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

We tested the ability of recombinant outer membrane proteins of Pseudomonas aeruginosa to serve as a protective vaccine against this gram negative pathogen under two main pathophysiological events leading to P. aeruginosa sepsis. i) systemic infection during immunosuppression, and ii) bacterial translocation. A hybrid vaccine was cloned combining protective epitopes of outer membrane protein F (OprF) and outer membrane protein I (OprI). This vaccine proved to be highly protective against an intraperitoneal challenge with P. aeruginosa in immunosuppressed mice. Oral immunization of mice, with recombinant Salmonella dublin expressing OprI induced s-IgA antibodies in the gut mucosa against OprI and provided protection against translocation of P. aeruginosa in an immunosuppressed mouse model. To test whether OprI is safe for use in humans, recombinant OprI was purified and used for immunization of volunteers. Vaccination was well tolerated and no major side effects were observed. The induction of serum antibodies against OprI was found to be dose-dependent and was observed in total in 65% of the volunteers.
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PMID:Outer membrane proteins of Pseudomonas aeruginosa as vaccine candidates. 753 52

Preterm infants and infants unable to breast feed are particularly susceptible to gut origin sepsis. Many studies have shown the benefits of breast milk in decreasing the incidence of bacterial infections in neonates. Little in vivo work has focused on prevention of neonatal gut origin sepsis with breast milk components. The aim of this study was to determine whether supplementation of a standard neonatal formula with exogenous, luminally administered, human secretory IgA protects against gut origin sepsis in a newborn rabbit model. Sixty New Zealand white rabbit pups were delivered by cesarean section 1 day preterm and divided into two groups--the IgA group (n = 26) and the non-IgA group (n = 34). Animals were gavage-fed a standard artificial formula (KMR) twice daily. The IgA group was supplemented on days 3 and 4 with 6.25 mg/kg of human secretory IgA. The non-IgA group received an equal volume of saline. On the evening of day 3, the animals were orally challenged with Escherichia coli K100. The quantity of bacteria that colonized the cecum was similar in the two groups. The quantity of bacteria that translocated to the mesenteric lymph node, liver, and spleen was significantly lower in the IgA group (P < .05). The incidence of translocation to the organs was also significantly lower in the IgA group (P < .05). The exogenous secretory IgA showed specificity to E coli K100 by ELISA. These data show that neonatal formula supplemented with human secretory IgA decreases the incidence and quantity of bacterial translocation of E coli K100 in a neonatal rabbit model.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The protective role of enteral IgA supplementation in neonatal gut origin sepsis. 773 44

We studied 125 clinically suspected septicemic neonates (Patient) aged from 1 to 28 days and 25 healthy neonates (control) of comparable age and sexes. Cultures of blood were done and serum immunoglobulins (IgG, IgA) were estimated in all the subjects. Blood cultures were found positive in 45 (36%) patients. Preterm patients showed significantly higher number of positive blood cultures as compared to term patients. The mean serum IgG level in patients was found significantly lower than that of the controls. The serum IgG levels were also found significantly lower in 75 preterm as compared to 50 term, and in 45 blood culture positive patients as compared to 80 blood culture negative patients. On the other hand, the mean serum IgM level in patients was found significantly higher as compared to controls. Similarly, serum IgM levels were found higher in preterm patients as compared to term patients and in blood culture positive patients as compared to blood culture negative patients. No significant difference of mean serum IgA level was found among the subjects. It is evident from our study, that blood culture positive patients were mostly preterm, in whom transplacental passage of IgG is insufficient and due to low IgG level, preterm baby cannot counteract bacterial invasion and as such, suffer from septicemia more frequently. Septicemic neonates as a rule showed higher level of serum IgM due to synthesis by themselves in primary response to infection.
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PMID:Serum immunoglobulin profiles of septicemic versus healthy neonates. 774 54

Transfusion of blood components is usually required in the management of critically ill patients. However, pathologic interactions between blood products and organ function may result from transfusion reactions. Emerging understanding of the mediation and interruption of clinical inflammatory responses is applicable to severe transfusion reactions. The pathophysiology of four types of severe transfusion reactions are reviewed: a) acute hemolysis; b) bacterial contamination of blood components; c) transfusion-related acute lung injury (TRALI); and d) anaphylaxis. Acute hemolytic reactions are often caused by preventable errors in sample or patient identification. Renal toxicity, coagulopathy, and hypotension may result from circulating red cell stroma and immune-complex activation of complement and cytokine secretion. Bacterial contamination of blood components has caused patient sepsis in many cases; platelets stored at 20 degrees to 24 degrees C are of particular concern. Careful blood collection and handling is essential for prevention. TRALI is manifested by acute respiratory distress, which is usually caused by infusion of plasma containing antibodies against the patient's leukocytes. Complement activation and cytokine stimulation cause edema and neutrophil accumulation in the lungs. Anaphylactic reactions may result from patient immunoglobulin (Ig)E antibodies against donor plasma constituents. IgA-deficient patients are at risk for anaphylactic reactions if these patients develop anti-IgA antibodies. Vasoactive or complement-activating factors in a blood product may also cause anaphylactoid reactions in some patients.
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PMID:The pathophysiology and organ-specific consequences of severe transfusion reactions. 780 6

Over a follow-up period of ten years, nine of our 100 patients with multiple myeloma (MM), developed myelodysplastic syndrome (MDS, preleukaemia). MDS occurred 19-156 (median 35) months from the diagnosis of MM. Six patients presented with pancytopenia and no patients had active MM at the time of MDS diagnosis. Three patients were defined as having refractory anaemia (RA) and six as refractory anaemia with excess blasts (RAEB) or RAEB in transformation (RAEBT), according to the FAB classification. The clinical course is characterized by increasing red blood cell and platelet transfusion requirements, recurrent infections and bleeding episodes. All patients, except for one, died within 3 to 8 (median 5) months from MDS diagnosis. The causes of death were sepsis or bleeding; three patients underwent leukaemic transformation. Thus, the clinical course of this small group of myeloma patients who developed secondary MDS (sMDS), was similar to other series of patients with sMDS. Serial bone marrow examinations suggest an initial hypercellular phase, followed by a rapidly evolving preterminal hypocellular marrow. In an attempt to detect MM patients at risk of developing sMDS, the epidemiological (including ethnic), clinical and laboratory data of the 9 MDS patients at the time of the MM presentation were reviewed and compared to the other MM patients. No significant differences were observed between the two groups in most parameters, except for two. All MDS patients were Ashkenazi Jews and no patients of Sepharadic origin developed MDS. Also, no IgA-myeloma patient developed MDS. If these findings are confirmed in a larger series, it may point to subgroups at risk which may require a different approach.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secondary myelodysplastic syndrome in multiple myeloma--a study of nine patients with an attempt to detect myeloma patients at risk. 789 Feb 64

Patients with cystic fibrosis (CF) and chronic Pseudomonas aeruginosa lung infection have a very high load of endotoxins in their lungs. However, sepsis practically never occurs in this group of patients and the presence of tumor necrosis factor (TNF)-alpha (one of the mediators of septic shock) in serum from chronically infected CF patients is contentious. The purpose of this study was to investigate the effect of hyperimmune serum from patients with CF on lipopolysaccharide (LPS, endotoxin)-induced TNF secretion from human peripheral blood mononuclear cells (PBMC). PBMC were purified from healthy donors and stimulated with a mixture of purified LPS from P. aeruginosa and serum from chronically infected CF patients or healthy controls. TNF in the cell supernatants was detected by an enzyme-linked immunosorbent assay method. CF sera showed a pronounced potentiating effect on TNF secretion from human PBMC induced by LPS from P. aeruginosa. In comparison, serum from healthy controls did not have this effect. By contrast, CF serum and serum from healthy controls showed only little potentiating effect when using LPS from Salmonella abortus equi at concentrations above 0.01 microgram/ml per 2 x 10(6) PBMC. This indicates a specific interaction between P. aeruginosa LPS and CF serum which enhances TNF secretion. The TNF responses varied depending on the sera used in the preincubation with LPS, and correlated positively to the specific IgG, IgA, and IgM anti-P. aeruginosa LPS titers of the sera. However, since TNF is hardly detectable in sera from these patients another LPS- and/or TNF-inhibitory activity may be present in these sera.
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PMID:Enhancement of lipopolysaccharide-induced tumor necrosis factor secretion by hyperimmune serum from chronic infected patients. 812 31

The efficacy, as oral vaccines, of hepta- and mono-valent, Klebsiella-containing bacterial lysates and a number of control preparations was tested in mice. The preparations were administered during two periods of four days each, interrupted by an interval of 3 days. Fourteen days after the first dose, the animals were challenged either intraperitoneally (i.p.; peritonitis/sepsis model) or intranasally (i.n.; pneumonia model). Animals treated with low doses of Klebsiella lysate, in the form of either a 7-valent lysate or a Klebsiella monolysate, showed enhanced survival in both the peritonitis/sepsis and the pneumonia models. Hexa- and tetra-valent preparations without Klebsiella were not protective in the models tested. Furthermore, it was found that the protection is accompanied by priming for Klebsiella-specific IgG responsiveness (probably at the T cell level) and by significant IgA anti-Klebsiella serum antibody levels in about one third of the animals. The oral efficacy of Klebsiella-containing lysates suggests the presence of an adjacent component that directs Klebsiella antigen(s) to follow a selective intestinal pathway which renders them immunogenic. The identity of this component is under investigation.
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PMID:Protective effects of orally administered, Klebsiella-containing bacterial lysates in mice. 815 53

The clinical presentation, course and outcome of Yersinia enterocolitica infection was studied prospectively in 125 children. Enteric forms occurred in 114 children (92 enteritis, 20 pseudoappendicitis, 2 chronic ileitis), of whom 17 also had extramesenteric manifestations; 11 children had one or more extramesenteric forms without enteric disease. Enteritis occurred more frequently in young children whereas serious forms and extramesenteric forms were more common in children older than 6 years of age (P < 0.001). Arthritis was observed in 13 children and extensive lymphadenopathy in 11; 1 child had septicemia with pleurisy, 1 had vasculitis, 1 had cholecystitis and 4 had erythema nodosum. Diagnosis was established by positive culture in 100 (80%) children and by agglutinin test in 11 of 45 (24%), demonstration of circulating specific anti-IgA and anti-IgG to Yersinia outer membrane proteins in 47 of 48 (98%) and detection of antigen in biopsies in 28 of 33 (85%) children. The 2 latter methods were superior to the agglutinin test. Serotype O3 and O9 predominated. The frequency and seriousness of complications may justify the use of antibiotics for Yersinia enteritis in children 6 years of age or older.
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PMID:Yersinia enterocolitica infection in children. 855 26

We tested the ability of the recombinant outer membrane proteins of Pseudomonas aeruginosa to serve as a protective vaccine against this Gram-negative pathogen in the presence of two main pathophysiological events leading to P. aeruginosa sepsis: (i) systemic infection during immunosuppression; and (ii) bacterial translocation. A hybrid vaccine was cloned which combined the protective epitopes of outer membrane protein F (OprF) and outer membrane protein I (OprI). This vaccine proved to be highly protective against an intraperitoneal challenge with P. aeruginosa in immunosuppressed mice. Oral immunization of mice with recombinant OprI expressing Salmonella dublin, induced s-IgA antibodies in the gut mucosa against OprI. These provided protection against translocation of P. aeruginosa in an immunosuppressed mouse model. To test whether OprI is effective in man, recombinant OprI was purified and used for the immunization of human volunteers. Immunization was tolerated well, and no side effects were observed. Antibody titers against OprI were measured in 90% of the volunteers after immunization.
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PMID:Outer membrane proteins of Pseudomonas aeruginosa as vaccine candidates. 871 98

Group A streptococci (S. pyogenes) possess a number of capsule and cell wall associated components and release many extracellular proteins (toxins and hydrolytic enzymes) that are known or thought to contribute to the virulence and pathogenicity of the microorganism. Groupe A streptococci cause a wide array of infections, the most frequent of which are acute pharyngitis and pyoderma with two severe sequelae (acute rheumatic fever and glomerulonephritis). Other manifestations are scarlet fever and various soft tissue infections as well as sepsis and the recently characterized streptococcal toxic shock syndrome. The somatic components of group A streptococci include cell wall M protein, capsular hyaluronic acid, lipoteichoic acid, peptidoglycan, fibronectin binding protein, C5a peptidase and receptors for various human plasma proteins particularly IgA and IgG. The extracellular products are numerous and consist of among others the hemolytic toxins streptolysins S and O, hyaluronidase, streptokinase and cysteinyl proteinase as well as the superantigens erythrogenic toxins A and C also known as pyrogenic exotoxins.
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PMID:[Cellular constituents and extracellular proteins involved in the pathogenic capacity of Streptococcus group A]. 873 28


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