA. Groups were repeated (n = 10/group) to assess mortality. Serum was collected at 3 and 24 hr to measure serum aspartate aminotransferase (AST) levels. HO-1 mRNA expression increased significantly by 3 hr after CLP and with HO inhibition alone (P < 0.05 vs sham + NS). HO-1 mRNA remained elevated through 24 hr. CLP animals with HO inhibition showed a significant reduction of hepatic cGMP following CLP compared with CLP + saline at 24 hr (P < 0.05). Mortality was significantly increased in the CLP + ZN PP group at 24 hr (P < 0.05 CLP NS vs CLP ZN PP). CLP caused a marked increase in AST activity, which was increased further with HO inhibition. HO-1 mRNA expression was induced by CLP. AST levels following CLP were markedly increased with HO inhibition. HO-1 function appeared to contribute to elevation of hepatic cGMP during peritonitis and may be an important hepatic adaptive response to infection.
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PMID:Heme oxygenase-dependent carbon monoxide production is a hepatic adaptive response to sepsis. 927 Dec 71

Tumor necrosis factor (TNF) is involved in the pathogenesis of acute sepsis-induced organ injury and has been implicated as a mediator of metabolic alterations observed during sepsis. Pancreatic islet cell function may be significantly compromised during sepsis or endotoxemia, and sepsis also increases plasma levels of epinephrine, a modifier of islet insulin secretion. We proposed that islets exposed to bacterial lipopolysaccharide (LPS) produce TNF and that epinephrine attenuates islet secretory activity. We monitored the effects of LPS and epinephrine on TNF and insulin activity of isolated Wistar-Furth rat islets (pancreas digested with collagenase, islets isolated using Ficoll gradients; n = 4 islet populations, each with 632 +/- 11 islets/2.5 ml culture medium). Islets were incubated (37 degrees C, 5% CO2) 3 days. LPS (Escherichia coli, 1 microgram/ml) and epinephrine (14 micrograms/ml) were added to the islets, and incubations were continued for 1-4 h. Glucose (Beckman Glucose Analyzer), insulin (radioimmunoassay), and TNF (L929 cytotoxicity assay) were measured in the islet medium samples at 1- to 4-h time points. In the conditioned medium, glucose decreased (P < 0.05), insulin increased (P < 0.05), and exposure to LPS did not alter these levels [P = not significant (NS)] but did increase TNF activity by 400% (P < 0.05). Epinephrine reduced insulin by 38-43% (P < 0.05) and TNF by 20-25% (P < 0.05) but had no effect on glucose levels (P = NS). We conclude that insulin is secreted from isolated islets and that exposure to LPS acutely increases islet-derived TNF activity, whereas epinephrine modifies TNF and insulin secretion of rat pancreatic islets.
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PMID:Tumor necrosis factor activity of pancreatic islets. 927 98

This study was performed to quantify the impact of Haldane effect (HE) on the relationship between O2 extraction (O2Ex; mL O2/dL blood) and venous pH in 247 measurements performed in 91 septic patients (73 patients with intra-abdominal sepsis, 11 with retroperitoneal abscesses, 6 with severe cholangitis, and 1 with gangrenous fasclitis). The severity of sepsis varied from relatively compensated to extremely diseased conditions. This allowed a detailed assessment of the impact of HE over a wide range of cardiorespiratory and metabolic abnormalities. A recently developed model was used to quantify blood CO2 exchange and Haldane relationships and, in particular, the buffering of venous pH allowed by O2Ex (O2-linked H+ binding) on the basis of arterial and mixed venous blood gas measurements. Arterio-venous pH difference (a-vDpH) was .033 +/- .024 (mean +/- SD). It increased with venoarterial CO2 concentration difference (v-aDCO2; mL CO2/dL blood), but the increase was moderated by a simultaneous increase in O2Ex, as the likely consequence of HE: a-vDpH = .006 + .017 (v-aDCO2) - .009 (O2Ex) [r2 = .96, p < < .001]. To confirm this, the moderation of a-vDpH allowed by the HE (DpH) was calculated. A first component, due to O2-linked H+ binding, had a value of .016 +/- .012, and a second component, due to the Haldane-mediated reduction in venous CO2 tension and plasma carbonic acid concentration, had a value of .019 +/- .006. Their sum (total DpH) was .033 +/- .017 and was related directly and strongly to O2Ex: DpH = -.002 + .009 (O2Ex) [r2 = .85, p < < .001], thus confirming the quantitative impact of HE in moderating the decrease in venous pH relative to arterial pH. The loss of this effect was responsible for the larger decreases in venous pH observed in hypodynamic patients developing impaired O2Ex. These results allow an easy quantification of the Haldane component, separated from the other components affecting pH, and are also useful for assessing the protective role exerted by HE against excessive decreases in venous pH in circulatory failure.
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PMID:The relationship between oxygen extraction and venous pH in sepsis. 936 49

Tissue hypoxia, especially in the splanchnic area, is still considered to be an important cofactor in the pathogenesis of multiple organ failure. Thus, in the treatment of septic shock the specific effects of ino-tropic drugs on the splanchnic perfusion are of particular interest. To give strict recommendations for monitoring and for therapeutic strategies in the treatment of gastrointestinal failure in patients with sepsis is difficult not only due to the lack of data on clinical outcome and organ dysfunction, but also due to some limitations in the methods applied to assess splanchnic perfusion and oxygenation. A reasonable approach in the management of splanchnic underperfusion in septic patients includes: Measurement of gastric mucosal pH or CO2-gap because it is the only method for the assessment of splanchnic perfusion which can be useful in the clinical routine. Adequate volume loading likely is the most important step in the supportive treatment of patients with septic shock. Unfortunately, what kind of fluids, endpoints, and monitoring techniques should be used is still controversial. Nevertheless, techniques allowing us to achieve and tightly control volume loading and regional perfusion, e.g. the measurement of pHi or CO2-gap, may be helpful. Patients with high DO2 have had better outcome. However, measurement of parameters assessing global and regional oxygenation may be superior than to guide therapy by DO2. To maximize DO2 by the use of very high dosages of catecholamines can be harmful. The recommendation to use dobutamine as catecholamine of first choice seems to be justified. In critically ill patients, no negative effects of norepinephrine on regional perfusion have been demonstrated provided the patient is adequately volume resuscitated and the DO2 is normal or slightly elevated. Therefore, after volume resuscitation and treatment with dobutamine, norepinephrine should be used for achieving an adequate perfusion pressure. Epinephrine and dopamine should be avoided because they seem to restribute blood flow away from the splanchnic region. There are no convincing data yet to support the routine use of low dose dopamine or dopexamine in patients with sepsis. These recommendations are limited by the lack of outcome studies and optimal methods for the assessment of splanchnic perfusion/oxygenation.
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PMID:[Aspects in monitoring and treatment of gastrointestinal underperfusion in sepsis. Diagnosis and therapy of gastrointestinal underperfusion in sepsis]. 968 8

Early detection of pathophysiological factors associated with permanent brain damage is a major issue in neonatal medicine. The aim of our study was to evaluate the significance of the CO2 reactivity of cerebral blood flow (CBF) in neonates with perinatal risk factors. Fourteen ventilated neonates with perinatal risk factors (pathological cardiotocogramm, low cord pH, postpartal encephalopathy) were enrolled into this prospective study. The study was performed 18-123 h after birth. CBF was measured using the noninvasive intravenous 133Xe method. Two measurements were taken with a minimal PaCO2-difference of 5 mm Hg. From the two CBF values the CO2 reactivity was calculated. Outcome was evaluated 1 year after birth. The CBF values at a lower PaCO2 ranged from 6.6 to 115. 2 ml/100 g brain issue/min (median = 18.2) and at a higher PaCO2 level from 7.1 to 125.7 ml/100 g brain tissue/min (median = 18.75). The calculated CO2 reactivity ranged from -9.6 to 6.6% (median 1.1%) change in CBF/mm Hg change in PaCO2. CO2 reactivity correlated with lowest pH (r2 = 0.35, p = 0.02). Two infants died, one of neonatal sepsis, the other of heart failure. Neurological outcome at the age of 1 year was normal in 11 patients, 1 had severe cerebral palsy. From the 12 surviving patients the patient with severe neurological deficit showed the highest CBF values (125.7 ml/100 g/min). Impaired chemical coupling of cerebral blood flow is compatible with intact neurological outcome in neonates with perinatal risk factors. CO2 reactivity in these newborns correlates with the lowest pH and may reflect the severity of perinatal asphyxia.
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PMID:Impaired chemical coupling of cerebral blood flow is compatible with intact neurological outcome in neonates with perinatal risk factors. 983 79

Cu,Zn-superoxide dismutase (SOD1) acts as a peroxidase in the presence of H2O2 at high pH (pH > 9). The high pH species of H2O2, HO2-, was previously implicated as the reactive species. However, recent EPR studies of the enzyme performed in the physiological pH range 7.4-7.6 with the spin trap 5,5'-dimethyl-1-pyrolline-N-oxide attributed the intense EPR signal of 5, 5'-dimethyl-1-pyrolline-N-oxide-OH obtained from SOD1 and H2O2 to the peroxidase activity of the enzyme. The present study establishes that this intense signal is obtained only in the presence of bicarbonate. To explore the critical role of HCO3-, a comprehensive EPR investigation of the radical production and redox state of the active site copper was performed. The results indicate that HCO3- competes with other anions for the anion-binding site of SOD1 (Arg141) but does not bind directly to the copper. Structurally different anions that bind to Arg141 did not stimulate, but rather blocked, peroxidase function, ruling out an effect due to mere anion binding. However, the structurally similar anions HSeO3- and HSO3- mimic HCO3- in stimulating peroxidase function. These data suggest that HCO3- bound to Arg141 anchors the neutral H2O2 molecule at the active site copper, enabling its redox cleavage. Thus, SOD1 acquires peroxidase activity at physiological pH only in the presence of HCO3- or structurally similar anions. Alterations in pH that shift the HCO3-/CO2 equilibrium as occur in disease processes such as ischemia, sepsis, or shock would modulate the peroxidase function of SOD1.
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PMID:Bicarbonate is required for the peroxidase function of Cu, Zn-superoxide dismutase at physiological pH. 988 Apr 90

Bronchial rupture is a rare but severe complication of intubation with a double-lumen tube. Cardinal symptoms are mediastinal and subcutaneous emphysema as well as pneumothorax. Larger injuries result in an air leak and the endtidal carbon dioxide decreases. The gas exchange may worsen drastically when mucosal prolapse or bronchial haemorrhagia lead to bronchial occlusion. Mediastinitis or sepsis can be the sequel of the opened mediastinum. If bronchial injury is suspected probably fibreoptic bronchoscopy is indicated. We report on a case of bronchial rupture due to overinflation of the endobronchial cuff or movement of the inflated cuff when repositioning the patient. The conservative therapy was successful in spite of the fact that surgical intervention is recommended in the literature following bronchial rupture. To avoid tracheobronchial injuries an adequate tubus size must be selected. The more flexible polyvinylchloride (PVC) tubes without a carinal hook should be preferred to the Carlens tube. An atraumatic intubation is promoted by leaving the stylet inside after the tip of the tube has passed the vocal cords. To identify the minimum occlusive pressure of the endobronchial cuff for lung isolation different methods are described and should be used. The cuff has to be deflated when the patient is repositioned and when one-lung-ventilation is not required. Tumours of the tracheobronchial tree and weakness of the bronchial wall caused by steroid hormone therapy or COPD may increase the risk of tracheobronchial laceration.
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PMID:[Diagnosis, procedures and conservative therapy of a bronchial rupture after intubation with double-lumen tube]. 1007 58

Almost half of patients respond acutely to resuscitation but most die within the first several days after arrest. The incidence of survival to discharge from the hospital after cardiopulmonary arrest is about 15%; one third of those surviving have evidence of neurologic deficits. Although some prognostic variables are useful in determining which patients are most likely to die prior to discharge from the hospital, each patient needs to be evaluated on an individual basis and the various risk factors weighed carefully. As additional data accumulate, we may well be more effective at deciding which patients are more likely to benefit from CPR so that we can more judiciously apply this therapeutic modality. A number of studies have identified factors that contribute to poor outcome. Patients over 70 years of age usually fare poorly after CPR, but this is more a reflection of the number of coexisting diagnoses rather than years. Although initial survival may not be different from younger patients, fewer elderly patients live to discharge and more are likely to have neurologic sequelae. Concurrent diagnoses such as sepsis, AIDS, gastrointestinal bleeding, renal failure, cancer, and central nervous system disease have a universally poor response to CPR. If defibrillation occurs more than 6 minutes after arrest or on the general ward or if the resuscitative attempt lasts longer than 15 minutes, mortality is greater than 95%. If CPR continues for more than 30 minutes, there are no survivors. A low exhaled CO2 concentration (< 2%) during cardiac massage, asystole or EMD as the first identified rhythm, and recurrent arrest also carry a poor prognosis. On the other hand, at the time of arrest or during the immediate postarrest period, poor neurologic status is a less helpful predictor. The absence of spontaneous respiration is the only variable at the time of admission after out-of-hospital arrest that is particularly ominous. There is no evidence to suggest that the absence of spontaneous respiration implies any better prognosis for patients arresting in the hospital. Coma, hypoxic myoclonus, and absent reflexes, while not useful immediately following arrest, are of greater prognostic significance 48 hours later. Only 5% of patients who are unconscious 48 hours after arrest will have a full neurologic recovery. The Glasgow Coma Scale has also been used for prognostication.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Resuscitation: when is enough, enough? 1014 87

The hypothesis that induction of chronic peritoneal sepsis would produce depression of serum testosterone due to a decrease in Leydig cell steroidogenic acute regulatory (StAR) protein or P450c17 steroidogenic enzyme was tested. Male Sprague-Dawley rats (350-400 g) were randomized to septic and nonseptic groups. Sepsis was induced with a cecal slurry (200 mg/kg in 5 mL of 5% dextrose in water (D5W); intraperitoneal) while nonseptic rats received only sterile D5W. Animals (n = 6, in each group) were killed by CO2 asphyxiation and blood samples were collected by direct cardiac puncture at 24 h after induction of sepsis/sham sepsis. The serum concentration of corticosterone, progesterone, estradiol, and testosterone was determined using radioimmunoassay. Western blot analysis was utilized to quantify Leydig cell StAR protein and P450c17 enzyme. Sepsis produced a significant decrease in the serum concentration of testosterone, a down-regulation of StAR protein, and an increase in serum estradiol 24 h after induction of sepsis (as compared with the nonseptic group). Protein levels of P450c17 in Leydig cells and serum concentrations of progesterone and corticosterone 24 h after induction of sham sepsis or sepsis were not different. It is concluded that the decreases in serum testosterone after 24 h of chronic peritoneal sepsis correlated with reductions in StAR protein.
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PMID:Sepsis produces depression of testosterone and steroidogenic acute regulatory (StAR) protein. 1022 Mar 9


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