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)

Anthrax, a disease of mammals (including humans), is caused by a spore-forming Gram-positive bacilli called Bacillus anthracis. Anthrax is one of the oldest threats to humanity, and remains endemic in animals in many parts of the world. The incidence of anthrax has decreased in developed countries, but it remains a considerable health problem in developing countries. The disease is transmitted to humans by contact with sick animals or their products, such as wool, skin, meat etc. Capsular polypeptide and anthrax toxin are the principal virulence factors of B. anthracis. Anthrax toxin consists of three proteins called protective antigen, edema factor, and lethal factor, each of which is nontoxic but acts synergistically. Human anthrax has three major clinical forms: cutaneous, inhalational, and gastrointestinal. The diagnosis is easily established in cutaneous cases, characterized by black eschar. Severe intoxication and collapse during the course of bronchopneumonia or hemorrhagic enteritis should prompt suspicion of anthrax. Treatment with antibiotics is mandatory. If untreated, anthrax in all forms can lead to septicemia and death. Recently, considerable attention has been focused on the potential for B. anthracis to be used in acts of biological terrorism. The ease of laboratory production and its dissemination via aerosol led to its adoption by terrorists, as shown by recent events in the USA. A good knowledge of anthrax, its epidemiology, pathogenesis, clinical forms and potential as a biological weapon is essential for timely prevention and treatment. This review summarizes the current knowledge on anthrax.
Med Sci Monit 2003 Nov
PMID:Anthrax--an overview. 1458 93

During a 5-year period, 1997 to 2002, therapeutic drug monitoring of midazolam plasma concentrations in combination with the level of sedation as assessed by the Ramsay sedation scale was performed in 648 critically ill patients requiring artificial ventilation. In a subgroup of 189 patients sepsis-related organ failure assessment procedure was additionally performed. A total number of 3354 samples were analyzed. Significantly reduced clearance of midazolam was observed within the first 4 days of midazolam treatment of critically ill patients. As a result, accumulation of midazolam and its metabolites occurred within the first week of treatment. In contrast, parameters such as serum bilirubin or creatinine, which are commonly used to adapt drug therapy to organ dysfunction, showed significant changes with a delay of more than 10 days as compared with the findings of midazolam monitoring. Midazolam plasma concentrations showed a good correlation with the sedative capacity of the drug (r2 = 0.906). However, a great variability of the drug effect between patients could be demonstrated, which, as a consequence, may complicate the development of dosing strategies based on midazolam plasma concentrations to better control sedation in critically ill patients. Furthermore, patient age seems to be an important factor for the considerable variability of the sedative effect of midazolam. To achieve a certain levels of sedation, significantly lower midazolam infusion rates as well as plasma concentrations were required as the patients age increased. No significant sex-related differences could be observed for any pharmacologic parameter obtained in this study. Our findings suggest that midazolam therapeutic drug monitoring might be a useful tool to individualize midazolam therapy, especially in critically ill patients developing organ dysfunction and requiring long-term sedation to minimize the risk of drug accumulation and excessive sedation.
Ther Drug Monit 2004 Dec
PMID:Midazolam therapeutic drug monitoring in intensive care sedation: a 5-year survey. 1557 Jan 89

Sepsis is an infection-induced syndrome characterized by a generalized inflammatory state and represents a frequent complication in the surgical patient. The normal reaction to infection involves a series of complex immunologic processes. A potent, complex immunologic cascade ensures a prompt protective response to microbial invasion in humans. Although activation of the immune system during microbial invasion is generally protective, septic shock develops in a number of patients as a consequence of excessive or poorly regulated immune response to the offending organism (Gram-negative or Gram-positive bacteria, fungi, viruses, or microbial toxins). This unbalanced reaction may harm the host through a maladaptive release of endogenously generated inflammatory compounds. Many mechanisms are involved in the pathogenesis of septic shock, including the release of cytokines, the activation of neutrophils, monocytes, and microvascular endothelial cells, as well as the activation of neuroendocrine reflexes and plasma protein cascade systems, such as the complement system, the intrinsic (contact system) and extrinsic pathways of coagulation, and the fibrinolytic system. In critically ill patients, the gastrointestinal tract plays a central role in the pathogenesis of septic shock. The potential for complementary and synergistic interaction of the different components in this cascade highlights the difficulty encountered in trying to identify a single means of altering the progression of sepsis and septic shock to multiple organ dysfunction syndrome (MODS) and multiple organ failure (MOF).
Med Sci Monit 2005 Mar
PMID:Septic shock; current pathogenetic concepts from a clinical perspective. 1686 72

Pyruvic acid, an intermediate metabolite of glucose, an effective scavenger of reactive oxygen species (ROS), inhibits tumor necrosis factor-alpha production and NF-kappaB signaling pathways, reduces circulating levels of HMGB1 (high mobility group B1), decreases COX-2 (cyclo-oxygenase-2), iNOS (inducible nitric oxide synthase), and IL-6 (interleukin-6) mRNA expression in liver, ileal mucosa, and colonic mucosa in animal models with endotoxemia. These studies suggest that pyruvate has potent anti-oxidant and anti-inflammatory actions. Insulin influences the production of pyruvate by its action on glucose metabolism and pyruvate is an insulin secretagogue. This suggests that in metabolic syndrome X, obesity, hypertension, diabetes mellitus, and cancer (where insulin resistance is common due to enhanced TNF-alpha production) pyruvate plays a role. This may have relevance to the use of glucose-insulin-potassium regimen in these clinical conditions, sepsis, and cancer.
Med Sci Monit 2006 May
PMID:Pyruvate is an endogenous anti-inflammatory and anti-oxidant molecule. 1664 87

Because of changing demographics, increasing numbers of patients with IHD are presenting for noncardiac surgery, and the risks of perioperative morbidity and mortality are significant. The Lee Cardiac Risk Index is applicable in defining perioperative cardiac risk: however, ACC/AHA guidelines may not be applicable comprehensively. The role of biomarkers in risk stratification still needs to be defined. Structured management protocols that help assess, diagnose, and treat patients with IHD preoperatively are likely to help decrease postoperative morbidity and mortality, but clearly are not applicable to all patients. Augmented hemodynamic control with beta-blockers or alpha-2 agonists and modulating inflammation by statins can play an important role in improving outcomes in many patients with IHD; preoperative coronary revascularization may be of limited value. Intraoperative anesthetic management that minimizes hemodynamic perturbations is important; however, the choice of a particular technique typically is not critical. Of critical importance is the postoperative management of the patient. Postoperative myocardial injury should be identified, evaluated, and managed aggressively. Secondary stresses such as sepsis, extubation, and anemia, which can increase demand on the heart, should be treated or minimized. Clearly, optimal care of the patient with IHD entails closely coordinated assessment and management throughout the preoperative, intraoperative, and postoperative phases, if one is to optimize short- and long-term outcomes.
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PMID:Ischemic heart disease. 1724 Jun 2

The isoxazolyl penicillins, including flucloxacillin, have the highest levels of plasma protein binding among the semisynthetic penicillins. Because only the free fraction of the penicillin is pharmacologically active, it would be useful to measure both protein-bound and free flucloxacillin to determine its protein binding. Until now, flucloxacillin protein binding in newborn infants has been investigated in only two studies with relatively small populations. In the present study, flucloxacillin protein binding was investigated in 56 (preterm) infants aged 3 to 87 days (gestational age, 25-41 weeks). Surplus plasma samples from routine gentamicin assays of each infant were collected and combined to obtain a sufficiently large sample for analysis. Free flucloxacillin was separated from protein-bound flucloxacillin using ultrafiltration. Reversed-phase high-performance liquid chromatography with ultraviolet detection was used to measure free flucloxacillin concentrations in ultrafiltrate and total flucloxacillin concentrations in pooled plasma. Flucloxacillin protein binding was 74.5% +/- 13.1% (mean +/- standard deviation) with a high variability among the infants (34.3% to 89.7%). High Pearson correlations were found between protein binding and the covariates-plasma albumin concentration (r = 0.804, P < 0.001, n = 18) and plasma creatinine concentration (r = -0.601, P < 0.001, n = 45). Statistically significant but less striking correlations were found between protein binding and gestational age, postconceptional age, body weight, and triglyceride concentration. Because of the high variability of protein binding among infants, it is difficult to devise a flucloxacillin dosage regimen effective for all infants. Individualized dosing, based on free flucloxacillin concentrations, might help to optimize treatment of late-onset neonatal sepsis, but practical obstacles will probably prevent analysis of free flucloxacillin concentrations in newborn infants on a routine basis.
Ther Drug Monit 2007 Jun
PMID:Protein binding of flucloxacillin in neonates. 1752 83

Critically ill patients frequently suffer from sepsis or localized infections. Diagnosing sepsis can be a challenge since several of its signs overlap with those found with other inflammatory states. Recognition of localized infections can at times be difficult too. While microbiological cultures of blood or other specimens are frequently used to distinguish infection from non-infectious conditions, this diagnostic technique lacks sensitivity and specificity. In addition, there is often a considerable time delay since bacterial cultures may require 24-48 h for analysis, which may be too long for a treatment decision in critically ill patients. Also, the reliability of microbiological cultures decreases in case of prior antimicrobial therapy. Use of biologic markers such as procalcitonin (PCT) or soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) have been suggested to improve recognition of patients with true infection and facilitate decisions of whether or not to treat. Unfortunately, neither PCT nor sTREM-1 fulfill all expectations. Data on the diagnostic value, in particular of sTREM-1, are contradicting. The combination of systemic PCT and local and/or systemic sTREM-1 could be useful in distinguishing patients with infection from those with non-infectious illness, though. Results from several randomized intervention studies on PCT-guided antimicrobial therapy in sepsis or lower respiratory tract infections show the superiority of PCT in clinical decision making. At present, randomized intervention studies on the potential antimicrobial stewardship of sTREM-1 are lacking.
Med Sci Monit 2008 Dec
PMID:PCT and sTREM-1: the markers of infection in critically ill patients? 1904 81

Because the sepsis-induced pharmacokinetic (PK) modifications need to be considered in aminoglycoside dosing, the present study aimed to develop a population PK model for amikacin (AMK) in severe sepsis and to subsequently propose an optimal sampling strategy suitable for Bayesian estimation of the drug PK parameters. Concentration-time profiles for AMK were obtained from 88 critically ill septic patients during the first 24 hours of antibiotic treatment. The population PK model was developed using a nonlinear mixed effects modeling approach. Covariate analysis included demographic data, pathophysiological characteristics, and comedication. Optimal sampling times were selected based on a robust Bayesian design criterion. Taking into account clinical constraints, a two-point sampling approach was investigated. A two-compartment model with first-order elimination best fitted the AMK concentrations. Population PK estimates were 19.2 and 9.34 L for the central and peripheral volume of distribution and 4.31 and 2.21 L/h for the intercompartmental and total body clearance. Creatinine clearance estimated using the Cockcroft-Gault equation was retained in the final model. The two optimal sampling times were 1 hour and 6 hours after onset of the drug infusion. Predictive performance of individual Bayes estimates computed using the proposed optimal sampling strategy was reported: mean prediction errors were less than 5% and root mean square errors were less than 30%. The present study confirmed the significant influence of the creatinine clearance on the PK disposition of AMK during the first hours of treatment in critically ill septic patients. Based on the population estimates, an optimal sampling strategy suitable for Bayesian estimation of the drug PK parameters was developed, meeting the need of clinical practice.
Ther Drug Monit 2010 Dec
PMID:Population pharmacokinetic modeling and optimal sampling strategy for Bayesian estimation of amikacin exposure in critically ill septic patients. 2096 8

'Standard' or 'extracellular' base excess (SBE) is a modified calculation using one-third the normal hemoglobin concentration. It is a 'CO(2)-invariant' expression of meta- bolic acid-base status integrated across interstitial, plasma and erythrocytic compartments (IPE). SBE also integrates conflicting physical chemical influences on metabolic acid-base status. Until recently attempts to quantify individual contributions to SBE, for example the plasma strong ion gap, failed to span the 'CO(2-)stable' IPE dimension. The first breakthrough was from Anstey, who determined the con- centration of unmeasured charged species referenced to the IPE domain using Wooten's physical chemical version of the Van Slyke equation. In this issue Drs Wolf and DeLand present a diagnostic tool based on an IPE model which dissects a version of SBE (BEnet) into nine independent (BEind) components, all referenced to the IPE domain. The reported components are excess/deficits of free water, chlo- ride, albumin, unmeasured ions, sodium, potassium, lactate, 'Ca-Mg' (a composite divalent cation entity), and phosphate. The model also reports individualised volumes of plasma, erythrocytes and interstitial fluid. The tool is an original contribution, but there are concerns. The impact of assum- ing fixed relationships between arterial and venous acid-base and saturation values in sepsis, anaemia and in differing shock states is unclear. Clinicians are also unlikely to accept that unique, accurate IPE volume determinations can be derived from a single set of blood gas and biochemistry results. Nevertheless, volume determinations aside, the tool is likely to become a valuable addition to the diagnostic armamentarium.
J Clin Monit Comput 2011 Dec
PMID:Partitioning standard base excess: a new approach. 2210 2

One of the main goals of hemodynamic support is to preserve tissue perfusion. However issue perfusion is related more to microvascular perfusion than aortic blood flow. Monitoring the microcirculation has long been difficult. Recent technologic advances have made feasible monitoring of the microcirculation at bedside of critically ill patients. In this review, we will discuss the relevance of the various tools available to monitor the microcirculation. Videomicroscopic devices such as sidestream darkfield imaging are the most appropriate techniques to evaluate the microcirculation, taking into account the heterogeneous aspect of diseased microcirculation, as in sepsis. The microcirculation can also be indirectly assessed by measuring tissue PCO2. Transcutaneous PCO2 measurement at ear lobe is particularly promising. Finally, near infrared spectroscopy can also provide interesting information, especially using vascular occlusion tests which reactivity of the microcirculation to a transient hypoxic insult. These different devices have provided important data helping us to better understand the pathophysiology of sepsis and multiple organ failure.
J Clin Monit Comput 2012 Oct
PMID:Monitoring the microcirculation. 2283 80


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