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)

Asymmetric dimethylarginine (ADMA) and monomethyl arginine (L-NMMA) are endogenously produced amino acids that inhibit all three isoforms of nitric oxide synthase (NOS). ADMA accumulates in various disease states, including renal failure, diabetes and pulmonary hypertension, and its concentration in plasma is strongly predictive of premature cardiovascular disease and death. Both L-NMMA and ADMA are eliminated largely through active metabolism by dimethylarginine dimethylaminohydrolase (DDAH) and thus DDAH dysfunction may be a crucial unifying feature of increased cardiovascular risk. However, despite considerable interest in this pathway and in the role of ADMA as a cardiovascular risk factor, there is little evidence to support a causal role of ADMA in pathophysiology. Here we reveal the structure of human DDAH-1 and probe the function of DDAH-1 both by deleting the DDAH1 gene in mice and by using DDAH-specific inhibitors which, as we demonstrate by crystallography, bind to the active site of human DDAH-1. We show that loss of DDAH-1 activity leads to accumulation of ADMA and reduction in NO signaling. This in turn causes vascular pathophysiology, including endothelial dysfunction, increased systemic vascular resistance and elevated systemic and pulmonary blood pressure. Our results also suggest that DDAH inhibition could be harnessed therapeutically to reduce the vascular collapse associated with sepsis.
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PMID:Disruption of methylarginine metabolism impairs vascular homeostasis. 1787 60

In a context of asthma, lactic acidosis may occur during beta2-agonist therapy. Several cases have been reported during its administration by intravenous and/or inhaled route. This side-effect seems rather unknown and the mechanism for compensation of metabolic acidosis by hyperventilation may worsen dyspnoea and mislead clinicians. Other causes of lactic acidosis such as a major hypoxemia, a cardiovascular collapse or sepsis may also be experienced in this context and must be ruled out before attributing the lactic acidosis to beta2-agonist treatment. We report the case of a 50-year-old man hospitalized for an acute major asthma, who received a salbutamol continuous infusion associated with inhaled terbutaline. A serum lactate level of 13 mmol/l was noted eight hours after the introduction of the bronchodilator treatment. After reducing doses of beta2-agonists, the evolution was favourable, regarding both respiratory and metabolic aspects, with a rapid decrease of the serum lactate level, which finally returned to normal level after 32 hours of hospitalization.
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PMID:[Metabolic acidosis in a context of acute severe asthma]. 1734 73

A rare complication of infection with the Epstein-Barr virus is the development of hemophagocytic lymphohistiocytosis. Although most cases of Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis develop in immunocompetent individuals, the rare immunodeficiency X-linked lymphoproliferative disease is often unmasked by Epstein-Barr virus infection and is clinically indistinguishable from Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis. We describe the clinical course and management of a previously healthy 17-year-old boy who presented with hemodynamic collapse and severe systemic inflammatory response syndrome resulting from overwhelming hemophagocytosis in the setting of X-linked lymphoproliferative disease. A novel therapeutic approach using anti-tumor necrosis factor alpha therapy was instituted, aimed at attenuating the viral-induced hyperinflammatory state. Given the similarity to overwhelming sepsis, yet a substantially different therapeutic approach, this case illustrates the importance of early recognition and prompt treatment that are necessary to reduce the high morbidity and mortality associated with Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease.
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PMID:Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease: a mimicker of sepsis in the pediatric intensive care unit. 1740 20

Although the accumulation of gas is the most common cause of an expanding interpleural space, the presence of other structures or substances (hydrothorax, gastrothorax, hemothorax, urohemothorax, pyothorax, and chylothorax) under pressure may be sufficient to cause hemodynamic and respiratory compromise. We present two pediatric patients that developed hemodynamic and respiratory effects secondary to a chylothorax. The first patient presented in respiratory distress and cardiovascular collapse 4 weeks after a Fontan procedure. Placement of a chest tube resulted in the release of chyle under pressure and prompt resolution of hemodynamic and respiratory symptoms. The second patient was a 2100 g neonate who developed a chylothorax during an episode of sepsis following gastroschisis repair. On two separate occasions, the development of the chylothorax was associated with tachycardia, oliguria, and increased requirements during mechanical ventilation. Chest tube placement resulted in the release of chyle under pressure and resolution of the symptoms. These two cases demonstrate that chylothorax like pneumothorax can have deleterious effects on hemodynamic and respiratory function.
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PMID:Tension chylothorax in two pediatric patients. 1747 58

Acute pancreatitis begins with pancreatic injury, elicits an acute inflammatory response, and encompasses a variety of potential complications in a subset of patients. Early determination of severity and risk of complications is crucial for instituting immediate interventions to improve outcome. The severity of acute pancreatitis is a function of the amount of pancreas that is injured and the intensity of the inflammatory response. Early death is mainly linked to an overwhelming inflammatory response leading to cardiovascular collapse or acute respiratory distress syndrome, whereas late death is associated with infected pancreatic necrosis and sepsis. This article reviews recent advancements in understanding the pathogenesis, immunology, and genetics of severe acute pancreatitis, and the literature on laboratory-based markers, which predict a severe clinical course and pancreatic necrosis.
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PMID:Risk and markers of severe acute pancreatitis. 1753 79

We reviewed a single-center experience of pediatric lung resections for various congenital and acquired benign lung conditions. Thirty-five children underwent lung resections between 1998 and 2006, their age ranging from 8 days to 12 years (mean 3 years), with a male:female ratio of 4:1. Twelve patients were neonates. Antenatal diagnosis was available in only one patient. The presenting symptoms were respiratory distress and respiratory tract infections. Imaging with chest X-ray with/without a CT scan picked up the lesion in all cases. Preoperative ventilation was required for five patients. One patient had pneumothorax at presentation; however, ten patients had inadvertent intercostal tube insertion before surgical referral. The surgical procedures performed included lobectomy (28), segmentectomy (3), and pneumonectomy in 4 cases. Twenty-one patients underwent emergency surgery. Six patients required postoperative ventilation. The histopathological diagnosis was congenital lobar emphysema (CLE) (9), congenital cystic adenomatoid malformation (CCAM) (9), bronchiectasis (9), sequestration (3), atelectasis (1), lung abscess (1), unilobar tuberculosis (1), hydatid cyst (1), and foreign body with collapse (1). There was considerable discrepancy between the preoperative diagnosis based on imaging and the postoperative histopathological diagnosis. Postoperative complications included atelectasis (2), pneumothorax (2) and fluid collection (4 cases). Three patients died, one from compromised cardiac function, one from overwhelming sepsis and one from respiratory failure due to severe bilateral CCAM; the rest of the patients made a satisfactory recovery. At short-term follow-up all patients were doing well. Pulmonary resections are necessary for various congenital and acquired lung lesions in children and can be done safely in a pediatric hospital setup. Proper preoperative diagnosis can avoid inadvertent intercostal tube insertion in patients with congenital cystic lung lesions. The histopathological diagnosis often differs from the radiological diagnosis. Emergency lobectomies for acute respiratory distress, even in neonates, result in a satisfactory outcome.
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PMID:Lung resections in children for congenital and acquired lesions. 1767 88

The pattern of neonatal gastrointestinal perforation has changed with the previous high frequency of gastric rupture being replaced by necrotizing enterocolitis (NEC) in recent years. NEC has become the most common cause of gastrointestinal perforation resulting in a surgical emergency in the Neonatal Intensive Care Unit (NICU). Over the last 20 years, the infant mortality rate attributable to NEC has not decreased. However, in our institutions, more than 70% of babies with NEC are premature infants weighing less than 1,000g, which is one of the main reasons why the mortality rate due to neonatal gastrointestinal perforation has not improved in recent years. NEC totalis or massive necrosis of nearly all of the intestine is uniformly fatal. Limited resection followed by second-look laparotomy after abdominal drainage is one method used to limit the length of intestinal resection but most of these infants died from sepsis with cardiovascular collapse and multisystem organ failure. Among extremely low birth weight infants surviving after NEC significant growth delay and adverse neurodevelopmental outcome are common sequelae. More recently, many extremely low birth-weight infants are commenced on early low-volume feeds of breast milk or probiotics. This appears to be reducing the incidence of NEC and may explain a drop in the mortality rate over the last five years.
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PMID:[Bowel perforation in the newborn baby]. 1805 77

High-mobility group box 1 (HMGB1) released from necrotic cells or macrophages functions as a late inflammatory mediator and has been shown to induce cardiovascular collapse during sepsis. Thus far, however, the effect(s) of HMGB1 in the heart are not known. We determined the effects of HMGB1 on isolated feline cardiac myocytes by measuring sarcomere shortening in contracting cardiac myocytes, intracellular Ca2+ transients by using fluo-3, and L-type calcium currents by using whole cell perforate configuration of the patch-clamp technique. Treatment of isolated myocytes with HMGB1 (100 ng/ml) resulted in a 70% decrease in sarcomere shortening and a 50% decrease in the height of the peak Ca2+ transient within 5 min (P < 0.01). The immediate negative inotropic effects of HMGB1 on cell contractility and calcium homeostasis were partially reversible upon washout of HMGB1. A significant inhibition of the inward l-type calcium currents was also documented by the patch-clamp technique. HMGB1 induced the PKC-epsilon translocation, and a PKC inhibitor significantly attenuated the negative inotropic effects of HMGB1. These studies show for the first time that HMGB1 impairs sarcomere shortening by decreasing calcium availability in cardiac myocytes through modulating membrane calcium influx and suggest that HMGB1 maybe acts as a novel myocardial depressant factor during cardiac injury.
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PMID:Negative inotropic effects of high-mobility group box 1 protein in isolated contracting cardiac myocytes. 1822 93

Two autopsy cases of fulminant-type infection associated with necrotizing fasciitis were analyzed clinicopathologically. Both cases involved 57-year-old alcohol abusers. The former was a woman with group A (beta) hemolytic Streptococcus pyogenes infection, and the latter was a man with Vibrio vulnificus infection. The sudden onset of shock with high fever resulted in sepsis, decreased clotting, and hepatorenal symptoms, followed by death within a few days. Post-mortem examination showed widespread congestion and bleeding, and alcoholic liver cirrhosis was observed. Necrotizing fasciitis was identified in both cases. Bacteria from the pharynx or intestinal tract invaded the blood, and marked bacterial proliferation produced sepsis, resulting in necrotizing fasciitis. Despite the presence of sepsis, bilateral pulmonary congestion and bleeding were observed without pneumonia. Due to the rapid progression of sepsis, there was no time for granulocyte migration from the bone marrow. It seems that almost all mature granulocytes which had already existed in the bone marrow accumulated at the focus of necrotizing fasciitis because the bone marrow had few mature granulocytes and lacked hypercellularity. The cause of death in each case was circulatory collapse due to septic shock. It was difficult to distinguish the type of infection on histopathology. Cultures were necessary to determine the bacterial agents involved.
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PMID:Autopsy cases of fulminant-type bacterial infection with necrotizing fasciitis: group A (beta) hemolytic Streptococcus pyogenes versus Vibrio vulnificus infection. 1825 85

Abscess of the residual lobe after lobectomy is a rare but potentially lethal complication. Between January 1975 and December 2006, 1,460 patients underwent elective pulmonary lobectomy for non-small-cell lung cancer at our institution. Abscess of the residual lung parenchyma occurred in 5 (0.3%) cases (4 bilobectomies and 1 lobectomy). Postoperative chest radiography showed incomplete expansion and consolidation of residual lung parenchyma. Flexible bronchoscopy revealed persistent bronchial occlusion from purulent secretions and/or bronchial collapse. Computed tomography in 3 patients demonstrated lung abscess foci. Surgical treatment included completion right pneumonectomy in 3 patients and a middle lobectomy in one. Complications after repeat thoracotomy comprised contralateral pneumonia and sepsis in 1 patient. Residual lobar abscess after lobectomy should be suspected in patients presenting with fever, leukocytosis, bronchial obstruction and lung consolidation despite antibiotic therapy, physiotherapy and bronchoscopy. Computed tomography is mandatory for early diagnosis. Surgical resection of the affected lobe is recommended.
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PMID:Abscess of residual lobe after pulmonary resection for lung cancer. 1838 67


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