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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Irreversible sepsis, in spite of advancements in topical therapy and antimicrobial agents, remains the leading cause of death in major thermal injury. A defect in intracellular bactericidal capacity in leukocytes from severely burned patients appears to correspond with increases in bacterial wound colonization and ultimate sepsis. This leukocyte defect has been demonstrated by abnormally low nitroblue tetrazolium reduction (NBT) and oxygen consumption of white cells in patients with major thermal injury. The subcellular mechanisms responsible for decreased bactericidal capacity were therefore investigated. Nicotinamide-adenine dinucleotide (NADH) and nicotinamide-adenine phosphodinucleotide (NADPH) oxidase activity was measured in patients with major burns, controls (normals), and in patients with nonburn stress or infection. NADH and NADPH oxidase levels in leukocytes from burn patients were not significantly different from those of normal nonchallenged controls but were significantly lower than the leukocyte values found in the patients with nonburn infections or stress. This NADH and NADPH defect in the subcellular leukocyte fraction suggests that it may be a significant factor in the reduced bactericidal function of the intact leukocyte in thermally injured patients.
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PMID:The role of NADH-NADPH oxidase activity in the leukocyte function of burned patients. 76 16

Clinical and postmortem findings of a case that had combined alcoholic pellagra encephalopathy and Wernicke disease are described. This 51-year-old malnourished and chronic alcoholic man presented with progressive mental deterioration, pellagra dermatitis, hypertonus of the neck and other musculatures, myoclonic jerks with bizarre involuntary movements, in addition to total external ophthalmoplegia and gait disturbance. After administration of multivitamins, including thiamine and nicotinamide, these neurologic abnormalities were dramatically improved in a few days. However, the patient died thereafter because of sepsis associated with pneumonia. Postmortem examination revealed marked abnormalities in CNS, characterized by diffuse atrophy of gray matter and widespread neuronal degeneration and characteristic central chromatolysis in pontine nuclei, dentate nuclei, cranial nerve nuclei in the brain stem, Betz cells of the cerebral cortex, and Clarke's column and anterior horn cells of the spinal cord. There were also atrophy and gliosis of the mammillary bodies, degeneration and vascular proliferation of periaqueductal gray matter, and massive gliosis around the third ventricle. These neuropathological changes were compatible with symptoms of both alcoholic pellagra encephalopathy and Wernicke's disease, but they were also strongly suspected on clinical grounds.
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PMID:Alcoholic pellagra encephalopathy combined with Wernicke disease. 188 55

Various metabolic, cellular, and subcellular alterations in cell function and morphology occur during shock or low-flow conditions. In attempting to find treatment programs that would be beneficial following shock, various substrates have been used. Infusion of hypertonic glucose during shock has been shown to improve survival; however, it is unlikely that the effect of glucose is by provision of energy until the circulation is restored. Infusion of glucose--insulin--potassium during shock has also been reported to be beneficial in certain clinical situations. Controversies exist concerning the efficacy of infusions of cyclic AMP, nicotinamide, and Krebs cycle intermediates during shock. Pretreatment of kidneys with inosine or raising glycogen stores of the myocardium have been shown to have protective effects of kidneys and myocardium during ischemia and these procedures may be suitable for organ preservation. Pretreatment with allopurinol has been shown to be beneficial in shock; however, it is unlikely that allopurinol by itself if given following shock would have any salutary effects. Treatment with ATP-MgCl2 has been shown to be beneficial following hemorrhagic shock, sepsis, endotoxin shock, burns, postischemic hepatic failure, and postischemic renal failure. Thus, provision of energy directly in the form of ATP during adverse circulatory conditions appears to be the most advantageous and direct method for the treatment of shock.
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PMID:The use of substrates and energy in the treatment of shock. 627 59

During a study of the nutritional requirements of clinical isolates of Escherichia coli, we found that 21 (7.0%) of 301 strains required nicotinamide to grow in minimal medium. The nicotinamide-requiring strains were present in 16 (15.8%) of 101 cultures of urine from young women with acute cystitis, in 5 (5.0%) of 100 stool specimens from healthy adults, and in none of 100 blood samples from adult patients with bacteremia. Most of the strains belonged to serogroup O18:K1:H7, were hemolytic, possessed type 1 fimbriae, and exhibited similar patterns of antibiotic susceptibility. Two of the urinary isolates expressed S fimbriae, and all 16 urinary isolates contained the sfaS homologue gene on their chromosomes. One of the stool isolates contained the sfaS gene. The urinary isolates closely resembled a large clone of E. coli that is reportedly associated with neonatal meningitis and sepsis. It may be possible to detect this and related clones by their requirement for nicotinamide and to screen strains for S fimbriae by relatively inexpensive hemagglutination methods, including the use of avian P1 antigens to detect mannose-resistant, non-P-fimbriated E. coli; the agglutination of bovine erythrocytes; and the use of bovine mucin to detect sialyl galactosides in S fimbriae.
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PMID:Isolation of a nicotinamide-requiring clone of Escherichia coli O18:K1:H7 from women with acute cystitis: resemblance to strains found in neonatal meningitis. 809 16

1. The pulmonary vasculature is constantly exposed to oxygen and reactive oxygen species such as nitric oxide (NO) and superoxide anions which can combine at a near diffusion limited rate, to form the powerful, oxidant, peroxynitrite (ONOO-). When formed in large amounts, ONOO- is thought to contribute to tissue injury and vascular dysfunction seen in diseases such as the acute respiratory distress syndrome (ARDS) and septic shock. Recent studies have shown that ONOO- can cause vasodilatation and at higher concentrations can activate poly (adenosine 5'-diphosphoribose) synthase (PARS) leading to consumption of nicotinamide adenine dinucleotide (NAD+) and adenosine 5'-triphosphate (ATP). As the lung represents a prime site for ONOO- formation, we characterized its effects on pulmonary vascular tone and on endothelial function. In addition, we have assessed the role of PARS in producing the vasoactive properties of ONOO- on pulmonary artery rings. 2. Isolated pulmonary artery rings from rats were mounted in organ baths containing warmed and gassed (95% O2: 5% CO2) Krebs buffer. Force was measured with isometric force transducers. After equilibration, ONOO- (10 nM-100 microM) was added in a cumulative manner. In separate experiments designed to assess any vasodilator properties of ONOO-, tissues were pre-contracted with the thromboxane mimetic U46619 (1 microM). Once a stable base-line was achieved, ONOO- was added in a cumulative fashion. ONOO- had no significant effect on resting pulmonary artery tone but caused concentration-dependent relaxations of pre-contracted vessels in the range 1 microM to 100 microM. In some experiments the effects of freshly prepared ONOO- solutions were compared with those allowed to decay at 4 degrees C for 2 days. 3. In some experiments either vehicle or ONOO- (1, 10 or 100 microM) was added for 15 min before U46619 (1 microM). Concentration-response curves to the endothelium-dependent vasodilator, acetylcholine (10 nM-100 microM) were then constructed. In these experiments, ONOO- (1 microM or 10 microM) had no effect on the actions of acetylcholine. However, at the highest concentration tested (100 microM), ONOO- increased acetylcholine-induced relaxations. 4. The vasodilator actions of ONOO- were unaffected by the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 100 microM) or by removal of superoxide anions with superoxide dismutase (SOD) (30 units ml-1). However, the relaxations induced by ONOO- were significantly inhibited by the PARS inhibitor, 3-aminobenzamide (10 microM). In contrast to its effects on ONOO-, 3-aminobenzamide had no effect on the relaxation caused by acetylcholine or sodium nitrite, but actually increased that induced by sodium nitroprusside. 5. These data show that ONOO- causes vasodilatation of rat pulmonary arteries, probably via activation of PARS. Moreover, at concentrations where relaxation was achieved, ONOO- did not affect the ability of pulmonary artery rings to relax to acetylcholine. We propose that ONOO-, but not endothelially derived NO, activates PARS resulting in the rapid depletion of ATP and a consequent reduction in contraction as well as other active processes of vascular smooth muscle. The finding that 3-aminobenzamide inhibited the actions of ONOO- but not acetylcholine, suggests that NO and ONOO- cause relaxation by independent mechanisms. It has been suggested that ONOO- is responsible for the vascular hyporesponsiveness to constrictor agents seen in experimental sepsis. This observation together with our current finding, that 3-aminobenzamide inhibits the relaxation induced by ONOO- but not by acetylcholine, suggests that inhibitors of PARS may reduce the persistent hypotension seen in sepsis without affecting the actions of endothelium-derived NO. Thus, the use of PARS inhibitors may represent a novel therapeutic approach to the treatment of septic shock.
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PMID:Characterization of the vasodilator properties of peroxynitrite on rat pulmonary artery: role of poly (adenosine 5'-diphosphoribose) synthase. 917 90

Muscle biopsies for histochemical and ultrastructural analysis were obtained from seven critically ill patients admitted to the Intensive Care Unit of the "Domingo Luciani" Hospital, Caracas, Venezuela. The sample included two patients with sepsis of abdominal origin, and five that presented sepsis/MOFS, with renal, hepatic, and respiratory disturbances and muscular weakness. Sections were examined for myosin adenosine triphosphatase (ATPase) after pre-incubation with both acid buffer (pH 4.37 and 4.6) and alkaline buffer (pH 10.3), for reduced nicotinamide dinucleotide diaphorase (NADHd), and for alpha-glycerophosphate dehydrogenase (alpha-GPDH). Sections were stained with hematoxilin and eosin to look for pathological changes and examined with a transmission electron microscope. Skeletal muscle of patients in early stage of sepsis showed a normal aspect with light microscopy, but at the ultrastructural level some of the fibres showed atrophy and some capillaries looked altered. Patients with sepsis/MOFS exhibited an evident muscle disorder with oedema, infiltrate, atrophy and segmental necrosis. All fibre types showed decrease in diameter; specially fibre types IIA and IIB. Intramuscular capillaries were thickened and occluded, indexes of capillarity were slightly reduced, and fibre oxidative activity was decreased. At ultrastructural level fibres showed severe atrophy, contractile system disorganization and segmental necrosis. Capillaries were also altered and the mononuclear cell infiltrate was abundant and represented by macrophages, lymphocytes and mastocytes.
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PMID:Histochemical and ultrastructural study of skeletal muscle in patients with sepsis and multiple organ failure syndrome (MOFS). 947 42

Data from a registry of 368 patients with chronic granulomatous disease (CGD) documenta shift in the most common infecting organisms away from staphylococci and enteric bacteria to Aspergillus species, although staphylococci remain a threat. A. nidulans appears to have a particular virulence in CGD. Burkholderia cepacia sepsis/pneumonia was the second most lethal infection in patients in the registry. Seventy-six percent of registry patients had the X-linked recessive (XLR) form of CGD. Chorioretinitis may be more common than previously appreciated, and boys with the XLR disease should probably have routine full eye exams. A new variant of CGD has been described that is caused by an inhibitory mutation in Rac2, which regulates activity of the neutrophil respiratory burst and actin assembly. Interferon-gamma, antibacterial prophylaxis, and, probably, antifungal prophylaxis with itraconazole reduce the rate of infection, and bone marrow transplantation can cure the disease if a histocompatible donor is available. Gene therapy can cure CGD in knockout mouse models. Having even a small percentage of phagocytes that are nicotinamide adenine dinucleotide phospate oxidase-positive can reduce the risk of serious infection, and procedures now under study appear close to achieving that goal, if not a cure.
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PMID:Clinical aspects of chronic granulomatous disease. 1113 21

The rate of oxygen consumption by certain tissues is impaired when mice or rats are injected with lipopolysaccharide. A similar change in the rate of oxygen consumption is observed when Caco-2 human enterocyte-like cells are incubated in vitro with cytomix, a cocktail of cytokines containing tumor necrosis factor, IL-1beta, and IFN-gamma. The decrease in the rate of oxygen consumption is not due to a change in oxygen delivery (e.g. on the basis of diminished microvascular perfusion), but rather to an acquired intrinsic defect in cellular respiration, a phenomenon that we have termed 'cytopathic hypoxia'. A number of different biochemical mechanisms have been postulated to account for cytopathic hypoxia in sepsis, including reversible inhibition of cytochrome a,a3 by nitric oxide, and irreversible inhibition of one or more mitochondrial respiratory complexes by peroxynitrite. Recently, however, our laboratory has obtained data to suggest that the most important mechanism underlying the development of cytopathic hypoxia is depletion of cellular stores of nicotinamide adenine dinucleotide (NAD+/NADH) as a result of activation of the enzyme, poly(ADP-ribose) polymerase-1. If cytopathic hypoxia is important in the pathophysiology of established sepsis and multiorgan dysfunction syndrome, then efforts in the future will need to focus on pharmacological interventions designed to preserve normal mitochondrial function and energy production in sepsis.
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PMID:Bench-to-bedside review: Cytopathic hypoxia. 1249 70

Peritonitis generally results from gastrointestinal perforation, with systemic sepsis developing over hours or days from an initially localized nidus of infection. The consecutive inflammatory response induces the widespread generation of oxidants and free radicals, which are potent inducers of breaks and nicks in double-stranded DNA. This genetic damage triggers the activation of the nuclear enzyme poly(ADP-ribose) polymerase 1, which, in turn, cleaves the respiratory coenzyme nicotinamide adenine dinucleotide into nicotinamide and ADP ribose. The consecutive decrease in cellular nicotinamide adenine dinucleotide inhibits glycolysis and mitochondrial respiration, leading to cellular energy collapse and necrotic cell death. In parallel, poly(ADP-ribose) polymerase 1 positively regulates inflammatory signal transduction pathways through a functional association with the transcription factor nuclear factor kappaB, resulting in a progressive amplification of local inflammation. Recent data indicate that these molecular mechanisms are instrumental in the development of cardiovascular collapse and multiple organ dysfunction in sepsis, supporting the view that pharmacologic inhibitors of poly(ADP-ribose) polymerase 1 may represent useful tools for the treatment of this condition.
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PMID:Role of poly(adenosine diphosphate-ribose) polymerase 1 in septic peritonitis. 1265 79

Cyanosis is a physical finding that can occur at any age but presents the greatest challenge when it occurs in the newborn. The cause is multiple, and it usually represents an ominous sign, especially when it occurs in association with neonatal sepsis, cyanotic congenital heart disease, and airway abnormalities. Cyanosis caused by abnormal forms of hemoglobin can also be life-threatening, and early recognition is mandatory to prevent unnecessary investigations and delay in management. Abnormal hemoglobin, such as hemoglobin M, is traditionally discovered by electrophoresis, so the newborn screen, which is mandatory in several states, is a useful tool for the diagnosis. Although acquired methemoglobinemia, caused by environmental oxidizing agents, is common, congenital deficiency of the innate reducing enzyme is so rare that only a few cases are documented in the medical literature around the world. We present a neonate with cyanosis as a result of congenital deficiency of the reduced nicotinamide adenine dinucleotide-cytochrome b5 reductase enzyme. This infant was found to be blue at a routine newborn follow-up visit. Sepsis, structural congenital heart disease, prenatal administration, and ingestion of oxidant dyes were excluded as a cause of the cyanosis by history and appropriate tests. Chocolate discoloration of arterial blood provided a clue to the diagnosis. A normal newborn screen and hemoglobin electrophoresis made the diagnosis of hemoglobin M unlikely as the cause of the methemoglobinemia (Hb A 59.4%, A2 1.8%, and F 38.8%). Red blood cell enzyme activity and DNA analysis revealed a homozygous form of the cytochrome b5 reductase enzyme deficiency. He responded very well to daily methylene blue and ascorbic acid administration, and he has normal growth and developmental parameters, although he shows an exaggerated increase in his methemoglobin level with minor oxidant stress such as diarrhea.
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PMID:Congenital methemoglobinemia: a rare cause of cyanosis in the newborn--a case report. 1289 22


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