fibrin and Bacterial-Infections

Topics: Animals; Bacterial Infections; Cecum; Colon; Disease Models, Animal; Fibrin; Ligation; Lipopolysaccharides; Mice; Pneumonia; Sepsis; Stents

Coagulation factor XIII (FXIII), a plasma transglutaminase, is best known as the final enzyme in the coagulation cascade, where it is responsible for cross-linking of fibrin. However, a growing body of evidence has demonstrated that FXIII targets a wide range of additional substrates that have important roles in health and disease. These include antifibrinolytic proteins, with cross-linking of α2-antiplasmin to fibrin, and potentially fibrinogen, being the principal mechanism(s) whereby plasmin-mediated clot degradation is minimised. FXIII also acts on endothelial cell VEGFR-2 and αvβ3 integrin, which ultimately leads to downregulation of the antiangiogenic protein thrombospondin-1, promoting angiogenesis and neovascularisation. Under infectious disease conditions, FXIII cross-links bacterial surface proteins to fibrinogen, resulting in immobilisation and killing, while during wound healing, FXIII induces cross-linking of the provisional matrix. The latter process has been shown to influence the interaction of leukocytes with the provisional extracellular matrix and promote wound healing. Through these actions, there are good rationales for evaluating the therapeutic potential of FXIII in diseases in which tissue repair is dysregulated or perturbed, including systemic sclerosis (scleroderma), invasive bacterial infections, and tissue repair, for instance healing of venous leg ulcers or myocardial injuries. Adequate levels of FXIII are also required in patients undergoing surgery to prevent or treat perioperative bleeding, and its augmentation in patients with/at risk for perioperative bleeding may also have potential clinical benefit. While there are preclinical and/or clinical data to support the use of FXIII in a range of settings, further clinical evaluation in these underexplored applications is warranted.

Topics: Angiogenesis Inducing Agents; Animals; Bacterial Infections; Blood Coagulation; Blood Loss, Surgical; Coagulants; Factor XIII; Factor XIII Deficiency; Factor XIIIa; Fibrin; Humans; Neovascularization, Physiologic; Postoperative Hemorrhage; Scleroderma, Systemic; Signal Transduction; Substrate Specificity; Thrombospondin 1; Wound Healing

Activation of the plasma contact system triggers several cascade systems such as the kallikrein-kinin system, the intrinsic pathway of coagulation, the classical complement cascade and the fibrinolytic system. Recent studies have shown a critical role of the contact system for arterial and venous thrombus formation and thromboembolic disease. In contrast, the function of the contact system for host-defense reactions and its physiological functions have remained enigmatic. Experimental animal studies and clinical data have linked the contact system to bacterial infections with implications for sepsis disease. The present review summarizes the role of the contact system and its activation for bacterial infections.

Topics: Animals; Bacteria; Bacterial Infections; Blood Coagulation; Capillary Permeability; Complement Pathway, Classical; Fibrin; Fibrinolysis; Humans; Immunity, Innate; Kallikrein-Kinin System; Sepsis; Signal Transduction

Bacterial pathogens have frequently evolved and maintained the capacity to engage and/or activate hemostatic system components of their vertebrate hosts. Recent studies of mice with selected alterations in host plasminogen and other hemostatic factors have begun to reveal a seminal role of bacterial plasminogen activators and fibrin clearance in microbial pathogenesis. Bacterial pathogens appear to exploit host plasmin-mediated proteolysis to both support microbial dissemination and evade innate immune surveillance systems. The contribution of bacterial plasminogen activation to the evasion of the inflammatory response is particularly conspicuous with the plague agent, Yersinia pestis. Infection of control mice with wild-type Y. pestis leads to the formation of widespread foci containing massive numbers of free bacteria with little inflammatory cell infiltrate, whereas the loss of either the bacterial plasminogen activator, Pla, or the elimination of host plasminogen results in the accumulation of robust inflammatory cell infiltrates at sites of infection and greatly improved survival. Interestingly, fibrin(ogen) deficiency undermines the local inflammatory response observed with Pla-deficient Y. pestis and effectively eliminates the survival benefits posed by the elimination of either host plasminogen or bacterial Pla. These studies, and complementary studies with other human pathogens, illustrate that plasminogen and fibrinogen are extremely effective modifiers of the inflammatory response in vivo and critical determinants of bacterial virulence and host defense. Detailed studies of the inflammatory response in mice with genetically-imposed modifications in coagulation and fibrinolytic factors underscore the regulatory crosstalk between the hemostatic and immune systems.

Topics: Animals; Bacterial Infections; Fibrin; Fibrinolysis; Humans; Mice; Plasminogen; Yersinia pestis

Topics: Animals; Anticoagulants; Bacteria; Bacterial Infections; Blood Coagulation; Blood Coagulation Factor Inhibitors; Blood Coagulation Factors; Fibrin; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Sepsis; Shock, Septic

Anaerobic bacteria are frequent isolates from the mixed bacterial flora of surgical infections. Recent studies have defined an important role for these microorganisms in determining the overall virulence of these infections. One mechanism underlying this effect is the ability of anaerobes to interact with leukocytes, resulting in impairment of host defense mechanisms. This review will address two such mechanisms. First, short-chain fatty acids generated by Bacteroides species during the stationary phase of culture have been shown to cause global impairment of the microbicidal activity of neutrophils. The observation that inhibition was maximal at low extracellular pH led to the finding that the fatty acids mediated this effect by shuttling protons from the extracellular to cytoplasmic space, thereby causing intracellular acidification with resultant cell dysfunction. Second, local fibrin deposition at the site of infection appears to impair bacterial clearance. Interaction between Bacteroides species and peritoneal macrophages has been shown to induce cell-associated procoagulant activity. This may represent another potential mechanism by which anaerobes impair leukocyte function and predispose to abscess formation.

Topics: Abscess; Animals; Bacteria, Anaerobic; Bacterial Infections; Fibrin; Humans; Hydrogen-Ion Concentration; Leukocytes; Neutrophils; Succinates; Succinic Acid; Surgical Wound Infection

Fibrin is an integral component of intravascular thrombus, surgical wounds, haematomas, vegetations and foreign bodies which predispose to infection. The tropism that many pathogens have for fibrin may favour bacterial growth and lead to infection. To improve our understanding of the pharmacodynamic interaction between antibiotics and pathogens infecting fibrin clots, this review will: define the role of fibrin as a protective environment for microorganisms; give an historical perspective of in-vitro and in-vivo fibrin clots; describe the pharmacodynamic model of infected fibrin clots; review pharmacodynamic determinants of outcome; and discuss intramicrobial pharmacokinetics. Fibrin clots are hard to penetrate following antibiotic administration and there is a major gradient of concentration from the surface to the core of the clots which has great influence on bacterial growth and lysis. Resistance can develop and morphological and structural changes in bacteria may vary within the different regions of the clot.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Biotransformation; Blood Coagulation; Drug Resistance, Microbial; Fibrin; Humans; Protein Binding

A multicenter randomized controlled clinical trial, which was carried out in 10 hospitals in the Federal Republic of Germany between 1979 and 1983, studied the influence of i.v. immunoglobulin G on the mortality in patients with diffuse acute fibrinopurulent peritonitis. Altogether 288 patients were enrolled in the trial. There was no statistically significant difference in the mortality rates within the treated group (46%) vs the control group (41%). The power of the statistical test to detect a decrease of the mortality by 20% was calculated to be 0.93. This result did not change when we eliminated 50 patients not strictly obeying the entrance criteria of the analysis, or when we focused on a subgroup of patients with initial deficiency of immunoglobulin G. Factors influencing mortality were a preceding laparotomy, serum creatinine level above 2 mg/100 ml, and necessity for artificial respiration. These factors, reflecting the surgical situation and the severity of shock, essentially explain the mortality differences observed between the participating hospitals.

Topics: Bacterial Infections; Clinical Trials as Topic; Fibrin; Humans; Immunoglobulin G; Peritonitis; Prognosis; Random Allocation

To assess whether adding low-dose heparin to the infusate of patients receiving parenteral nutrition reduced the incidence of septic complications related to the central venous catheter, 80 consecutive patients requiring intravenous feeding were studied. Half of these patients received heparin 1 unit/ml of infusate, while in the remaining 40 (controls) an equal volume of physiological saline was added to the infusate. Strict criteria for the management of the indwelling CVC were observed. The catheter tips were cultured after removal: only one was infected in the heparin group compared with nine in the control group. This significant reduction may have been due to the heparin preventing a fibrin sleeve from forming around the catheter tip. It is recommended that, as well as observing the usual aseptic precautions in managing the cannula, 500 units of heparin are added to each 500 ml of fluid infused to reduce the incidence of catheter-associated sepsis.

Topics: Bacterial Infections; Catheters, Indwelling; Drug Administration Schedule; Fibrin; Heparin; Humans; Injections, Intravenous; Parenteral Nutrition; Sepsis

Anaerobes are the causative agents of many wound infections. B. fragilis is the most prevalent endogenous anaerobic bacterium causes a wide range of diseases, including wound infections. This study aimed to assess the antibacterial effect of mouse adipocyte derived-mesenchymal stem cell (AD-MSCs) encapsulated in collagen-fibrin (CF) hydrogel scaffolds on B. fragilis wound infection in an animal model.. Stem cells were extracted from mouse adipose tissue and confirmed by surface markers using flow cytometry analysis. The possibility of differentiation of stem cells into osteoblast and adipocyte cells was also assessed. The extracted stem cells were encapsulated in the CF scaffold. B. fragilis wound infection was induced in rats, and then following 24 h, collagen and fibrin-encapsulated mesenchymal stem cells (MSCs) were applied to dress the wound. One week later, a standard colony count test monitored the bacterial load in the infected rats.. MSCs were characterized as positive for CD44, CD90, and CD105 markers and negative for CD34, which were able to differentiate into osteoblast and adipocyte cells. AD-MSCs encapsulated with collagen and fibrin scaffolds showed ameliorating effects on B. fragilis wound infection. Additionally, AD-MSCs with a collagen scaffold (54 CFU/g) indicated a greater effect on wound infection than AD-MSCs with a fibrin scaffold (97 CFU/g). The combined CF scaffold demonstrated the highest reduction in colony count (the bacteria load down to 29 CFU/g) in the wound infection.. Our findings reveal that the use of collagen and fibrin scaffold in combination with mouse AD-MSCs is a promising alternative treatment for B. fragilis.

Topics: Animals; Anti-Infective Agents; Bacterial Infections; Bacteroides fragilis; Base Composition; Cell Differentiation; Collagen; Fibrin; Hydrogels; Mesenchymal Stem Cells; Mice; Phylogeny; Rats; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Tissue Scaffolds; Wound Infection

A strategy to synthesize water-soluble and fluorescent flavonoid-silica nanocomposites (FSiNCs) simultaneously featuring anti-tumor and anti-bacterial abilities is developed. Furthermore, it is demonstrated that the therapeutic effects of FSiNCs are associated with the selective accumulation of reactive oxide species in both tumor and bacteria cells. Following that, the resultant FSiNCs are incorporated with thrombin and fibrinogen, being sprayed onto the tumor surgical wound site to in situ form fibrin gel (FSiNCs@Fibrin). Remarkably, such FSiNCs@Fibrin results in an ≈18-fold reduction in intratumoral bacteria numbers and ≈12-fold decrease in tumor regrowth compared to equivalent free flavonoid-loaded gel.

Topics: Bacterial Infections; Fibrin; Fibrinogen; Flavonoids; Humans; Neoplasm Recurrence, Local; Silicon Dioxide; Thrombin

Platelets crucially facilitate wound healing but can become depleted in traumatic injury or chronic wounds. Previously, our group developed injectable platelet-like particles (PLPs) comprised of highly deformable, ultralow crosslinked pNIPAm microgels (ULCs) coupled to fibrin binding antibodies to treat post-trauma bleeding. PLP fibrin-binding facilitates homing to sites of injury, promotes clot formation, and, due to high particle deformability, induces clot retraction. Clot retraction augments healing by increasing clot stability, enhancing clot stiffness, and promoting cell migration into the wound bed. Because post-traumatic healing is often complicated by infection, the objective of these studies was to develop antimicrobial nanosilver microgel composite PLPs to augment hemostasis, fight infection, and promote healing post-trauma. A key goal was to maintain particle deformability following silver incorporation to preserve PLP-mediated clot retraction. Clot retraction, antimicrobial activity, hemostasis after trauma, and healing after injury were evaluated via confocal microscopy, colony-forming unit assays, a murine liver trauma model, and a murine full-thickness injury model in the absence or presence of infection, respectively. We found that nanosilver incorporation does not affect base PLP performance while bestowing significant antimicrobial activity and enhancing infected wound healing outcomes. Therefore, Ag-PLPs have great promise for treating hemorrhage and improving healing following trauma.

Topics: Acrylic Resins; Animals; Anti-Infective Agents; Bacterial Infections; Blood Platelets; Clot Retraction; Colony-Forming Units Assay; Fibrin; Gels; Hemorrhage; Hemostasis; Liver; Male; Metal Nanoparticles; Mice; Mice, Inbred C57BL; Microgels; Silver; Wound Healing

Hydrogel-based regenerative endodontic procedures (REPs) are considered to be very promising therapeutic strategies to reconstruct the dental pulp (DP) tissue in devitalized human teeth. However, the success of the regeneration process is limited by residual bacteria that may persist in the endodontic space after the disinfection step and contaminate the biomaterial. The aim of this work was to develop an innovative fibrin hydrogel incorporating clindamycin (CLIN)-loaded Poly (d,l) Lactic Acid (PLA) nanoparticles (NPs) to provide the hydrogel with antibacterial properties. CLIN-PLA-NPs were synthesized by a surfactant-free nanoprecipitation method and their microphysical properties were assessed by dynamic light scattering, electrophoretic mobility and scanning electron microscopy. Their antimicrobial efficacy was evaluated on Enteroccocus fæcalis by the determination of the minimal inhibitory concentration (MIC) and the minimal biofilm inhibition and eradication concentrations (MBIC and MBEC). Antibacterial properties of the nanocomposite hydrogel were verified by agar diffusion assays. NP distribution into the hydrogel and release from it were evaluated using fluorescent PLA-NPs. NP cytotoxicity was assessed on DP mesenchymal stem cells (DP-MSCs) incorporated into the hydrogel. Type I collagen synthesis was investigated after 7 days of culture by immunohistochemistry. We found that CLIN-PLA-NPs displayed a drug loading of 10 ± 2 μg per mg of PLA polymer and an entrapment efficiency of 43 ± 7%. Antibiotic loading did not affect NP size, polydispersity index and zeta potential. The MIC for Enterococcus fæcalis was 32 μg mL-1. MBIC50 and MBEC50 were 4 and 16 μg mL-1, respectively. CLIN-PLA-NPs appeared homogenously distributed throughout the hydrogel. CLIN-PLA-NP-loaded hydrogels clearly inhibited E. faecalis growth. DP-MSC viability and type I collagen synthesis within the fibrin hydrogel were not affected by CLIN-PLA-NPs. In conclusion, CLIN-PLA-NP incorporation into the fibrin hydrogel gave the latter antibacterial and antibiofilm properties without affecting cell viability and function. This formulation could help establish an aseptic environment supporting DP reconstruction and, accordingly, might be a valuable tool for REPs.

Topics: Anti-Bacterial Agents; Bacterial Infections; Biofilms; Clindamycin; Dental Pulp; Drug Liberation; Enterococcus faecalis; Female; Fibrin; Humans; Hydrogels; Mesenchymal Stem Cells; Microbial Sensitivity Tests; Nanocomposites; Nanoparticles; Polyesters; Regeneration; Tissue Engineering

Many patients with hemophilia, particularly those with inhibitory antibodies, utilize central venous access devices (CVADs) to facilitate frequent infusions. Infection of these devices is a common complication of factor replacement therapy. This communication reports our center's experience with CVAD infection in three patients with severe hemophilia A undergoing immune tolerance therapy (ITT) in whom intermittent infusions of recombinant tissue plasminogen activator (rTPA, Cathflo Activase) were utilized. In this small experience, patients experienced a decreased frequency of gram-positive infections when receiving routine rTPA treatments. Larger randomized trial should be performed in this patient population at high risk of CVAD infection.

Topics: Anti-Bacterial Agents; Bacterial Infections; Catheterization, Central Venous; Child, Preschool; Desensitization, Immunologic; Disease Susceptibility; Drug Evaluation; Factor VIII; Fibrin; Fibrinolysis; Hemophilia A; Humans; Isoantibodies; Recombinant Proteins; Thrombophilia; Tissue Plasminogen Activator

Infectious process frequently results in extensive bone resorption and defect, periradicular or periapical lesions, or vertical fracture with infected sinus tract. When tooth extraction is mandated it typically results in additional bone loss in the buccal or lingual cortical plate. Immediate guided bone regeneration (GBR) and implant fixation at an infected site is frequently complicated by soft-tissue dehiscence, membrane exposure, and implant failure. The objective of this research is to assess the feasibility of immediate bone augmentation (IBA) after purulent tooth extraction, employing a dedicated titanium membrane. An intrasulcular incision was made around the tooth to be extracted and extended to 2 adjacent teeth while maintaining the papillae. Vertical releasing incisions were made to mobilize the mucoperiosteal flap. Cautious tooth extraction was executed utilizing conventional measures and was followed by meticulous curettage of the infected and granulated tissue in the socket. Titanium membranes were applied to the socket walls followed by socket filling with autologous platelet-rich fibrin and primary closure. Eight or more weeks later membrane removal and implant placement were performed. Of the 15 patients who underwent this procedure, 7 patients (47%) had early membrane exposure (between weeks 2 and 6), which was treated conservatively. No infection or early membrane removal was reported. All patients achieved sufficient bone augmentation, and 8 patients received implants without any additional GBR. IBA after infected tooth extraction, using titanium membrane application was feasible and safe and yielded adequate bone filling to support implant fixation at > or =8 weeks. Further studies need to evaluate if the titanium membrane helped in any way to inhibit plaque accumulation or resist infection in cases of early membrane exposure.

Topics: Adult; Bacterial Infections; Biocompatible Materials; Bone Regeneration; Curettage; Dental Fistula; Dental Implants; Feasibility Studies; Female; Fibrin; Granulation Tissue; Guided Tissue Regeneration, Periodontal; Humans; Male; Membranes, Artificial; Middle Aged; Periapical Diseases; Periodontal Diseases; Platelet-Rich Plasma; Titanium; Tooth Diseases; Tooth Extraction; Tooth Socket; Treatment Outcome

Fibrinogen-like protein 2 (Fgl2, fibroleukin) is a leukocyte product that exhibits significant homology to secreted proteins of diverse function, including growth factors, lectins, and components of extracellular matrix. Prior studies found that Fgl2 is IFN gamma-inducible, possesses direct coagulant activity, and inhibits T cell proliferation and dendritic cell maturation in vitro. Here, we demonstrate that Fgl2 expression is up-regulated during type 1 immunity in vivo and establish that such up-regulation is IFN gamma-, signal transducer and activation of transcription protein 1-, and IFN response factor 1-dependent. To investigate functional roles for Fgl2 during type 1 immunity, we generated Fgl2-deficient mice. Those animals are born at predicted Mendelian frequencies, appear overtly healthy, and contain normal numbers and frequencies of lymphoid cells. Although Fgl2 is IFN gamma-inducible and putatively regulates T cell activation/proliferation, we demonstrate that Fgl2-deficient and control mice exhibit similar degrees of T cell expansion, immunopathology, and/or pathogen burdens during protozoan (Toxoplasma gondii), bacterial (Yersinia enterocolitica, Listeria monocytogenes, and Mycobacterium tuberculosis), and viral (murine gamma-herpesvirus-68 and Sendai) infections. Fgl2-deficient mice also reject allografts with similar kinetics as control mice. Moreover, despite prior reports that Fgl2 functions as a procoagulant enzyme, we demonstrate that Fgl2-deficient and control mice produce similar levels of fibrin, a product of the coagulation cascade, during T. gondii infection and allograft rejection. Together, our findings suggest that Fgl2, although highly conserved and IFN gamma-inducible, is not a critical mediator of either type 1 immunity or immune-associated coagulant activity.

Topics: Animals; Bacterial Infections; Blood Coagulation; Disease Models, Animal; DNA Primers; Fibrin; Heart Transplantation; Interferon-gamma; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; RNA, Messenger; T-Lymphocytes; Toxoplasmosis; Transplantation, Homologous; Virus Diseases

From a registry of 136 patients undergoing pericardiocentesis, 14 patients with autoimmune and 15 patients with neoplastic effusions were selected. All underwent pericardioscopy, epicardial and pericardial biopsy with histologic, immunohistologic, and polymerase chain reaction/or in situ hybridization analysis for microbial DNAs and RNA. Pericardioscopy identified neoplastic effusions by the high occurrence of protrusions. Fibrin threads and layers and neovascularization were found in both groups. For identification of the inflammatory and neoplastic process, the combined analysis of the cytology of the effusion and epicardial biopsy evaluation proved to be most important. Epicardial biopsy demonstrated a slightly higher sensitivity for identifying neoplastic disorders in the pericardium than cytology alone. Pericardial biopsy was inconclusive. Intrapericardial administration of 1 g of crystalloid triamcinolone in autoreactive pericarditis prevented recurrence in 13 of the 14 cases after 3 months and in 12 of the 14 cases after 1 year. In neoplastic effusion, intrapericardial administration of 50 mg cis-platin for 24 h prevented recurrence of a hemodynamically relevant effusion after 3 months in all, and after 6-12 months in 14 of 15 patients. Mortality in neoplastic effusion due to noncardiac tumor progression was 47 and 80%, respectively, after 3 and 6 months, as can be expected in endstage neoplastic disease. This pilot study demonstrates that local drug application is feasible, life-saving, and well tolerated by the patients. It opens perspectives for local drug application in other cardiac disorders as well.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Antineoplastic Agents; Autoimmune Diseases; Bacterial Infections; Biopsy; Cisplatin; Endoscopy; Female; Fibrin; Glucocorticoids; Humans; Male; Middle Aged; Neoplasms; Neovascularization, Pathologic; Paracentesis; Pericardial Effusion; Pericarditis; Pericardium; Pilot Projects; Sensitivity and Specificity; Survival Rate; Triamcinolone

Measurement of the fibrinolytic response of the peritoneum to experimental peritonitis and ischaemia.. Controlled study. Academic surgical unit, UK MATERIAL: Male Wistar rats. Peritoneal injuries were caused in four groups of male Wistar rats (n = 35 in each group): (1) control group ("open and close" laparotomy); (2) bacterial peritonitis (mixed faecal flora); (3) chemical peritonitis (10 mg/ml tetracycline) and; (4) ischaemic peritoneum (ligated peritoneal buttons). Peritoneal biopsy specimens were taken from five animals in each group at seven time intervals and plasminogen activating activity (PAA) measured by fibrin plate assay.. Compared with the control group the three peritoneal injuries produced a uniform reduction in PAA during the first 6 and 12 hours: at 6 hours the median PAA was 0.029 IU/cm2 for bacterial peritonitis, 0.021 IU/cm2 for chemical peritonitis, and 0.05 IU/cm2 for ischaemic peritoneum compared with 0.112 IU/cm2 for the control group; p < 0.001, ANOVA. At 12 hours the median PAA was 0.024 IU/cm2 for bacterial peritonitis, < or = 0.014 IU/cm2 for chemical peritonitis, and 0.05 IU/cm2 for ischaemic peritoneum compared with 0.112 IU/cm2 for the control group; p < 0.001, ANOVA. There then followed a rebound peak in all groups, maximal at 4-7 days, before a return to baseline values at two weeks.. Peritoneal fibrinolysis was appreciably inhibited after three different standardised peritoneal injuries. The data support the hypothesis that there is a single pathophysiological mechanism of adhesion formation.

Topics: Animals; Bacterial Infections; Fibrin; Fibrinolysis; Ischemia; Male; Models, Biological; Peritoneum; Peritonitis; Plasminogen; Postoperative Period; Rats; Rats, Wistar; Tetracycline; Time Factors

Intracatheter streptokinase (SK) is advocated as effective treatment with minimal adverse effects in both recurrent bacterial peritonitis and catheter fibrin blockage in continuous ambulatory peritoneal dialysis (CAPD) patients. We reviewed 35 instillations in 20 patients noting a high (86%) side effect profile consisting of fever, onset of turbid dialysis effluent and/or abdominal pain. SK probably releases fibrin clot containing bacteria, leukocytes and debris from the colonized catheter into the peritoneal cavity causing a "peritonitis-like syndrome" of 1 to 3 days duration. Fungal peritonitis occurred after SK in 2 patients. Failure of SK therapy was encountered in Staphylococcus epidermidis infection (p less than 0.05 versus other organisms), which may be related to its protective capsular polysaccharide slime and ability to adhere to plastic prosthetic devices. SK, in this study, was useful treatment in relapsing bacterial peritonitis (50% overall cure) but failed to correct catheter malfunction.

Topics: Adult; Aged; Bacterial Infections; Catheterization; Catheters, Indwelling; Drug Evaluation; Equipment Failure; Female; Fibrin; Humans; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Peritonitis; Recurrence; Retrospective Studies; Streptokinase

We have determined the plasma concentrations of types 1 and 2 of plasminogen activator inhibitor (PAI-1 and PAI-2), tumor necrosis factor (TNF-alpha) and endotoxin in 47 patients with bacterial infection (22 patients presented with positive blood cultures). Results were compared with those observed in 30 healthy subjects. There was a significant increase in PAI-1 and TNF-alpha in patients as compared to controls (p less than 0.0001), whereas no differences for PAI-2 were observed. PAI-1 and TNF-alpha were significantly higher in 18 patients with gram-negative bacteremia as compared to all other patients (p less than 0.0001). However, no correlation between the analyzed parameters and either endotoxin or clinical outcome was observed. We conclude that there is an increase of PAI-1 and TNF-alpha in patients with sepsis, which is not related to the endotoxin concentration. Our results suggest that PAI-1, but not PAI-2, is the main plasminogen activator inhibitor in human sepsis.

Topics: Adolescent; Adult; Aged; Bacterial Infections; Endotoxins; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Plasminogen Inactivators; Tumor Necrosis Factor-alpha

Sclerosing peritonitis is a severe complication after CAPD treatment. The visceral peritoneum is thickened and interenteric adhesive parts are found. Myofibroblasts are proliferated and the collageneous tissue is hyperplastic. The mean clinical symptom is the mechanical obstruction of the small bowel. We observed this illness in three out of sixty patients under CAPD. These patients had higher incidence of bacterial peritonitis. In the ascites high concentrations of PG E2 and Thromboxan B2 were observed. After treatment of the infection the concentrations fell down to normal values. Electronoptical observations from peritoneal biopsies showed a proliferation of myofibroblasts and extracellular lysosomes. It is known from these lysosomes that they are able to set free proteasis. These lead to degredation of fibrin and fibrinogen. These splits are mitogen to myofibroblasts. release from HIT cells could also be evoked by the sulphonylureas glibenclamide and tolbutamide and by an increase in concentration of extracellular K+ to 40 mmol/l. The content of cyclic AMP in HIT cells was increased modestly by glucose but not by an increase in extracellular K+. Forskolin elicited a 4-fold increase in cyclic AMP content. We conclude that HIT cells retain the essential features of the insulin secretory response of normal B cells and represent an important tool for further biochemical characterisation of the secretory system.

Topics: Adult; Bacterial Infections; Dinoprostone; Female; Fibrin; Humans; Intestinal Obstruction; Intestine, Small; Male; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Peritonitis; Prostaglandins E; Sclerosis; Thromboxane B2

Topics: Adult; Aged; Aged, 80 and over; Animals; Bacterial Infections; Blood Coagulation; Complement System Proteins; Disseminated Intravascular Coagulation; Dogs; Endotoxins; Female; Fibrin; Humans; Male; Microcirculation; Middle Aged; Multiple Organ Failure

The effect of heparin upon the clinical and pathologic course of experimentally induced peritonitis in the rat was studied. Peritonitis was induced in 40 rats by creating a closed ileal loop 4 centimeters long at a distance of 5 centimeters from the ileocecal valve. The rats were divided into two groups of 20 each. The first group served as the control group while each rat of the second group received 30 units of heparin subcutaneously per day postoperatively. Survival was drastically increased in the group receiving heparin (p = 0.001). Adhesion or abscess formation was considerably reduced in this group. The results of peritoneal cultures showed decreased incidence of Escherichia coli and clostridia in the heparin-treated group. Blood cultures also showed decreased incidence of both aerobes and anaerobes in the treated group. It is concluded from this that the administration of heparin significantly prolongs survival time of animals with peritonitis and reduces the development of adhesions and abscesses in the peritoneal cavity. This beneficial effect could be attributed to decreased fibrinogen deposits within the peritoneal cavity, thus rendering the bacteria more susceptible to cellular and noncellular clearing mechanisms.

Topics: Abscess; Animals; Bacterial Infections; Clostridium; Escherichia coli; Female; Fibrin; Heparin; Male; Peritoneal Cavity; Peritonitis; Rats; Rats, Inbred Strains; Tissue Adhesions

Bacterial adherence as a result of specific surface properties may be a contributory factor in the pathogenesis of bacterial endocarditis giving certain types of bacteria a selective advantage to cause this disease. Adherence could interact with other pathogenetic mechanisms, and this interaction could promote or hamper the development of endocarditis. Dextran production by streptococci, the activation of the clotting system by monocyte tissue thromboplastin, and phagocytic removal of bacteria from the vegetational surface by granulocytes and monocytes are examples of interacting mechanisms that could contribute to the pathogenesis of bacterial endocarditis.

Topics: Adhesiveness; Animals; Aortic Valve; Bacterial Infections; Bacterial Physiological Phenomena; Dogs; Endocarditis, Bacterial; Etoposide; Fibrin; Humans; In Vitro Techniques; Mechlorethamine; Rabbits; Staphylococcus; Streptococcus; Virulence; Warfarin

Plasma fibronectin (cold-insoluble globulin) is known to be cross-linked to fibrin during the final stage of blood coagulation and is probably the major nonspecific opsonin of blood. We measured the concentration of plasma fibronectin in 36 hospitalized patients (11 with malignancy, 12 with infection, 13 with other underlying diseases) with evidence of fibrin depostion and lysis. Plasma fibronectin concentration was greater than 2 S.D. below the mean of normals in 17 of the patients (p less than 0.001). Depression of fibronectin was not related to severity of disseminated intravascular coagulation, as assessed by fibrinogen concentration and the quantity of FDP in serum. Depressed plasma fibronectin concentration and the quantity of FDP in serum. Depressed plasma fibronectin concentration was an unfavorable prognostic finding, inasmuch as 12 of the 17 patients with depressed fibronectin concentrations died during hospitalization as compared to five of the 19 patients with normal fibronectin concentrations (p less than 0.02). We speculate that specific depletion of plasma fibronectin, because of codeposition with fibrin or due to increased utilization as a nonspecific opsonin, may contribute to the organ failure seen in severely ill patients.

Topics: Adult; Bacterial Infections; Cold Temperature; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Glycoproteins; Humans; Male; Membrane Proteins; Middle Aged; Neoplasms; Virus Diseases

Radially oriented acicular crystalline aggregates could be induced by incubating heparinised blood with bacterial endotoxins. These aggregates did not appear in the blood of 37 healthy volunteers but were observed in the blood of 130 patients, predominantly those with vasculitis, psoriasis, and bacterial infections. Study of these asteroid structures, which resemble 'sunbursts', led to the view that they are oriented crystals of fibrin radiating from a central platelet mass undergoing lysis.

Topics: Bacterial Infections; Blood Platelets; Crystallization; Dermatitis; Endotoxins; Enterobacteriaceae; Fibrin; Hemolysis; Humans; Hypersensitivity; In Vitro Techniques; Pseudomonas aeruginosa; Psoriasis; Streptococcus; Vascular Diseases

Of 35 newborn infants who died from an infection 19 had postmortem evidence of massive pulmonary hemorrhage. All but 1 of the 19 had evidence of antimortem formation of intravascular fibrin clots in lung tissue. Seventeen infants had low platelet counts. Of the 11 infants in whom coagulation studies were done, 8 had evidence of disseminated intravascular coagulation (DIC) during life. Vasculitis in the lungs, associated with fibrin clots and hemorrhages, was detected in two infants. It is postulated that sepsis is an important cause of hemorrhage in the newborn, probably as a result of the development of DIC.

Topics: Bacterial Infections; Disseminated Intravascular Coagulation; Escherichia coli Infections; Fibrin; Hemoptysis; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Klebsiella Infections; Lung; Male

Ninety-three postoperative patients 1 day to 13 years of age had blood cultures, limulus lysate assay, determination of fibrin degradation products, white blood cell and platelet counts. Seven groups were studied. The limulus lysate assay was often positive (64%) in the presence of gram negative septicemia but there were false positives and negatives. The tests for fibrin degradation products were inconsistent. The white blood cell count was low in babies with gram negative septicemia. One hundred per cent of the infants with gram negative septicemia had a platelet count below 150,000; 71% below 100,000 (average 67,000 septic babies, 257,000 non-septic babies). The drop in platelet count with gram negative septicemia was abrupt---as much as 222,000 in 24 hours. Platelets increased when therapy was effective. Two children with gram negative septicemia had platelet counts of 50,000 and 20,000. The platelet count for patients with gram positive septicemia was 299,000, and above 150,000 in all children with ruptured and non-ruptured appendicitis and major surgery without gram negative septicemia. It was concluded that serial measurements of platelet count in the postoperative infant and child was a rapid and reliable method for early detection of gram negative septicemia and changes in platelet count in response to treatment was an indicator of the effectiveness of therapy.

Topics: Abdominal Muscles; Adolescent; Appendicitis; Bacteria; Bacterial Infections; Blood Cell Count; Blood Platelets; Child; Child, Preschool; Enterocolitis, Pseudomembranous; Escherichia coli Infections; Fibrin; Gangrene; Humans; Infant; Infant, Newborn; Intestinal Obstruction; Klebsiella Infections; Leukocyte Count; Liver Neoplasms; Platelet Aggregation; Postoperative Complications; Pseudomonas Infections; Sepsis; Time Factors

Topics: Adolescent; Adult; Aged; Bacterial Infections; Blood Cell Count; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Child; Female; Fibrin; Fibrinogen; Humans; Male; Methods; Middle Aged; Mycoplasma Infections; Sepsis; Virus Diseases

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Blood Vessels; Disseminated Intravascular Coagulation; Drug Hypersensitivity; Female; Fibrin; Humans; Lupus Erythematosus, Systemic; Prednisone; Purpura, Thrombotic Thrombocytopenic; Splenectomy

Infection is well recognized as a complication of intrauterine transfusion. The majority of cases are fortunately mild and consist merely of chorio-amnionitis. The present case, of severe type, resulted from contamination of the donor blood with Acinetobacter calcoaceticus. Spread of infection from foetus to mother has been carefully studied and an entirely new type of lesion in the placenta described. This takes the form of acute villous inflammation with resultant micro-abscess formation beneath the trophoblast layer and eventual rupture into the intervillous space. Attempts at localization are poor.

Topics: Abscess; Alcaligenes; Bacterial Infections; Blood Transfusion, Intrauterine; Coombs Test; Female; Fetal Diseases; Fibrin; Humans; Inflammation; Male; Myocardium; Placenta Diseases; Pregnancy; Pregnancy Complications; Trophoblasts

Topics: Animals; Antigens; Bacterial Infections; Brain; Cross Reactions; Demyelinating Diseases; Disease Models, Animal; Edema; Encephalomyelitis, Autoimmune, Experimental; Exudates and Transudates; Fibrin; Guinea Pigs; Haplorhini; Hemorrhage; Heparin; Humans; Immunization, Passive; Inflammation; Leukocytes; Lymphocytes; Multiple Sclerosis; Myelin Sheath; Pertussis Vaccine; Proteins; Rats; Virus Diseases