Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476273 (respiratory distress)
 19,632 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The previously reported activated intravascular coagulation system in the acute phase of respiratory distress syndrome (RDS) has not been evaluated in the long term. We assessed the activities of coagulation system of a cohort of premature infants with RDS in comparison with healthy premature infants (HPIs), healthy mature infants (HMIs), and pediatric laboratory controls over a 6-month period. Cord and venous blood samples were taken at birth, at the first month and sixth month. Protein C (PC), free protein S (f-PS), and antithrombin (AT) activities, thrombin-antithrombin (TAT) complex, prothrombin fragment 1 + 2 (PF1 + 2), and fibrinogen levels were measured. Mean PC, f-PS, d-dimer, and fibrinogen values were similar at all periods for HPI and RDS groups. Low neonatal anticoagulant proteins increased within 6 months in HMI and HPI groups. However, in RDS group, the AT activity remained significantly lower together with significantly higher TAT and PF1 + 2 levels both at the first month and at sixth month, suggesting a long-term consumption coagulopathy.
...
PMID:Long-term ongoing coagulopathy in premature infants with respiratory distress syndrome. 2255 72

Care of patients with sepsis has improved over the last decade. However, in the recent two years, there was no significant progress in the development of a new drug for critically ill patients. In January 2011, it was announced that the worldwide phase 3 randomized trial of a novel anti-Toll-like receptor-4 compound, eritoran tetrasodium, had failed to demonstrate an improvement in the mortality of patients with severe sepsis. In October 2011, Xigris (drotrecogin alfa, a recombinant activated protein C) was withdrawn from the market following the failure of its worldwide trial that had attempted to demonstrate improved outcome. These announcements were disappointing. The recent failure of 2 promising drugs to further reduce mortality suggests that new approaches are needed. A study was published showing that sepsis can be associated to a state of immunosuppression and loss of immune function in human. However, the timing, incidence, and nature of the immunosuppression remain poorly characterized, especially in humans. This emphasizes the need for a better understanding of sepsis as well as new therapeutic strategies. Many clinical experiences of the extracorporeal membrane oxygenator (ECMO) treatment for adult acute respiratory distress syndrome (ARDS) patients, which is caused by the H1N1 influenza A virus, were reported. The use of ECMO in severe respiratory failure, particularly in the treatment of adult ARDS, is occurring more commonly.
 ...
PMID:Critical care paper review 2012. 2310 Oct 19

Enhanced intrapulmonary fibrin deposition as a result of abnormal broncho-alveolar fibrin turnover is a hallmark of acute respiratory distress syndrome (ARDS), pneumonia and ventilator-induced lung injury (VILI), and is important to the pathogenesis of these conditions. The mechanisms that contribute to alveolar coagulopathy are localized tissue factor-mediated thrombin generation, impaired activity of natural coagulation inhibitors and depression of bronchoalveolar urokinase plasminogen activator-mediated fibrinolysis, caused by the increase of plasminogen activator inhibitors. There is an intense and bidirectional interaction between coagulation and inflammatory pathways in the bronchoalveolar compartment. Systemic or local administration of anticoagulant agents (including activated protein C, antithrombin and heparin) and profibrinolytic agents (such as plasminogen activators) attenuate pulmonary coagulopathy. Several preclinical studies show additional anti-inflammatory effects of these therapies in ARDS and pneumonia.
 ...
PMID:Bronchoalveolar hemostasis in lung injury and acute respiratory distress syndrome. 2311 8

Severe sepsis and septic shock remains the most urgent problem. In severe sepsis and septic shock should be early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition; -appropriate diagnostic studies to ascertain causative organisms before starting antibiotics; -early administration of broad-spectrum antibiotic therapy; -reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate; -a usual 7-10 days of antibiotic therapy guided by clinical response; -source control with attention to the method that balances risks and benefits; -equivalence of crystalloid and colloid resuscitation; aggressive fluid challenge to restore mean circulating filling pressure; -vasopressor preference for norepinephrine and dopamine; -cautious use of vasopressin pending further studies; -avoiding low-dose dopamine administration for renal protection; consideration of dobutamine inotropic therapy in some clinical situations; -stress-dose steroid therapy for septic shock; use of recombinant activated protein C in patients with severe sepsis and high risk for death; -with resolution of tissue hypoperfusion and in the absence of coronary artery disease or acute hemorrhage, targeting a hemoglobin of 7-9 g/dL; -a low tidal volume and limitation of inspiratory plateau pressure strategy for acute lung injury and acute respiratory distress syndrome; -application of a minimal amount of positive end-expiratory pressure in acute lung injury/acute respiratory distress syndrome; -protocols for weaning and sedation, using either intermittent bolus sedation or continuous infusion sedation with daily interruptions/lightening; -avoidance of neuromuscular blockers, if at all possible; -maintenance of blood glucose <150 mg/dL after initial stabilization.
 ...
PMID:[Protocol of the management of patients with severe sepsis and septic shock]. 2322 Nov 37

Factor V Leiden is a procoagulant mutation associated with venous and arterial thrombosis and pregnancy complications. Its high prevalence of 5% in Caucasians suggests that there are evolutionary benefits as well. Carriers are indeed reported to have various advantageous phenotypes related to haemostasis, inflammation and fertility: less acute blood loss; less menstrual blood loss; decreased risk of intracranial haemorrhage; milder phenotypes of haemophilia; higher survival in and lower susceptibility to severe sepsis; higher survival in acute respiratory distress syndrome; less severe diabetic nephropathy and higher fecundity in both men and women. Not all these associations come from high quality adequately powered studies and many have not been confirmed by further research. The evolutionary influence of the alleged associations varies and is difficult to establish, partly due to a shift over time in risk factors of the diseases concerned. For most of the phenotypes possible mechanistic explanations can be provided. The procoagulant phenotype and perhaps also certain pregnancy complications follow from activated protein C (APC) resistance. Elevated APC levels possibly mediate anti-inflammatory effects. Higher sperm counts and more successful embryo implantation seem to play a role in the increased fecundity.
...
PMID:Evolution of Factor V Leiden. 2361 10

Pneumonia, severe sepsis, and acute respiratory distress syndrome (ARDS) are frequent complications after head trauma. Recombinant human activated protein C (APC) reportedly improves circulation and respiration in severe sepsis, but is contraindicated after head injury because of increased risk of intracranial bleeding. A 21-year-old man with severe head injury after a car accident was endotracheally intubated, mechanically ventilated, and hemodynamically stabilized before transfer to our university hospital. His condition became complicated with pneumonia, septic shock, ARDS, coagulation dysfunction, and renal failure. In spite of intensive therapy, oxygenation and arterial blood pressure fell to critically low values. Simultaneously, his intracranial pressure peaked and his pupils dilated, displaying no reflexes to light. His antibiotic regimen was changed and ventilation was altered to high frequency oscillations, and despite being ethically problematic, we added APC to his treatment. The patient recovered with modest neurological sequelae.
 ...
PMID:Controversial treatment of a victim of severe head injury complicated by septic shock and acute respiratory distress syndrome. 2375 4

The protein C system plays an active role in modulating severe systemic inflammatory processes such as sepsis, trauma, and acute respiratory distress syndrome (ARDS) via its anticoagulant and anti-inflammatory properties. Plasma levels of activated protein C (aPC) are lower than normal in acute inflammation in humans, except early after severe trauma when high plasma levels of aPC may play a mechanistic role in the development of posttraumatic coagulopathy. Thus, following positive results of preclinical studies, a clinical trial (PROWESS) with high continuous doses of recombinant human aPC given for 4 days demonstrated a survival benefit in patients with severe sepsis. This result was not confirmed by subsequent clinical trials, including the recently published PROWESS-SHOCK trial in patients with septic shock and a phase II trial with patients with nonseptic ARDS. A possible explanation for the major difference in outcome between PROWESS and PROWESS-SHOCK trials is that lung-protective ventilation was used for the patients included in the recent PROWESS-SHOCK, but not in the original PROWESS trial. Since up to 75% of sepsis originates from the lung, aPC treatment may not have added enough to the beneficial effect of lung-protective ventilation to show lower mortality. Thus whether aPC will continue to be used to modulate the acute inflammatory response in humans remains uncertain. Because recombinant human aPC has been withdrawn from the market, a better understanding of the complex interactions between coagulation and inflammation is needed before considering the development of new drugs that modulate both coagulation and acute inflammation in humans.
 ...
PMID:Protein C and acute inflammation: a clinical and biological perspective. 2391 36

Pediatric diffuse lung diseases are rare disorders with an onset in the neonatal period or in infancy, characterized by chronic respiratory symptoms and diffuse interstitial changes on imaging studies. Genetic disorders of surfactant homeostasis represent the main etiology. Surfactant protein B and ABCA3 deficiencies typically cause neonatal respiratory failure, which is often lethal within a few weeks or months. Although heterozygous ABCA3 mutation carriers are mostly asymptomatic, there is growing evidence that monoallelic mutations may affect surfactant homeostasis. Surfactant protein C mutations are dominant or sporadic disorders leading to a broad spectrum of manifestations from neonatal respiratory distress syndrome to adult pulmonary fibrosis. The authors performed pathology and ultrastructural studies in 12 infants who underwent clinical lung biopsy. One carried a heterozygous SP-B mutation, 3 carried SP-C mutations, and 7 carried ABCA3 mutations (5 biallelic and 2 monoallelic). Optical microscopy made it possible to distinguish between surfactant-related disorders and other forms. One of the ABCA3 monoallelic carriers had morphological features of alveolar capillary dysplasia, a genetic disorder of lung alveolar, and vascular development. One patient showed no surfactant-related anomalies but had pulmonary interstitial glycogenosis, a developmental disorder of unknown origin. Electron microscopy revealed specific lamellar bodies anomalies in all SP-B, SP-C, and ABCA3 deficiency cases. In addition, the authors showed that heterozygous ABCA3 mutation carriers have an intermediate ultrastructural phenotype between homozygous carriers and normal subjects. Lung biopsy is an essential diagnostic procedure in unexplained diffuse lung disorders, and electron microscopy should be performed systematically, since it may reveal specific alterations in genetic disorders of surfactant homeostasis.
 ...
PMID:Ultrastructural characterization of genetic diffuse lung diseases in infants and children: a cohort study and review. 2404 51

Protease activated receptors (PARs) are a small family of G protein-coupled receptors (GPCR) mediating the cellular effects of some proteases of the coagulation system, such as thrombin, or other proteases, such as trypsin or metalloproteinase 1. As the prototype of PARs, PAR1 is a seven transmembrane GPCR that, upon cleavage by thrombin, unmasks a new amino-terminus able to bind intramolecularly to PAR1 itself thus inducing signaling. In the vascular system, thrombin and other proteases of the coagulation-fibrinolysis system, such as plasmin, factor VIIa and factor Xa, activated protein C, are considered physiologically relevant agonists, and PARs appear to largely account for the cellular effects of these enzymes. In the vasculature, PARs are expressed on platelets, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs). In the vessel wall, under physiological conditions, PARs are mainly expressed in ECs and participate in the regulation of vascular tone, by inducing endothelium-dependent relaxation. PAR activation on ECs promotes conversion of these cells into a proinflammatory phenotype, causes increase of vascular permeability, and the exposure/secretion of proteins and cytokines mediating the local accumulation of platelets and leukocytes. These effects contribute to the vascular consequences of sepsis and of diseases such as acute lung injury and acute respiratory distress syndrome. In normal arteries PARs are to a much lesser amount expressed on VSMCs. However, in conditions associated with endothelial dysfunction, PARs mediate contraction, proliferation, migration, hypertrophy of VSMCs and their production of extracellular matrix, thereby contributing to the pathophysiology of atherosclerosis and hypertension. Inhibition of protease-PAR interaction might thus become a potential therapeutic target in various vascular diseases.
...
PMID:Functional role of protease activated receptors in vascular biology. 2492 9

Thromboembolic disease in newborn infants is a serious problem. The most important risk factors are iatrogenic factors, including indwelling umbilical catheters or central catheters. Other risk factors include asphyxia, dehydration, sepsis, cardiac disease, respiratory distress syndrome (RDS), disseminated intravascular coagulation, congenital thrombophilia (i.e., protein C or protein S deficiency), maternal diabetes mellitus, and passive transfer of maternal antiphospholipid antibodies. Neonates are more vulnerable to thrombosis than adults due to their reduced fibrinolytic capability. We describe a case of a 1-day-old female newborn with arterial thromboembolism in the lower leg without a central line catheter. The thromboembolismin in this case was associated with RDS. The infant underwent thrombolysis, anticoagulation therapy, and surgical thrombectomy. The leg of the infant was subsequently amputated below the knee. The case is described here with a brief review of relevant literatures.
...
PMID:Neonatal arterial thromboembolism and limb loss following respiratory distress syndrome: Case report. 2599 36


<< Previous 1 2 3 4 5 6 7 Next >>