Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031154 (peritonitis)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two unrelated families are described, of which four adult members were found to be suffering from severe protein C deficiency (less than or equal to 5% of normal plasma level). Newborn deaths were reported in the first family but the second family had no history of neonatal purpura fulminans and infant death. Thrombotic symptoms developed mainly in their early twenties, consisting chiefly of recurrent superficial and deep iliofemoral vein thromboses and pulmonary emboli. Other clinical features included generalized peritonitis due to massive mesenteric vein thrombosis, thrombosis of the cavernus sinus, renal vein thrombosis and priapism. In the second family, five members (all aged approximately 40 years) died of intravascular abdominal thrombosis. Massive thromboembolic episodes were associated with a compensated disseminated intravascular coagulation syndrome as evidenced by high concentrations of D-dimer (mean levels 5000 ng/ml plasma) and by a moderate reduction in platelet count and fibrinogen concentrations. D-dimer levels in noncrisis periods were also raised above normal (mean levels 400 ng/ml). The thrombotic problems of these patients were controlled satisfactorily by long-term administration of low molecular weight heparin alone or in combination with low dose warfarin.
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PMID:Congenital severe protein C deficiency in adults. 254 23

Careful interpretation of the vascular pathology is important in cases of intestinal ischemia caused by primary mesenteric vein thrombosis because it suggests antithrombin III (AT III) deficiency. This deficiency, an autosomal dominant hereditary disorder, predisposes the patient to venous thrombosis. Similar or acquired deficiencies may also predispose the patient to thrombosis. In hereditary AT III deficiency, 90% of the cases have thrombosis of the leg or iliac veins; 8.3% of the cases, thrombosis of the mesenteric veins. Additionally, some families have a tendency to develop mesenteric vein thrombosis specifically. In this case report, a daughter with probable AT III deficiency had a history of 3 episodes of deep vein thrombosis in the previous 5 years while taking oral contraceptives. Her father, with the same deficiency, died from massive intestinal infarction resulting from portal and mesenteric vein thrombosis. The 19-year old woman developed gradually worsening abdominal pain, signs of peritonitis, and hematemesis. A laparotomy revealed peritonitis that was due to segmental small-bowel infarction; the underlying pathologic condition was mesenteric vein thrombosis. Coagulation study results revealed AT III activity by chromogenic assay, 0.48 u/mL; AT III antigen, 0.5 u/mL; and protein C antigen, 1.15 u/mL. 10 days after discharge, she developed a hemicranial headache with nausea, vomiting, neck tenderness, and photophobia; she was readmitted. A CT scan showed a left posterior parietal cerebral infarct. Repeat AT III activity by chromogenic assay was 0.51 u/mL and AT III antigen level was 0.50 u/mL. Before anticoagulant therapy could be initiated, the patient died 7 days after readmission. The combined lowering of AT III activity and antigen levels to half of normal suggests AT III deficiency. Earlier diagnosis of this deficiency could have been made in light of the patient's own history of thrombosis and the paternal history.
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PMID:Mesenteric venous thrombosis due to antithrombin III deficiency. 333 17

We carried out a retrospective study to analyse clinical, paraclinical and therapeutic aspects of acute appendicitis cases as the National University Hospital (CNHU) at Bangui in the Central African Republic. We compared our findings with those for other African countries and for industrialized countries. From September 15 1990 to February 15 1992, 285 patients underwent laparotomy to treat acute appendicitis. We carried out a study of clinical, paraclinical and therapeutic aspects on 57 patients with complete case histories (20% of the patients undergoing surgery). The appendices of these patients were sent to the Laboratory of Pathological Anatomy of the Faculty of Medicine at Marseille, France, for analysis. The frequency of appendectomy among patients undergoing visceral surgery by laparotomy with no acute traumatic abdominal syndrome was 42.3%. The incidence of appendectomy for the city of Bangui in 1991 was 36.5 per 100,000 inhabitants. These cases of appendicitis were diagnosed essentially on clinical grounds. Leukocyte counts exceeded 10,000 per mm3 in 30% of the patients. Histological examination revealed the presence of parasites in 10 cases : Schistosoma mansoni eggs (seven cases) and Ascaris lumbricoides eggs (one case) in patients with acute appendicitis and one case each of Schistosoma mansoni eggs and Ascaris lumbricoides eggs at the time of diagnosis but normal histological results for the removed appendix. Most of the patients consulted late, a mean of four days after the onset of symptoms. The frequency of appendectomy on principle was 12.7% and parenteral antibiotic treatment was prescribed systematically follow- ing surgery. The mean duration of hospital stay after surgery was 7.6 days. No early postoperative complications were noted. However, two late postoperative complications resulting in the death of the patient were observed, giving a mortality rate of 3.5%. These complications were one case of peritonitis after appendectomy involving intestinal resection and one case of occlusive syndrome with septic shock. The frequency of acute appendicitis at the CNHU at Bangui was similar to that reported in another tropical African country (~ 1%). However, the incidence of appendectomies at Bangui is lower than generally reported for western countries (15 to 40%). Positive diagnosis was made on classic data obtained on clinical examination and on associated biological data, if available. Parasites were identified on histological examination in some cases of acute appendicitis, but it is unclear whether these parasites were actually responsible for the appendicitis. Efficient examinations for the exploration of acute nonspecific abdominal pain, such as the measurement of inflammation indicators, particularly serum activated protein C levels, graded-compression ultrasound scans and celioscopy, should be made available in the hospitals of African countries to increase the precision of diagnosis and to decrease the still too high frequency of appendectomies performed on principle. The postoperative mortality rate at the CNHU of Bangui is higher than the low rates (0.1 to 0.25%) reported for industrialized countries but is close to those reported for African countries. This high rate of mortality results partly from the lateness of consultations, because patients in tropical Africa often consult a traditional healer before resorting to modern medicine, and partly from misdiagnoses.
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PMID:[Acute appendicitis at the National University Hospital in Bangui, Central African Republic: epidemiologic, clinical, paraclinical and therapeutic aspects]. 1144 Aug 89

Streptococcus pneumoniae is an important cause of upper and lower respiratory tract infections, meningitis, peritonitis, bacterial arthritis, and sepsis. Here we have studied a novel immune evasion mechanism of serotype 3 pneumococci, which are particularly resistant to phagocytosis. On their surfaces the bacteria express the factor H-binding inhibitor of complement (Hic), a protein of the pneumococcal surface protein C family. Using radioligand binding, microtiter plate assays, surface plasmon resonance analysis, and recombinant constructs of factor H, we located the binding site of Hic to short consensus repeats (SCRs) 8-11 in the middle part of factor H. This represents a novel microbial interaction region on factor H. The only other ligand known so far for SCRs 8-11 of factor H is C-reactive protein (CRP), an acute phase protein that binds to the pneumococcal C-polysaccharide. The binding sites of Hic and CRP within the SCR8-11 region were different, however, because CRP did not inhibit the binding of Hic and required calcium for binding. Binding of factor H to Hic-expressing pneumococci promoted factor I-mediated cleavage of C3b and restricted phagocytosis of pneumococci. Thus, virulent pneumococci avoid complement attack and opsonophagocytosis by recruiting functionally active factor H with the Hic surface protein. Hic binds to a previously unrecognized microbial interaction site in the middle part of factor H.
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PMID:Streptococcus pneumoniae evades complement attack and opsonophagocytosis by expressing the pspC locus-encoded Hic protein that binds to short consensus repeats 8-11 of factor H. 1182 23

During the systemic inflammatory state induced by sepsis, the potential for coagulopathy exists because of up-regulation of natural procoagulants and anti-fibrinolytics, and down-regulation of natural anti-coagulants, with protein C (PC) being a critical example of the latter case. PC functions as an anti-coagulant, profibrinolytic, and anti-inflammatory agent, and, thus, its administration or deficiency may affect the course and outcome of sepsis in patients. In this study, a cecal ligation and puncture model of septic peritonitis was applied to wild-type mice and littermates with a targeted heterozygous deficiency of PC (PC(+/-)) to characterize the importance of a PC-deficiency on polymicrobial sepsis. An enhanced mortality rate was found to accompany a PC deficiency. Plasma cytokines, as well as organ-specific expression of cytokine transcripts, were elevated in PC(+/-) mice. No signs of severe disseminated intravascular coagulation (DIC) were observed in wild-type or PC(+/-) mice, as indicated by an increase in fibrinogen levels and the invariability of platelet counts after cecal ligation and puncture. Consumption of coagulation factors was similar in both genotypes and a decrease in the PC mRNA and protein levels was more prominent in PC(+/-) mice. Renal and organ muscle damage was enhanced in PC(+/-) mice, as shown by increases in plasma blood urea nitrogen, creatinine, and creatinine kinase. Hypotension and bradycardia were more enhanced in PC(+/-) mice than in wild-type mice, thus provoking a more severe septic shock response. Thus, the hemodynamic role of PC during sepsis is of critical importance to the outcome of the disease.
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PMID:A protein C deficiency exacerbates inflammatory and hypotensive responses in mice during polymicrobial sepsis in a cecal ligation and puncture model. 1546 7

To evaluate the predictive value of protein C as a marker of severity in patients with diffuse peritonitis and abdominal sepsis, protein C levels were repeatedly determined and compared with serum levels of antithrombin III, plasminogen, alpha(2)-antiplasmin, Plasminogen activator inhibitor, D-dimer, C1-inhibitor, high molecular weight kininogen, and the C5a, C5b-9 fragments of the complement system. We carried out a prospective study from 44 patients with severe peritonitis confirmed by laparotomy and 15 patients undergoing elective ventral hernia repair who acted as controls. Analyzed biochemical parameters were determined before operations and on days 1, 2, 3, 5, 7, 10, and 14 after operations. For the study group, preoperative average protein C level was significantly lower in the patients who developed septic shock in the late course of the disease, with lethal outcome, than in the patients with severe peritonitis and sepsis who survived (p = 0.0001). In non-survivors, protein C activity remained decreased below 70%, whereas the course of survivors was characterized by increased values that were significantly higher (p < 0.03) at every time point than in those patients who died. Protein C was of excellent predictive value and achieved a sensitivity of 80% and a specificity of 87.5% in discriminating survivors from non-survivors within the first 48 hours of the study (AUC-0.917; p < 0.001), with a "cut-off" level of 66.0%. As for the control group, throughout the study period, protein C activity was permanently maintained within the range of normal, with significant differences with reference to the study group (p < 0.01). These results suggest that protein C represents a sensitive and early marker for the prediction of severe septic complications during diffuse peritonitis, and of outcome.
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PMID:Protein C as an early marker of severe septic complications in diffuse secondary peritonitis. 1588 Feb 75

We present our experience with recombinant human activated protein C (rhAPC) to treat a 40-year-old preemptive simultaneous pancreas-kidney transplant (spktx) recipient who developed septic shock due to graft pancreatitis. We diagnosed intra-abdominal septic complications with septicemia induced by multiple pathogens and cardiopulmonary insufficiency. Until the 59th posttransplant day, 21 peritoneal lavages were performed to treat peritonitis and intra-abdominal abscesses. On the 53rd day when septic shock was diagnosed, rhAPC was administered, after which the patient improved, vasoconstrictive agents were reduced, and respiratory insufficiency resolved. The Physiologic and Operative Severity Score for enumeration of Mortality and Morbidity (POSSUM) scale showed a decrease in predicted mortality from 93% to 17% on day 7 after rhAPC initiation. The patient was discharged at 128 days after spktx with good function of both grafts. Administration of rhAPC limited systemic inflammatory response syndrome (SIRS) and may be considered when faced with the dilemma of stopping immunosuppression to save a recipient's life but at the cost of rejection of a functioning graft.
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PMID:Use of drotrecogin alpha (recombinant human activated protein C, rhAPC) in the treatment of severe sepsis induced by graft pancreatitis after simultaneous pancreas and kidney transplantation: a case report. 1650 24

Generation of thrombin and activated protein C in the inflammatory focus was demonstrated in rats with experimental acute peritonitis. The contents of thrombin and activated protein C peaked by the 30th and 120th minute of inflammation, respectively. In vitro study showed a decrease in spontaneous and compound 48/80-induced secretion of beta-hexosaminidase by peritoneal mast cells under the influence of activated protein C in low concentrations. The antiinflammatory effect of protein C in the focus of acute peritonitis is probably realized through NO release from peritoneal mast cells. This conclusion is derived from the data that L-NAME abolishes the protective effect of activated protein C.
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PMID:Effect of activated protein C on secretory activity of rat peritoneal mast cells. 1741 21

Activated protein C (APC) reduces mortality of severe sepsis patients but increases the risk of serious bleeding. APC exerts anticoagulant activity by proteolysis of factors Va/VIIIa. APC also exerts antiinflammatory and antiapoptotic effects and stabilizes endothelial barrier function by APC-initiated cell signaling that requires two receptors, endothelial cell protein C receptor (EPCR) and protease-activated receptor 1 (PAR1). The relative importance of APC's various activities for efficacy in sepsis is unknown. We used protein engineering of mouse APC and genetically altered mice to clarify mechanisms for the efficacy of APC in mouse sepsis models. Mortality reduction in LPS-induced endotoxemia required the enzymatic active site of APC, EPCR, and PAR-1, highlighting a key role for APC's cytoprotective actions. A recombinant APC variant with normal signaling but <10% anticoagulant activity (5A-APC) was as effective as wild-type APC in reducing mortality after LPS challenge, and enhanced the survival of mice subjected to peritonitis induced by gram-positive or -negative bacteria or to polymicrobial peritoneal sepsis triggered by colon ascendens stent implantation. Thus, APC's efficacy in severe sepsis is predominantly based on EPCR- and PAR1-dependent cell signaling, and APC variants with normal cell signaling but reduced anticoagulant activities retain efficacy while reducing the risk of bleeding.
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PMID:Endotoxemia and sepsis mortality reduction by non-anticoagulant activated protein C. 1789 98

In 2002, severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged in humans, causing a global epidemic. By phylogenetic analysis, SARS-CoV is distinct from known CoVs and most closely related to group 2 CoVs. However, no antigenic cross-reactivity between SARS-CoV and known CoVs was conclusively and consistently demonstrated except for group 1 animal CoVs. We analyzed this cross-reactivity by an enzyme-linked immunosorbent assay (ELISA) and Western blot analysis using specific antisera to animal CoVs and SARS-CoV and SARS patient convalescent-phase or negative sera. Moderate two-way cross-reactivity between SARS-CoV and porcine CoVs (transmissible gastroenteritis CoV [TGEV] and porcine respiratory CoV [PRCV]) was mediated through the N but not the spike protein, whereas weaker cross-reactivity occurred with feline (feline infectious peritonitis virus) and canine CoVs. Using Escherichia coli-expressed recombinant SARS-CoV N protein and fragments, the cross-reactive region was localized between amino acids (aa) 120 to 208. The N-protein fragments comprising aa 360 to 412 and aa 1 to 213 reacted specifically with SARS convalescent-phase sera but not with negative human sera in ELISA; the fragment comprising aa 1 to 213 cross-reacted with antisera to animal CoVs, whereas the fragment comprising aa 360 to 412 did not cross-react and could be a potential candidate for SARS diagnosis. Particularly noteworthy, a single substitution at aa 120 of PRCV N protein diminished the cross-reactivity. We also demonstrated that the cross-reactivity is not universal for all group 1 CoVs, because HCoV-NL63 did not cross-react with SARS-CoV. One-way cross-reactivity of HCoV-NL63 with group 1 CoVs was localized to aa 1 to 39 and at least one other antigenic site in the N-protein C terminus, differing from the cross-reactive region identified in SARS-CoV N protein. The observed cross-reactivity is not a consequence of a higher level of amino acid identity between SARS-CoV and porcine CoV nucleoproteins, because sequence comparisons indicated that SARS-CoV N protein has amino acid identity similar to that of infectious bronchitis virus N protein and shares a higher level of identity with bovine CoV N protein within the cross-reactive region. The TGEV and SARS-CoV N proteins are RNA chaperons with long disordered regions. We speculate that during natural infection, antibodies target similar short antigenic sites within the N proteins of SARS-CoV and porcine group 1 CoVs that are exposed to an immune response. Identification of the cross-reactive and non-cross-reactive N-protein regions allows development of SARS-CoV-specific antibody assays for screening animal and human sera.
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PMID:Two-way antigenic cross-reactivity between severe acute respiratory syndrome coronavirus (SARS-CoV) and group 1 animal CoVs is mediated through an antigenic site in the N-terminal region of the SARS-CoV nucleoprotein. 1791 99


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