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)

In order to assess the thrombin and plasmin generation in vivo in disseminated intravascular coagulation (DIC), plasma levels of thrombin-antithrombin III (ATIII) complex (TAT) and plasmin-alpha 2-antiplasmin (a2AP) complex (PAP) were measured together with standard coagulation and fibrinolytic parameters in 80 patients with DIC. Both TAT and PAP were markedly elevated in patients with DIC. When plotted by the underlying disease categories, differences in the magnitude of the elevations of these complexes were recognized among groups. Patients with acute promyelocytic leukemia (APL) had the highest PAP, the lowest TAT/PAP ratio, low a2AP, and low fibrinogen, indicating that the most excessive fibrinolysis can occur in APL. Similar profiles, although less marked, were observed in patients with other leukemias and vascular diseases. Patients with sepsis showed the highest TAT/PAP ratio and the lowest PAP with no decrease in a2AP or fibrinogen, demonstrating a relatively impaired fibrinolysis. Patients with cancer had a relatively high TAT and high TAT/PAP ratio. In addition, both TAT and PAP were markedly elevated in patients with shock. From these, it was suggested that, although laboratory manifestations in DIC are extremely variable from patient to patient, underlying disorders are, at least in part, responsible for the observed variations. Recognition of this variable activation of coagulation and fibrinolysis would be helpful for the proper management of patients with DIC.
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PMID:Thrombin vs. plasmin generation in disseminated intravascular coagulation associated with various underlying disorders. 200 32

Groups of calves (6-7, 12-14 and 24-28 weeks old) were orally infected with different numbers of the virulent Salmonella dublin strain SVA47. For the 6-7 weeks old calves the LD50-dose was estimated to be 1 x 10(7) bacteria. A dose of 10(9) bacteria was lethal within 24 hrs with the calves dying from septicemia and an acute necrotizing panenteritis. Calves 12-14 weeks old given 2 x 10(10) SVA47 bacteria succumbed to a progressive enteritis within one week. The 24-28 weeks old calves were resistant to an infective dose of 1 x 10(10) SVA47 bacteria. In the 6-7 and 12-14 weeks old calves SVA47 could be recovered from the entire intestinal tract, the liver and the spleen. In the oldest calves S. dublin SVA47 was recovered only from fecal specimens. However, the immunohistopathological examinations, using an S. dublin O-antigen-specific mouse monoclonal antibody and PAP-staining, showed the presence of S. dublin SVA47 in all tissues of the intestinal canal from calves of all ages and with a special affinity for the columnar enterocytes of the terminal jejunum and ileum, the follicle-associated epithelium over the Peyer's patches, and glandular tissues in the duodenum, tonsillar area and the lungs. Surviving calves responded with serum antibody titers against the O-antigenic lipopolysaccharide which appeared in the order IgM followed by IgA, IgG1 and IgG2.
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PMID:Experimental oral Salmonella dublin infection in calves. A bacteriological and pathological study. 185 56

The distribution of immunoglobulins IgG, IgA and IgM in the inner ear tissue from a patient who died of lung bleeding followed after sepsis was studied, and also the normal guinea pig inner ears and the inner ear disorders induced by Kanamycin injection were studied for the distribution of IgG. The temporal bones were fixed in formaldehyde, decalcified in EDTA and embedded in paraffin. The PAP method was used for the demonstration of the immunoglobulins. In both the human inner ear tissue and the normal control inner ear tissue of the guinea pigs deposits of IgG were found in the sensory organs and the endolymphatic sac, however, in the stria vascularis was slight. The severe damaged inner ears induced by Kanamycin the remarkable decreased deposits of IgG were found in the cochlea, but in the endolymphatic sac the remarkable increased deposits of IgG were found. No IgA and IgM were found in the human inner ear tissue.
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PMID:[Detection of immunoglobulin in the inner ear tissue by PAP method]. 219 Oct 98

Four cases of midfacial necrotizing lesions are reported. All patients were males with ages ranging from 25 to 76 years. The relationship between subjective symptoms and laboratory data prior to therapy (leukopenia, elevated ESR, increment of IgA and IgG), as well as between fever crisis with sweats and chills and the progression of the lesions were pathognomonic clinical signs for us. In all cases, paranasal sinus and nasopharynx were involved. Middle ear, eye and kidney involvement was present in 2 cases, and joints lesions only in one. Three patients died (2 of sepsis and one from hemorrhage) despite therapy. A pleomorphic cellular infiltrate with atypical lymphocytes and a tendency to angiocentricity was found in these cases. Such features and PAP positivity to beta and kappa chains led us to consider these lesions as an extranodal B-lymphocyte lymphoma-like. In the fourth case the histological picture was that of a necrotizing granuloma with clustered giant cells. This patient, treated only with prednisone, had a total remission of his symptomatology up to 11 years after the onset of the disease.
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PMID:Midfacial granuloma syndrome. A clinic and pathological report on four patients. 361 71

Although studies with interleukin-1 receptor antagonist (IL-1ra) in animal models have shown that IL-1 contributes to mortality in sepsis, the mechanisms whereby IL-1 mediates lethal effects are not well established. A possible mechanism is that IL-1 enhances the activation and release of other inflammatory mediator systems such as coagulation, fibrinolysis, neutrophils, and secretory-type phospholipase A2 (sPLA2). We investigated this possibility by assessing the effect of intravenously injected recombinant human IL-1 alpha (rhIL-1 alpha) on these plasma parameters in baboons. In addition, we examined the course of these inflammatory parameters in baboons after a challenge with a lethal dose of Escherichia coli and while receiving a 24-hour constant infusion of IL-1ra or placebo. Intravenous administration of IL-1 alpha (10 micrograms/kg) induced the formation of thrombin, as evidenced by the appearance of thrombin-antithrombin III (TAT) complexes into the circulation (peak levels, 188 +/- 92 ng/mL at 2 hours), as well as the activation of fibrinolysis, assessed by circulating plasmin-alpha 2-antiplasmin complexes (PAP complexes; peak levels, 0.4% +/- 0.03% of fully activated plasma at 1 hour), the release of tissue-type plasminogen activator (t-PA; peak levels, 6 +/- 2 ng/mL at 2 hours), and its inhibitor, plasminogen activator inhibitor (PAI; peak levels, 724 +/- 246 ng/mL at 4 hours). Il-1 alpha administration also induced the release of sPLA2 (maximal levels, 336 +/- 185 ng/mL at 8 hours), but not degranulation of neutrophils. In the septic baboons, a significant reduction of the formation of thrombin (peak TAT levels decreased from 582 +/- 78 ng/mL to 219 +/- 106 ng/mL; P < .005), the release of t-PA (peak levels decreased from 37 +/- 11 ng/mL to 17 +/- 2 ng/mL; P < .001), and its inhibitor, PAI (peak levels decreased from 2,639 +/- 974 ng/mL to 1,110 +/- 153 ng/mL; P <.001), was observed in the group receiving IL-1ra compared to that receiving placebo. The release of neutrophilic elastase was also significantly attenuated in IL-1a-treated animals (peak levels, 1,024 +/- 393 and 655 +/- 104 ng/mL in control and treatment groups, respectively; P < .05). The difference between sPLA2 levels in both groups, although higher in the controls (maximal levels, 3,140 +/- 1,435 ng/mL in control v 2,217 +/- 1,375 ng/mL in IL-1ra-treated group), was not significant. Thus, IL-1 contributes to activation of various other mediator systems in severe sepsis in nonhuman primates. We propose that these effects may explain the lethal actions of IL-1 in this sepsis model and suggest a similar role for IL-1 in severe human sepsis.
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PMID:Contribution of interleukin-1 to activation of coagulation and fibrinolysis, neutrophil degranulation, and the release of secretory-type phospholipase A2 in sepsis: studies in nonhuman primates after interleukin-1 alpha administration and during lethal bacteremia. 762 Jan 56

The therapeutic efficacy of a new nitrofuran, N-(5-nitrofurilidene)-5-nitrofuran-2-(N'-acetyl)carboxamidra zone (difuracil or PAP-49) in experimental staphylococcal and Coli septicemia was stated and compared to that of furazolidone. It was shown in the models of staphylococcal and Coli septicemia of albino mice that by its therapeutic efficacy difuracil (PAP-49) was 1.3 times more active as furazolidone and by 1-2 days earlier eradicated the pathogens in the host.
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PMID:[Therapeutic effectiveness of furazolidone and difuracil (PAP-49) in experimental staphylococcal and Escherichia septicemia]. 765 99

We describe the cases of two individuals with advanced AIDS who sought treatment for rapidly progressive respiratory failure due to T gondii pneumonia. The first patient responded to specific therapy after an early diagnosis but died 2 months later of bacterial sepsis. In the second case, the diagnosis was made at autopsy. This led to a meticulous retrospective review of the original slides of material obtained from BAL. T gondii tachyzoites not previously identified during the initial analysis of the slides were seen on both GIE and PAP stains. Neither of our severely immunocompromised patients had evidence of central nervous system involvement. Even though we cannot exclude dissemination to other organs, a progressive pneumonitis mimicking a classic P carinii infection was the primary presentation. Trophozoites were identified by BAL in both cases, underscoring the diagnostic potential of this minimally invasive procedure.
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PMID:Toxoplasma gondii pneumonia in patients with the acquired immunodeficiency syndrome: diagnosis by bronchoalveolar lavage. 820 79

1. In patients with sepsis syndrome, plasma levels of ET-LI and NA were elevated. In the porcine endotoxin shock model, plasma ET-1-L1 levels were also elevated and increased plasma levels of NA, A and NPY-LI indicated enhanced sympatho-adrenal activation. 2. ET-1 infusion in healthy human subjects to arterial plasma levels of ET-1-LI below or similar to those seen in patients with sepsis syndrome, induced a fall in splanchnic and renal blood flow, indicating that circulating ET-1-LI at levels seen in sepsis syndrome, have vasoactive effects. 3. In man, ET-1-LI was extracted in the pulmonary, splanchnic, renal and skeletal muscle vascular beds, but not in the cerebral circulation. The pulmonary circulation eliminated almost half of the administered ET-1. Apart from an initial short half-life of plasma ET-1-LI (1-2 min) after infusion, a prolonged presence of slightly elevated plasma ET-1-LI may have contributed to the long-lasting vasoconstrictor effect of the peptide in lung, splanchnic and renal circulations. In contrast, signs of vasodilation were present in the cerebral and skeletal muscle circulations, indicating net ETB receptor activation in these vascular beds. In the pig, upon infusion of similar doses of ET-1, the vascular response was slightly smaller than that in man while the pulmonary fractional extraction of ET-1-LI was similar in both species. At high levels of ET-1-LI the extraction capacity in the pig lung was saturated. Pretreatment with diclofenac did not significantly change the cardiovascular response to ET-1 nor plasma levels of ET-1-LI or the disappearance rate of ET-1-LI after infusion. 4. In the pig, pretreatment with diclofenac led to a more stable haemodynamic course during endotoxin infusion. Further, it abolished the first peak in the biphasic increase in PAP and PVR seen in endotoxin controls, indicating participation of products from the cyclooxygenase pathway in both the pulmonary hypertension and systemic hypotension seen in endotoxin shock. The increase in arterial plasma levels of ET-1-LI was delayed but not reduced by diclofenac whereas the activation of the sympathetic nervous system was attenuated. 5. A low dose of inhaled NO (10 ppm) markedly reduced the second, more prolonged phase of pulmonary hypertension during endotoxaemia. No signs of tachyphylaxis was seen during 2.5 h of NO inhalation, and upon cessation a rapid (within 15 min) elevation of PAP and PVR was seen. The effect was selective to the lung circulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Circulatory responses to endothelin-1 and nitric oxide with special reference to endotoxin shock and nitric oxide inhalation. 837 40

Activation of thrombin and of the coagulation system plays an important role in the pathophysiology of sepsis-associated organ dysfunction. Antithrombin III (AT III) is a natural inhibitor of thrombin, a central procoagulatory factor with pleiotropic activities. Experimental supplementation of AT III improved coagulation parameters and ameliorated organ dysfunction. To determine whether long-term AT III supplementation has beneficial effects on organ function, we conducted a randomized, prospective study in surgical patients with severe sepsis. The study evaluated the long-term effect of AT III supplementation (duration of treatment: 14 days). After randomization (AT III vs. control group), AT III was infused continuously over 14 days to obtain plasma AT III activities > 120%. Forty consecutive patients were recruited (20 AT III/20 control group). Eleven patients had a rapid fatal course and did not met the criterion of a 14 day treatment period. From these 11 patients, 8 patients (5 AT III/3 control group) died within 72 h due to septic shock. The remaining 14 AT III patients and 15 controls survived 14 days and showed no differences in baseline parameters of organ function. AT III caused a disappearance of disseminated intravascular coagulation (DIC) in all patients with DIC, whereas in control patients, the frequency of DIC remained constant (p < .05). In AT III patients a progressive increase in oxygenation index (PaO2/FiO2 ratio) and a continuous decrease in pulmonary hypertension index (mean pulmonary artery pressure/mean arterial pressure (PAP/MAP) ratio) indicated an improvement of lung function (p < .05 vs. control). AT III prevented the continuous rise in total serum bilirubin concentration observed in control patients and diminished the frequency of artificial renal support therapy (p < .05). Long-term supplementation with AT III may improve lung function and prevent the development of septic liver and kidney failure in patients with severe sepsis.
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PMID:Antithrombin III supplementation in severe sepsis: beneficial effects on organ dysfunction. 936 42

A combined hemostatic defect consisting of a reduction in certain procoagulants, anticoagulants (antithrombin III-ATIII-, protein C-PC-) and components of the fibrinolytic system (plasminogen-Plg-) was demonstrated in very-low-birth-weight infants (VLBW <1,500 g) with gestational age 26-32 weeks. Sixteen of them were healthy, 28 were suffering from RDS and 24 from septicemia. The hemostatic defect was more profound in the RDS group, nevertheless increased TAT (thrombin + ATIII complex) and/or PAP values (plasmin + a2-antiplasmin complex) was a more frequent finding in the septicemic group of infants (91.8 vs. 17.9%). Moderate-to-severe thrombocytopenia was detected in a higher percentage in the septicemic (70.8%) than in the RDS group (50%), and increased D-dimers were demonstrated in 34.8 and 28.6% of the infants, respectively. Elevated TAT or PAP values were not always associated with gross coagulation abnormalities, and advanced disseminated intravascular coagulation (DIC) was only documented in 16.7% of the septicemic and 7.1% of the RDS infants. None of the VLBW neonates presented with clinical evidence of thrombosis, although hemorrhagic manifestations were apparent in 34.8 and 14.3% of the neonates with septicemia or RDS, respectively, mainly due to DIC or severe thrombocytopenia. In conclusion, increased TAT and/or PAP values are good indicators of the in vivo activation of the hemostatic system, but still their impact on sick neonates morbidity and mortality remains unknown.
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PMID:Indications of coagulation and/or fibrinolytic system activation in healthy and sick very-low-birth-weight neonates. 974 62


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