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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We hypothesized that plasma nitric oxide (NO), generated via inducible NO synthase (iNOS) or endothelial constitutive NO synthase and measured via its by-products NO2- and NO3- (NO2- + NO3- = NOx) would increase and remain elevated during chronic peritoneal sepsis. We further hypothesized that treatment with aminoguanidine (AG; 50 mg/kg), a selective iNOS inhibitor, would decrease NO production and alter blood flow. Sprague Dawley rats were randomized to septic and nonseptic groups. Septic rats received an intraperitoneal cecal slurry (200 mg of cecal material/5 mL 5% dextrose-H2O/kg); control rats received sterile 5% dextrose-H2O (5 mL/kg) only. Plasma NOx and hemodynamics were measured 0, 4, 12, 24, and 48 h after sepsis or sham induction. We also examined the effect of AG, an iNOS inhibitor, on plasma NOx levels and tissue blood flow at 24 h. Septic rats uniformly displayed signs of sepsis, including lethargy, piloerection, and diarrhea. NOx levels were significantly elevated compared with controls at 4, 12, 24, and 48 h (p < or = .05). Septic rats also demonstrated hypotension (t = 12, 24, and 48 h) and tachycardia (t = 4, 12, 24, and 48 h). The infusion of AG (50 mg/kg intravenously for 30 min) at 24 h significantly decreased plasma NOx in septic animals. Plasma NOx concentrations returned to basal levels by 90 min after infusion of AG. In addition, blood flow studies demonstrated that AG treatment in nonseptic rats resulted in a significant decrease in blood flow to the stomach, skin, and adipose tissue, whereas AG infusion did not significantly alter the regional perfusion profile in septic animals. Furthermore, treatment with AG did not significantly alter mean arterial pressure in either group; however, nonseptic animals exhibited a decrease in stroke volume, and septic animals demonstrated an increase in heart rate. In contrast to the rise and fall of NOx levels in endotoxemia, this study demonstrates that the initial rise is sustained during 48 h of peritoneal sepsis. This sustained increase in NOx levels in this model correlated with the observable signs of systemic infection and may relate to enhanced iNOS activity. AG infusion demonstrated variable effects on regional tissue blood flow profiles in septic and nonseptic animals and attenuated the increase in plasma NOx levels in septic animals, an index of iNOS activity.
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PMID:Effect of aminoguanidine on plasma nitric oxide by-products and blood flow during chronic peritoneal sepsis. 956 58

Recent advances in the diagnosis and treatment of inborn errors of metabolism have improved substantially the prognosis for many of these conditions. This makes it essential that the practicing pediatrician be familiar with the clinical presentation of these disorders. A practical clinical approach to the recognition of inborn errors of metabolism in the young infant is presented in this review. Indications for specific laboratory studies are discussed. Guidelines are provided for the stabilization and emergency treatment of critically ill infants. This approach will identify those infants who will benefit from additional evaluation and specific treatment. Many of the inborn errors of metabolism, including urea cycle defects, organic acidemias, and certain disorders of amino acid metabolism, present in the young infant with symptoms of an acute or chronic metabolic encephalopathy. Typical symptoms include lethargy, poor feeding, apnea or tachypnea, and recurrent vomiting. Metabolic acidosis and/or hyperammonemia are observed in many of these conditions, but there are notable exceptions, including nonketotic hyperglycinemia and molybdenum co-factor deficiency. Therefore, appropriate laboratory testing for metabolic disorders should be performed in any infant who exhibits these findings. Although sepsis may be the initial consideration in a neonate with these symptoms, inborn errors of metabolism should always be in the differential diagnosis, particularly in a full-term infant with no specific risk factors. Hypoglycemia may be the predominant finding in a number of inborn errors of metabolism, including glycogen storage disorders, defects in gluconeogenesis, and fatty acid oxidation defects. The latter disorders, among the most common encountered, exhibit marked clinical variability and also may present as a sudden death, a Reye's-like episode, or a cardiomyopathy. Jaundice or other evidence of hepatic dysfunction is the mode of presentation of another important group of inborn errors of metabolism including galactosemia, hereditary tyrosinemia, neonatal hemochromatosis, and a number of other conditions. A subset of lysosomal storage disorders may present very early with coarse facial features, organomegaly, or even hydrops fetalis. Specific patterns of dysmorphic features and congenital anomalies characterize yet another group of inherited metabolic disorders, such as Zellweger syndrome and the Smith-Lemli-Opitz syndrome. Each of these symptom complexes, and the appropriate evaluation of the affected infants, is discussed in more detail in this review.
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PMID:Inborn errors of metabolism in infancy: a guide to diagnosis. 983 97

Isovaleric acidemia, an autosomal recessive disorder, is due to isovaleryl-coenzyme A dehydrogenase deficiency and is one of the branched-chain aminoacidopathies. Isovaleric acidemia may present in the neonatal period with an acute episode of severe metabolic acidosis, ketosis, and vomiting and may lead to coma and death in the first 2 months of life. This report concerns an infant who presented at 10 days of age because of lethargy, poor feeding, hypothermia, cholestasis, and thrombocytopenia, leukopenia, and profound pancytopenia. Death occurred at 19 days of age. Autopsy showed mild fatty change in the liver and extramedullary hematopoiesis, generalized Escherichia coli sepsis, and myelodysplasia of the bone marrow with arrest of the myeloid series at the promyelocytic stage. The appearance resembled promyelocytic leukemia, but the diagnostic 15:17 translocation was not present. The maturation arrest in granulopoiesis in isovaleric acidemia appears to be most likely due to a direct metabolic effect on granulocyte precursor cells.
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PMID:Isovaleric acidemia with promyelocytic myeloproliferative syndrome. 1019 53

During the summer of 1996, an outbreak of Flavobacterium meningosepticum infection developed in a colony of South African clawed frogs (Xenopus laevis). Clinical signs were consistent with septicemia: ascites, anasarca, dyspnea, extreme lethargy, congestion of web vessels, petechial hemorrhages, and sudden death. Mortality rate reached 35%, and all infections were fatal. The organism was resistant to most antibiotics but was susceptible to enrofloxacin, chloramphenicol, and trimethoprim-sulfadiazine. Treatment with trimethoprim-sulfadiazine was unsuccessful. Although the point source of the infection was not determined, several environmental reservoirs were identified, including a communal water barrel and various pieces of equipment. Molecular strain typing by pulsed-field gel electrophoresis and biochemical analyses revealed that frogs were infected with a single strain of F meningosepticum. Sanitation and management procedures were effective in controlling the outbreak.
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PMID:Identification and management of an outbreak of Flavobacterium meningosepticum infection in a colony of South African clawed frogs (Xenopus laevis). 1038 28

The central nervous dysfunctions of lethargy, fever and anorexia are manifestations of sepsis that seem to be mediated by increased cytokine production. Here we demonstrate that tumor necrosis factor (TNF)-alpha, an essential mediator of endotoxin-induced sepsis, prevents the proteasome-dependent degradation of RGS7, a regulator of G-protein signaling. The stabilization of RGS7 by TNF-alpha requires activation of the stress-activated protein kinase p38 and the presence of candidate mitogen-activated protein kinase phosphorylation sites. In vivo, RGS7 is rapidly upregulated in mouse brain after exposure to either endotoxin or TNF-alpha, a response that is nearly abrogated in mice lacking TNF receptor 1. Our findings indicate that TNF-mediated upregulation of RGS7 may contribute to sepsis-induced changes in central nervous function.
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PMID:Upregulation of RGS7 may contribute to tumor necrosis factor-induced changes in central nervous function. 1042 8

Intrahepatic cholestasis is characterized by a decrease in bile flow in the absence of overt bile duct obstruction, resulting in the accumulation of bile constituents in the liver and blood. Various etiological factors have been incriminated including drugs, total parenteral nutrition, sepsis, pregnancy, graft-versus-host disease and systemic disorders such as sarcoidosis, amyloidosis and Hodgkin's disease. The pathogenesis of cholestasis is unclear and several mechanisms have been hypothesized, without convincing evidence that any of these play a role in clinical cholestasis. Despite the uncertainty about the pathophysiology of intrahepatic cholestasis, several forms of therapy have been employed. Ursodeoxycholic acid may relieve pruritus and lethargy, and in some cases may modify disease progression. If cholestasis persists, supportive therapy is important to maintain optimal physical and nutritional well-being. In patients with advanced liver disease associated with hepatocellular failure, liver transplantation is the only viable option.
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PMID:Intrahepatic cholestatic syndromes: pathogenesis, clinical features and management. 1043 57

A 7-month-old child presented to the emergency department (ED) with 2 hours of painless, nonprojectile emesis and a normal mental status. Over a 3-hour period in the ED, the child remained pain-free, but developed hematemesis, hematochezia, and lethargy, progressing to unresponsiveness. The patient was evaluated for toxic ingestion, intracranial bleed, sepsis/meningitis, and intraabdominal pathology. The diagnosis was made by an abdominal ultrasound, which demonstrated an ileal-cecal intussusception that ultimately required surgical reduction. This case illustrates an insidious and poorly understood presentation of a common childhood affliction, as well as the utility of abdominal ultrasound in evaluating a hemodynamically stable patient with intussusception.
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PMID:Painless intussusception and altered mental status. 1045 29

A 6-mo-old hand-raised male western lowland gorilla (Gorilla gorilla gorilla) was diagnosed with acute lymphocytic leukemia based on complete blood count and bone marrow cytology. Clinical signs of the disease were pyrexia, abdominal distention, splenomegaly, and lethargy. Acute lymphocytic leukemia has rarely been reported in this species, and therapy was based on human oncologic protocols. Remission induction chemotherapy resulted in complete clearing of leukemia cells from the bone marrow. Consolidation and maintenance chemotherapy followed. Therapy was facilitated by the use of an infusion port for i.v. treatments and an indwelling lumbar catheter for intrathecal therapy. Side effects associated with chemotherapy were inappetence, moderate alopecia, pancytopenia resulting in sepsis, and bleeding tendency. In spite of initial success, the leukemia reappeared 120 days into treatment. The gorilla was euthanized 7 days later when respiratory distress developed. Intensive care by the animal staff was a key factor in the treatment of this gorilla.
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PMID:Acute lymphocytic leukemia in a six-month-old western lowland gorilla (Gorilla gorilla gorilla). 1048 44

A 22-year-old man developed unconsciousness, severe quadriplegia and muscle atrophy, and had markedly elevated serum creatine kinase levels after using the high-dose steroid and nondepolarizing neuromuscular blocking agents during the course of sepsis and DIC. On neurological examination, he was lethargic. The patient had generalized muscle weakness and wasting, and diminished deep tendon reflexes. He weakly responsed to painful stimuli on the legs. The motor nerve conduction study demonstrated decreased CMAP (compound muscle action potential) amplitudes. Motor and sensory nerve conduction velocities and their distal latencies were normal. Muscle biopsy revealed marked muscle fiber atrophy predominantly in type 2 fibers and numerous basophilic and a few necrotic fibers. Some atrophic fibers had decreased to absent myosin adenosine triphosphatase activity in their center. Accordingly, he was diagnosed as having acute quadriplegic myopathy (AQM), which has been reported mainly in Western countries. The mechanism of muscle fiber degradation in this myopathy is still unknown. On immunohistochemical analysis to our patient, enzyme activities of various proteases such as calpain, cathepsin B, and proteasomes were increased in the sarcoplasm, especially in the atrophic fibers. We suggest that lysosomal cathepsin, nonlysosomal calpain, and ATP-ubiquitin-proteasome proteolytic pathways participate in muscle fiber degradation in AQM.
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PMID:[A case of acute quadriplegic myopathy]. 1108 98

In a retrospective and prospective audit of 55 children presenting to the paediatric assessment unit of a district general hospital with fever and petechial rash, 9% had significant bacterial sepsis. The "ILL criteria" (irritability, lethargy, low capillary refill) for the management of children with fever and petechiae are proposed.
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PMID:The management of fever and petechiae: making sense of rash decisions. 1146 79


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